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Mishra D, Yadav P, Iqbal H, Parashar S, Negi AS, Chanda D. Dehydroepiandrosterone (DHEA), a circulating steroid hormone precursor produced potent vasorelaxation in rat aorta and mesenteric arteries through blockade of L-type voltage-dependent calcium channels. Microvasc Res 2025; 157:104758. [PMID: 39505234 DOI: 10.1016/j.mvr.2024.104758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/30/2024] [Accepted: 11/01/2024] [Indexed: 11/08/2024]
Abstract
Dehydroepiandrosterone (DHEA) is known for potent cardioprotective properties and diminished DHEA level in plasma is often associated with hypertension and age-related anomalies. However, putative ex-vivo vasorelaxation potential of DHEA in systemic resistance vessels like mesenteric arteries and conduit arteries like aorta are still to be worked out. The study aimed to explore vasorelaxation potential of DHEA in superior and resistance mesenteric arteries and aorta in rats and to determine the contribution L-type Voltage dependent calcium channel (L-VDCC) in the relaxation response in these arterial tissues. Ex-vivo vasorelaxation potential of DHEA in isolated arterial tissues were evaluated and the mechanism of vasorelaxation induced by DHEA was characterized by contraction experiment in isolated arterial tissue and in-vitro calcium imaging assay using Fluo-4 in primary vascular smooth muscle cells derived from aorta. In the current study, DHEA was found to exhibit potent concentration dependent, endothelium and potassium channel independent vasorelaxation response in conduit and resistance arteries. The block of L-type VDCCs was evident from the findings that DHEA in a concentration-dependent manner inhibited both BAY K-8644 and CaCl2-induced contractions. The results of the contraction experiment were further substantiated by Fluo-4 mediated calcium imaging assay in primary rat vascular smooth muscle wherein DHEA concentration dependently blocked noradrenaline and BAY K-8644-induced rise in intracellular calcium fluorescence. The present study showed potent endothelium and potassium channel independent vasorelaxation properties of DHEA in aorta, superior and resistance mesenteric artery mediated predominantly through blockade of L-VDCC.
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MESH Headings
- Animals
- Calcium Channels, L-Type/metabolism
- Calcium Channels, L-Type/drug effects
- Vasodilation/drug effects
- Dehydroepiandrosterone/pharmacology
- Male
- Muscle, Smooth, Vascular/drug effects
- Muscle, Smooth, Vascular/metabolism
- Mesenteric Arteries/drug effects
- Mesenteric Arteries/metabolism
- Myocytes, Smooth Muscle/drug effects
- Myocytes, Smooth Muscle/metabolism
- Vasodilator Agents/pharmacology
- Calcium Channel Blockers/pharmacology
- Cells, Cultured
- Dose-Response Relationship, Drug
- Rats
- Calcium Signaling/drug effects
- Mesenteric Artery, Superior/metabolism
- Mesenteric Artery, Superior/drug effects
- Rats, Sprague-Dawley
- Aorta/drug effects
- Aorta/metabolism
- Rats, Wistar
- Aniline Compounds/pharmacology
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Affiliation(s)
- Divya Mishra
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India
| | - Pankaj Yadav
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India
| | - Hina Iqbal
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India
| | - Shweta Parashar
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India
| | - Arvind Singh Negi
- Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India
| | - Debabrata Chanda
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
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Davis SR, Azene ZN, Tonkin AM, Woods RL, McNeil JJ, Islam RM. Higher testosterone is associated with higher HDL-cholesterol and lower triglyceride concentrations in older women: an observational study. Climacteric 2024; 27:282-288. [PMID: 38345304 PMCID: PMC11196127 DOI: 10.1080/13697137.2024.2310530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 01/20/2024] [Indexed: 05/12/2024]
Abstract
OBJECTIVE This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women. METHODS The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography-tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders. RESULTS The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7-77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) (p = 0.002 and p < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol (p = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) (p = 0.024, p = 0.003 and p < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C (p = 0.024). CONCLUSIONS In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women.
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Affiliation(s)
- Susan R Davis
- Women’s Health Research Program, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 3004
- Department of Endocrinology and Diabetes, Alfred Health, Melbourne, Victoria Australia 3004
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 3004
| | - Zelalem N Azene
- Women’s Health Research Program, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 3004
| | - Andrew M Tonkin
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 3004
| | - Robyn L Woods
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 3004
| | - John J McNeil
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 3004
| | - Rakibul M Islam
- Women’s Health Research Program, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 3004
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia 3004
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Mourino-Alvarez L, Juarez-Alia C, Sastre-Oliva T, Perales-Sánchez I, Hernandez-Fernandez G, Chicano-Galvez E, Peralbo-Molina Á, Madruga F, Blanco-Lopez E, Tejerina T, Barderas MG. Dysregulation of Lipid Metabolism Serves as A Link Between Alzheimer's and Cardiovascular Disease, As Witnessed in A Cross-Sectional Study. Aging Dis 2024; 16:1769-1784. [PMID: 39012677 DOI: 10.14336/ad.2024.0434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 05/31/2024] [Indexed: 07/17/2024] Open
Abstract
Cardiovascular risk factors and established cardiovascular disease (CVD) increase the risk of suffering dementia of the Alzheimer's type (DAT). Here, we set out to define specific molecular profiles of CVD in patients with DAT to better understand its relationship, to unravel the mechanisms underlying the high risk of developing DAT in CVD patients and to define new markers of early disease. Plasma samples from patients with DAT, with and without CVD, were analyzed through a multiomics approach, with integration of metabolomics and proteomics datasets using the OmicsNet web-based tool. Metabolomics results showed an enrichment in lipids and lipid-like molecules. Similarly, the most significant cluster identified through proteomics was formed by 5 proteins related to lipoprotein and cholesterol metabolism. After integration and functional enrichment, glycerolipid metabolism, fatty acid degradation and sphingolipid metabolism were among the most significant functions. Finally, the differential expression of ABCA1 and APOH proteins was verified, in an independent cohort also including controls and patients with CVD alone. Both proteins positively correlated with phospho-Tau (181), a classical hallmark of DAT. Different molecular profiles exist in patients with DAT, with and without CVD, with exacerbated alterations in patients in which DAT and CVD co-exist. This information may help to define biomarkers like ABCA1 and APOH that identify patients with cardiovascular dysfunction that are at high risk of developing DAT. Such markers will allow more personalized interventions to be selected, a further step towards precision medicine for individuals whose molecular profiles indicate a distinct response to the same management strategies.
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Affiliation(s)
- Laura Mourino-Alvarez
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, SESCAM, 45071 Toledo, Spain
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, IDISCAM, 45071 Toledo, Spain
| | - Cristina Juarez-Alia
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, SESCAM, 45071 Toledo, Spain
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, IDISCAM, 45071 Toledo, Spain
| | - Tamara Sastre-Oliva
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, SESCAM, 45071 Toledo, Spain
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, IDISCAM, 45071 Toledo, Spain
| | - Inés Perales-Sánchez
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, SESCAM, 45071 Toledo, Spain
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, IDISCAM, 45071 Toledo, Spain
| | - German Hernandez-Fernandez
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, SESCAM, 45071 Toledo, Spain
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, IDISCAM, 45071 Toledo, Spain
| | - Eduardo Chicano-Galvez
- IMIBIC Mass Spectrometry and Molecular Imaging Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba (UCO), Córdoba, Spain
| | - Ángela Peralbo-Molina
- IMIBIC Mass Spectrometry and Molecular Imaging Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba (UCO), Córdoba, Spain
| | - Felipe Madruga
- Departament of Geriatrics, Hospital Virgen del Valle, SESCAM, Toledo, Spain
| | - Emilio Blanco-Lopez
- Department of Cardiology, Ciudad Real General University Hospital, Ciudad Real, Spain
| | - Teresa Tejerina
- Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - María G Barderas
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, SESCAM, 45071 Toledo, Spain
- Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, IDISCAM, 45071 Toledo, Spain
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Chen S, Li S, Zhang X, Fan Y, Liu M. Low serum dehydroepiandrosterone is associated with diabetic dyslipidemia risk in males with type 2 diabetes. Front Endocrinol (Lausanne) 2023; 14:1272797. [PMID: 38075062 PMCID: PMC10704365 DOI: 10.3389/fendo.2023.1272797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/07/2023] [Indexed: 12/18/2023] Open
Abstract
Objective Sex steroid hormones are associated with the advancement of metabolic diseases such as dyslipidemia. This cross-sectional study aimed to investigate the relationship between dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels and the risk of dyslipidemia in people with type 2 diabetes mellitus. Materials and Methods The analysis included 1,927 patients with type 2 diabetes mellitus. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone levels were determined using lipid chromatography-tandem mass spectrometry. Multivariable analyses were performed to investigate the association between the variables and dyslipidemia. Results The multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) of dyslipidemia across DHEA tertiles were 0.39 and 0.24-0.64, respectively (p trend = 0.001). This relationship was still maintained when analyzed as a continuous variable (odds ratio, 0.96; 95% confidence interval, 0.92-0.99; P < 0.01). However, in males with type 2 diabetes mellitus, no significant correlations were found between rising levels of dehydroepiandrosterone sulfate, androstenedione, and total testosterone and the risk of dyslipidemia (all P > 0.05). Furthermore, there was no significant association between androgen precursors and total testosterone with regard to the risk of developing dyslipidemia (all P > 0.05). Conclusions Serum dehydroepiandrosterone levels were substantially and adversely correlated with dyslipidemia in adult men with T2DM. These results indicated that dehydroepiandrosterone may have an essential role in the development of dyslipidemia. More prospective research is required to validate this link.
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Affiliation(s)
| | | | | | - Yuxin Fan
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Ming Liu
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
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5
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Jethwani P, Rastogi A, Shukla R. Dehydroepiandrosterone sulfate supplementation in health and diseases. World J Meta-Anal 2023; 11:102-111. [DOI: 10.13105/wjma.v11.i4.102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/09/2023] [Accepted: 04/10/2023] [Indexed: 04/14/2023] Open
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Xie D, Deng T, Zhai Z, Qin T, Song C, Xu Y, Sun T. Moschus exerted protective activity against H 2O 2-induced cell injury in PC12 cells through regulating Nrf-2/ARE signaling pathways. Biomed Pharmacother 2023; 159:114290. [PMID: 36708701 DOI: 10.1016/j.biopha.2023.114290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 01/13/2023] [Accepted: 01/19/2023] [Indexed: 01/27/2023] Open
Abstract
The pivotal characteristics of Alzheimer's disease (AD) are irreversible memory loss and progressive cognitive decline, eventually causing death from brain failure. In the various proposed hypotheses of AD, oxidative stress is also regarded as a symbolic pathophysiologic cascade contributing to brain diseases. Using Chinese herbal medicine may be beneficial for treating and preventing AD. As a rare and valuable animal medicine, Moschus possesses antioxidant and antiapoptotic efficacy and is extensively applied for treating unconsciousness, stroke, coma, and cerebrovascular diseases. We aim to evaluate whether Moschus protects PC12 cells from hydrogen peroxide (H2O2)-induced cellular injury. The chemical constituents of Moschus are analyzed by GC-MS assay. The cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP) levels, oxidative stress-related indicators, and apoptotic proteins are determined. Through GC-MS analysis, nineteen active contents were identified. The cell viability loss, lactate dehydrogenase releases, MMP levels, ROS productions, and Malondialdehyde (MDA) activities decreased, and BAX, Caspase-3, and Kelch-like ECH-associated protein 1 expression also significantly down-regulated and heme oxygenase 1, nuclear factor erythroid-2-related factor 2 (Nrf-2), and quinine oxidoreductase 1 expression upregulated after pretreatment of Moschus. The result indicated Moschus has neuroprotective activity in relieving H2O2-induced cellular damage, and the potential mechanism might be associated with regulating the Nrf-2/ARE signaling pathway. A more in-depth and comprehensive understanding of Moschus in the pathogenesis of AD will provide a fundamental basis for in vivo AD animal model research, which may be able to provide further insights and new targets for AD therapy.
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Affiliation(s)
- Danni Xie
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Ting Deng
- Jintang Second People' s Hospital, Chengdu 610404, China.
| | - Zhenwei Zhai
- School of Medical Information Engineering, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Tao Qin
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Caiyou Song
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Ying Xu
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
| | - Tao Sun
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; School of Medical Information Engineering, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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7
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Stamou MI, Colling C, Dichtel LE. Adrenal aging and its effects on the stress response and immunosenescence. Maturitas 2023; 168:13-19. [PMID: 36370489 PMCID: PMC10426230 DOI: 10.1016/j.maturitas.2022.10.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 10/14/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022]
Abstract
Normal aging is linked to various endocrine gland changes, including changes in the adrenal glands. Aging is linked to alterations of the hypothalamic-pituitary-adrenal (HPA) axis, including an increase in cortisol levels, a disruption of the negative cortisol feedback, and attenuation of cortisol's diurnal pattern. In addition, secretion of aldosterone and adrenal androgens [dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)] from the adrenal cortex decreases with aging. In this review, we describe normal adrenal function, the adrenal response to stress and immunomodulation in aging individuals as well as the effects of adrenal aging on body composition, metabolic profile, bone health and cognition.
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Affiliation(s)
- Maria I Stamou
- Endocrine Division, Massachusetts General Hospital, Boston, MA, USA.
| | - Caitlin Colling
- Endocrine Division, Massachusetts General Hospital, Boston, MA, USA
| | - Laura E Dichtel
- Endocrine Division, Massachusetts General Hospital, Boston, MA, USA
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Liang J, Zhang B, Hu Y, Na Z, Li D. Effects of steroid hormones on lipid metabolism in sexual dimorphism: A Mendelian randomization study. Front Endocrinol (Lausanne) 2023; 13:1119154. [PMID: 36726474 PMCID: PMC9886494 DOI: 10.3389/fendo.2022.1119154] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 12/28/2022] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Although the role of steroid hormones in lipid levels has been partly discussed in the context of separate sexes, the causal relationship between steroid hormones and lipid metabolism according to sex has not been elucidated because of the limitations of observational studies. We assessed the relationship between steroid hormones and lipid metabolism in separate sexes using a two-sample Mendelian randomization (MR) study. METHODS Instrumental variables for dehydroepiandrosterone sulfate (DHEAS), progesterone, estradiol, and androstenedione were selected. MR analysis was performed using inverse-variance weighted, MR-Egger, weighted median, and MR pleiotropy residual sum and outlier tests. Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis were used for sensitivity analyses. RESULTS The results showed that the three steroid hormones affected lipid metabolism and exhibited sex differences. In males, DHEAS was negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (P = 0.007; P = 0.006; P = 0.041, respectively), and progesterone was negatively correlated with TC and LDL-C (P = 0.019; P = 0.038, respectively). In females, DHEAS was negatively correlated with TC (P = 0.026) and androstenedione was negatively correlated with triglycerides and apolipoprotein A (P = 0.022; P = 0.009, respectively). No statistically significant association was observed between the estradiol levels and lipid metabolism in male or female participants. CONCLUSIONS Our findings identified sex-specific causal networks between steroid hormones and lipid metabolism. Steroid hormones, including DHEAS, progesterone, and androstenedione, exhibited beneficial effects on lipid metabolism in both sexes; however, the specific lipid profiles affected by steroid hormones differed between the sexes.
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Affiliation(s)
- Junzhi Liang
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bowen Zhang
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yannan Hu
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhijing Na
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Reproductive and Genetic Medicine (China Medical University), National Health Commission, Shenyang, China
| | - Da Li
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
- Key Laboratory of Reproductive and Genetic Medicine (China Medical University), National Health Commission, Shenyang, China
- Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodeling of Liaoning Province, Shengjing Hospital of China Medical University, Shenyang, China
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9
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Pezel T, Michos ED, Varadarajan V, Shabani M, Venkatesh BA, Vaidya D, Kato Y, De Vasconcellos HD, Heckbert SR, Wu CO, Post WS, Bluemke DA, Allison MA, Henry P, Lima JAC. Prognostic value of a left atrioventricular coupling index in pre- and post-menopausal women from the Multi-Ethnic Study of Atherosclerosis. Front Cardiovasc Med 2022; 9:1066849. [PMID: 36479563 PMCID: PMC9719991 DOI: 10.3389/fcvm.2022.1066849] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 11/02/2022] [Indexed: 10/08/2024] Open
Abstract
BACKGROUND Sex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in women, but the association of menopause status with left atrioventricular coupling is not established. AIM To assess the prognostic value of a left atrioventricular coupling index (LACI) in peri-menopausal women without a history of cardiovascular disease (CVD). MATERIALS AND METHODS In all women participating in MESA study with baseline cardiovascular MRI, the LACI was measured as the ratio of the LA end-diastolic volume to the LV end-diastolic volume. Cox models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), coronary heart disease (CHD) death, and hard CVD. RESULTS Among the 2,087 women participants (61 ± 10 years), 485 cardiovascular events occurred (mean follow-up: 13.2 ± 3.3 years). A higher LACI was independently associated with AF (HR 1.70; 95%CI [1.51-1.90]), HF (HR 1.62; [1.33-1.97]), CHD death (HR 1.36; [1.10-1.68]), and hard CVD (HR 1.30; [1.13-1.51], all p < 0.001). Adjusted models with the LACI showed significant improvement in model discrimination and reclassification when compared to traditional models to predict: incident AF (C-statistic: 0.82 vs. 0.79; NRI = 0.325; IDI = 0.036), HF (C-statistic: 0.84 vs. 0.81; NRI = 0.571; IDI = 0.023), CHD death (C-statistic: 0.87 vs. 0.85; NRI = 0.506; IDI = 0.012), hard CVD (C-statistic: 0.78 vs. 0.76; NRI = 0.229; IDI = 0.012). The prognostic value of the LACI had a better discrimination and reclassification than individual LA or LV parameters. CONCLUSION In a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, CHD death, and hard CVD. CLINICAL TRIAL REGISTRATION [https://clinicaltrials.gov/], identifier [NCT00005487].
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Affiliation(s)
- Théo Pezel
- Division of Cardiology, Johns Hopkins University, Baltimore, MD, United States
- Université de Paris Cité, Service de Cardiologie, Hôpital Universitaire Lariboisière – APHP, Paris, France
| | - Erin D. Michos
- Division of Cardiology, Johns Hopkins University, Baltimore, MD, United States
| | | | - Mahsima Shabani
- Division of Cardiology, Johns Hopkins University, Baltimore, MD, United States
| | | | - Dhananjay Vaidya
- Department of Medicine Division of General Medicine, The Johns Hopkins University, Baltimore, MD, United States
| | - Yoko Kato
- Division of Cardiology, Johns Hopkins University, Baltimore, MD, United States
| | | | - Susan R. Heckbert
- Department of Epidemiology, University of Washington, Seattle, WA, United States
| | - Colin O. Wu
- Division of Intramural Research, National Heart Lung and Blood Institute, Bethesda, MD, United States
| | - Wendy S. Post
- Division of Cardiology, Johns Hopkins University, Baltimore, MD, United States
| | - David A. Bluemke
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Matthew A. Allison
- Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, United States
| | - Patrick Henry
- Université de Paris Cité, Service de Cardiologie, Hôpital Universitaire Lariboisière – APHP, Paris, France
| | - Joao A. C. Lima
- Division of Cardiology, Johns Hopkins University, Baltimore, MD, United States
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Takeshita RS, Edler MK, Meindl RS, Sherwood CC, Hopkins WD, Raghanti MA. Age, adrenal steroids, and cognitive functioning in captive chimpanzees ( Pan troglodytes). PeerJ 2022; 10:e14323. [PMID: 36389417 PMCID: PMC9653054 DOI: 10.7717/peerj.14323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 10/10/2022] [Indexed: 11/11/2022] Open
Abstract
Background Dehydroepiandrosterone-sulfate is the most abundant circulating androgen in humans and other catarrhines. It is involved in several biological functions, such as testosterone production, glucocorticoid antagonist actions, neurogenesis and neuroplasticty. Although the role of dehydroepiandrosterone-sulfate (DHEAS) in cognition remains elusive, the DHEAS/cortisol ratio has been positively associated with a slower cognitive age-decline and improved mood in humans. Whether this relationship is found in nonhuman primates remains unknown. Methods We measured DHEAS and cortisol levels in serum of 107 adult chimpanzees to investigate the relationship between DHEAS levels and age. A subset of 21 chimpanzees was used to test the potential associations between DHEAS, cortisol, and DHEAS/cortisol ratio in cognitive function, taking into account age, sex, and their interactions. We tested for cognitive function using the primate cognitive test battery (PCTB) and principal component analyses to categorize cognition into three components: spatial relationship tasks, tool use and social communication tasks, and auditory-visual sensory perception tasks. Results DHEAS levels, but not the DHEAS/cortisol ratio, declined with age in chimpanzees. Our analyses for spatial relationships tasks revealed a significant, positive correlation with the DHEAS/cortisol ratio. Tool use and social communication had a negative relationship with age. Our data show that the DHEAS/cortisol ratio, but not DHEAS individually, is a promising predictor of spatial cognition in chimpanzees.
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Affiliation(s)
- Rafaela S.C. Takeshita
- Department of Anthropology, Kent State University, Kent, OH, USA,School of Biomedical Sciences, Kent State University, Kent, OH, USA,Brain Health Research Institute, Kent State University, Kent, OH, USA
| | - Melissa K. Edler
- Department of Anthropology, Kent State University, Kent, OH, USA,School of Biomedical Sciences, Kent State University, Kent, OH, USA,Brain Health Research Institute, Kent State University, Kent, OH, USA
| | - Richard S. Meindl
- Department of Anthropology, Kent State University, Kent, OH, USA,School of Biomedical Sciences, Kent State University, Kent, OH, USA
| | - Chet C. Sherwood
- Department of Anthropology, The George Washington University, Washington, DC, USA
| | - William D. Hopkins
- Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA
| | - Mary Ann Raghanti
- Department of Anthropology, Kent State University, Kent, OH, USA,School of Biomedical Sciences, Kent State University, Kent, OH, USA,Brain Health Research Institute, Kent State University, Kent, OH, USA
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11
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Oh ES, Steele CN, You Z, Nowak KL, Jovanovich AJ. Sex hormones and the risk of cardiovascular disease and mortality in male and female patients with chronic kidney disease: A systematic review and meta-analysis. Physiol Rep 2022; 10:e15490. [PMID: 36394074 PMCID: PMC9669609 DOI: 10.14814/phy2.15490] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 09/20/2022] [Indexed: 11/18/2022] Open
Abstract
Patients with chronic kidney disease (CKD) commonly experience sex hormone disturbances, which may be associated with the risk of cardiovascular disease (CVD) and mortality. This review aimed to systematically evaluate current findings on the association of sex hormone levels with the risk of CVD events and mortality (CVD and all-cause) in the CKD population. Articles were systematically searched in CINAHL, Cochrane, and PubMed. A total of 1739 articles were independently screened by two reviewers and 17 prospective cohort studies were included. The clinical conditions of the patients were those with non-dialysis CKD [mean/median estimated glomerular filtration rate (eGFR) between 15-51 ml/min/1.73 m2 ] and those on chronic dialysis (mean/median vintage between 6-125 months). The sample size ranged from 111 to 2419 and the mean/median age of subjects ranged from 52 to 72 years. The sex hormones studied were testosterone, estradiol, prolactin, dehydroepiandrosterone sulfate, and relaxin. A random-effects model was used to generate a pooled hazard ratio (HR) to evaluate the association of total testosterone levels with the risk of CVD and all-cause mortality. Most studies examined total testosterone levels (11 out of 17 studies) and studied only male patients (12 out of 17 studies). A lower total testosterone level was associated with a higher risk of CVD mortality [HR 4.37 (95% CI 1.40-13.65)] and all-cause mortality [1.96 (1.35-2.83)] in males with CKD. To conclude, there is a strong need for additional studies examining the association of sex hormones with cardiovascular and mortality risk in female patients with CKD.
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Affiliation(s)
- Ester S. Oh
- Division of Renal Diseases and HypertensionUniversity of Colorado Anschutz Medical CampusAuroraColoradoUSA
| | - Cortney N. Steele
- Division of Renal Diseases and HypertensionUniversity of Colorado Anschutz Medical CampusAuroraColoradoUSA
| | - Zhiying You
- Division of Renal Diseases and HypertensionUniversity of Colorado Anschutz Medical CampusAuroraColoradoUSA
| | - Kristen L. Nowak
- Division of Renal Diseases and HypertensionUniversity of Colorado Anschutz Medical CampusAuroraColoradoUSA
| | - Anna J. Jovanovich
- Division of Renal Diseases and HypertensionUniversity of Colorado Anschutz Medical CampusAuroraColoradoUSA
- VA Eastern Colorado Healthcare SystemAuroraColoradoUSA
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12
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Czapla-Iskrzycka A, Świątkowska-Stodulska R, Sworczak K. Comorbidities in Mild Autonomous Cortisol Secretion - A Clinical Review of Literature. Exp Clin Endocrinol Diabetes 2022; 130:567-576. [PMID: 35817047 DOI: 10.1055/a-1827-4113] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Mild autonomous cortisol secretion (mACS) is a state of cortisol excess usually associated with existence of adrenal incidentaloma. Because of the lack of symptoms of the disease, the biochemical evaluation is the most important to determine a diagnosis. However, scientific societies have different diagnostic criteria for mACS, which makes the treatment of this disease and using results of original papers in daily practice more difficult. Chronic hypercortisolemic state, even if mild, may lead to diseases that are mostly connected with overt Cushing's syndrome. Some of them can cause a higher mortality of patients with mACS and those problems need to be addressed. In this review we describe the comorbidities associated with mACS: cardiovascular disorders, arterial hypertension, diabetes mellitus, insulin resistance, dyslipidemia, obesity, metabolic syndrome, non-alcoholic fatty liver disease, vertebral fractures and osteoporosis. The point of this paper is to characterise them and determine if and how these conditions should be managed. Two databases - PubMed and Web of Science were searched. Even though the evidence are scarce, this is an attempt to lead clinicians through the problems associated with this enigmatic condition.
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Affiliation(s)
- Aleksandra Czapla-Iskrzycka
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - Renata Świątkowska-Stodulska
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - Krzysztof Sworczak
- Department of Endocrinology and Internal Medicine, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
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13
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Tasić T, Tadić M, Lozić M. Hypertension in Women. Front Cardiovasc Med 2022; 9:905504. [PMID: 35722103 PMCID: PMC9203893 DOI: 10.3389/fcvm.2022.905504] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 05/17/2022] [Indexed: 12/14/2022] Open
Abstract
Hypertension is one of the main causes of morbidity and mortality in the human population. Nevertheless, the intricate network of pathophysiological mechanisms that lead to the development of hypertension in women still awaits to be fully understood. From young age to maturity and senescence, the female body transits through different stages, each of them characterized with specific physiological features and disposition to particular pathological conditions, and that is exactly what makes the understanding of the genesis and adequate treatment of hypertension in women so challenging. Clinical and experimental findings emphasize the role of sex hormones, autonomic nervous system, renin-angiotensin-aldosterone system and arterial stiffness in the development of chronically elevated blood pressure in females. The purpose of this review is to briefly summarize the knowledge of the mechanisms and treatment of hypertension in women.
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Affiliation(s)
- Tatjana Tasić
- School of Dental Medicine, University of Belgrade, Belgrade, Serbia
| | - Marijana Tadić
- Clinic for Internal Medicine II, Cardiology Department, University Clinic of Ulm, Ulm, Germany
- *Correspondence: Marijana Tadić
| | - Maja Lozić
- Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
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14
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Sinha B, Ghosal S. A Meta-Analysis of the Effect of Sodium Glucose Cotransporter-2 Inhibitors on Metabolic Parameters in Patients With Polycystic Ovary Syndrome. Front Endocrinol (Lausanne) 2022; 13:830401. [PMID: 35265039 PMCID: PMC8900375 DOI: 10.3389/fendo.2022.830401] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 01/17/2022] [Indexed: 11/28/2022] Open
Abstract
Objective Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of childbearing age and is associated with multiple morbidities. However, treatment for this condition is mainly applied for symptomatic relief and does not address the complex pathophysiology of this condition. This meta-analysis was conducted on the usage of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in PCOS because this group of drugs presents an attractive strategy to address the metabolic and hormonal defects by managing the pathophysiological defects observed in this syndrome. Methods We included prospective trials that enrolled patients with established PCOS and compared an SGLT-2i group versus a control group with at least 2 weeks of follow-up. The standardized mean difference (SMD) was used for effect size estimation from individual studies and was pooled using the fixed effect model. Results We included four trials with a pooled population of 158 patients with documented PCOS who received either an SGLT-2i or standard management. From a metabolic perspective, significant improvements were observed in the reduction in body weight (SMD: -0.68, 95% CI -1.16 to -0.19, <0.01), fasting plasma glucose (FPG) (SMD: -0.59, 95% CI -0.99 to -0.19, P<0.01), and insulin resistance as assessed with the HOMA-IR (SMD: -0.39, 95% CI -0.76 to -0.03, P=0.03). In addition, a significant improvement was noted in dehydroepiandrosterone sulphate (DHEAS) levels (SMD: -0.55, 95% CI -0.94 to -0.16, P<0.01). Conclusion SGLT-2i use is associated with salutary outcomes of metabolic and anthropometric markers of PCOS and likely favourable hormonal effects. Clinical Trial Registration [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021268564], PROSPERO 2021 CRD42021268564.
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Affiliation(s)
- Binayak Sinha
- Department of Endocrinology, AMRI Hospitals, Kolkata, India
| | - Samit Ghosal
- Department of Endocrinology, Nightingale Hospital, Kolkata, India
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15
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Islam RM, Bell RJ, Handelsman DJ, McNeil JJ, Nelson MR, Reid CM, Tonkin AM, Wolfe RS, Woods RL, Davis SR. Associations between blood sex steroid concentrations and risk of major adverse cardiovascular events in healthy older women in Australia: a prospective cohort substudy of the ASPREE trial. THE LANCET. HEALTHY LONGEVITY 2022; 3:e109-e118. [PMID: 35252940 PMCID: PMC8896500 DOI: 10.1016/s2666-7568(22)00001-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Blood testosterone concentrations in women decline during the reproductive years and reach a nadir in the seventh decade, after which concentrations increase and are restored to those of reproductive-aged women early in the eighth decade. We aimed to establish the association between the concentration of testosterone in the blood and risk of major adverse cardiovascular events (MACE) and all-cause mortality in healthy older women. METHODS SHOW was a prospective cohort substudy of the longitudinal randomised ASPREE trial. Eligible participants were women aged at least 70 years from Australia with unimpaired cognition, no previous MACE, and a life expectancy of at least 5 years. Participants who were receiving hormonal or steroid therapy were ineligible for inclusion. We measured serum concentrations of sex steroids with liquid chromatography-tandem mass spectrometry and of SHBG with immunoassay. We compared lower concentrations of sex hormones with higher concentrations using four quartiles. Primary endpoints were risk of MACE and all-cause mortality, the associations of which with sex steroid concentrations were assessed using Cox proportional hazards regression that included age, body-mass index, smoking status, alcohol consumption, diabetes, hypertension, dyslipidaemia, impaired renal function, and treatment allocation in the ASPREE trial (aspirin vs placebo). ASPREE is registered with ClinicalTrials.gov, NCT01038583. FINDINGS Of the 9180 women recruited to the ASPREE trial between March 10, 2010, and Dec 31 2014, 6358 participants provided sufficient biobank samples at baseline and 5535 were included in the final analysis. Median age at entry was 74·0 years (IQR 71·7-77·7). During a median 4·4 years of follow-up (24 553 person-years), 144 (2·6%) women had a first MACE (incidence 5·9 per 1000 person-years). During a median 4·6 years of follow-up (3·8-5·6), 200 women died (7·9 per 1000 person-years). In the fully adjusted models, higher concentrations of testosterone were associated with a lower incidence of MACE (quartile 4 vs quartile 1: hazard ratio 0·57 [95% CI 0·36-0·91]; p=0·02), as were higher concentrations of DHEA (quartile 4 vs quartile 1: 0·61 [0·38-0·97]; p=0·04). For oestrone, a lower risk of MACE was seen for concentrations in quartile 2 only, compared with quartile 1 (0·55 [0·33-0·92]; p=0·02). In fully adjusted models, no association was seen between SHBG and MACE, or between any hormone or SHBG and all-cause mortality. INTERPRETATION Blood concentrations of testosterone and DHEA above the lowest quartile in older women were associated with a reduced risk of a first-ever MACE. Given that the physiological effects of DHEA are mediated through its steroid metabolites, if the current findings were to be replicated, trials investigating testosterone therapy for the primary prevention of ischaemic cardiovascular disease events in older women would be warranted. FUNDING The National Health and Medical Research Council of Australia, US National Institute on Aging, the Victorian Cancer Agency, the Commonwealth Scientific and Industrial Research Organisation, and Monash University.
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Affiliation(s)
- Rakibul M Islam
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
| | - Robin J Bell
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
| | - David J Handelsman
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
| | - John J McNeil
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
| | - Mark R Nelson
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
| | - Christopher M Reid
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
| | - Andrew M Tonkin
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
| | - Rory S Wolfe
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
| | - Robyn L Woods
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
| | - Susan R Davis
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (R M Islam PhD, Prof R J Bell MBBS, Prof J J McNeil MBBS, Prof M R Nelson MBBS, Prof C M Reid PhD, Prof R S Wolfe PhD, R L Woods PhD, Prof S R Davis MBBS); ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia (Prof D J Handelsman MBBS); Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia (Prof M R Nelson); School of Population Health, Curtin University, Bentley, WA, Australia (Prof C M Reid)
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16
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Zhang X, Xiao J, Liu T, He Q, Cui J, Tang S, Li X, Liu M. Low Serum Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate Are Associated With Coronary Heart Disease in Men With Type 2 Diabetes Mellitus. Front Endocrinol (Lausanne) 2022; 13:890029. [PMID: 35832423 PMCID: PMC9271610 DOI: 10.3389/fendo.2022.890029] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 05/17/2022] [Indexed: 11/13/2022] Open
Abstract
AIMS Sex hormones play an important role in the pathogenesis of cardiovascular disease (CVD). This cross-sectional study aimed to explore the associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with coronary heart disease (CHD) and stroke in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS A total of 995 patients with T2DM were included in the study analysis. Serum levels of DHEA and DHEAS were quantified using liquid chromatography-tandem mass spectrometry. Binary logistic regression analyses were performed to assess the associations of DHEA and DHEAS with CHD and stroke. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal DHEA and DHEAS cutoff values for the detection of CHD in men with T2DM. RESULTS In men with T2DM, after adjustment for potential confounders in model 3, the risk of CHD decreased with an increasing serum DHEA level [odds ratio (OR) = 0.38, quartile 4 vs. quartile 1; 95% confidence interval (CI) = 0.16-0.90; p = 0.037 for trend). Consistently, when considered as a continuous variable, this association remained significant in the fully adjusted model (OR = 0.59, 95% CI = 0.40-0.87, p < 0.05). When taken as a continuous variable in model 3, serum DHEAS level was also inversely related to the risk of CHD among men (OR = 0.56, 95% CI = 0.38-0.82, p < 0.05). Similarly, this relationship remained statistically significant when DHEAS was categorized into quartiles (OR = 0.27, quartile 4 vs. quartile 1; 95% CI = 0.11-0.67; p = 0.018 for trend). ROC curve analyses revealed that the optimal cutoff values to detect CHD in men with T2DM were 6.43 nmol/L for DHEA and 3.54 μmol/L for DHEAS. In contrast, no significant associations were found between DHEA and DHEAS on the one hand and stroke on the other in men and women with T2DM (all p > 0.05). CONCLUSIONS Serum DHEA and DHEAS were significantly and negatively associated with CHD in middle-aged and elderly men with T2DM. This study suggests potential roles of DHEA and DHEAS in CHD pathogenesis.
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Affiliation(s)
| | | | | | | | | | - Shaofang Tang
- *Correspondence: Ming Liu, ; Xin Li, ; Shaofang Tang,
| | - Xin Li
- *Correspondence: Ming Liu, ; Xin Li, ; Shaofang Tang,
| | - Ming Liu
- *Correspondence: Ming Liu, ; Xin Li, ; Shaofang Tang,
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17
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Hu P, Huang J, Lu Y, Zheng M, Li H, Duan X, Deng H, Zhao W, Liu X. Circulating sex hormones and risk of atrial fibrillation: A systematic review and meta-analysis. Front Cardiovasc Med 2022; 9:952430. [PMID: 36072857 PMCID: PMC9441879 DOI: 10.3389/fcvm.2022.952430] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 07/28/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Sex hormones are associated with many cardiovascular risk factors, but their effects on atrial fibrillation (AF) incidence remain unclear. This systematic review and meta-analysis aimed to evaluate the association of circulating sex hormones with AF risk by pooling available data from observational studies. METHODS A systematic literature search for pertinent articles with case-control and cohort designs was conducted via five databases up to 7 July 2021. A meta-analysis with six cohort studies was conducted separately on men and women. Adjusted relative risk (RR) with a 95% confidence interval (CI) was derived by comparing the highest with the lowest levels of a specific sex hormone and by using a random-effect or fixed-effect model. Heterogeneity was tested using the I 2 statistic and the Q-test. RESULTS A total of six cohort studies and four case-control studies were included. In a meta-analysis of cohort studies, dehydroepiandrosterone sulfate (DHEAS) was associated with a decreased risk of AF in men (RR: 0.729, 95% CI: 0.559-0.952, I 2 = 50.0%, P -heterogeneity = 0.157) after combining results from two cohort studies; total testosterone was not associated with any risk of AF in men and postmenopausal women, and AF risk was not associated with estradiol in men after synthesizing available studies. CONCLUSION This study indicates that a higher endogenous DHEAS level was associated with a lower AF risk in men, whereas total testosterone and estradiol were not associated with AF risk. Longitudinal studies with multiple monitoring are needed to further promulgate the relationship between various circulating sex hormones and AF risk.
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Affiliation(s)
- Peng Hu
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
| | - Jun Huang
- Department of Geriatrics, Institute of Geriatrics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, China
| | - Yi Lu
- Health Effects Institute, Boston, MA, United States
| | - Murui Zheng
- Guangzhou Center for Disease Control and Prevention, Guangzhou, China
| | - Haiyi Li
- Shantou University Medical College, Shantou, China
| | - Xueru Duan
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Hai Deng
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou, China
- Hai Deng,
| | - Wenjing Zhao
- School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, China
- Wenjing Zhao,
| | - Xudong Liu
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
- *Correspondence: Xudong Liu,
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18
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Somagutta MR, Jain M, Uday U, Pendyala SK, Mahadevaiah A, Mahmutaj G, Jarapala N, Gad MA, Srinivas PM, Sasidharan N, Mustafa N. Novel Antidiabetic Medications in Polycystic Ovary Syndrome. Discoveries (Craiova) 2022; 10:e145. [PMID: 36518222 PMCID: PMC9745014 DOI: 10.15190/d.2022.4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 03/24/2022] [Accepted: 03/31/2022] [Indexed: 09/14/2024] Open
Abstract
Polycystic ovary syndrome is a very common endocrine disorder prevalent in premenopausal women. Patients with polycystic ovary syndrome present with abnormal menstruation, ovulation disorders, and hyperandrogenemia. They are often accompanied by insulin resistance, metabolic disorders, and other cardiovascular abnormalities. Also, they have comorbidities, such as dyslipidemia, obesity, diabetes type 2, non-alcoholic fatty liver disease, which all influence the treatment plan. Metformin has been defined as a treatment option in patients with polycystic ovary syndrome. However, the clinical responses to metformin are limited. Thus, the need for novel treatments with a broad range of coverage for the complications is warranted. Sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, incretin analogs are novel drugs approved for treating type-2 diabetes. Because of their recorded benefit with weight loss, improved insulin resistance, and cardiovascular benefits in recent studies, they may help polycystic ovary syndrome women address the polycystic ovary syndrome-related risk of metabolic, reproductive, and psychological consequences. Limited literature is available on the safety and efficacy of these novel antidiabetic drugs in patients with polycystic ovary syndrome. Thus, this review is investigating the role and effectiveness of novel antidiabetic medication as an early therapeutic option in polycystic ovary syndrome.
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Affiliation(s)
| | - Molly Jain
- Saint James School of Medicine, Park Ridge, Illinois, USA
| | - Utkarsha Uday
- West Bengal University of Health Sciences, Kolkata, India
| | | | | | | | | | - Mohamed A. Gad
- Saint George's School of Medicine, St. George's, Grenada
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Singh P, Covassin N, Marlatt K, Gadde KM, Heymsfield SB. Obesity, Body Composition, and Sex Hormones: Implications for Cardiovascular Risk. Compr Physiol 2021; 12:2949-2993. [PMID: 34964120 PMCID: PMC10068688 DOI: 10.1002/cphy.c210014] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Cardiovascular disease (CVD) continues to be the leading cause of death in adults, highlighting the need to develop novel strategies to mitigate cardiovascular risk. The advancing obesity epidemic is now threatening the gains in CVD risk reduction brought about by contemporary pharmaceutical and surgical interventions. There are sex differences in the development and outcomes of CVD; premenopausal women have significantly lower CVD risk than men of the same age, but women lose this advantage as they transition to menopause, an observation suggesting potential role of sex hormones in determining CVD risk. Clear differences in obesity and regional fat distribution among men and women also exist. While men have relatively high fat in the abdominal area, women tend to distribute a larger proportion of their fat in the lower body. Considering that regional body fat distribution is an important CVD risk factor, differences in how men and women store their body fat may partly contribute to sex-based alterations in CVD risk as well. This article presents findings related to the role of obesity and sex hormones in determining CVD risk. Evidence for the role of sex hormones in determining body composition in men and women is also presented. Lastly, the clinical potential for using sex hormones to alter body composition and reduce CVD risk is outlined. © 2022 American Physiological Society. Compr Physiol 12:1-45, 2022.
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Affiliation(s)
- Prachi Singh
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
| | | | - Kara Marlatt
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
| | - Kishore M Gadde
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
| | - Steven B Heymsfield
- Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
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Tang J, Chen LR, Chen KH. The Utilization of Dehydroepiandrosterone as a Sexual Hormone Precursor in Premenopausal and Postmenopausal Women: An Overview. Pharmaceuticals (Basel) 2021; 15:46. [PMID: 35056103 PMCID: PMC8781653 DOI: 10.3390/ph15010046] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 12/16/2021] [Accepted: 12/27/2021] [Indexed: 12/03/2022] Open
Abstract
Dehydroepiandrosterone (DHEA), and its metabolite, dehydroepiandrosterone sulfate ester (DHEAS), are the most abundant circulating steroid hormones, and are synthesized in the zona reticularis of the adrenal cortex, in the gonads, and in the brain. The precise physiological role of DHEA and DHEAS is not yet fully understood, but these steroid hormones can act as androgens, estrogens, and neurosteroids, and perform many roles in the human body. Since both levels decline with age, use of DHEA supplements have gained more attention due to being advertised as an antidote to aging in postmenopausal women, who may have concerns on age-related diseases and overall well-being. However, current research has not reached an overall consensus on the effects of DHEA on postmenopausal women. This overview is a summary of the current literature, addressing the metabolic pathway for DHEA synthesis and utilization, as well as the effects of DHEA on premenopausal and postmenopausal women with disease states and other factors. As for the therapeutic effects on menopausal syndrome and other age-related diseases, several studies have found that DHEA supplementations can alleviate vasomotor symptoms, preserve the integrity of the immune system, reduce bone loss, and increase muscle mass. Intravaginal DHEA has shown significant beneficial effects in menopausal women with severe vulvovaginal symptoms. On the other hand, DHEA supplements have not shown definitive effects in cardiovascular disease, adrenal insufficiency, insulin sensitivity, and cognition. Due to inadequate sample sizes and treatment durations of current studies, it is difficult to assess the safety and efficacy of DHEA and draw reliable conclusions for the physiological role, the optimal dosage, and the effects on premenopausal and postmenopausal women; therefore, the study of DHEA warrants future investigation. Further research into the roles of these steroid hormones may bring us closer to a therapeutic option in the future.
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Affiliation(s)
- Justine Tang
- School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan;
| | - Li-Ru Chen
- Department of Physical Medicine and Rehabilitation, Mackay Memorial Hospital, Taipei 104, Taiwan;
- Department of Mechanical Engineering, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan
| | - Kuo-Hu Chen
- Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, Taipei 231, Taiwan
- School of Medicine, Tzu-Chi University, Hualien 970, Taiwan
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21
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Cipriani S, Maseroli E, Di Stasi V, Scavello I, Todisco T, Rastrelli G, Fambrini M, Sorbi F, Petraglia F, Jannini EA, Maggi M, Vignozzi L. Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction. J Endocrinol Invest 2021; 44:2765-2776. [PMID: 34118018 PMCID: PMC8572206 DOI: 10.1007/s40618-021-01598-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023]
Abstract
PURPOSE To explore the effects of 6-month systemic testosterone (T) administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD). METHODS 81 women with FSD were retrospectively recruited. Data on CDU parameters at baseline and after 6 months with four different treatments were available and thus further longitudinally analyzed: local non-hormonal moisturizers (NH group), n = 37; transdermal 2% T gel 300 mcg/day (T group), n = 23; local estrogens (E group), n = 12; combined therapy (T + E group), n = 9. Patients underwent physical, laboratory, and genital CDU examinations at both visits and completed different validated questionnaires, including the Female Sexual Function Index (FSFI). RESULTS At 6-month visit, T therapy significantly increased clitoral artery peak systolic velocity (PSV) when compared to both NH (p < 0.0001) and E (p < 0.0001) groups. A similar increase was found in the T + E group (p = 0.039 vs. E). In addition, T treatment was associated with significantly higher FSFI desire, pain, arousal, lubrication, orgasm, and total scores at 6-month visit vs. baseline. Similar findings were observed in the T + E group. No significant differences in the variations of total and high-density lipoprotein-cholesterol, triglycerides, fasting glycemia, insulin and glycated hemoglobin levels were found among the four groups. No adverse events were observed. CONCLUSION In women complaining for FSD, systemic T administration, either alone or combined with local estrogens, was associated with a positive effect on clitoral blood flow and a clinical improvement in sexual function, showing a good safety profile. TRIAL REGISTRATION NUMBER NCT04336891; date of registration: April 7, 2020.
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Affiliation(s)
- S Cipriani
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy
| | - E Maseroli
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy
| | - V Di Stasi
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy
| | - I Scavello
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy
| | - T Todisco
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy
| | - G Rastrelli
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy
| | - M Fambrini
- Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", Gynecology Unit, University of Florence, Florence, Italy
| | - F Sorbi
- Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", Gynecology Unit, University of Florence, Florence, Italy
| | - F Petraglia
- Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", Gynecology Unit, University of Florence, Florence, Italy
| | - E A Jannini
- Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - M Maggi
- Endocrinology Unit, Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
- I.N.B.B. (Istituto Nazionale Biostrutture E Biosistemi), Rome, Italy
| | - L Vignozzi
- Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences "Mario Serio", University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy.
- I.N.B.B. (Istituto Nazionale Biostrutture E Biosistemi), Rome, Italy.
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22
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Zhang S, Zhou J, Li L, Pan X, Lin J, Li C, Leung WT, Wang L. Effect of dehydroepiandrosterone on atherosclerosis in postmenopausal women. Biosci Trends 2021; 15:353-364. [PMID: 34759119 DOI: 10.5582/bst.2021.01320] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
In China, cardiovascular disease (CVD) has surpassed malignant tumours to become the disease with the highest mortality rate, and atherosclerosis (AS) is an important pathological cause of CVD. Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in circulating human blood and is a precursor of estrogen and androgen. DHEA is converted into a series of sex hormones in local peripheral tissues where its acts physiologically. DHEA also acts therapeutically, thereby avoiding the adverse systemic reactions to sex hormones. DHEA inhibits AS, thus inhibiting the development of CVD, and it improves the prognosis for CVD. The incidence of CVD in postmenopausal women is substantially higher than that in premenopausal women, and that incidence is believed to be related to a decrease in ovarian function. The current review analyzes the mechanisms of postmenopausal women's susceptibility to AS. They tend to have dyslipidemia, and their vascular smooth muscle cells (VSMCs) proliferate and migrate more. In addition, oxidative stress and the inflammatory response of endothelial cells (ECs) are more serious in postmenopausal women. This review also discusses how DHEA combats AS by countering these mechanisms, which include regulating the blood lipid status, protecting ECs (including coping with oxidative stress and inflammatory reactions of the vascular endothelium, inhibiting apoptosis of ECs, and inducing NO production) and inhibiting the proliferation and migration of VSMCs. As a result, DHEA has great value in preventing AS and inhibiting its progression in postmenopausal women.
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Affiliation(s)
- Siwei Zhang
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Jing Zhou
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Lijuan Li
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Xinyao Pan
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Jing Lin
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Chuyu Li
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Wing Ting Leung
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
| | - Ling Wang
- Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China.,The Academy of Integrative Medicine of Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China
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23
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Pott J, Horn K, Zeidler R, Kirsten H, Ahnert P, Kratzsch J, Loeffler M, Isermann B, Ceglarek U, Scholz M. Sex-Specific Causal Relations between Steroid Hormones and Obesity-A Mendelian Randomization Study. Metabolites 2021; 11:738. [PMID: 34822396 PMCID: PMC8624973 DOI: 10.3390/metabo11110738] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 12/15/2022] Open
Abstract
Steroid hormones act as important regulators of physiological processes including gene expression. They provide possible mechanistic explanations of observed sex-dimorphisms in obesity and coronary artery disease (CAD). Here, we aim to unravel causal relationships between steroid hormones, obesity, and CAD in a sex-specific manner. In genome-wide meta-analyses of four steroid hormone levels and one hormone ratio, we identified 17 genome-wide significant loci of which 11 were novel. Among loci, seven were female-specific, four male-specific, and one was sex-related (stronger effects in females). As one of the loci was the human leukocyte antigen (HLA) region, we analyzed HLA allele counts and found four HLA subtypes linked to 17-OH-progesterone (17-OHP), including HLA-B*14*02. Using Mendelian randomization approaches with four additional hormones as exposure, we detected causal effects of dehydroepiandrosterone sulfate (DHEA-S) and 17-OHP on body mass index (BMI) and waist-to-hip ratio (WHR). The DHEA-S effect was stronger in males. Additionally, we observed the causal effects of testosterone, estradiol, and their ratio on WHR. By mediation analysis, we found a direct sex-unspecific effect of 17-OHP on CAD while the other four hormone effects on CAD were mediated by BMI or WHR. In conclusion, we identified the sex-specific causal networks of steroid hormones, obesity-related traits, and CAD.
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Affiliation(s)
- Janne Pott
- Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany; (K.H.); (H.K.); (P.A.); (M.L.)
- LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (J.K.); (B.I.); (U.C.)
| | - Katrin Horn
- Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany; (K.H.); (H.K.); (P.A.); (M.L.)
- LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (J.K.); (B.I.); (U.C.)
| | - Robert Zeidler
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany;
| | - Holger Kirsten
- Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany; (K.H.); (H.K.); (P.A.); (M.L.)
- LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (J.K.); (B.I.); (U.C.)
| | - Peter Ahnert
- Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany; (K.H.); (H.K.); (P.A.); (M.L.)
- LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (J.K.); (B.I.); (U.C.)
| | - Jürgen Kratzsch
- LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (J.K.); (B.I.); (U.C.)
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany;
| | - Markus Loeffler
- Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany; (K.H.); (H.K.); (P.A.); (M.L.)
- LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (J.K.); (B.I.); (U.C.)
| | - Berend Isermann
- LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (J.K.); (B.I.); (U.C.)
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany;
| | - Uta Ceglarek
- LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (J.K.); (B.I.); (U.C.)
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, 04103 Leipzig, Germany;
| | - Markus Scholz
- Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, 04107 Leipzig, Germany; (K.H.); (H.K.); (P.A.); (M.L.)
- LIFE Research Center for Civilization Diseases, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany; (J.K.); (B.I.); (U.C.)
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24
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Thomas Q, Crespy V, Duloquin G, Ndiaye M, Sauvant M, Béjot Y, Giroud M. Stroke in women: When gender matters. Rev Neurol (Paris) 2021; 177:881-889. [PMID: 34172293 DOI: 10.1016/j.neurol.2021.01.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 12/22/2020] [Accepted: 01/11/2021] [Indexed: 12/12/2022]
Abstract
Stroke in women may be considered as a distinct entity due to numerous differences compared with men, including specific epidemiological, etiological, and outcome features along with unique pathophysiological mechanisms. Stroke is the second cause of death in women worldwide with sex-specific causes of stroke in youger women such as pregnancy, post-partum period, oral contraception and migraine. Substitutive hormone treatment in older women is no more recommended in regard of the increased thromboembolic risk it generates. Venous thrombolysis with rtPA and mechanical thrombectomy are now proven to be as efficacious in women as in men. After a stroke, women present poorer quality of life than men attributable to age, more severe stroke, pre-stroke dependency and depression. Recent data concerning the latest epidemiological surveys reveal a shift in trends with the rise of incidence of strokes in young women (≤55 years and 64 years) contrasting with the stability of incidence rates in older women. As science is unvealing sex-related differences in cardiovascular disorders, health policies need to be adapted accordingly to improve stroke prevention and pre-stroke health in women. In the meantime, therapeutical trials should include more women in order to be able to formulate adequate management.
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Affiliation(s)
- Q Thomas
- Department of General, Vascular and Degenerative Neurology, CHU Dijon, Bourgogne, France.
| | - V Crespy
- Dijon Stroke Registry (Inserm-Santé Publique France)-EA7460 (Pathophysiology and Epidemiology of Cerebro-Cardio-Vascular Diseases), University of Burgundy, UBFC, Dijon, France
| | - G Duloquin
- Department of General, Vascular and Degenerative Neurology, CHU Dijon, Bourgogne, France; Dijon Stroke Registry (Inserm-Santé Publique France)-EA7460 (Pathophysiology and Epidemiology of Cerebro-Cardio-Vascular Diseases), University of Burgundy, UBFC, Dijon, France
| | - M Ndiaye
- Department of General, Vascular and Degenerative Neurology, CHU Dijon, Bourgogne, France
| | - M Sauvant
- Department of General, Vascular and Degenerative Neurology, CHU Dijon, Bourgogne, France
| | - Y Béjot
- Department of General, Vascular and Degenerative Neurology, CHU Dijon, Bourgogne, France; Dijon Stroke Registry (Inserm-Santé Publique France)-EA7460 (Pathophysiology and Epidemiology of Cerebro-Cardio-Vascular Diseases), University of Burgundy, UBFC, Dijon, France
| | - M Giroud
- Department of General, Vascular and Degenerative Neurology, CHU Dijon, Bourgogne, France; Dijon Stroke Registry (Inserm-Santé Publique France)-EA7460 (Pathophysiology and Epidemiology of Cerebro-Cardio-Vascular Diseases), University of Burgundy, UBFC, Dijon, France
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25
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Genazzani AR, Monteleone P, Giannini A, Simoncini T. Pharmacotherapeutic options for the treatment of menopausal symptoms. Expert Opin Pharmacother 2021; 22:1773-1791. [PMID: 33980106 DOI: 10.1080/14656566.2021.1921148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Introduction: Menopausal symptoms can be very overwhelming for women. Over the years, many pharmacotherapeutic options have been tested, and others are still being developed. Hormone therapy (HT) is the most efficient therapy for managing vasomotor symptoms and related disturbances. The term HT comprises estrogens and progestogens, androgens, tibolone, the tissue-selective estrogen complex (TSEC), a combination of bazedoxifene and conjugated estrogens, and the selective estrogen receptor modulators, such as ospemifene. Estrogens and progestogens and androgens may differ significantly for chemical structure and can be delivered through different routes, thereby displaying various pharmacological and clinical properties. Tibolone, TSEC and SERM also exhibit unique pharmacodynamics that can be exploited to obtain distinctive therapeutic effects. Non-hormonal options fall mainly into the selective serotonin reuptake inhibitor (SSRI) and selective noradrenergic reuptake inhibitor (SNRI), GABA-analogue drug classes.Areas covered: Herein, the authors describe the pharmacokinetics and pharmacodynamics of hormonal (androgens, estrogens, progestogens, tibolone, TSEC, SERMs) and non-hormonal (SSRIs, SNRIs, Gabapentin, Pregabalin, Oxybutynin, Neurokinin antagonists) treatments for menopausal symptoms and report essential clinical trial data in humans.Expert opinion: Patient tailoring of treatment is key to managing symptoms of menopause. Physicians must have in-depth knowledge of the pharmacology of compounds to tailor therapy to the individual patient's characteristics and needs.
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Affiliation(s)
- Andrea R Genazzani
- Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Patrizia Monteleone
- Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Andrea Giannini
- Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Tommaso Simoncini
- Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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26
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Kim JH, Ha MS, Ha SM, Kim DY. Aquatic Exercise Positively Affects Physiological Frailty among Postmenopausal Women: A Randomized Controlled Clinical Trial. Healthcare (Basel) 2021; 9:healthcare9040409. [PMID: 33918160 PMCID: PMC8065774 DOI: 10.3390/healthcare9040409] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/19/2021] [Accepted: 03/25/2021] [Indexed: 12/25/2022] Open
Abstract
Frailty is a risk factor associated with aging. Physical exercise is an important lifestyle factor that can help to avoid risks associated with aging. Therefore, we aimed to determine the effects of aquatic exercise for 12 weeks on body composition, cardiovascular disease risk factors, insulin resistance, and aging-related sex hormones in elderly South Korean women. Twenty-two women aged 70–82 years were randomly assigned to groups that participated or did not participate (controls; n = 10 in aquatic exercise for 60 min, three times per week for 12 weeks (n = 12). Exercise intensity defined as the rating of perceived exertion (RPE), was increased from 12–13 to 13–14, and to 14–15 during weeks 1–4, 5–8, and 9–12, respectively. Body composition (skeletal muscle mass, ratio (%) body fat, and waist circumference), cardiovascular disease risk factors (total, high-density lipoprotein, and low-density lipoprotein cholesterol), insulin resistance (glucose, insulin, and homeostatic model assessment of insulin resistance [HOMA-IR]), and aging-related sex hormone changes (dehydroepiandrosterone-sulfate [DHEA-S]) and sex hormone-binding globulin [SHBG]) were assessed. Aquatic exercise safely improved body composition, reduced insulin resistance, and positively affected the sex hormones DHEA-S and SHBG as well as blood lipid profiles. Our findings suggested that the aquatic exercise program positively altered blood lipids, regulated glucose levels, and sex hormone levels. Therefore, regular, and continuous aquatic exercise is recommended to prevent frailty, decrease cardiovascular risk, and provide older women with an optimal quality of life as they age.
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Affiliation(s)
- Ji-Hyeon Kim
- Department of Liberal Arts, Mokpo National Maritime University, Jeollanam-do 58628, Korea;
| | - Min-Seong Ha
- Department of Sports Culture, College of the Arts, Dongguk University-Seoul, Seoul 04620, Korea;
| | - Soo-Min Ha
- Laboratory of Exercise Physiology, Department of Physical Education, Pusan National University, Busan 46241, Korea;
| | - Do-Yeon Kim
- Laboratory of Exercise Physiology, Department of Physical Education, Pusan National University, Busan 46241, Korea;
- Correspondence: ; Tel.: +82-51-510-2718
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27
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Matulevicius V, Urbanavicius V, Lukosevicius S, Banisauskaite I, Donielaite G, Galkine A. Importance of Dehydroepiandrosterone Sulfate Assessment with Special Attention for Adrenal Tumours and Arterial Hypertension. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2021; 17:68-76. [PMID: 34539912 PMCID: PMC8417495 DOI: 10.4183/aeb.2021.68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
OBJECTIVE To investigate the significance of DHEAS assessment in males of different ages. METHODS Retrospective cohort study of patients investigated in two large academic centres. RESULTS The data of DHEAS assessment of 3533 patients (3013 females and 520 males) was analysed. DHEAS was 1.6 - 13.5 times more frequently investigated in women than in men. A peak of DHEAS evaluation test for women was at 25 years old and distribution was uniform in males over decades, excepting being lower in 0-9 and 75+ages. In the age group 10-24 years, DHEAS levels were higher in females. After 45 years, DHEAS was higher in men than in women. Analysis of 510 case records showed low DHEAS levels in boys (0-9 years) and in men aged 65 - 84+. Higher DHEAS levels were detected as a peak at 30 years old, but never after 55 years. In individuals with low DHEAS levels prevailed congenital adrenal hyperplasia (32%), adrenal tumours (30%) and primary or secondary adrenal insufficiency (19%). High DHEAS levels prevailed in patients with arterial hypertension (26%), overweight-obesity -(19%), non-toxic goiter (17%) and alopecia (9%). In the normal DHEAS miscellaneous diagnoses were met most frequently - 40%. Disorders exceeding 5% were non-toxic goiter (19%), adrenal tumours - 17%, overweight/obesity - 16% and arterial hypertension- 8%. In 71 women and 124 men adrenal neoplasms were detected. Higher frequency of these was observed in women in their 30s. A peak of adrenal neoplasms in men was at their 70s. This gender difference was not conditioned by earlier attempts to seek medical care by women. A significant correlation of DHEAS, weight, body mass index and systolic blood pressure with diastolic blood pressure was found. CONCLUSION Our study permits to determine which DHEAS secretion and clinical pattern might be associated in males of different ages.
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Affiliation(s)
- V. Matulevicius
- Lithuanian University of Health Sciences - Institute of Endocrinology, Department of Endocrinology
| | - V. Urbanavicius
- Lithuanian University of Health Sciences - Institute of Endocrinology, Vilnius University - Faculty of Medicine, Department of Endocrinology, Vilnius, Lithuania
| | - S. Lukosevicius
- Lithuanian University of Health Sciences - Institute of Endocrinology, Department of Radiology, Kaunas
| | - I. Banisauskaite
- Lithuanian University of Health Sciences - Institute of Endocrinology, Department of Endocrinology
| | - G. Donielaite
- Lithuanian University of Health Sciences - Institute of Endocrinology, Department of Endocrinology
| | - A. Galkine
- Lithuanian University of Health Sciences - Institute of Endocrinology, Vilnius University - Faculty of Medicine, Department of Endocrinology, Vilnius, Lithuania
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28
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Relationship of dehydroepiandrosterone sulfate levels with atherosclerosis in patients with subclinical hypothyroidism. Wien Klin Wochenschr 2021; 134:45-50. [PMID: 33788012 DOI: 10.1007/s00508-021-01844-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 02/27/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Subclinical hypothyroidism is related with increased risk of cardiovascular diseases. The decreased levels of dehydroepiandrosterone sulphate (DHEA-S) are associated with hyperlipidemia, atherosclerosis and obesity. The lower levels of DHEA‑S might be an important factor in development of atherosclerosis in subclinical hypothyroidism. METHODS A total of 126 patients (62 with subclinical hypothyroidism and 64 healthy individuals) were included in this prospectively designed study between January 2017 and December 2019. All individuals were evaluated according to DHEA‑S levels, carotid intima media thickness (CIMT) and anthropometric measurements. Blood samples were obtained from patients after 8 h fasting. The groups were statistically compared. RESULTS The mean ages of control group and patients with subclinical hypothyroidism were 36.9 ± 11.0 years and 39.6 ± 11.0 years, respectively (p = 0.165). The mean waist circumferences in controls and patients were 89 ± 10.7 cm and 91.3 ± 11.1 cm, respectively (p < 0.001). The DHEA‑S levels were 131.04 ± 96.02 µg/dl in patients, and these levels were significantly decreased in patients with subclinical hypothyroidism (p = 0.024). The levels of DHEA‑S were found to be negatively correlated with CIMT (p < 0.001, c = 0.406). CONCLUSIONS The early detection of cardiac and metabolic dysfunctions in subclinical hypothyroidism is important to avoid complications. We found a negative correlation between DHEA‑S levels and metabolic and cardiovascular risk factors in subclinical hypothyroidism. We believe that our results would attract more attention to the studies investigating relationships between DHEA‑S levels and cardiovascular complications of subclinical hypothyroidism.
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Taubøll E, Isojärvi JIT, Herzog AG. The interactions between reproductive hormones and epilepsy. HANDBOOK OF CLINICAL NEUROLOGY 2021; 182:155-174. [PMID: 34266590 DOI: 10.1016/b978-0-12-819973-2.00011-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
There are complex interactions between hormones, epilepsy, and antiepileptic drugs (AEDs). While there is ample evidence that hormones influence epilepsy, it is also apparent that epileptic activity influences hormones in both women and men. In addition, AEDs may disturb endocrine function. The clinical importance of these interactions is primarily related to the effects on reproductive hormones, which is the focus of this article. Reproductive endocrine dysfunction is common among women and men with epilepsy. Menstrual disorders, polycystic ovaries, and infertility have been described among women with epilepsy, while reduced potency and sperm abnormalities have been found in men. Sexual problems and endocrine changes have been frequently described in both sexes. Epilepsy and AEDs can target a number of substrates to impact hormone levels. These include the limbic system, hypothalamus, pituitary, peripheral endocrine glands, liver, and adipose tissue. AEDs may also alter the synthesis of steroids and binding proteins, as well as hormone metabolism, and produce direct gonadal effects.
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Affiliation(s)
- Erik Taubøll
- Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
| | | | - Andrew G Herzog
- Harvard Neuroendocrine Unit, Beth Israel Deaconess Medical Center, Boston, MA, United States; Faculty of Medicine, Harvard Medical School, Boston, MA, United States
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Barsky L, Merz CNB, Wei J, Shufelt C, Handberg E, Pepine C, Rutledge T, Reis S, Doyle M, Rogers W, Shaw L, Sopko G. Even "WISE-R?"-an Update on the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation. Curr Atheroscler Rep 2020; 22:35. [PMID: 32556630 PMCID: PMC7388776 DOI: 10.1007/s11883-020-00852-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW For over 20 years, the Women's Ischemia Syndrome Evaluation (WISE), a program sponsored by the National Heart, Lung, and Blood Institute, has explored diverse and important aspects of ischemic heart disease in women. RECENT FINDINGS Women with symptoms and signs of ischemia but no significant epicardial obstructive coronary artery disease (INOCA) were documented to be at elevated risk for recurrent angina hospitalization, major adverse cardiac events, death, and health resource consumption rivaling those with obstructive coronary disease. WISE investigators have advanced our understanding of cardiovascular outcomes, systemic manifestations, psychological variables, socioeconomic factors, genetic contributions, hormonal status, advanced imaging, coronary functional findings, biomarkers, patient-reported outcomes, and treatments pertaining to women with this disease entity. This review delves into the WISE findings subsequent to a prior review1, postulates directions for future research, and asks are we "Even 'WISE-R?'".
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Affiliation(s)
- Lili Barsky
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, 127 S. San Vicente Blvd, Suite A3600, Los Angeles, CA, 90048, USA
| | - C Noel Bairey Merz
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, 127 S. San Vicente Blvd, Suite A3600, Los Angeles, CA, 90048, USA.
| | - Janet Wei
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, 127 S. San Vicente Blvd, Suite A3600, Los Angeles, CA, 90048, USA
| | - Chrisandra Shufelt
- Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, 127 S. San Vicente Blvd, Suite A3600, Los Angeles, CA, 90048, USA
| | - Eileen Handberg
- Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Carl Pepine
- Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Thomas Rutledge
- VA San Diego Healthcare System, San Diego, CA, USA
- University of California, San Diego, CA, USA
| | - Steven Reis
- Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mark Doyle
- Division of Cardiology, Department of Medicine, Allegheny University of the Health Sciences, Pittsburgh, PA, USA
| | - William Rogers
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Leslee Shaw
- Dalio Institute of Cardiovascular Imaging, Weill Cornell Medicine and New York-Presbyterian Hospital, New York, NY, USA
| | - George Sopko
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
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Pesce G, Triebner K, van der Plaat DA, Courbon D, Hustad S, Sigsgaard T, Nowak D, Heinrich J, Anto JM, Dorado-Arenas S, Martinez-Moratalla J, Gullon-Blanco JA, Sanchez-Ramos JL, Raherison C, Pin I, Demoly P, Gislason T, Torén K, Forsberg B, Lindberg E, Zemp E, Jogi R, Probst-Hensch N, Dharmage SC, Jarvis D, Garcia-Aymerich J, Marcon A, Gómez-Real F, Leynaert B. Low serum DHEA-S is associated with impaired lung function in women. EClinicalMedicine 2020; 23:100389. [PMID: 32529179 PMCID: PMC7280766 DOI: 10.1016/j.eclinm.2020.100389] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Emerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS). METHODS Lung function and serum DHEA-S concentrations were measured in n = 2,045 and n = 1,725 women in 1999-2002 and in 2010-2013, respectively. Cross-sectional associations of DHEA-S levels (expressed as age-adjusted z-score) with spirometric outcomes were investigated, adjusting for smoking habits, body mass index, menopausal status, and use of corticosteroids. Longitudinal associations of DHEA-S levels in 1999-2002 with incidence of restrictive pattern and airflow limitation in 2010-2013 were also assessed. FINDINGS Women with low DHEA-S (z-score<-1) had lower FEV1 (% of predicted, adjusted difference: -2.2; 95%CI: -3.5 to -0.9) and FVC (-1.7; 95%CI: -2.9 to -0.5) and were at a greater risk of having airflow limitation and restrictive pattern on spirometry than women with higher DHEA-S levels. In longitudinal analyses, low DHEA-S at baseline was associated with a greater incidence of airflow limitation after an 11-years follow-up (incidence rate ratio, 3.43; 95%CI: 1.91 to 6.14). INTERPRETATION Low DHEA-S levels in women were associated with impaired lung function and a greater risk of developing airflow limitation later in adult life. Our findings provide new evidence supporting a role of DHEA-S in respiratory health. FUNDING EU H2020, grant agreement no.633212.
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Affiliation(s)
- Giancarlo Pesce
- Sorbonne Université and INSERM UMR-S 1136, Epidemiology of Allergic and Respiratory Diseases (EPAR), Pierre Louis Institute of Epidemiology and Public Health (IPLESP), Saint-Antoine Medical School, F-75012, Paris, France
- Corresponding authors. Giancarlo Pesce. Sorbonne Université and Inserm UMR-S 1136, Pierre Louis Institute of Epidemiology and Public Health (IPLESP), Saint-Antoine Medical School, 27, rue Chaligny 75012 Paris, France. Phone: +39 34 58 13 42 19.
| | - Kai Triebner
- Department of Clinical Science, University of Bergen, Bergen, Norway
- Core Facility for Metabolomics, University of Bergen, Bergen, Norway
| | - Diana A. van der Plaat
- Population Health and Occupational Disease, National Heart and Lung Institute (NHLI), Imperial College, London, United Kingdom
| | - Dominique Courbon
- INSERM UMR 1152, Pathophysiology and Epidemiology of Respiratory Diseases, Paris, France. University Paris Diderot Paris 7, UMR 1152, F-75890, Paris, France
| | - Steinar Hustad
- Department of Clinical Science, University of Bergen, Bergen, Norway
- Core Facility for Metabolomics, University of Bergen, Bergen, Norway
| | | | - Dennis Nowak
- Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Centre Munich, German Centre for Lung Research (DZL), Munich, Germany
| | - Joachim Heinrich
- Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Centre Munich, German Centre for Lung Research (DZL), Munich, Germany
- Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany
| | - Josep M. Anto
- ISGlobal, Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | | | | | | | | | - Chantal Raherison
- Université de Bordeaux, Inserm, Bordeaux Population Health Research Center, Team EPICENE, UMR 1219, Bordeaux, France
| | - Isabelle Pin
- Pédiatrie CHU Grenoble Alpes; Inserm Unité E2R2H; Université Grenoble Alpes, Grenoble, France
| | - Pascal Demoly
- Sorbonne Université and INSERM UMR-S 1136, Epidemiology of Allergic and Respiratory Diseases (EPAR), Pierre Louis Institute of Epidemiology and Public Health (IPLESP), Saint-Antoine Medical School, F-75012, Paris, France
| | - Thorarinn Gislason
- Department of Sleep, Landspitali, The National University Hospital of Iceland, Reykjavík (Iceland)
- University of Iceland, Faculty of Medicine, Reykavík, Iceland
| | - Kjell Torén
- Occupational and environmental medicine, School of Public Health, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Bertil Forsberg
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Eva Lindberg
- Department of Medical Sciences: Respiratory, Allergy and Sleep research, Uppsala University, Uppsala, Sweden
| | - Elisabeth Zemp
- Department Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Rain Jogi
- Lung Clinic, Tartu University Hospital, Tartu, Estonia
| | - Nicole Probst-Hensch
- Department Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Shyamali C. Dharmage
- Allergy and Lung Health Unit, School of Population and Global Health, The University of Melbourne, Melbourne, Australia
| | - Debbie Jarvis
- National Heart and Lung Institute, Imperial College, London UK
| | - Judith Garcia-Aymerich
- ISGlobal, Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
| | - Alessandro Marcon
- Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Francisco Gómez-Real
- Department of Clinical Science, University of Bergen, Bergen, Norway
- Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway
| | - Bénédicte Leynaert
- Inserm UMR-S 1168, VIMA, Villejuif, France
- UMR-S 1168, UVSQ, Université Versailles St-Quentin-en-Yvelines, St-Quentin-en-Yvelines, France
- Corresponding authors. Bénédicte Leynaert, Inserm UMR-S 1168, VIMA: Aging and chronic diseases. Epidemiological and public health approaches, 16, avenue Paul Vaillant Couturier, 94807 Villejuif, France. Phone: +33 (0)1 45 59 51 96.
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Orta OR, Huang T, Kubzansky LD, Terry KL, Coull BA, Williams MA, Tworoger SS. The association between abuse history in childhood and salivary rhythms of cortisol and DHEA in postmenopausal women. Psychoneuroendocrinology 2020; 112:104515. [PMID: 31784054 PMCID: PMC6935398 DOI: 10.1016/j.psyneuen.2019.104515] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 08/22/2019] [Accepted: 11/12/2019] [Indexed: 12/11/2022]
Abstract
A history of child abuse (CA) is associated with morbidity and mortality in adulthood, and one proposed mechanism is dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we evaluated whether a history of physical and sexual CA was associated with daily rhythms of HPA hormones (cortisol and dehydroepiandrosterone (DHEA)) among postmenopausal women (mean age: 60.6 years). In 2013, 233 participants from the Nurses' Health Study II provided up to 5-timed saliva samples over the course of a day: immediately upon awakening, 45 min, 4 h, and 10 h after waking, and prior to going to sleep. Among these 233 participants, 217 provided ≥4 timed saliva samples. Assessment of physical and sexual CA history occurred in 2001 using the Revised Conflict Tactics Scale. Cumulative CA history was derived by combining reports of physical and sexual abuse prior to age 18. Piecewise linear mixed models compared diurnal rhythms of cortisol and DHEA between participants with none-to-moderate CA (n = 104, reference group) versus high-to-severe CA (n = 113). Models adjusted for characteristics at each saliva collection, health status, sleep quality, medications, and hormone use. Compared to those with none-to-moderate CA, women with high-to-severe CA had different diurnal rhythms in the early and evening hours, including blunted (less steep) early declines in DHEA (% difference (%D) = 10.7, 95 % Confidence Interval (CI) 4.3, 17.5), and steeper late declines in both cortisol and DHEA (cortisol %D = -2.5, 95 % CI -4.8, -0.1, and DHEA %D= -3.9, 95 % CI -6.0, -1.8). In conclusion, high-to-severe abuse history prior to age 18 was more strongly associated with differences in DHEA rather than cortisol, suggesting that early life abuse may be related to dysregulation of stress-response mechanisms later in life.
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Affiliation(s)
- Olivia R Orta
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States.
| | - Tianyi Huang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women'S Hospital and Harvard Medical School, Boston, MA, United States
| | - Laura D Kubzansky
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Kathryn L Terry
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Ob/Gyn Epidemiology, Department of Obstetrics and Gynecology, Brigham and Women'S Hospital and Harvard Medical School, Boston, MA, United States
| | - Brent A Coull
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Michelle A Williams
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Shelley S Tworoger
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, United States
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Twelve weeks of resistance band exercise training improves age-associated hormonal decline, blood pressure, and body composition in postmenopausal women with stage 1 hypertension: a randomized clinical trial. ACTA ACUST UNITED AC 2020; 27:199-207. [DOI: 10.1097/gme.0000000000001444] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Teixeira CJ, Veras K, de Oliveira Carvalho CR. Dehydroepiandrosterone on metabolism and the cardiovascular system in the postmenopausal period. J Mol Med (Berl) 2020; 98:39-57. [PMID: 31713639 DOI: 10.1007/s00109-019-01842-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 09/16/2019] [Accepted: 10/09/2019] [Indexed: 12/16/2022]
Abstract
Dehydroepiandrosterone (DHEA), mostly present as its sulfated ester (DHEA-S), is an anabolic hormone that naturally declines with age. Furthermore, it is the most abundant androgen and estrogen precursor in humans. Low plasma levels of DHEA have been strongly associated with obesity, insulin resistance, dyslipidemia, and high blood pressure, increasing the risk of cardiovascular disease. In this respect, DHEA could be regarded as a promising agent against metabolic syndrome (MetS) in postmenopausal women, since several age-related metabolic diseases are reported during aging. There are plenty of experimental evidences showing beneficial effects after DHEA therapy on carbohydrate and lipid metabolism, as well as cardiovascular health. However, its potential as a therapeutic agent appears to attract controversy, due to the lack of effects on some symptoms related to MetS. In this review, we examine the available literature regarding the impact of DHEA therapy on adiposity, glucose metabolism, and the cardiovascular system in the postmenopausal period. Both clinical studies and in vitro and in vivo experimental models were selected, and where possible, the main cellular mechanisms involved in DHEA therapy were discussed. Schematic representation showing some of the general effects observed after administration DHEA therapy on target tissues of energy metabolism and the cardiovascular system. ↑ represents an increase, ↓ represents a decrease, - represents a worsening and ↔ represents no change after DHEA therapy.
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Affiliation(s)
- Caio Jordão Teixeira
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 105 Alexander Fleming St, Campinas, SP, 13083-881, Brazil
- Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo, SP, 05508-900, Brazil
| | - Katherine Veras
- Department of Nutrition, University of Mogi das Cruzes, 200 Dr. Cândido X. A. Souza Ave., Sao Paulo, SP, 08780-911, Brazil
| | - Carla Roberta de Oliveira Carvalho
- Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Sao Paulo, SP, 05508-900, Brazil.
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Hester J, Ventetuolo C, Lahm T. Sex, Gender, and Sex Hormones in Pulmonary Hypertension and Right Ventricular Failure. Compr Physiol 2019; 10:125-170. [PMID: 31853950 DOI: 10.1002/cphy.c190011] [Citation(s) in RCA: 111] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Pulmonary hypertension (PH) encompasses a syndrome of diseases that are characterized by elevated pulmonary artery pressure and pulmonary vascular remodeling and that frequently lead to right ventricular (RV) failure and death. Several types of PH exhibit sexually dimorphic features in disease penetrance, presentation, and progression. Most sexually dimorphic features in PH have been described in pulmonary arterial hypertension (PAH), a devastating and progressive pulmonary vasculopathy with a 3-year survival rate <60%. While patient registries show that women are more susceptible to development of PAH, female PAH patients display better RV function and increased survival compared to their male counterparts, a phenomenon referred to as the "estrogen paradox" or "estrogen puzzle" of PAH. Recent advances in the field have demonstrated that multiple sex hormones, receptors, and metabolites play a role in the estrogen puzzle and that the effects of hormone signaling may be time and compartment specific. While the underlying physiological mechanisms are complex, unraveling the estrogen puzzle may reveal novel therapeutic strategies to treat and reverse the effects of PAH/PH. In this article, we (i) review PH classification and pathophysiology; (ii) discuss sex/gender differences observed in patients and animal models; (iii) review sex hormone synthesis and metabolism; (iv) review in detail the scientific literature of sex hormone signaling in PAH/PH, particularly estrogen-, testosterone-, progesterone-, and dehydroepiandrosterone (DHEA)-mediated effects in the pulmonary vasculature and RV; (v) discuss hormone-independent variables contributing to sexually dimorphic disease presentation; and (vi) identify knowledge gaps and pathways forward. © 2020 American Physiological Society. Compr Physiol 10:125-170, 2020.
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Affiliation(s)
- James Hester
- Department of Medicine, Division of Pulmonary, Allergy, Critical Care, Occupational and Sleep Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Corey Ventetuolo
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA.,Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, Rhode Island, USA
| | - Tim Lahm
- Department of Medicine, Division of Pulmonary, Allergy, Critical Care, Occupational and Sleep Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.,Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.,Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana, USA
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Fahy GM, Brooke RT, Watson JP, Good Z, Vasanawala SS, Maecker H, Leipold MD, Lin DTS, Kobor MS, Horvath S. Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell 2019; 18:e13028. [PMID: 31496122 PMCID: PMC6826138 DOI: 10.1111/acel.13028] [Citation(s) in RCA: 296] [Impact Index Per Article: 49.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Revised: 07/16/2019] [Accepted: 08/04/2019] [Indexed: 12/15/2022] Open
Abstract
Epigenetic “clocks” can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many age‐related diseases, and a mean epigenetic age approximately 1.5 years less than baseline after 1 year of treatment (−2.5‐year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from −1.6 year/year from 0–9 month to −6.5 year/year from 9–12 month. The GrimAge predictor of human morbidity and mortality showed a 2‐year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention.
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Affiliation(s)
| | | | - James P. Watson
- UCLA Division of Plastic and Reconstructive Surgery David Geffen School of Medicine Los Angeles CA USA
| | - Zinaida Good
- Departments of Microbiology and Immunology Stanford University Stanford CA USA
| | | | - Holden Maecker
- Institute for Immunity, Transplantation and Infection, Stanford School of Medicine Human Immune Monitoring Center Stanford CA USA
| | - Michael D. Leipold
- Institute for Immunity, Transplantation and Infection, Stanford School of Medicine Human Immune Monitoring Center Stanford CA USA
| | - David T. S. Lin
- Department of Medical Genetics, BC Children's Hospital Research Institute Centre for Molecular Medicine and Therapeutics, University of British Columbia Vancouver BC Canada
| | - Michael S. Kobor
- Department of Medical Genetics, BC Children's Hospital Research Institute Centre for Molecular Medicine and Therapeutics, University of British Columbia Vancouver BC Canada
| | - Steve Horvath
- Human Genetics, David Geffen School of Medicine University of California Los Angeles CA USA
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Pott J, Bae YJ, Horn K, Teren A, Kühnapfel A, Kirsten H, Ceglarek U, Loeffler M, Thiery J, Kratzsch J, Scholz M. Genetic Association Study of Eight Steroid Hormones and Implications for Sexual Dimorphism of Coronary Artery Disease. J Clin Endocrinol Metab 2019; 104:5008-5023. [PMID: 31169883 DOI: 10.1210/jc.2019-00757] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 05/31/2019] [Indexed: 02/09/2023]
Abstract
CONTEXT Steroid hormones are important regulators of physiological processes in humans and are under genetic control. A link to coronary artery disease (CAD) is supposed. OBJECTIVE Our main objective was to identify genetic loci influencing steroid hormone levels. As a secondary aim, we searched for causal effects of steroid hormones on CAD. DESIGN We conducted genome-wide meta-association studies for eight steroid hormones: cortisol, dehydroepiandrosterone sulfate (DHEAS), estradiol, and testosterone in two independent cohorts (LIFE-Adult, LIFE-Heart, maximum n = 7667), and progesterone, 17-hydroxyprogesterone, androstenedione, and aldosterone in LIFE-Heart only (maximum n = 2070). All genome-wide significant loci were tested for sex interactions. Furthermore, we tested whether previously reported CAD single-nucleotide polymorphisms were associated with our steroid hormone panel and investigated causal links between hormone levels and CAD status using Mendelian randomization (MR) approaches. RESULTS We discovered 15 novel associated loci for 17-hydroxyprogesterone, progesterone, DHEAS, cortisol, androstenedione, and estradiol. Five of these loci relate to genes directly involved in steroid metabolism, that is, CYP21A1, CYP11B1, CYP17A1, STS, and HSD17B12, almost completing the set of steroidogenic enzymes with genetic associations. Sexual dimorphisms were found for seven of the novel loci. Other loci correspond, for example, to the WNT4/β-catenin pathway. MR revealed that cortisol, androstenedione, 17-hydroxyprogesterone, and DHEA-S had causal effects on CAD. We also observed enrichment of cortisol and testosterone associations among known CAD hits. CONCLUSION Our study greatly improves insight into genetic regulation of steroid hormones and their dependency on sex. These results could serve as a basis for analyzing sexual dimorphism in other complex diseases.
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Affiliation(s)
- Janne Pott
- Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
- Leipzig University Medical Center, IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany
| | - Yoon Ju Bae
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
- Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital, Leipzig, Germany
| | - Katrin Horn
- Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Andrej Teren
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
- Heart Center Leipzig, Leipzig, Germany
| | - Andreas Kühnapfel
- Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
- Leipzig University Medical Center, IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany
| | - Holger Kirsten
- Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Uta Ceglarek
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
- Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital, Leipzig, Germany
| | - Markus Loeffler
- Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Joachim Thiery
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
- Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital, Leipzig, Germany
| | - Jürgen Kratzsch
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
- Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital, Leipzig, Germany
| | - Markus Scholz
- Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany
- LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
- Leipzig University Medical Center, IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany
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Son DH, Park WJ, Lee YJ. Recent Advances in Anti-Aging Medicine. Korean J Fam Med 2019; 40:289-296. [PMID: 31558007 PMCID: PMC6768834 DOI: 10.4082/kjfm.19.0087] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 09/16/2019] [Indexed: 01/01/2023] Open
Abstract
A rapidly aging population in Korea has led to increased attention in the field of anti-aging medicine. The purpose of anti-aging medicine is to slow, stop, or reverse the aging process and its associated effects, such as disability and frailty. Anti-aging medicine is emerging as a growing industry, but many supplements or protocols are available that do not have scientific evidence to support their claims. In this review, the mechanisms of action and the clinical implications of anti-aging interventions were examined and explained. Calorie restriction mimetics define compounds that imitate the outcome of calorie restriction, including an activator of AMP protein kinase (metformin), inhibitor of growth hormone/insulin-like growth factor-1 axis (pegvisomant), inhibitor of mammalian target of rapamycin (rapamycin), and activator of the sirtuin pathway (resveratrol). Hormonal replacement has also been widely used in the elderly population to improve their quality of life. Manipulating healthy gut microbiota through prebiotic/probiotics or fecal microbiota transplantation has significant potential in anti-aging medicine. Vitamin D is expected to be a primary anti-aging medicine in the near future due to its numerous positive effects in the elderly population.
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Affiliation(s)
- Da-Hye Son
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Woo-Jin Park
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Yong-Jae Lee
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea
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Zhao D, Guallar E, Ouyang P, Subramanya V, Vaidya D, Ndumele CE, Lima JA, Allison MA, Shah SJ, Bertoni AG, Budoff MJ, Post WS, Michos ED. Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women. J Am Coll Cardiol 2019; 71:2555-2566. [PMID: 29852978 DOI: 10.1016/j.jacc.2018.01.083] [Citation(s) in RCA: 279] [Impact Index Per Article: 46.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 01/13/2018] [Accepted: 01/18/2018] [Indexed: 01/18/2023]
Abstract
BACKGROUND Higher androgen and lower estrogen levels are associated with cardiovascular disease (CVD) risk factors in women. However, studies on sex hormones and incident CVD events in women have yielded conflicting results. OBJECTIVES The authors assessed the associations of sex hormone levels with incident CVD, coronary heart disease (CHD), and heart failure (HF) events among women without CVD at baseline. METHODS The authors studied 2,834 post-menopausal women participating in the MESA (Multi-Ethnic Study of Atherosclerosis) with testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) levels measured at baseline (2000 to 2002). They used Cox hazard models to evaluate associations of sex hormones with each outcome, adjusting for demographics, CVD risk factors, and hormone therapy use. RESULTS The mean age was 64.9 ± 8.9 years. During 12.1 years of follow-up, 283 CVD, 171 CHD, and 103 HF incident events occurred. In multivariable-adjusted models, the hazard ratio (95% confidence interval [CI]) associated with 1 SD greater log-transformed sex hormone level for the respective outcomes of CVD, CHD, and HF were as follows: total testosterone: 1.14 (95% CI: 1.01 to 1.29), 1.20 (95% CI: 1.03 to 1.40), 1.09 (95% CI: 0.90 to 1.34); estradiol: 0.94 (95% CI: 0.80 to 1.11), 0.77 (95% CI: 0.63 to 0.95), 0.78 (95% CI: 0.60 to 1.02); and testosterone/estradiol ratio: 1.19 (95% CI: 1.02 to 1.40), 1.45 (95% CI: 1.19 to 1.78), 1.31 (95% CI: 1.01 to 1.70). Dehydroepiandrosterone and SHBG levels were not associated with these outcomes. CONCLUSIONS Among post-menopausal women, a higher testosterone/estradiol ratio was associated with an elevated risk for incident CVD, CHD, and HF events, higher levels of testosterone associated with increased CVD and CHD, whereas higher estradiol levels were associated with a lower CHD risk. Sex hormone levels after menopause are associated with women's increased CVD risk later in life.
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Affiliation(s)
- Di Zhao
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Eliseo Guallar
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Pamela Ouyang
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Vinita Subramanya
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dhananjay Vaidya
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Chiadi E Ndumele
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Joao A Lima
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Matthew A Allison
- Division of Preventive Medicine, University of California-San Diego, La Jolla, California
| | - Sanjiv J Shah
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Alain G Bertoni
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Matthew J Budoff
- Los Angeles Biomedical Research Center at Harbor-UCLA, Torrance, California
| | - Wendy S Post
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Erin D Michos
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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Wang C, Zhang W, Wang Y, Wan H, Chen Y, Xia F, Zhang K, Wang N, Lu Y. Novel associations between sex hormones and diabetic vascular complications in men and postmenopausal women: a cross-sectional study. Cardiovasc Diabetol 2019; 18:97. [PMID: 31366359 PMCID: PMC6668151 DOI: 10.1186/s12933-019-0901-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 07/24/2019] [Indexed: 02/06/2023] Open
Abstract
Background Associations between sex hormones and vascular remodeling have been extensively studied, but the results vary widely among different races and sex. We aimed to investigate whether total testosterone (TT), estrogen (E2), and dehydroepiandrosterone (DHEA) associate with macrovascular complications and diabetic kidney disease (DKD) among community-dwelling patients with diabetes. Methods A total of 4720 participants with type 2 diabetes were recruited from Shanghai, China. Common carotid artery (CCA) plaques and diameter were assessed by ultrasound. Cardiovascular disease (CVD) was defined by prior diagnosis of coronary heart disease, myocardial infarction or stroke. DKD was defined according to the ADA Guidelines. Results (1) In men, TT was negatively associated with CCA diameter (regression coefficient (β) − 0.044, 95% CI − 0.087, 0). E2 levels were positively associated with CVD and CCA plaque prevalence (OR 1.151, 95% CI 1.038, 1.277 and OR 1.13, 95% CI 1.017, 1.255, respectively). DHEA was negatively associated with CVD (OR 0.809, 95% CI 0.734, 0.893). In postmenopausal women, TT levels were negatively associated with CCA diameter (β − 0.046, 95% CI − 0.083, − 0.010) and positively associated with CVD (OR 1.154, 95% CI 1.038, 1.284). (2) In both men and postmenopausal women, TT levels were negatively associated with the albumin/creatinine ratio and DKD (β − 0.098, 95% CI − 0.154, − 0.043 and OR 0.887, 95% CI 0.790, 0.997 vs. β − 0.084, 95% CI − 0.137, − 0.031 and OR 0.822, 95% CI 0.731, 0.924, respectively) and DHEA levels were positively associated with DKD (OR 1.167, 95% CI 1.038, 1.313 vs. OR 1.251, 95% CI 1.104, 1.418, respectively). Conclusions Our study indicates that macrovascular complications were associated with low TT, DHEA and high E2 in men and with high TT in postmenopausal women. DKD was associated with low TT and high DHEA levels in both genders. Sex hormone replacement therapy requires careful and comprehensive consideration. Trial registration ChiCTR1800017573, http://www.chictr.org.cn. Registered 04 August 2018 Electronic supplementary material The online version of this article (10.1186/s12933-019-0901-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Chiyu Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Wen Zhang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Yuying Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Heng Wan
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Yi Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Fangzhen Xia
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Kun Zhang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Ningjian Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
| | - Yingli Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
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Matulevicius V, Urbanavicius V, Lukosevicius S, Ciaplinskiene L, Ostrauskas R. THE RARE CASE OF MIXED GONADAL DYSGENESIS, MOSAIC KARYOTYPE, PETROCLIVAL MENINGIOMA AND IDIOPATHIC HYPERDEHYDROEPIANDROSTERONISM. ACTA ENDOCRINOLOGICA-BUCHAREST 2019; 14:527-532. [PMID: 31149308 DOI: 10.4183/aeb.2018.527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Background Mosaic karyotype 45,X/46,XY related mixed gonadal dysgenesis. Aim To report a case of mosaic karyotype and petroclival meningioma. Methods Presentation of a clinical case with comments. Results The case of a 37-year-old woman mosaic karyotype - 45,X/46,XY, infertility, virilisation, Turner syndrome-like phenotype, primary amenorrhea, the absence of labia majora and petroclival meningioma. Concentrations of dehydroepiandrosterone sulphate (DHEAS), testosterone, luteinizing hormone (LH) and follicular stimulating hormone (FSH) were increased indicating hypergonadotropic hypogonadism. Low and high dose dexamethasone suppression tests demonstrated incomplete suppression of DHEAS concentration without connection between pulses of LH/FSH and DHEAS. Response to adrenocorticotropic hormone (ACTH) was normal. The morning/evening concentration ratio of DHEAS was very low in comparison with cortisol, ACTH and testosterone. Head magnetic resonance imaging (MRI) demonstrated petroclival meningioma without any adrenal or ovary abnormality. Menstruation started after treatment with 2 mg of estradiol. At control visit 1.5 years later she had no complaints. MRI did not demonstrate any signs of tumour progression. Conclusions The main lesson learned from this case is that in searching the DHEAS secreting tumours one can find unusual cases with sustained high DHEAS and lack of confirmations of polycystic ovary syndrome, adrenal or ovary tumours using available ultrasound, CT and MRI.
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Affiliation(s)
- V Matulevicius
- Lithuanian University of Health Sciences - Institute of Endocrinology, Lithuania
| | - V Urbanavicius
- Lithuanian University of Health Sciences - Vilnus University, Faculty of Medicine, Vilnus, Lithuania
| | - S Lukosevicius
- Lithuanian University of Health Sciences - Department of Radiology, Kaunas, Lithuania
| | - L Ciaplinskiene
- Lithuanian University of Health Sciences - Institute of Endocrinology, Lithuania
| | - R Ostrauskas
- Lithuanian University of Health Sciences - Institute of Endocrinology, Lithuania
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Jiménez MC, Tucker KL, Rodriguez F, Porneala BC, Meigs JB, López L. Cardiovascular Risk Factors and Dehydroepiandrosterone Sulfate Among Latinos in the Boston Puerto Rican Health Study. J Endocr Soc 2018; 3:291-303. [PMID: 30623167 PMCID: PMC6320241 DOI: 10.1210/js.2018-00205] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 11/27/2018] [Indexed: 11/19/2022] Open
Abstract
Low blood dehydroepiandrosterone sulfate (DHEAS) levels have strong positive associations with stroke and coronary heart disease. However, it is unclear whether DHEAS is independently associated with cardiovascular risk factors. Therefore, we examined the association between cardiovascular risk factors and DHEAS concentration among a high-risk population of Latinos (Puerto Ricans aged 45 to 75 years at baseline) in a cross-sectional analysis of the Boston Puerto Rican Health Study. Of eligible participants, 72% completed baseline interviews and provided blood samples. Complete data were available for 1355 participants. Associations between cardiovascular risk factors (age, sex, total cholesterol, high-density lipid cholesterol, triglycerides, and glucose) and log-transformed DHEAS (μg/dL) were assessed. In robust multivariable regression analyses, DHEAS was significantly inversely associated with age (β = -12.4; 95% CI: -15.2, -9.7; per 5 years), being female (vs. male) (β = -46; 95% CI: -55.3, -36.6), and plasma triglyceride concentration (β = -0.2; 95% CI: -0.3, -0.1; per 10 mg/dL) and was positively associated with total cholesterol and plasma glucose levels (β = 1.8; 95% CI: 0.6, 3 and β = 0.2; 95% CI: 0.04, 0.3, respectively, per 10 mg/dL) after adjustment for smoking, alcohol, and physical activity and for postmenopausal hormone use in women. Estimates were unchanged after adjustment for measures of chronic disease and inflammation. Women exhibited a stronger age-related decline in DHEAS and a positive association with glucose in contrast to findings among men (P interaction < 0.05). In conclusion, in this large study of Latinos with a heavy cardiovascular risk factor burden, we observed significant associations between cardiovascular disease (CVD) risk factors and DHEAS, with variations by sex. These findings improve our understanding of the role DHEAS may play in CVD etiology.
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Affiliation(s)
- Monik C Jiménez
- Division of Women's Health, Brigham and Women's Hospital, Boston, Massachusetts.,Department of Medicine, Harvard Medical School, Boston, Massachusetts
| | - Katherine L Tucker
- Clinical Laboratory and Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts
| | - Fátima Rodriguez
- Division of Cardiovascular Medicine, Stanford University, Palo Alto, California
| | - Bianca C Porneala
- Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - James B Meigs
- Department of Medicine, Harvard Medical School, Boston, Massachusetts.,Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Lenny López
- Division of Hospital Medicine, University of California San Francisco, San Francisco, California
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Serum Amyloid A, Paraoxonase-1 Activity, and Apolipoprotein Concentrations as Biomarkers of Subclinical Atherosclerosis Risk in Adrenal Incidentaloma Patients. Arch Med Res 2018; 49:182-190. [PMID: 30031631 DOI: 10.1016/j.arcmed.2018.07.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 07/02/2018] [Indexed: 11/21/2022]
Abstract
BACKGROUND Adrenal incidentalomas (AIs), particularly subclinical hypercortisolism (SH), are related to an increased risk of atherosclerosis. The anti-oxidative enzyme paraoxonase-1 (PON1) and the acute phase reactant serum amyloid A (SAA) are transported by highdensity lipoprotein and reciprocally regulated in acute inflammatory response. Our aim was to investigate serum SAA, PON1, and apolipoprotein levels as indicators of subclinical atherosclerosis in patients with nonfunctioning AI (NFAI) and SH. METHODS The study group consisted of 60 controls, 14 SH, and 86 NFAI subjects. Serum amyloid A (SAA), PON1 activity, lipid profiles, apoA and B, lipoprotein A (LpA), hsCRP, and HOMA-IR levels were compared in all groups. RESULTS Serum insulin, triglyceride, SAA, SAA/PON1 ratio, LpA, apoB, hsCRP, and morning cortisol levels were found to be higher while PON1 and apoAI levels were lower in the SH and NFAI groups compared with the controls, and these parameters were found to be more impaired in SH group than NFAI group (p <0.001). HOMA-IR was higher and DHEAS was lower in the SH group than in the other groups. The SAA/PON1 ratio was positively correlated with LpA (r = 0.460; p <0.001), apoB (r = 0.515; p <0.001), insulin (r = 0.275; p = 0.026), triglyceride (r = 0.248; p = 0.002), morning cortisol (r = 0.259; p = 0.045), and UFC (r = 0.274; p <0.001) and negatively correlated with apoAI (r = 0.329; p <0.001), ACTH (r = -0.384; p <0.001), and DHEAS (r = -0.521, p <0.001) levels. The cut-off value of the SAA/PON1 ratio for NFAI was >0.23, and for SH it was >1.33. CONCLUSION The serum SAA/PON1 ratio was high in both the NFAI and SH groups and also exhibited higher levels in SH group. An increased SAA/PON1 ratio and low DHEAS could be attributable to subclinical atherosclerosis risk in SH patients.
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Bianchi VE, Locatelli V. Testosterone a key factor in gender related metabolic syndrome. Obes Rev 2018; 19:557-575. [PMID: 29356299 DOI: 10.1111/obr.12633] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 09/21/2017] [Indexed: 12/15/2022]
Abstract
Metabolic syndrome (MetS) is highly correlated with cardiovascular diseases. Although an excess of body fat is a determinant factor for MetS development, a reduced level of testosterone plays a fundamental role in its regulation. Low testosterone level is highly related to insulin resistance, visceral obesity and MetS. We have searched in Pubmed clinical trial with the password: testosterone and insulin resistance, and testosterone and MetS. We found 19 studies on the correlation between testosterone level with insulin resistance and 18 on the effect of testosterone therapy on MetS. A high correlation between low testosterone and insulin resistance has been found in men, but not in women. Testosterone administration in hypogonadal men improved MetS and reduced the mortality risk. Androgen and oestrogen receptors are expressed in adipocytes, muscle and liver tissue, and their activation is necessary to improve metabolic control. Normalization of testosterone level should be the primary treatment in men, along with caloric restriction and physical exercise. These findings come mainly from correlative data, and there remains a need for randomized trials to strengthen this evidence. This review will consider the effects of testosterone on the regulation and development of MetS in men and women.
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Affiliation(s)
- V E Bianchi
- Nutrition and Metabolism, Clinical Center Stella Maris, Falciano, San Marino
| | - V Locatelli
- Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
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Demel SL, Kittner S, Ley SH, McDermott M, Rexrode KM. Stroke Risk Factors Unique to Women. Stroke 2018; 49:518-523. [PMID: 29438077 PMCID: PMC5909714 DOI: 10.1161/strokeaha.117.018415] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 11/28/2017] [Accepted: 12/01/2017] [Indexed: 12/28/2022]
Affiliation(s)
- Stacie L Demel
- From the Department of Neurology and Ophthalmology and Department of Pharmacology and Toxicology, Michigan State University, East Lansing (S.L.D.); Baltimore Veterans Administration Medical Center and Department of Neurology, University of Maryland School of Medicine (S.K.); Channing Division of Network Medicine and Division of Women's Health (K.M.R.), Department of Medicine, Brigham and Women's Hospital, Boston, MA (S.H.L.); Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA (S.H.L.); and University of Michigan Stroke Program, Ann Arbor (M.M.)
| | - Steven Kittner
- From the Department of Neurology and Ophthalmology and Department of Pharmacology and Toxicology, Michigan State University, East Lansing (S.L.D.); Baltimore Veterans Administration Medical Center and Department of Neurology, University of Maryland School of Medicine (S.K.); Channing Division of Network Medicine and Division of Women's Health (K.M.R.), Department of Medicine, Brigham and Women's Hospital, Boston, MA (S.H.L.); Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA (S.H.L.); and University of Michigan Stroke Program, Ann Arbor (M.M.)
| | - Sylvia H Ley
- From the Department of Neurology and Ophthalmology and Department of Pharmacology and Toxicology, Michigan State University, East Lansing (S.L.D.); Baltimore Veterans Administration Medical Center and Department of Neurology, University of Maryland School of Medicine (S.K.); Channing Division of Network Medicine and Division of Women's Health (K.M.R.), Department of Medicine, Brigham and Women's Hospital, Boston, MA (S.H.L.); Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA (S.H.L.); and University of Michigan Stroke Program, Ann Arbor (M.M.)
| | - Mollie McDermott
- From the Department of Neurology and Ophthalmology and Department of Pharmacology and Toxicology, Michigan State University, East Lansing (S.L.D.); Baltimore Veterans Administration Medical Center and Department of Neurology, University of Maryland School of Medicine (S.K.); Channing Division of Network Medicine and Division of Women's Health (K.M.R.), Department of Medicine, Brigham and Women's Hospital, Boston, MA (S.H.L.); Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA (S.H.L.); and University of Michigan Stroke Program, Ann Arbor (M.M.)
| | - Kathryn M Rexrode
- From the Department of Neurology and Ophthalmology and Department of Pharmacology and Toxicology, Michigan State University, East Lansing (S.L.D.); Baltimore Veterans Administration Medical Center and Department of Neurology, University of Maryland School of Medicine (S.K.); Channing Division of Network Medicine and Division of Women's Health (K.M.R.), Department of Medicine, Brigham and Women's Hospital, Boston, MA (S.H.L.); Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA (S.H.L.); and University of Michigan Stroke Program, Ann Arbor (M.M.).
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Chiu HF, Chen BK, Lu YY, Han YC, Shen YC, Venkatakrishnan K, Golovinskaia O, Wang CK. Hypocholesterolemic efficacy of royal jelly in healthy mild hypercholesterolemic adults. PHARMACEUTICAL BIOLOGY 2017; 55:497-502. [PMID: 27937077 PMCID: PMC6130454 DOI: 10.1080/13880209.2016.1253110] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Revised: 10/17/2016] [Accepted: 10/22/2016] [Indexed: 06/01/2023]
Abstract
CONTEXT Royal jelly (RJ) has been reported for its health promoting factors such as antioxidant, anti-inflammatory and lipid lowering activities. OBJECTIVE The present randomized, placebo-controlled study examines the hypolipidemic beneficial effect of RJ through evaluating anthropometric measurements, lipid profile and various hormone levels in mildly hypercholesterolemic participants. MATERIALS AND METHODS Forty subjects with mild hypercholesterolemia (180-200 mg/dL) were randomly selected and divided into two groups as experimental or placebo, who requested to intake nine capsules (350 mg/capsule) of RJ or placebo/day, respectively, for three months with one month of follow-up without any supplementation. RESULTS No significant changes were noted in any of the anthropometric parameters like body weight, waist and body fat. The serum total cholesterol (TC; 207.05-183.15 mg/dL) and low-density lipoprotein cholesterol (LDL-c; 126.44-120.31 mg/dL) levels were reduced significantly (p < 0.05) after administration of RJ. However, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-c) levels were not considerably altered. Moreover, three months of RJ consumption significantly ameliorated (p < 0.05) the concentration of sex hormones like dehydroepiandrosterone sulphate (DHEA-S; 1788.09-1992.31 ng/mL). Also, intake of RJ did not elicit any hepatic or renal damage. DISCUSSION AND CONCLUSION Intervention with RJ for three months considerably lowered the TC and LDL-c levels through improving the levels of DHEA-S and thus alleviates the risk of cardiovascular disease (CVD).
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Affiliation(s)
- Hui-Fang Chiu
- Department of Chinese Medicine, Taichung Hospital, Ministry of Health and Well-being, Taichung City, Taiwan, ROC
| | - Bo-Kai Chen
- School of Nutrition, Chung Shan Medical University, Taichung City, Taiwan, ROC
| | - Yan-Ying Lu
- Department of Neurology, Chung Shan Medical University, Taichung City, Taiwan, ROC
| | - Yi-Chun Han
- School of Nutrition, Chung Shan Medical University, Taichung City, Taiwan, ROC
| | - You-Cheng Shen
- School of Health Diet and Industry Management, Chung Shan Medical University, Taichung City, Taiwan, ROC
| | | | | | - Chin-Kun Wang
- School of Nutrition, Chung Shan Medical University, Taichung City, Taiwan, ROC
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Papierska L. Adrenopause - does it really exist? PRZEGLAD MENOPAUZALNY = MENOPAUSE REVIEW 2017; 16:57-60. [PMID: 28721131 PMCID: PMC5509973 DOI: 10.5114/pm.2017.68593] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 05/30/2017] [Indexed: 12/23/2022]
Abstract
In ageing human adrenal glands there occur some morphological changes which result in alterations of their cortex endocrine function. Glucocorticoid-excreting cells in the zona glomerulosa live longer than androgen-producing cells in the zona reticularis, which undergo significant apoptosis. Therefore, in elderly humans cortisol levels are normal (significantly higher than at young age), while adrenal androgen concentrations decline with ageing. Function of the zona glomerulosa is affected by the adrenal status, circulatory system condition, efficiency of the kidneys and liver and medication. An important problem of ageing is the rising incidence of non-secreting, incidentally detected, benign adrenal tumors, called incidentalomas. They necessitate clear-sighted radiological and hormonal diagnosis.
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Affiliation(s)
- Lucyna Papierska
- Department of Endocrinology, Centre of Postgraduate Medical Education, Bielański Hospital, Warsaw, Poland
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Liu Y, Almeida DM, Rovine MJ, Zarit SH. Care Transitions and Adult Day Services Moderate the Longitudinal Links between Stress Biomarkers and Family Caregivers' Functional Health. Gerontology 2017; 63:538-549. [PMID: 28521309 DOI: 10.1159/000475557] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Accepted: 04/09/2017] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Stress biomarkers have been linked to health and well-being. There are, however, few studies on how dysregulation in the hypothalamic-pituitary-adrenal axis and sympathetic nervous system actually affects functional health of family caregivers of persons with dementia. Further, it is not clear whether and how factors affecting caregiving stressor exposures such as care transitions and adult day services (ADS) use may affect such association. OBJECTIVE First, to examine the association of daily stress biomarkers and functional health over time among family caregivers of persons with dementia. Second, to examine effects of care transitions and ADS use on the association between baseline stress biomarkers and functional health over time. METHODS At baseline, caregivers provided 5 saliva samples each day during an 8-day diary study, where all caregivers were having a varying number of ADS days per week. There were 2 longitudinal follow-ups at 6 and 12 months on ADS use, care transitions, and caregivers' functional health. The average daily total output across days was computed at baseline for salivary cortisol, the sulfated form of dehydroepiandrosterone (DHEA-s), and salivary alpha amylase (sAA), which were used as predictors of caregivers' longitudinal functional limitation trajectories. Care transitions and total number of ADS days per week at baseline were considered as moderators of the associations between stress biomarkers and health over time. RESULTS The associations between functional limitation trajectories and daily total outputs of cortisol and sAA were modified by ADS use and care transitions. Among caregivers who experienced a transition, and who used less than average ADS days per week, lower daily cortisol total output and lower daily sAA total output were associated with increasing functional limitations. Caregivers who experienced a transition but used greater than average ADS days per week did not show such patterns of association. No significant effect was found for DHEA-s. CONCLUSION The study contributes to an important but largely unanswered question regarding implications of stress biomarkers on functional health. Assessments of the association between stress biomarkers and health among family caregivers of persons with dementia need to consider changes in stressor exposures over time, such as care transitions and ADS use.
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Affiliation(s)
- Yin Liu
- Center for Healthy Aging, The Pennsylvania State University, University Park, PA, USA
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Wu TT, Chen Y, Zhou Y, Adi D, Zheng YY, Liu F, Ma YT, Xie X. Prognostic Value of Dehydroepiandrosterone Sulfate for Patients With Cardiovascular Disease: A Systematic Review and Meta-Analysis. J Am Heart Assoc 2017; 6:e004896. [PMID: 28476876 PMCID: PMC5524067 DOI: 10.1161/jaha.116.004896] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 02/24/2017] [Indexed: 11/16/2022]
Abstract
BACKGROUND The aim of the present study was to estimate the impact of dehydroepiandrosterone sulfate (DHEAS) on the prognosis of patients with cardiovascular disease by performing a systematic review and meta-analysis. METHODS AND RESULTS The Embase, PubMed, Web of Science, CNKI, and WanFang databases were searched up to September 5, 2016, to identify eligible studies. The quality of each study was assessed using the Newcastle-Ottawa Scale. The association between DHEAS, either on admission or at discharge, and cardiovascular disease outcomes were reviewed. The overall risk ratio for the effect of DHEAS on all-cause mortality and fatal and nonfatal cardiovascular events was pooled using a fixed-effects or a random-effects model. The publication bias was evaluated using funnel plots. Twenty-five studies were included for systematic review. The follow-up duration ranged from 1 to 19 years. Eighteen studies were included in the meta-analysis. We found that lower DHEAS levels indicated a significant increased risk for all-cause mortality (risk ratio, 1.47; 95% CI, 1.38-1.56 [P<0.00001]), fatal cardiovascular event (risk ratio, 1.58; 95% CI, 1.30-1.91 [P<0.00001]), and nonfatal cardiovascular event (risk ratio, 1.42; 95% CI, 1.24-1.62 [P<0.0001]) in patients with cardiovascular disease. CONCLUSIONS Patients with cardiovascular disease who have lower DHEAS levels may have poorer prognosis than those with higher DHEAS levels.
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Affiliation(s)
- Ting-Ting Wu
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Yuan Chen
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Yun Zhou
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Dilare Adi
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Ying-Ying Zheng
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Fen Liu
- Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, China
| | - Yi-Tong Ma
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Xiang Xie
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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