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Kwon SA, Cho YS. Identification of loci associated with women's reproductive traits and exploration of a shared genetic basis with obesity. Hum Genomics 2025; 19:58. [PMID: 40394640 PMCID: PMC12093848 DOI: 10.1186/s40246-025-00773-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 05/07/2025] [Indexed: 05/22/2025] Open
Abstract
BACKGROUND The timing of menarche and menopause significantly affects women's health, with influences on cancer, cardiovascular disease, obesity, type 2 diabetes, and psychosocial problems. In addition, observational studies have reported that ages at menarche (AAM) and natural menopause (ANM) are correlated with obesity. To understand the genetic bases of these reproductive traits, we conducted a genome-wide association study (GWAS) of AAM and ANM in the Korean population. We also investigated the genetic correlation and causal relationship to explore the shared genetic architecture between reproductive traits and obesity in women. RESULTS Our GWA analyses of 45,608 and 21,599 adult women identified two and six genome-wide significant associations (P-value < 5 × 10- 8) for AAM and ANM, respectively. Although most of the loci that we detected have been reported in previous studies, we have newly linked the JHY locus containing the SNP rs11605693 to AAM. Leveraging the GWAS results, we tested the shared genetic basis underlying AAM and ANM, which appear to be closely related to female hormone activity. Linkage disequilibrium score regression (LDSC) analysis did not identify a significant genetic correlation between the two traits. Our LDSC analyses indicated that AAM was inversely correlated with two obesity traits, body mass index (BMI) and waist circumference (WC). However, Mendelian randomization (MR) analyses did not provide evidence of a causal relationship between AAM and obesity traits. CONCLUSIONS Overall, our study provides insights into the genetic architecture of women's reproductive traits and the shared genetic basis between AAM and obesity. Our MR analyses suggest that the genetic correlation between AAM and obesity traits results from the direct effects of genetic variants on both traits rather than a causal relationship between them.
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Affiliation(s)
- Seong-Ah Kwon
- Department of Biomedical Science, Hallym University, Chuncheon, 24252, Gangwon State, Republic of Korea
| | - Yoon Shin Cho
- Department of Biomedical Science, Hallym University, Chuncheon, 24252, Gangwon State, Republic of Korea.
- Department of Neuroscience, Hallym University College of Medicine, Chuncheon, 24252, Gangwon State, Republic of Korea.
- GenoMax Co., Ltd., Life Science Building 8406, Hallymdaehakgil 1, Chuncheon, Gangwon State, Republic of Korea.
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Kalluru S, Akande CM, Bellon MB, Mahendru N, Jalili D, Sampson A, Goldstein SR, Nachtigall MJ, Nachtigall LE, Dunham SM, Phillips KA, Quinn GP. Achieving Menopausal Health Equity Network (AMEN): an educational intervention to improve OB/GYN knowledge of menopause-related racial and ethnic health disparities. Menopause 2025:00042192-990000000-00449. [PMID: 40327447 DOI: 10.1097/gme.0000000000002545] [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: 10/28/2024] [Accepted: 01/29/2025] [Indexed: 05/08/2025]
Abstract
OBJECTIVES To study the impact of an educational intervention on obstetrician-gynecologist clinicians' knowledge of racial and ethnic disparities in the menopause experience. METHODS Twenty-five obstetrician-gynecologist physicians (residents, fellows, and attendings) at an academic medical center in New York, NY, completed the Achieving Menopausal Health Equity Network course, a brief web-based intervention consisting of four modules delivered through narrated didactic videos and interactive tools, a 10-item pretest and posttest, and a course evaluation survey. The primary outcome was a change in knowledge scores after the completion of the educational intervention. Item analysis was also performed to assess item discrimination, item difficulty, and response frequency. Feedback on modules was obtained, and thematic analysis was performed. RESULTS In this study, 25 participants completed the educational intervention. There was a statistically significant increase in mean test scores after participation (pretest mean score=7.1/10 vs. posttest mean score=8.1/10, P =0.0021). The following themes emerged in thematic analysis: knowledge building with potential for practical application for clinicians and non-clinicians, clarity and relevance, and opportunities for growth for future iterations of the modules. CONCLUSIONS This brief, online educational curriculum focused on racial and ethnic disparities in menopause significantly improved the knowledge of obstetrician-gynecologist clinicians at various levels of training and provides a useful model for introducing more formal training on menopause medicine for obstetrician-gynecologist clinicians.
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Affiliation(s)
- Shilpa Kalluru
- Department of OBGYN, Grossman School of Medicine, New York, NY
| | - Celine M Akande
- Department of OBGYN, Grossman School of Medicine, New York, NY
| | | | - Nikhita Mahendru
- University of California San Francisco School of Medicine, San Francisco, CA
| | - Dona Jalili
- Department of OBGYN, Grossman School of Medicine, New York, NY
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Liang Y, Ou J, Fu J, Wang Y, Li Y, Li J, Yi Y. Smoking, Genetic Susceptibility and Early Menopause: Unveiling Biological Mechanisms and Potential Therapy Targets. BJOG 2025; 132:625-637. [PMID: 39727065 DOI: 10.1111/1471-0528.18052] [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: 09/25/2024] [Revised: 12/04/2024] [Accepted: 12/13/2024] [Indexed: 12/28/2024]
Abstract
OBJECTIVE To explore the association between smoking, genetic susceptibility and early menopause (EM) and clarify the potential mechanisms underlying this relationship. DESIGN An observational and Transcriptome-wide association analysis (TWAS) study. SETTING UK Biobank and public summary statistics. POPULATION 139 869 women with full baseline and menopause data, and no gynaecological surgery history. METHODS Adjusted modified Poisson regression models were developed to determine the smoking and genetic risk effects on EM. TWAS was used to identify gene expression between smoking and EM, with Mendelian randomisation (MR) to infer causality. Enrichment analysis explored regulatory networks of transcription factors, microRNAs and potential therapeutic targets. Small molecule drugs were predicted using drug-gene interaction analysis. MAIN OUTCOME MEASURES EM prevalence and common gene expression patterns. RESULTS Women with over 30 pack-years of smoking had about 1.5 times higher EM risk, with RRs of 1.39 (95%CI, 1.23-1.56), 1.45 (1.33-1.59) and 1.45 (1.36-1.55) in the low, intermediate and high genetic risk groups. TWAS identified hub genes such as IMMP2L, BMPR2 and HMGN1. MR confirmed daily cigarette consumption as a causal factor in early menopause. Several potential therapeutic targets (e.g., SP600125, INCB18424 and ruxolitinib) were identified. CONCLUSIONS Smoking reduction significantly lowered the risk of EM. Hub genes and therapeutic targets identified provided new avenues for mitigating harmful effects of smoking.
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Affiliation(s)
- Yuhang Liang
- Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
- Bioinformatics Center, Furong Laboratory, National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
| | - Jie Ou
- Department of Gyneacology, Xiangya Hospital, Central South University, Changsha, China
| | - Jing Fu
- Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, China
| | - Yijing Wang
- Bioinformatics Center, Furong Laboratory, National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
| | - Yanping Li
- Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, China
| | - Jinchen Li
- Bioinformatics Center, Furong Laboratory, National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
- Centre for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Xiangya Hospital, Central South University, Changsha, China
| | - Yan Yi
- Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
- Bioinformatics Center, Furong Laboratory, National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China
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Liu L, Wei R, Tang Y, Zhang X, Zhao R, Lu C. Association of dietary flavonoid intake with reproductive lifespan: a cross-sectional study. Eur J Nutr 2025; 64:126. [PMID: 40080127 DOI: 10.1007/s00394-025-03641-w] [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: 03/15/2024] [Accepted: 01/20/2025] [Indexed: 03/15/2025]
Abstract
PURPOSE Reproductive lifespan was defined as the number of years between menarche and menopause, which is an important indicator for assessing female reproductive health. Dietary nutrient intake may have a significant impact on estrogen levels and reproductive capacity in women. However, the evidence for the correlation between dietary flavonoid intake and reproductive lifespan is unclear. Our study aimed to explore the relevance of dietary flavonoid intake and reproductive lifespan. METHODS Our research was based on a sample of 622 naturally menopausal females who participated in the 2007-2008, 2009-2010, and 2017-2018 National Health and Nutrition Examination Surveys (NHANES). We collected data on flavonoid intake using a 24-hour dietary intake assessment model and evaluated reproductive lifespan by surveying participants' ages at menarche and menopause. We used a linear regression model to explore the link between total flavonoids intake and reproductive lifespan, and a categorical logistic regression model was used to examine the relevance of dietary flavonoid subclasses intake and reproductive lifespan. The restricted cubic spline (RCS) was employed to evaluate the potential nonlinear relationship. RESULTS After adjusting for covariates, we discovered a potential linear positive correlation between total flavonoids intake and reproductive lifespan. Our multivariate logistic regression model showed that moderate elevations in anthocyanidins and flavan-3-ols intake were linked to extended reproductive lifespan. Furthermore, our findings suggest a possible non-linear positive association between flavones and flavonols intake and reproductive lifespan (p-value for non-linearity < 0.05). CONCLUSION Our study suggested that an appropriate increase in dietary flavonoids intake may prolong female reproductive lifespan and promote reproductive health.
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Affiliation(s)
- Lu Liu
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261000, Shandong, People's Republic of China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, People's Republic of China
| | - Ran Wei
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261000, Shandong, People's Republic of China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, People's Republic of China
| | - Yujie Tang
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261000, Shandong, People's Republic of China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, People's Republic of China
| | - Xuemei Zhang
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261000, Shandong, People's Republic of China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, People's Republic of China
| | - Runze Zhao
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261000, Shandong, People's Republic of China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, People's Republic of China
| | - Chao Lu
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261000, Shandong, People's Republic of China.
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, People's Republic of China.
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Moosazadeh M, Bordbari AH, Hashemi SM, Ghasemi Tirtashi M, Kargar-Soleimanabad S. The association between age at menarche and infertility: a systematic review and meta-analysis of observational studies. Contracept Reprod Med 2025; 10:15. [PMID: 39994726 PMCID: PMC11853611 DOI: 10.1186/s40834-025-00346-7] [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: 11/11/2024] [Accepted: 02/19/2025] [Indexed: 02/26/2025] Open
Abstract
OBJECTIVE Both early and late age at menarche have been associated with various health issues and may influence the risk of infertility. This present study investigated the relationship between age at menarche and infertility risk. METHODS This study follows PRISMA guidelines. Databases including PubMed, Scopus, Web of Science, Embase, and Cochrane were searched in December 2024. Odds ratios with 95% confidence intervals were estimated using a random-effects model. Heterogeneity was assessed with the I2 index and chi-square, and publication bias was evaluated using Egger's test and a funnel plot. Sensitivity analysis and meta-regression examined study impact and variable influence on heterogeneity. RESULTS Out of 7,267 articles screened, 18 primary studies were included, yielding 21 pieces of evidence. The odds ratio (OR) for infertility in the late menarche group compared to the normal menarche group was 1.44 (95% CI: 0.98-2.10), while the OR for the early menarche group versus the normal menarche group was 0.98 (95% CI: 0.68-1.42). Additionally, the OR for infertility in the early menarche group compared to the late menarche group was 0.77 (95% CI: 0.55-1.06). For primary infertility, the OR for the late menarche group relative to the normal menarche group was 1.98 (95% CI: 1.02-3.85), whereas the OR for the early menarche group compared to the late menarche group was 0.59 (95% CI: 0.36-0.97). CONCLUSION Although the overall meta-analysis lacked statistical significance, subgroup analysis revealed a notable association between late menarche and primary infertility. Women with late menarche had higher odds of infertility, supporting a dose-responsive relationship. The observed 44% increase in infertility odds highlights late menarche as a potential risk factor, warranting further investigation into its implications for reproductive health.
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Affiliation(s)
- Mahmood Moosazadeh
- Gastrointestinal Cancer Research Center, Non-Communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Amir-Hassan Bordbari
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Farah Abad Road, P.O. Box: 48471-91628, Sari, Iran.
| | - Seyyed Mohammad Hashemi
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Maliheh Ghasemi Tirtashi
- Department of Obstetrics and Gynecology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Saeed Kargar-Soleimanabad
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Farah Abad Road, P.O. Box: 48471-91628, Sari, Iran
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Guo M, Wu Y, Gross AL, Karvonen‐Gutierrez C, Kobayashi LC. Age at menopause and cognitive function and decline among middle-aged and older women in the China Health and Retirement Longitudinal Study, 2011-2018. Alzheimers Dement 2025; 21:e14580. [PMID: 39936226 PMCID: PMC11815216 DOI: 10.1002/alz.14580] [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: 11/04/2024] [Revised: 12/27/2024] [Accepted: 01/12/2025] [Indexed: 02/13/2025]
Abstract
INTRODUCTION Chinese women experience higher dementia rates than men, yet sex-specific risk factors are understudied. We examined how menopause age affects cognitive function and decline in aging Chinese women. METHODS Data were from 7419 postmenopausal women 45-101 years of age at baseline in the China Health and Retirement Longitudinal Study (CHARLS; 2011-2018). Menopause age was categorized using clinical cutoffs (<40, 40-44, 45-49, 50-55, >55 years). Cognitive function was assessed with neuropsychological tests up to four times over 7 years, and associations were analyzed using multivariable-adjusted linear mixed-effects regression. RESULTS Compared to menopause at 50-55 years (3661/7419; 49.3%), premature (<40; 235/7419; 3.2%), early (40-44; 623/7419; 8.4%), and late menopause (>55; 366/7419; 4.9%) were associated with lower baseline cognitive scores. Although the rate of cognitive decline did not differ significantly across menopause age groups, late menopause showed a trend toward faster decline. DISCUSSION Cognitive health interventions should consider extreme menopausal age as a risk factor. HIGHLIGHTS Extreme menopausal ages-premature (<40), early (40-44), and late (>55)-are linked to lower baseline cognition versus menopause ages 50-55, persisting over 7 years. Cognitive disadvantage for late menopause (>55) versus 50-55 tends to increase over time. Health interventions should consider extreme menopause ages in women's cognitive health.
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Affiliation(s)
- Muqi Guo
- Harvard T.H. Chan School of Public HealthBostonMassachusettsUSA
- Harvard Kenneth C. Griffin Graduate School of Arts and SciencesCambridgeMassachusettsUSA
| | - Yingyan Wu
- Department of Epidemiology, Fielding School of Public Health University of CaliforniaLos AngelesUSA
| | - Alden L. Gross
- Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreMarylandUSA
| | - Carrie Karvonen‐Gutierrez
- Department of EpidemiologyUniversity of Michigan School of Public HealthAnn ArborMichiganUSA
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and DiabetesUniversity of Michigan Medical SchoolAnn ArborMichiganUSA
| | - Lindsay C. Kobayashi
- Department of EpidemiologyUniversity of Michigan School of Public HealthAnn ArborMichiganUSA
- Survey Research Center, Institute for Social ResearchUniversity of MichiganAnn ArborMichiganUSA
- MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa
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Sievert LL. Evolutionary Perspectives, Comparative Approaches, and the Lived Experience of Menopause. AMERICAN JOURNAL OF BIOLOGICAL ANTHROPOLOGY 2025; 186:e70012. [PMID: 39949285 DOI: 10.1002/ajpa.70012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 11/16/2024] [Accepted: 12/19/2024] [Indexed: 03/20/2025]
Abstract
The purpose of this synthesis is to review age at menopause, symptom experience at midlife, and the evolution of menopause in a way that is helpful for biological anthropologists who are interested in the study of this challenging time of life. The synthesis begins with the biology of menopause, then shifts to the evolution of menopause with an emphasis on phylogenetic and adaptationist perspectives. Discussion of the biology and evolution of menopause incorporates a cross-species perspective, with particular attention to whales and primates. The synthesis continues with a cross-population review of variation in age at menopause. The final section is about symptom experience across populations with attention to the medical context of midlife, a focus on hot flashes, and consideration of the strengths and limitations of ethnographic and questionnaire-based research. The review ends with suggestions for where biological anthropology can make important contributions to the research of midlife and menopause.
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An S, Ren S, Ma J, Zhang Y. Association of Depression with Age at Natural Menopause: A Cross-Sectional Analysis with NHANES Data. Int J Womens Health 2025; 17:211-220. [PMID: 39911359 PMCID: PMC11794376 DOI: 10.2147/ijwh.s504748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/20/2025] [Indexed: 02/07/2025] Open
Abstract
Purpose To evaluate the association between depression and age of natural menopause in American women. Patients and Methods This cross-sectional study utilized eight cycles of the National Health and Nutrition Examination Survey (NHANES) conducted from 2005 to 2023. We assessed depression using the Patient Health Questionnaire-9 (PHQ-9). We obtained ANM information from the Reproductive Health questionnaire. We screened menopausal women between the ages of 40 and 70 years, excluding those with surgical menopause. We used multivariable logistic regression models to investigate the association between depression and ANM. Additionally, we conducted subgroup analyses and interaction tests. Results A total of 4732 women were included, and the mean age of natural menopause was 47.9 ± 6.8 years. Of these, 1123 (23.7%) were classified as early menopause, 2971 (62.8%) as normal menopause, and 638 (13.5%) as late menopause. Preliminary analysis showed a positive association between PHQ-9 score and the risk of early menopause (OR = 1.11, 95% CI = 1.06-1.16). After full adjustment in multivariate logistic regression, it was estimated that each one-unit increase in the PHQ-9 score was associated with a 7% increased risk of early menopause (OR = 1.07, 95% CI = 1.02-1.12). After classifying depression into three grades: no, mild, and severe, it was found that, compared with American women without depression, the risk of early menopause increased significantly. American women with major depression had an increased risk of early menopause (OR = 2.49, 95% CI = 1.10-5.63). In College or above (OR = 1.10, 95% CI = 1.02-1.19), PIR≤1 (OR = 1.10, 95% CI = 1.04-1.16), Current smoker (OR = 1.12, 95% CI = 1.00-1.24), the positive association between depression and early menopause was more significant. Conclusion In this cross-sectional study, the severity of depression in American women was positively correlated with the risk of early menopause. This suggests that women should pay more attention to their mental health and actively manage depression. For women with depression, early intervention and treatment may help improve their reproductive health and delay menopause.
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Affiliation(s)
- Shuaiqi An
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Shiyan Ren
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Jiawen Ma
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
| | - Yizhou Zhang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
- Zhejiang Famous Chinese Medicine Clinic, the Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China
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Sievert LL. Evolutionary Perspectives, Comparative Approaches, and the Lived Experience of Menopause. AMERICAN JOURNAL OF BIOLOGICAL ANTHROPOLOGY 2024; 186 Suppl 78:e25067. [PMID: 40071785 DOI: 10.1002/ajpa.25067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 11/16/2024] [Accepted: 12/19/2024] [Indexed: 04/02/2025]
Abstract
The purpose of this synthesis is to review age at menopause, symptom experience at midlife, and the evolution of menopause in a way that is helpful for biological anthropologists who are interested in the study of this challenging time of life. The synthesis begins with the biology of menopause, then shifts to the evolution of menopause with an emphasis on phylogenetic and adaptationist perspectives. Discussion of the biology and evolution of menopause incorporates a cross-species perspective, with particular attention to whales and primates. The synthesis continues with a cross-population review of variation in age at menopause. The final section is about symptom experience across populations with attention to the medical context of midlife, a focus on hot flashes, and consideration of the strengths and limitations of ethnographic and questionnaire-based research. The review ends with suggestions for where biological anthropology can make important contributions to the research of midlife and menopause.
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Monterrosa-Castro Á, Monterrosa-Blanco A, Sánchez-Zarza S. Possible association between subclinical hypothyroidism and age at menopause in Colombian women. Gynecol Endocrinol 2024; 40:2334798. [PMID: 38590105 DOI: 10.1080/09513590.2024.2334798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 03/20/2024] [Indexed: 04/10/2024] Open
Abstract
OBJECTIVE To evaluate the association between subclinical hypothyroidism with early menopause, premature menopause, and last menstrual bleeding before the natural age of menopause. METHODS This was a cross-sectional study conducted in 643 postmenopausal women aged 40-69 years. Groups were formed according to last menstrual episode: ≥45 [Natural age at menopause], 40-44 and [Early menopause], <40 [Premature menopause], and <45 [last menstrual episode before the natural age of menopause]. The Zulewski scale was applied to identify manifestations related to hypothyroidism and subclinical hypothyroidism, diagnosed with a serum TSH > 4.5 µIU/mL plus T4-free between 0.7 and 1.9 ng/dL. RESULTS It was found that 24.4% had the last menstrual episode before the natural age of menopause, 18.6% had early menopause, and 5.7% had premature menopause. Subclinical hypothyroidism was diagnosed in 4.5% of patients. Among women with subclinical hypothyroidism, there was a higher frequency of early menopause, premature menopause, and last menstrual episode before the natural age of menopause, than in women without subclinical hypothyroidism (p < 0.05). Paresthesia (50%) and dry skin (40.7%) were the most reported hypothyroidism-related manifestations. Early menopause, premature menopause, and last menstrual episode before the natural age of menopause were associated with subclinical hypothyroidism, OR: 3.37 [95% CI: 1.40-8.10], OR: 4.31 [95% CI: 1.24-14.97], and OR: 3.57 [95% CI: 1.57-8.10], respectively. CONCLUSIONS The last menstrual episode before the natural age of menopause, early menopause, and premature menopause were significantly associated with a higher chance of subclinical hypothyroidism.
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Affiliation(s)
- Álvaro Monterrosa-Castro
- Grupo de investigación Salud de la Mujer, Facultad de Medicina, Universidad de Cartagena, Cartagena, Colombia
| | - Angelica Monterrosa-Blanco
- Grupo de investigación Salud de la Mujer, Facultad de Medicina, Universidad de Cartagena, Cartagena, Colombia
| | - Sandra Sánchez-Zarza
- Grupo de investigación Salud de la Mujer, Facultad de Medicina, Universidad de Cartagena, Cartagena, Colombia
- Instituto de Previsión Social (IPS). Hospital Central, Dr. Emilio Cubas, Facultad de Ciencias de la Salud, Universidad Católica Nuestra Señora de la Asunción', Asunción, Paraguay
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Mani S, Srivastava V, Shandilya C, Kaushik A, Singh KK. Mitochondria: the epigenetic regulators of ovarian aging and longevity. Front Endocrinol (Lausanne) 2024; 15:1424826. [PMID: 39605943 PMCID: PMC11598335 DOI: 10.3389/fendo.2024.1424826] [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: 04/28/2024] [Accepted: 10/21/2024] [Indexed: 11/29/2024] Open
Abstract
Ovarian aging is a major health concern for women. Ovarian aging is associated with reduced health span and longevity. Mitochondrial dysfunction is one of the hallmarks of ovarian aging. In addition to providing oocytes with optimal energy, the mitochondria provide a co-substrate that drives epigenetic processes. Studies show epigenetic alterations, both nuclear and mitochondrial contribute to ovarian aging. Both, nuclear and mitochondrial genomes cross-talk with each other, resulting in two ways orchestrated anterograde and retrograde response that involves epigenetic changes in nuclear and mitochondrial compartments. Epigenetic alterations causing changes in metabolism impact ovarian function. Key mitochondrial co-substrate includes acetyl CoA, NAD+, ATP, and α-KG. Thus, enhancing mitochondrial function in aging ovaries may preserve ovarian function and can lead to ovarian longevity and reproductive and better health outcomes in women. This article describes the role of mitochondria-led epigenetics involved in ovarian aging and discusses strategies to restore epigenetic reprogramming in oocytes by preserving, protecting, or promoting mitochondrial function.
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Affiliation(s)
- Shalini Mani
- Centre for Emerging Diseases, Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Vidushi Srivastava
- Centre for Emerging Diseases, Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Chesta Shandilya
- Centre for Emerging Diseases, Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Aditi Kaushik
- Centre for Emerging Diseases, Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Keshav K. Singh
- Departments of Genetics, Dermatology and Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Center for Women’s Reproductive Health, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
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12
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Scime NV, Huang B, Brockway MM, Brown HK, Brennand EA. Association of lifetime lactation and characteristics of menopause: a longitudinal cohort study. BMC Public Health 2024; 24:3112. [PMID: 39529030 PMCID: PMC11552320 DOI: 10.1186/s12889-024-20508-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Lactation has many established benefits for women's long-term health; however, its influence on menopause is less clear. This study investigated the association between lifetime duration of lactation and the timing and type of menopause in midlife women. METHODS We analyzed survey data on 19,783 parous women aged 40 to 65 years at enrollment in the Alberta's Tomorrow Project (2000-2022), a prospective community-based cohort study in Alberta, Canada. Duration of lifetime lactation across all births was categorized as: <1 month (reference group; 19.8% of women), 1-3 months (12.1%), 4-6 months (11.7%), 7-12 months (18.8%), and ≥ 13 months (37.7%). Women were classified as premenopause, natural menopause (age at 1 year after the final menstrual period), surgical menopause (age at bilateral oophorectomy), or indeterminate menopause (age at premenopausal hysterectomy with ovarian preservation). Flexible parametric survival analysis and multinomial logistic regression were used to analyze menopause timing and type, respectively, according to lactation status and controlling for birth year, education, parity, hormonal contraceptive use, and smoking. RESULTS In a dose-response manner, longer lactation was associated with reduced risk of natural menopause before age 50 (for ≥ 13 months of lactation, adjusted hazard ratio at age 45: 0.68, 95% CI 0.59-0.78), surgical menopause before age 55 (age 45: 0.56, 0.50-0.63), and indeterminate menopause before age 50 (age 45: 0.75, 0.69-0.82). Longer lactation was associated with lower odds of surgical (adjusted odds ratio 0.54, 95% CI 0.45-0.66) and indeterminate menopause (0.63, 0.55-0.73), compared to natural menopause. CONCLUSIONS Optimizing the timing of natural menopause and reducing risks of early surgical and indeterminate menopause may be novel maternal benefits of breastfeeding.
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Affiliation(s)
- Natalie V Scime
- Department of Health and Society, University of Toronto Scarborough, Toronto, ON, Canada
| | - Beili Huang
- Department of Obstetrics and Gynecology, University of Calgary, Calgary, AB, Canada
| | | | - Hilary K Brown
- Department of Health and Society, University of Toronto Scarborough, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Erin A Brennand
- Department of Obstetrics and Gynecology, University of Calgary, Calgary, AB, Canada.
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13
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Farland LV, Degnan WJ, Bertone-Johnson ER, Eliassen AH, Wang S, Gaskins AJ, Chavarro JE, Rich-Edwards J, Missmer SA. History of infertility and anti-Müllerian hormone levels among participants in the Nurses' Health Study II. Menopause 2024; 31:952-958. [PMID: 39226412 PMCID: PMC11518641 DOI: 10.1097/gme.0000000000002424] [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] [Indexed: 09/05/2024]
Abstract
OBJECTIVES To better understand whether history of infertility is associated with anti-Müllerian hormone (AMH) levels later in life, outside of reproduction. METHODS Among 1,758 premenopausal women in the Nurses' Health Study II with measured AMH, we used multivariable generalized linear models to compare log-transformed plasma AMH for women with a history of infertility compared with fertile women. We investigated AMH levels by cause of infertility and effect modification by menstrual cycle regularity. Lastly, we investigated AMH levels by history of primary and secondary infertility and age at reported infertility. RESULTS Mean age at blood collection was 40 years. We observed no association between overall history of infertility and AMH levels (% difference AMH: -8.1% [CI, -19.4 to 4.8]). The association between overall infertility and AMH was strongest among women who first reported infertility at >30 years (-17.7% [CI, -32.1 to -0.3]). CONCLUSIONS Overall, we observed no association between the history of infertility and AMH levels later in life. However, specific subgroups of women with a history of infertility may have lower AMH levels throughout life compared with fertile women. This association was observed among subgroups, such as those who first experienced infertility at >30 years. These findings have implications for mechanisms through which infertility may be associated with premature menopause and chronic disease risk.
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Affiliation(s)
- Leslie V. Farland
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA
- Department of Obstetrics and Gynecology, College of Medicine-Tucson, University of Arizona, Tucson, AZ, USA
| | - William J. Degnan
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA
| | - Elizabeth R. Bertone-Johnson
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA, USA
- Department of Health Promotion and Policy, University of Massachusetts Amherst, Amherst, MA, USA
| | - A. Heather Eliassen
- Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Siwen Wang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Audrey J. Gaskins
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Jorge E. Chavarro
- Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Janet Rich-Edwards
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Stacey A. Missmer
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Obstetrics, Gynecology, and Reproductive Biology; College of Human Medicine, Michigan State University, Grand Rapids, MI, USA
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14
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Huang Y, Cui Y, Huang J, Xinyuan H, Zihang W, Luo T, Li J. Proanthocyanidins protects 3-NPA-induced ovarian function decline by activating SESTRIN2-NRF2-mediated oxidative stress in mice. Sci Rep 2024; 14:25643. [PMID: 39465303 PMCID: PMC11514188 DOI: 10.1038/s41598-024-76743-w] [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: 04/22/2024] [Accepted: 10/16/2024] [Indexed: 10/29/2024] Open
Abstract
Abnormal apoptosis of ovarian cells caused by oxidative stress is an important cause of premature ovarian failure (POF). Previous studies revealed that proanthocyanidins (PCs) are powerful natural antioxidants that can safely prevent oxidative damage in humans. However, the protective effect and mechanism of PCs on ovarian function during the course of POF remain unknown. In this study, female mice were injected with 3-nitropropionic acid (3-NPA) to establish an ovarian oxidative stress model; at the same time, the mice were treated with PC via gavage. Thereafter, the expression of various apoptosis genes, hormones, and related molecules was assessed. Compared with those in the control group, the ovarian index, follicle count at all levels, expression of MVH, PCNA and BCL2, and estradiol (E2) and progesterone (P) levels were significantly lower in the POF group, but significant recovery was observed in terms of MVH and PCNA expression and E2 and P levels in the POF + PCs group. The apoptosis marker genes BAX and ROS were significantly increased in the POF group but were notably restored in the POF + PCs group. In addition, the expression of Sestrin2, an antiapoptotic protein, was significantly increased in the PCs treatment group, as were the upstream and downstream regulatory factors NRF2 and SOD2, and the indices of the Sestrin2 overexpression group were similar to those of the PCs treatment group. In summary, these findings suggest that PCs have potential as innovative therapeutic agents for preventing and treating POF by activating the protective SESTRIN2-NRF2 pathway against oxidative stress.
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Affiliation(s)
- Yupei Huang
- School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Yanfan Cui
- School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Jian Huang
- Clinical Medicine Center, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Huang Xinyuan
- School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Wang Zihang
- School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Tao Luo
- School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
- Institute of Biomedical Innovation, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Jia Li
- School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China.
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15
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La Marca A, Diamanti M. Factors affecting age at menopause and their relationship with ovarian reserve: a comprehensive review. EUR J CONTRACEP REPR 2024; 29:245-255. [PMID: 39007753 DOI: 10.1080/13625187.2024.2375281] [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: 03/26/2024] [Accepted: 06/27/2024] [Indexed: 07/16/2024]
Abstract
OBJECTIVE The aim of this article was to discuss all the factors affecting the age at menopause and their correlation with ovarian reserve. MATERIALS AND METHODS A narrative review of original articles was performed using PubMed until December 2023. The following keywords were used to generate the list of citations: 'menopause', 'ovarian reserve' 'oocytes quality and quantity', 'ovarian ageing'. RESULTS Menopause is the final step in the process of ovarian ageing and is influenced by the oocyte pool at birth. Conditions that accelerate follicle depletion during the reproductive lifespan lead to premature ovarian insufficiency (POI) and premature ovarian failure (POF), while a higher ovarian reserve is associated with a delayed time to menopause. Reproductive history, sociodemographic, lifestyle and iatrogenic factors may impact ovarian reserve and the age at menopause. CONCLUSIONS Some factors affecting the age at menopause are modifiable and the risks of early menopause may be preventable. We hypothesise that by addressing these modifiable factors we may also preserve ovarian reserve. However, further interventional studies are needed to evaluate the effects of the described strategies on ovarian reserve.
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Affiliation(s)
- Antonio La Marca
- Obstetrics and Gynecology Unit, Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Modena, Italy
| | - Marialaura Diamanti
- Obstetrics and Gynecology Unit, Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Modena, Italy
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16
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Touraine P, Chabbert-Buffet N, Plu-Bureau G, Duranteau L, Sinclair AH, Tucker EJ. Premature ovarian insufficiency. Nat Rev Dis Primers 2024; 10:63. [PMID: 39266563 DOI: 10.1038/s41572-024-00547-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/31/2024] [Indexed: 09/14/2024]
Abstract
Premature ovarian insufficiency (POI) is a cause of infertility and endocrine dysfunction in women, defined by loss of normal, predictable ovarian activity before the age of 40 years. POI is clinically characterized by amenorrhoea (primary or secondary) with raised circulating levels of follicle-stimulating hormone. This condition can occur due to medical interventions such as ovarian surgery or cytotoxic cancer therapy, metabolic and lysosomal storage diseases, infections, chromosomal anomalies and autoimmune diseases. At least 1 in 100 women is affected by POI, including 1 in 1,000 before the age of 30 years. Substantial evidence suggests a genetic basis to POI. However, the cause of idiopathic POI remains unknown in most patients, indicating that gene variants associated with this condition remain to be discovered. Over the past 10 years, tremendous progress has been made in our knowledge of genes involved in POI. Genetic approaches in diagnosis are important as they enable patients with familial POI to be identified, with the opportunity for oocyte preservation. Moreover, genetic approaches could provide a better understanding of disease mechanisms, which will ultimately aid the development of improved treatments.
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Affiliation(s)
- Philippe Touraine
- Department of Endocrinology and Reproductive Medicine, AP-HP Pitié Salpêtrière Hospital, Sorbonne Université Médecine, Paris, France.
- Inserm U1151 INEM, Necker Hospital, Paris, France.
| | - Nathalie Chabbert-Buffet
- Department of Obstetrics, Gynecology and Reproductive Medicine, Tenon Hospital, AP-HP Sorbonne Université, Paris, France
- INSERM UMR S 938, CDR St Antoine, Paris, France
| | - Genevieve Plu-Bureau
- Department of Medical Gynecology, AP-HP Port Royal-Cochin Hospital, Université Paris Cité, Paris, France
- U1151 EPOPEE Team, Paris, France
| | - Lise Duranteau
- Department of Medical Gynecology, Bicêtre Hospital, AP-HP Université Paris-Saclay, Le Kremlin Bicêtre, France
| | - Andrew H Sinclair
- Murdoch Children's Research Institute, Melbourne, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Elena J Tucker
- Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
- Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
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17
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Sabu S, Corman H, Noonan K, Reichman NE, Kuhn KB, Radovick S. Small for gestational age and age at menarche in a contemporary population-based U.S. sample. PLoS One 2024; 19:e0309363. [PMID: 39240976 PMCID: PMC11379201 DOI: 10.1371/journal.pone.0309363] [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: 04/04/2024] [Accepted: 08/11/2024] [Indexed: 09/08/2024] Open
Abstract
Children born small for gestational age (SGA) may be at risk for earlier puberty and adverse long-term health sequelae. This study investigates associations between SGA and age at menarche using secondary data on 1,027 female children in a population-based U.S. birth cohort that over-sampled non-marital births, which in the U.S. is a policy-relevant population. SGA was defined as <10th percentile of weight for gestational age compared to the national U.S. distribution. We estimated unadjusted and adjusted Ordinary Least Squares (OLS) models of associations between SGA and age at menarche in years, as well as unadjusted and adjusted logistic regression models of associations between SGA and early menarche (before age 11). SGA was not significantly associated with earlier age at menarche, even when adjusting for maternal sociodemographic characteristics, prenatal smoking, and maternal pre-pregnancy overweight and obesity. Similarly, SGA was not significantly associated with the odds of menarche occurring before age 11. However, maternal non-Hispanic Black race-ethnicity, Hispanic ethnicity, and pre-pregnancy obesity all had independent associations with average earlier age at menarche and menarche before age 11. Thus, maternal risk factors appear to play more influential roles in determining pubertal development.
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Affiliation(s)
- Sruchika Sabu
- Department of Pediatrics, Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
| | - Hope Corman
- Department of Economics, Rider University and National Bureau of Economic Research, Lawrenceville, New Jersey, United States of America
| | - Kelly Noonan
- Department of Economics, Princeton University, Princeton, New Jersey, United States of America
| | - Nancy E Reichman
- Department of Pediatrics, Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
- Child Health Institute of New Jersey, Rutgers University, New Brunswick, New Jersey, United States of America
| | - Kirsten B Kuhn
- School of Public and International Affairs, Princeton University, Princeton, New Jersey, United States of America
| | - Sally Radovick
- Department of Pediatrics, Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
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18
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Te West N, Harris K, Chapman M, Moore KH. Does Urodynamic Stress Incontinence Increase After the Menopause?: Results from 2,994 Urodynamic Studies in Australian Women. Int Urogynecol J 2024; 35:1789-1796. [PMID: 39042153 PMCID: PMC11420294 DOI: 10.1007/s00192-024-05876-3] [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: 01/16/2024] [Accepted: 06/30/2024] [Indexed: 07/24/2024]
Abstract
INTRODUCTION AND HYPOTHESIS Most studies attempting to estimate the age-related prevalence of urinary incontinence (UI) have used questionnaires. In the present study we analysed a consecutive series of urodynamic test results to determine the distribution of the different types of UI in pre- and post-menopausal women. We hypothesised that the prevalence of urodynamic stress incontinence (USI) would be significantly greater in pre-menopausal than in post-menopausal women. METHODS All women from a large tertiary urogynaecology department, who underwent urodynamic tests during the years 2000-2015 were included. Patient history and test results were collected. A sample size of 1,475 was calculated, based on the hypothesis that the prevalence of USI will be 20% larger in the pre- versus the post-menopausal group. RESULTS A total of 2,994 women with UI on urodynamics were available. There was a significant difference between pre- and post-menopausal status for each of the three diagnoses: USI 483 (59.3%) versus 912 (41.8%), detrusor overactivity (DO) 125 (15.4%) versus 399 (18.3%) and USI with concomitant DO 206 (25.3%) versus 869 (39.9%). A bimodal pattern of age was seen in women with USI, with a peak in the 46-50 and 61-65 age group, before decreasing with age. DO generally increased with age. USI with concomitant DO increased steadily after the menopause, becoming the predominant type after the age of 66. CONCLUSIONS In this large cohort of women attending urodynamics, we have shown that USI is the predominant type of incontinence in pre-menopausal women; however, USI with concomitant DO increases after menopause, eventually predominating.
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Affiliation(s)
- Nevine Te West
- St George Hospital, School of Women's and Children's Health, University of New South Wales, Sydney, Kogarah, Australia.
| | - Katie Harris
- The George Institute for Global Health, University of New South Wales, Sydney, Australia
| | - Michael Chapman
- St George Hospital, School of Women's and Children's Health, University of New South Wales, Sydney, Kogarah, Australia
| | - Kate Hilda Moore
- St George Hospital, School of Women's and Children's Health, University of New South Wales, Sydney, Kogarah, Australia
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19
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Wang Y, Sun Y, Tan M, Lin X, Tai P, Huang X, Jin Q, Yuan D, Xu T, He B. Association Between Polymorphisms in DNA Damage Repair Pathway Genes and Female Breast Cancer Risk. DNA Cell Biol 2024; 43:219-231. [PMID: 38634815 DOI: 10.1089/dna.2023.0331] [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] [Indexed: 04/19/2024] Open
Abstract
Breast cancer risk have been discussed to be associated with polymorphisms in genes as well as abnormal DNA damage repair function. This study aims to assess the relationship between genes single nucleotide polymorphisms (SNPs) related to DNA damage repair and female breast cancer risk in Chinese population. A case-control study containing 400 patients and 400 healthy controls was conducted. Genotype was identified using the sequence MassARRAY method and expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) in tumor tissues was analyzed by immunohistochemistry assay. The results revealed that ATR rs13091637 decreased breast cancer risk influenced by ER, PR (CT/TT vs. CC: adjusted odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.04-2.27, p = 0.032; CT/TT vs. CC: adjusted OR = 1.63, 95%CI: 1.14-2.35, p = 0.008) expression. Stratified analysis revealed that PALB2 rs16940342 increased breast cancer risk in response to menstrual status (AG/GG vs. AA: adjusted OR = 1.72, 95%CI: 1.13-2.62, p = 0.011) and age of menarche (AG/GG vs. AA: adjusted OR = 1.54, 95%CI: 1.03-2.31, p = 0.037), whereas ATM rs611646 and Ku70 rs132793 were associated with reduced breast cancer risk influenced by menarche (GA/AA vs. GG: adjusted OR = 0.50, 95%CI: 0.30-0.95, p = 0.033). In a summary, PALB2 rs16940342, ATR rs13091637, ATM rs611646, and Ku70 rs132793 were associated with breast cancer risk.
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Affiliation(s)
- Ying Wang
- School of Basic-Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yalan Sun
- School of Basic-Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Mingjuan Tan
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xin Lin
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Ping Tai
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiaoqin Huang
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Qing Jin
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Dan Yuan
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Tao Xu
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Bangshun He
- School of Basic-Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Deparment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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20
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Jin Z, Tian C, Kang M, Hu S, Zhao L, Zhang W. The 100 top-cited articles in menopausal syndrome: a bibliometric analysis. Reprod Health 2024; 21:47. [PMID: 38589898 PMCID: PMC11003046 DOI: 10.1186/s12978-024-01770-9] [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: 10/28/2023] [Accepted: 03/10/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Significant scientific research has been conducted concerning menopausal syndrome(MPS), yet few bibliometric analyses have been performed. Our aim was to recognise the 100 most highly cited published articles on MPS and to analytically evaluate their key features. METHODS To identify the 100 most frequently cited articles, a search was conducted on Web of Science using the term 'menopausal syndrome'. Articles that matched the predetermined criteria were scrutinised to obtain the following data: citation ranking, year of publication, publishing journal, journal impact factor, country of origin, academic institution, authors, study type, and keywords. RESULTS The publication period is from January 1, 2000, to August 31, 2022. The maximum number of citations was 406 and in 2012. The median citations per year was 39.70. Most of the articles focused on treatment and complications. These articles were published in 36 different journals, with the Journal of MENOPAUSE having published the greatest number (14%). Forty-eight articles (48%) were from the United States, with the University of Pittsburgh being the leading institute (9%). Joann E. Manson was the most frequent first author (n = 6). Observational studies were the most frequently conducted research type (n = 53), followed by experimental studies (n = 33). Keyword analysis identified classic research topics, including genitourinary syndrome of menopause, bone mineral density (BMD), and anti-mullerian hormone (AMH) loci. CONCLUSION Using bibliometrics, we conducted an analysis to identify the inadequacies, traditional focal points, and potential prospects in the study of MPS across current scientific areas. Treatment and complications are at the core of MPS research, whereas prediction and biomarkers have less literature of high quality. There is a necessity for innovative analytical metrics to measure the real effect of these papers with a high level of citation on clinical application.
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Affiliation(s)
- Zishan Jin
- Beijing University of Chinese Medicine, Beijing, 100029, China
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Chuanxi Tian
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Mengjiao Kang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Shiwan Hu
- Beijing University of Chinese Medicine, Beijing, 100029, China
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Linhua Zhao
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
| | - Wei Zhang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
- Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China.
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21
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Saarinen T, Savukoski SM, Pesonen P, Vaaramo E, Laitinen J, Varanka-Ruuska T, Ala-Mursula L, Niinimäki M. Climacteric status at age 46 is associated with poorer work ability, lower 2-year participation in working life, and a higher 7-year disability retirement rate: a Northern Finland Birth Cohort 1966 study. Menopause 2024; 31:275-281. [PMID: 38412401 PMCID: PMC11896111 DOI: 10.1097/gme.0000000000002327] [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: 09/04/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
OBJECTIVE To study the association between an advanced climacteric status at 46 years of age and current perceived work ability, the consequent 2-year accumulation of disability and unemployment days, and the 7-year incidence of disability pensions. METHODS Study participants (n = 2,661) were recruited from the Northern Finland Birth Cohort 1966 study's 46-year follow-up in 2012. The participants' perceived work ability was investigated using the Work Ability Score (0-7 = poor vs 8-10 = good), along with potential covariates. Data concerning their consequent disability days, unemployment days, and disability pensions were collected from national registers. The association between their climacteric status at age 46 years, work ability, and working life participation was assessed using regression models. RESULTS The climacteric women were more often smokers and more often had a lower level of education. The odds ratio for poor perceived work ability was 1.41 (95% CI, 1.06-1.87), and the incidence rate ratios for disability and unemployment days during the 2-year follow-up were 1.09 (95% CI, 1.07-1.11) and 1.16 (95% CI, 1.14-1.18), respectively, for the climacteric women compared with the preclimacteric women in models adjusted for smoking and education. The 7-year hazard ratio for disability pensions was 1.72 (95% CI, 1.02-2.91) for the climacteric women. CONCLUSIONS An earlier menopausal transition is associated with poorer perceived work ability, and it predicts lower recorded work participation and a higher disability pension rate in subsequent years.
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Affiliation(s)
- Tiia Saarinen
- From the Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, Oulu, Finland
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Medical Research Center, University of Oulu and Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, Oulu, Finland
| | - Susanna M. Savukoski
- From the Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, Oulu, Finland
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Medical Research Center, University of Oulu and Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, Oulu, Finland
| | - Paula Pesonen
- Northern Finland Birth Cohorts, Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland
| | - Eeva Vaaramo
- Northern Finland Birth Cohorts, Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland
| | - Jaana Laitinen
- Finnish Institute of Occupational Health, Helsinki, Finland
| | - Tuulia Varanka-Ruuska
- Finnish Institute of Occupational Health, Helsinki, Finland
- Research Unit of Population Health, University of Oulu, Oulu, Finland
| | - Leena Ala-Mursula
- Research Unit of Population Health, University of Oulu, Oulu, Finland
| | - Maarit Niinimäki
- From the Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, Oulu, Finland
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Medical Research Center, University of Oulu and Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, Oulu, Finland
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22
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Alnjadat R, Momani EA, Etoom M, Hamdan F, ALrub SA. Level of adherence to diet and physical activity among menopausal women and influencing factors in Jordan: a descriptive cross-sectional study. Front Public Health 2024; 12:1333102. [PMID: 38371235 PMCID: PMC10869606 DOI: 10.3389/fpubh.2024.1333102] [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: 11/04/2023] [Accepted: 01/11/2024] [Indexed: 02/20/2024] Open
Abstract
Background During menopause, a woman's lifestyle may change significantly, which will have implications on her quality of life. Women will experience menopause for more than a third of their life; therefore, maintaining good health during this period is crucial. A healthy diet and physical activity can help women maintain their health during menopause. Hence, assessing adherence to a healthy diet and physical activity among menopausal women is important. Purpose This study aims to assess the degree of adherence to a healthy diet and physical activity of menopausal women in Jordan and determine the most influential factors. Methods A descriptive cross-sectional design was used in this study, and an online self-administered questionnaire was sent to 299 menopausal women selected through simple random sampling. A valid and reliable questionnaire was used to assess the menopausal women's adherence to a healthy diet and physical activity. The questionnaire consisted of 14 items covering two domains: 12 questions for the diet domain and two questions for the physical activity domain. Descriptive statistics were obtained, mean weight and body mass index (BMI) were calculated, and stepwise regression was conducted for the data analysis. Results The overall degree of adherence to a healthy diet and physical activity of the women was moderate (49.25, SD = 7.17). Most of the participants reported eating refined food items once a month or less (n = 188, 62.9%) and not exercising weekly (n = 119, 39.8%), and only a few reported eating refined food items at least once a day (n = 5, 1.7%) and exercising 5-6 times a week (n = 15, 5%). The regression analysis showed that age (B = 0.145, p = 0.014), having two children (B = 0.123, p = 0.034) and completing primary or secondary education (B = 0.120, p = 0.038) were statistically significant and the strongest predictors of adherence. The predictors accounted for 68% of the variance in adherence to a healthy diet and physical activity (R2 = 0.068, F [343.54] = 7.123, p = 0.000). Conclusion The majority of the middle-aged menopausal women in this study showed moderate adherence to a healthy diet and physical activity. Age, having two children and completing primary or secondary education were associated with degree of adherence to a healthy diet and physical activity. Therefore, healthcare intervention, such as physical activity and dietary control programs, should target women in this age group and stage in life.
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Affiliation(s)
- Rafi Alnjadat
- Department of Applied Health Sciences, Al-Balqa Applied University, Al-Salt, Jordan
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23
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Soliman AT, Alaaraj N, De Sanctis V, Hamed N, Alyafei F, Ahmed S. Long-term health consequences of central precocious/early puberty (CPP) and treatment with Gn-RH analogue: a short update. ACTA BIO-MEDICA : ATENEI PARMENSIS 2023; 94:e2023222. [PMID: 38054666 PMCID: PMC10734238 DOI: 10.23750/abm.v94i6.15316] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 10/23/2023] [Indexed: 12/07/2023]
Abstract
BACKGROUND The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors. METHODS We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk. RESULTS Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders. CONCLUSION Monitoring and early diagnosis of these conditions are of paramount importance for successful management.
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Affiliation(s)
| | - Nada Alaaraj
- Department of Pediatrics, Hamad General Hospital, Doha, Qatar.
| | - Vincenzo De Sanctis
- Pediatric and Adolescent Outpatient Clinic, Private Accredited Quisisana Hospital, Ferrara, Italy.
| | - Noor Hamed
- Department of Pediatrics, Hamad General Hospital, Doha, Qatar.
| | - Fawzia Alyafei
- Department of Pediatrics, Hamad General Hospital, Doha, Qatar.
| | - Shayma Ahmed
- Department of Pediatrics, Hamad General Hospital, Doha, Qatar.
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24
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Mohile AA, Hedaoo RP, Jadhav SJ, Ainapure AS, Patil MV, Khatwani NR. Unraveling the Link: A Comprehensive Literature Review of Type 2 Diabetes and Menopause Onset. Cureus 2023; 15:e50743. [PMID: 38234930 PMCID: PMC10794094 DOI: 10.7759/cureus.50743] [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] [Accepted: 12/18/2023] [Indexed: 01/19/2024] Open
Abstract
Women with diabetes mellitus (DM), a metabolic endocrine illness, may experience a variety of reproductive problems. The age at menopause onset has been extensively studied as a major predictor of women's health in the future; however, its relationship to diabetes in Indian women has received less attention. This literature review looked at the consequences of diabetes in women as well as the association between diabetes and the age at which menopause begins. The average age at menopause onset among women with type 2 diabetes mellitus (T2DM) has decreased globally. According to one Indian study, the average menopause age dropped to 45 years for 26% of women with T2DM. In the current review, 10 studies indicated that women with T2DM displayed an imbalanced hormonal profile resulting in an extended anovulatory period. Two investigations highlighted the significance of altered body composition of women with T2DM, thereby suggesting obesity as the primary risk factor of ovarian aging and early climacteric symptoms. T2DM may lower the average age at menopause onset; however, further research on Indian women is necessary. There is a need of studies on T2DM in premenopausal women are needed to demonstrate how the changes in body composition impact the age at which menopause begins. Delaying the onset of menopause in women with T2DM necessitates diet and lifestyle interventions to minimize ovarian aging and hormonal imbalance.
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Affiliation(s)
- Anuja A Mohile
- Nutrition and Dietetics, Symbiosis International (Deemed) University, Pune, IND
- School of Beauty, Wellness, Nutrition and Dietetics, Symbiosis Skills and Professional University, Pune, IND
| | - Radhika P Hedaoo
- Nutrition and Dietetics, Symbiosis Institute of Health Sciences, Symbiosis International (Deemed) University, Pune, IND
| | - Sammita J Jadhav
- Pathology, Symbiosis Institute of Health Sciences, Symbiosis International (Deemed) University, Pune, IND
| | - Archana S Ainapure
- School of Beauty, Wellness, Nutrition and Dietetics, Symbiosis Skills and Professional University, Pune, IND
| | | | - Nalini R Khatwani
- School of Beauty, Wellness, Nutrition and Dietetics, Symbiosis Skills and Professional University, Pune, IND
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25
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Yu Y, Hou L, Wu Y, Yu Y, Liu X, Wu S, He Y, Ge Y, Wei Y, Qian F, Luo Q, Feng Y, Cheng X, Yu T, Li H, Xue F. Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study. BMC Psychiatry 2023; 23:799. [PMID: 37915018 PMCID: PMC10621101 DOI: 10.1186/s12888-023-05203-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 09/18/2023] [Indexed: 11/03/2023] Open
Abstract
BACKGROUND The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders. METHODS Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods. RESULTS Univariable MR analyses provide evidence that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD) (based on p<7.14×10-4), respectively. However, after performing multivariable MR, only age at first sexual intercourse has direct effects on five psychiatric disorders (Depression, Attention deficit or hyperactivity disorder, Bipolar disorder, Posttraumatic stress disorder and schizophrenia) when accounting for other reproductive behaviors with significant effects in univariable analyses. CONCLUSION Our findings suggest that reproductive behaviors predominantly exert their detrimental effects on psychiatric disorders and age at first sexual intercourse has direct effects on psychiatric disorders.
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Affiliation(s)
- Yifan Yu
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Lei Hou
- Beijing International Center for Mathematical Research, Peking University, Beijing, People's Republic of China
| | - Yutong Wu
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Yuanyuan Yu
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Xinhui Liu
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Sijia Wu
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Yina He
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Yilei Ge
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Yun Wei
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Fengtong Qian
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Qingxin Luo
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Yue Feng
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China
| | - Xiaojing Cheng
- Shandong Mental Health Center, Shandong Province, Jinan, China
| | - Tiangui Yu
- Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
| | - Hongkai Li
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China.
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
| | - Fuzhong Xue
- Department of Epidemiology and Health Statistics, School of Public Health, , Cheeloo College of Medicine, Shandong University, 44 Wenhua West Road, Jinan, Shandong Province, China.
- Institute for Medical Dataology, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
- Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
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26
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Salin SAE, Savukoski SM, Pesonen PRO, Auvinen JP, Niinimäki MJ. Sleep disturbances in women with early-onset menopausal transition: a population-based study. Menopause 2023; 30:1106-1113. [PMID: 37788421 DOI: 10.1097/gme.0000000000002258] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/05/2023]
Abstract
OBJECTIVE The aim of this study was to investigate sleep disturbances in 46-yr-old women and their association with early-onset menopausal transition. METHODS The women of this cross-sectional birth cohort study were divided into climacteric (n = 359) and preclimacteric (n = 2,302) groups by their menopausal status, defined by follicle-stimulating hormone levels and menstrual history. Sleep disturbances were evaluated with Athens Insomnia Scale 5. We performed univariable and multivariable logistic regression models in which sleep parameters were dependent variables and climacteric status, hot flashes, smoking, and education level were independent variables. The use of hormone therapy was also evaluated in women suffering from sleeping disturbances. RESULTS On the basis of the scale questions, climacteric women experienced significantly delayed sleep induction (12.2% vs 8.7%, P = 0.047), more problems with awakenings during the night (23.4% vs 14.6%, P < 0.001), earlier final awakening (13.8% vs 9.9%, P = 0.039), and more unsatisfying sleep quality (11.9% vs 7.9%, P = 0.023). Climacteric women who were experiencing hot flashes reported unsatisfactory sleep quality more frequently compared with climacteric women who did not experience hot flashes (17.0% vs 9.2%, P = 0.047). In the univariable and multivariable logistic regression models, being climacteric was independently associated with different impaired sleeping parameters. Most climacteric women who had a scale score of 4 or greater were not using hormone therapy, according to their medicine purchases over the past year. CONCLUSIONS Being climacteric was associated with sleep disturbances in women in their mid-40s. However, this association seemed to be particularly driven by hot flashes. Most climacteric women with clinically significant sleeping disturbances were not using hormone therapy.
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Affiliation(s)
| | | | - Paula R O Pesonen
- Northern Finland Birth Cohort, Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland
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27
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Zhang X, Huangfu Z, Wang S. Review of mendelian randomization studies on age at natural menopause. Front Endocrinol (Lausanne) 2023; 14:1234324. [PMID: 37766689 PMCID: PMC10520463 DOI: 10.3389/fendo.2023.1234324] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023] Open
Abstract
Menopause marks the end of the reproductive phase of life. Based on epidemiological studies, abnormal age at natural menopause (ANM) is thought to contribute to a number of adverse outcomes, such as osteoporosis, cardiovascular disease, and cancer. However, the causality of these associations remains unclear. A powerful epidemiological method known as Mendelian randomization (MR) can be used to clarify the causality between ANM and other diseases or traits. The present review describes MR studies that included ANM as an exposure, outcome and mediator. The findings of MR analyses on ANM have revealed that higher body mass index, poor educational level, early age at menarche, early age at first live birth, early age at first sexual intercourse, and autoimmune thyroid disease appear to be involved in early ANM etiology. The etiology of late ANM appears to be influenced by higher free thyroxine 4 and methylene tetrahydrofolate reductase gene mutations. Furthermore, early ANM has been found to be causally associated with an increased risk of osteoporosis, fracture, type 2 diabetes mellitus, glycosylated hemoglobin, and the homeostasis model of insulin resistance level. In addition, late ANM has been found to be causally associated with an increased systolic blood pressure, higher risk of breast cancer, endometrial cancer, endometrioid ovarian carcinoma, lung cancer, longevity, airflow obstruction, and lower risk of Parkinson's disease. ANM is also a mediator for breast cancer caused by birth weight and childhood body size. However, due to the different instrumental variables used, some results of studies are inconsistent. Future studies with more valid genetic variants are needed for traits with discrepancies between MRs or between MR and other types of epidemiological studies.
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Affiliation(s)
- Xiao Zhang
- Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, China
- Graduate School of Peking Union Medical College, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhao Huangfu
- Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Shaowei Wang
- Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, China
- Graduate School of Peking Union Medical College, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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28
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Fitz VW, Soria-Contreras DC, Rifas-Shiman SL, Shifren JL, Oken E, Chavarro JE. Exploring the relationship between history of infertility and the experience of menopausal symptoms. Menopause 2023; 30:913-919. [PMID: 37527458 PMCID: PMC10527707 DOI: 10.1097/gme.0000000000002229] [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] [Indexed: 08/03/2023]
Abstract
OBJECTIVE The aim of the study is to examine longitudinal associations of history of infertility with menopausal symptoms in midlife. METHODS Six hundred ninety-five midlife women (≥45 y old or reporting ≥12 mo of amenorrhea at the midlife visit) in Project Viva, a prospective cohort enrolled 1999-2002 during pregnancy and followed for 18 years after enrollment ("midlife visit"). Exposure was history of infertility defined as time to pregnancy ≥12 months (≥6 mo if ≥35 y), use of medical treatment to conceive, or infertility consultation or treatment in the 6-month preceding enrollment. The primary outcome was score below or above the median on the Menopause Rating Scale (MRS). Secondary outcomes included individual symptom score on the MRS and self-reported age of menopause. RESULTS A total of 36.6% had a history of infertility in their lifetime. At the time of MRS completion, the women with prior infertility were older (53.4 [SD, 3.8] vs 51.2 [SD, 3.7] y) than those without infertility and a larger proportion had reached menopause (62% vs 40%). Women with prior infertility were more likely to score above the median on the MRS (Adjusted Odds Ratio [aOR], 1.45; 95% confidence interval [CI], 1.04-2.01) and had higher odds for reporting any depressive mood (aOR, 1.56; 95% CI, 1.12-2.16) and irritability (aOR, 1.57; 95% CI, 1.13-2.19). There was a trend toward greater severity of sleep problems among women with prior infertility. There was no association of prior infertility with report of other menopausal symptoms or age of menopause. CONCLUSIONS Our findings suggest that women with prior infertility are more likely to have an MRS score above the median and experience depressive mood, irritability, and sleep problems during midlife than women without infertility. These findings have implications for mental health screening among midlife women.
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Affiliation(s)
| | | | - Sheryl L Rifas-Shiman
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston MA
| | | | - Emily Oken
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston MA
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29
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Jambarsang S, Khodayarian M, Sefidkar R, Yoshany N. Prevalence of premature ovarian insufficiency (POI) and its relationship with female reproductive factors in Iranian women: a cross-sectional study from the Persian (Shahedieh) cohort data. BMC Womens Health 2023; 23:467. [PMID: 37658371 PMCID: PMC10474657 DOI: 10.1186/s12905-023-02620-9] [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: 03/19/2023] [Accepted: 08/24/2023] [Indexed: 09/03/2023] Open
Abstract
BACKGROUND In premature ovarian insufficiency, the cessation of menstruation, and cessation of ovarian function occurs before the age of 40, and this phenomenon is associated with many complications and problems for women. Since several factors can affect this situation, this study was conducted to determine the relationship between fertility history, and premature ovarian failure. METHODS This cross-sectional study was conducted on the data of the first phase of cohort study, which was a sample of 10,000 people from an Iranian adult population (age: 35-70 years). 1276 women were included who naturally experienced menopause from this population. They were separated into three groups based on the age of menopause: premature ovarian failure for those who reached menopause before the age of 40, early menopause for those who reached menopause between the ages of 40 and 45, and natural menopause for those who reached menopause at or after the age of 45. The demographic and fertility characteristics of two groups of women, one with premature ovarian failure and the other with early menopause, were compared with a group of women experiencing normal menopause. The comparison was based on frequency and percentage. Moreover, the odds ratio (OR) of these two groups compared to normal group was crudely calculated, and adjusted based on age at the time of the interview using a logistic regression model. SPSS 23 software was used to fit models and calculations. RESULTS The prevalence of premature ovarian failure was 3%. The likelihood of premature ovarian failure decreases as the number of live births rises. The risk is considerably higher for births ranging from zero to three children compared to those with more than four. Increased duration of breastfeeding is associated to a reduced risk of premature ovarian failure compared to the spontaneous occurrence (OR = 0.98, 95% CI (0.97, 0.99)). This relationship is maintained even after adjusting for age (OR = 0.98, 95% CI (0.97, 0.99). CONCLUSION Based on the results of present study, it can be concluded that the factor of the number of births, and the duration of breastfeeding affect reducing the occurrence of POI, therefore, in health and treatment programs and policies, encouragement to have children, which is now part of the policies population of Iran, and the importance, and benefits of breastfeeding for mother and baby should be emphasized more.
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Affiliation(s)
- Sara Jambarsang
- Center for Healthcare Data Modeling, Departments of Biostatistics and Epidemiology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mahsa Khodayarian
- Department of Health Education and Health Promotion, Social Determinants of Health Research Center, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Reyhane Sefidkar
- Center for Healthcare Data Modeling, Departments of Biostatistics and Epidemiology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nooshin Yoshany
- Department of Health Education and Health Promotion, Social Determinants of Health Research Center, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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30
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Beroukhim G, Kayani J, Taylor HS, Pal L. Examining the association between urinary triclosan levels and menopausal status: results from the National Health and Nutrition Examination Survey, 2003 to 2016. Menopause 2023; 30:906-912. [PMID: 37625087 DOI: 10.1097/gme.0000000000002233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/27/2023]
Abstract
OBJECTIVE To examine the association between urinary levels of triclosan (TCS), a ubiquitous endocrine disrupter, and menopausal status using the National Health and Nutrition Examination Survey. METHODS A retrospective cross-sectional study from 2003 to 2016 was conducted among US female participants who completed the reproductive health questionnaire and provided TCS-level measurements. Exposure was assessed by urinary TCS levels adjusted for urinary creatinine; levels were log-transformed to achieve normal distribution for parametric analyses. Menopausal status was based on participants' responses to: "What is the reason that you have not had a period in the past 12 months?" Multivariable linear regression analyses examined the association between creatinine-adjusted urinary TCS levels and menopausal status after adjusting for age at survey completion, body mass index, race, ethnicity, and smoking exposure. RESULTS Of the final sample of female participants (n = 6,958), 40% identified as postmenopausal, of whom 60% had experienced natural menopause, and of these, 11% had become menopausal at under 40 years of age. Triclosan levels correlated positively with advancing age (r = 0.09, P < 0.001) and inversely with body mass index (r = -0.09, P < 0.001). Smoking exposure was associated with significantly lower TCS levels (P < 0.001). Compared with premenopausal women, postmenopausal women had significantly higher log-transformed, creatinine-adjusted TCS levels (mean, -1.22 ± 1.79 vs -1.51 ± 1.79 ng/mg creatinine; P < 0.001). Triclosan levels were unrelated to the duration of menopause and did not differ between women who underwent natural versus surgical menopause, and premature menopause versus menopause at 40 years or older. In unweighted multivariate linear regression analyses, menopausal status was independently associated with higher urinary TCS levels after adjusting for covariates (β coefficient, 0.17; 95% CI, 0.020-0.323; P = 0.026). CONCLUSIONS In a nationally representative sample, postmenopausal status was associated with higher urinary TCS levels, observations that merit further investigation into potential exposures and health consequences.
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Affiliation(s)
- Gabriela Beroukhim
- From the Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT
| | | | - Hugh S Taylor
- From the Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT
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31
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Shi YQ, Zhu XT, Zhang SN, Ma YF, Han YH, Jiang Y, Zhang YH. Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants. Front Endocrinol (Lausanne) 2023; 14:1172481. [PMID: 37600717 PMCID: PMC10436748 DOI: 10.3389/fendo.2023.1172481] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 07/03/2023] [Indexed: 08/22/2023] Open
Abstract
Normal levels of reactive oxygen species (ROS) play an important role in regulating follicular growth, angiogenesis and sex hormone synthesis in ovarian tissue. When the balance between ROS and antioxidants is disrupted, however, it can cause serious consequences of oxidative stress (OS), and the quantity and quality of oocytes will decline. Therefore, this review discusses the interrelationship between OS and premature ovarian insufficiency (POI), the potential mechanisms and the methods by which antioxidants can improve POI through controlling the level of OS. We found that OS can mediate changes in genetic materials, signal pathways, transcription factors and ovarian microenvironment, resulting in abnormal apoptosis of ovarian granulosa cells (GCs) and abnormal meiosis as well as decreased mitochondrial Deoxyribonucleic Acid(mtDNA) and other changes, thus accelerating the process of ovarian aging. However, antioxidants, mesenchymal stem cells (MSCs), biological enzymes and other antioxidants can delay the disease process of POI by reducing the ROS level in vivo.
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Affiliation(s)
- Yu-Qian Shi
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xi-Ting Zhu
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Su-Na Zhang
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yi-Fu Ma
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yan-Hua Han
- Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yue Jiang
- Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yue-Hui Zhang
- Department of Obstetrics and Gynecology, Key Laboratory and Unit of Infertility in Chinese Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
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Leone T, Brown L, Gemmill A. Secular trends in premature and early menopause in low-income and middle-income countries. BMJ Glob Health 2023; 8:bmjgh-2023-012312. [PMID: 37308265 DOI: 10.1136/bmjgh-2023-012312] [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: 03/15/2023] [Accepted: 05/20/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND While secular trends in high-income countries show an increase in the mean age at menopause, it is unclear if there is a similar pattern in low-income and middle-income countries (LMICs), where women's exposure to biological, environmental and lifestyle determinants of menopause may differ. Premature (before age 40 years) and early (ages 40-44 years) menopause could have negative repercussions on later life health outcomes which in ageing societies could mean further stress on low-resource health systems. An evaluation of such trends in LMICs has been hampered by the suitability, quality and comparability of data from these countries. METHODS Using 302 standardised household surveys from 1986 to 2019, we estimate trends and CIs using bootstrapping in the prevalence of premature and early menopause in 76 LMICs. We also developed a summary measure of age at menopause for women who experience menopause before the age of 50 years based on demographic estimation methods that can be used to measure menopausal status in surveys with truncated data. RESULTS Trends indicate an increasing prevalence of early and premature menopause in LMICs, in particular in sub-Saharan Africa and South/Southeast Asia. These regions also see a suggested decline of the mean age at menopause with greater variation across continents. CONCLUSIONS This study enables the analysis of menopause timing by exploiting data generally used for the study of fertility by methodologically allowing the use of truncated data. Findings show a clear increase in prevalence of premature and early menopause in the regions with the highest fertility with possible consequences for later life health. They also show a different trend compared with high-income regions, confirming a lack of generalisability and the importance of accounting for nutritional and health transitions at the local level. This study calls for further data and research on menopause on a global scale.
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Affiliation(s)
- Tiziana Leone
- Department of International Development, London School of Economics and Political Science, London, UK
| | - Laura Brown
- Institute for Global Health, University College London, London, UK
| | - Alison Gemmill
- Department of Population, Family and Reproductive Health, Johns Hopkins University, Baltimore, Maryland, USA
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Kakinuma K, Kakinuma T. Analysis of oxidative stress and antioxidative potential in premature ovarian insufficiency. World J Clin Cases 2023; 11:2684-2693. [PMID: 37214574 PMCID: PMC10198121 DOI: 10.12998/wjcc.v11.i12.2684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/20/2023] [Accepted: 03/23/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Premature ovarian insufficiency (POI) is characterized by an early decline in ovarian function, inducing secondary amenorrhea. While the cause of POI has not yet been identified, the function of mitochondria in the ovaries and the cytotoxicity associated with reactive oxygen species (ROS) have been implicated in follicle pool depletion and a decline in follicle quality. Recently developed tests have enabled easy measurement of diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). The combination of these two tests is used to comprehensively assess oxidative stress in the blood.
AIM To comprehensively assess the oxidative stress of d-ROMs and BAP in POI.
METHODS Participants were classified into two groups: A POI group of 11 women aged < 40 years examined between January 2021 and June 2022 with a history of secondary amenorrhea for at least 4 mo in our hospital and an FSH value of ≥ 40 mIU/mL; and a control group of healthy women of the same age with normal ovarian function in our hospital. Plasma d-ROMs and BAP were measured in both these groups underwent. Differences between groups were assessed using the t-test.
RESULTS The mean age and mean body mass index (BMI) were 35.8 ± 3.0 years and 20.1 ± 1.9 kg/m2 in the control group and 35.8 ± 2.7 years and 19.4 ± 2.5 kg/m2 in the POI group, respectively. The mean gravidity and parity in control and POI groups were 0.6 ± 0.7 and 0.4 ± 0.5 and 0.6 ± 0.9 and 0.3 ± 0.5, respectively. The two groups did not differ significantly in terms of mean age, BMI, gravidity, or parity. The d-ROMs level was significantly higher in the POI group than in the control group (478.2 ± 58.7 vs 341.1 ± 35.1 U.CARR; P < 0.001); however, the BAP level did not significantly differ between the two groups (2078.5 ± 157.4 vs 2029.0 ± 186.4 μmol/L). The oxidase stress index (d-ROMs/BAP × 100) was significantly higher in the POI group than in the control group (23.7 ± 3.3 vs 16.5 ± 2.1; P < 0.001).
CONCLUSION Oxidative stress was significantly greater in the POI group than in the control group, suggesting oxidative stress as a factor that can serve as a POI biomarker.
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Affiliation(s)
- Kaoru Kakinuma
- Department of Obstetrics and Gynecology, International Health and Welfare Hospital, Nasushiobara 327-2763, Japan
| | - Toshiyuki Kakinuma
- Department of Obstetrics and Gynecology, International Health and Welfare Hospital, Nasushiobara 327-2763, Japan
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Alspaugh A. Research and Professional Literature to Inform Practice, March/April 2023. J Midwifery Womens Health 2023; 68:287-293. [PMID: 36965181 DOI: 10.1111/jmwh.13484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 02/16/2023] [Indexed: 03/27/2023]
Affiliation(s)
- Amy Alspaugh
- College of Nursing, University of Tennessee, Knoxville, Tennessee
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Brülle AL, Wu C, Rasch V, Simonsen MK, Schøyen IS, Dahl C, Nohr EA. How do reproductive history and anthropometry in midlife relate to later risk of pelvic organ prolapse? A prospective cohort study. Int Urogynecol J 2022; 33:3373-3380. [PMID: 35254470 DOI: 10.1007/s00192-022-05122-8] [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: 11/24/2021] [Accepted: 02/03/2022] [Indexed: 11/25/2022]
Abstract
INTRODUCTION AND HYPOTHESIS The objective was to examine the association between reproductive and anthropometric factors and later risk of pelvic organ prolapse (POP). METHODS We carried out a prospective cohort study including 11,114 female nurses > 44 years from the Danish Nurse Cohort. In 1993, the study population was recruited through the Danish Nurse Organization and self-reported data on age, height, weight, age at menarche, age at first birth and number of childbirths were obtained. POP diagnosis was obtained from the National Patient Registry. Risk of POP was estimated using COX regression and presented as hazard ratios (HR) with 95% confidence intervals (CI). RESULTS Overall, 10% of the women received a diagnosis of POP within a median follow-up of 22 years. A 4% increase in risk of POP was seen for each increasing BMI (kg/m2) unit at baseline. Compared to women of normal weight, higher risks of POP were seen in overweight (HR 1.18: 1.02-1.36) and obese women (HR 1.33: 1.02-1.74), while underweight had a lower risk (HR 0.51: 0.27-0.95). Compared to women with one childbirth, women with no childbirths had a reduced risk of 57% while increased risks of 46%, 78% and 137% were observed in women with two, three and four childbirths. Women with menarche before the age of 12 tended to have a higher risk of POP as did women who were 30-33 years at their first childbirth. CONCLUSIONS POP is a common health problem in women, and BMI and number of childbirths are strong predictors.
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Affiliation(s)
- Anne-Line Brülle
- Occupational and Environmental Medicine, Odense University Hospital, J.B. Winsløws Vej 4, 5000, Odense C, Denmark.
| | - Chunsen Wu
- Institute of Clinical Research, University of Southern Denmark, Winsløwparken 19, 5000, Odense C, Denmark
- Department of Gynaecology and Obstetrics, Odense University Hospital, Kløvervænget 23, 5000, Odense C, Denmark
| | - Vibeke Rasch
- Institute of Clinical Research, University of Southern Denmark, Winsløwparken 19, 5000, Odense C, Denmark
- Department of Gynaecology and Obstetrics, Odense University Hospital, Kløvervænget 23, 5000, Odense C, Denmark
| | - Mette Kildevæld Simonsen
- Department of Neurology and Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Ine Schmidt Schøyen
- Department of Gynaecology and Obstetrics, Sørlandet Sykehus HF, Kristiansand, Norway
| | - Carina Dahl
- Department of Paediatrics, Sørlandet Sykehus HF, Kristiansand, Norway
| | - Ellen Aagaard Nohr
- Institute of Clinical Research, University of Southern Denmark, Winsløwparken 19, 5000, Odense C, Denmark
- Department of Gynaecology and Obstetrics, Odense University Hospital, Kløvervænget 23, 5000, Odense C, Denmark
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Golezar S, Keshavarz Z, Ramezani Tehrani F, Ebadi A, Zayeri F, Golezar MH. Primary ovarian insufficiency quality of life scale (POIQOLS): development and psychometric properties. BMC Womens Health 2022; 22:481. [DOI: 10.1186/s12905-022-02008-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 10/11/2022] [Indexed: 11/29/2022] Open
Abstract
Abstract
Background
Primary ovarian insufficiency is menopause before the age of 40. It can affect the quality of life of afflicted women. Because there is no instrument available for measuring the quality of life of these women, the present study was carried out to develop and assess the psychometric properties of the quality of life scale for women with primary ovarian insufficiency.
Methods
This exploratory sequential mixed method study was performed in two phases. In the qualitative phase (item generation), semi-structured in-depth interviews were conducted with 16 women having primary ovarian insufficiency, and a literature review was performed to generate initial items pool. In the quantitative phase (psychometric evaluation), the face, content, and construct validity (exploratory factor analysis), as well as reliability (internal consistency and test–retest methods), were evaluated. Besides, the responsiveness and interpretability were investigated.
Results
During the first phase of the study, the initial item pool was generated with 132 items. After the face and content validity, the number of items was reduced to 40. The results of exploratory factor analysis yielded a 28 item scale with six factors. These factors explained 58.55% of the total variance. The Cronbach’s alpha for each factor was more than 0.7. Furthermore, the intraclass correlation coefficient for the entire scale was 0.95.
Conclusions
The primary ovarian insufficiency quality of life scale (POIQOLS) is a valid and reliable tool for accessing the quality of life of women with primary ovarian insufficiency.
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Diet and Nutrients Intakes during Infancy and Childhood in Relation to Early Puberty: A Systematic Review and Meta-Analysis. Nutrients 2022; 14:nu14235004. [PMID: 36501034 PMCID: PMC9739867 DOI: 10.3390/nu14235004] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/17/2022] [Accepted: 11/19/2022] [Indexed: 11/27/2022] Open
Abstract
The onset of puberty has become earlier over the decades, and nutrients and diet are related to the timing of puberty onset. Hence, we aimed to investigate the association between diet or nutrients in infancy, childhood and early puberty. PubMed, Embase, and Cochrane library were searched systematically up to 15 April 2022. The pooled relative risks (RRs) or regression coefficients (beta) were estimated using the random-effect model or fixed-effect model according to the heterogeneity between studies. Twenty-two articles on diet or nutrients in childhood and six about breastfeeding in infancy were included. The prolonged breastfeeding duration in infancy could reduce the risk of early menarche (beta 0.31, 95% CI: 0.01, 0.60, p = 0.045). The high intake of yogurt was associated with a 35% reduction in the risk of earlier menarche (RR 0.65, 95% CI: 0.47, 0.89, p = 0.008). Girls with severe food insecurity experienced later menarche (RR 0.81, 95% CI: 0.67, 0.98, p = 0.027). Conversely, due to the high intake of protein, the risk of early menarche increased by 8% (RR 1.08, 95% CI: 1.01, 1.16, p = 0.016). High intake of yogurt, longer duration of breastfeeding, and food insecurity decreased the possibility of earlier menarche, while high intake of protein increased that risk. As a modifiable factor, diet and nutrients in infancy and childhood provide new insights into the future prevention of early puberty.
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Peycheva D, Sullivan A, Hardy R, Bryson A, Conti G, Ploubidis G. Risk factors for natural menopause before the age of 45: evidence from two British population-based birth cohort studies. BMC Womens Health 2022; 22:438. [DOI: 10.1186/s12905-022-02021-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 10/22/2022] [Indexed: 11/09/2022] Open
Abstract
Abstract
Background
Menopause that occurs before the age of 45 and is not medically induced (referred to here as ‘early natural menopause’) affects around one in 10 women and has serious health consequences. These consequences include increased risk of all-cause mortality, cardiovascular disease, osteoporosis, and type 2 diabetes.
Methods
We investigate risk factors for the onset of natural menopause before the age of 45 in two population-based prospective cohort studies in Britain: the 1958 cohort following 8959 women and the 1970 cohort following 8655 women. These studies follow women from birth to adulthood, and we use harmonized data on birth and early life characteristics, reproductive health, health behaviour, and socioeconomic characteristics for 6805 women who were pre-menopausal, peri-menopausal or had undergone natural menopause. Of these 6805 women, 3614 participated in the 1958 cohort (of which 368 had early menopause) and 3191 participated in the 1970 cohort (of which 206 had early menopause). Taking a life course approach, we focus on three distinct life stages - birth/early life, childhood, and early adulthood - to understand when risk factors are most harmful. Respecting the temporal sequence of exposures, we use a series of multivariable logistic regression models to estimate associations between early menopause and each potential risk factor adjusted for confounders.
Results
We find that early menopause is influenced by circumstances at birth. Women born in lower social class families, whose mother smoked during the pregnancy or who were breastfed 1 month or less were more likely to undergo early menopause. Early menopause is also associated with poorer cognitive ability and smoking in childhood. Adult health behaviour also matters. Smoking is positively correlated with early menopause, while regular exercise and moderate frequency of alcohol drinking in women’s early thirties are associated with reduced risk of early menopause. The occurrence of gynaecological problems by women’s early thirties is also linked to early menopause.
Conclusions
We demonstrate that characteristics at different periods of life are associated with early menopause. Some of these associations relate to modifiable behaviours and thus the risks of early menopause and the adverse health outcomes associated with it may be preventable.
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Batista MS, Tsitsiou Y, Dar S, Ancillotti G, Minhas S, Varshney N. Life course reproductive dynamics associated with menopause in Ugandan women aged 40-49. Am J Hum Biol 2022; 34:e23791. [PMID: 36193636 DOI: 10.1002/ajhb.23791] [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: 07/26/2021] [Revised: 06/26/2022] [Accepted: 07/17/2022] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Early menopausal onset can increase adverse health outcomes in later life; meanwhile, reproductive experiences before menopause may affect its timing. Framed by life course methodology, the study tested for independent and interdependent associations between reproductive history (contraception, age at first birth, parity, terminated pregnancy) and socioeconomic factors (education, wealth, rural-urban residence, cigarette use, marital status, age at first cohabitation) with the occurrence of early menopause. METHODS The study population was ever-married women aged 40-49 from the 2016 Demographic & Health Survey (N = 2748). Analytical methods involved probability- and age-adjusted multivariate logistic regression models and predictive margins. RESULTS Connections between reproductive and socioeconomic characteristics were key dynamics associated with menopause in ages 40-49. Contraception, parity, and ages at first birth and marriage were found to be independently associated with menopause in this age group. Evidence of interactions was found where no contraceptive use was associated with higher probabilities of menopause for first-time mothers aged 12-15 and for women with no education. CONCLUSIONS Studying Ugandan women's reproductive histories highlighted the importance of regional knowledge about menopause. Though we hypothesized that risks would correlate in a chain, the results pointed to risks clustering around contraception, suggesting that improving contraceptive use and education for women could increase menopausal age. Furthermore, the positive association between low parity and early menopause supports the biological mechanism of faster oocyte depletion; however, high-parity populations like Uganda tend to have a younger menopausal age than low-parity populations. Declining mortality in the demographic transition could explain these inverse associations.
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Affiliation(s)
| | - Yvonne Tsitsiou
- Polygeia, London, UK
- Faculty of Medicine, Imperial College London, London, UK
| | - Sabeera Dar
- Polygeia, London, UK
- University College London Medical School, London, UK
| | - Giulia Ancillotti
- Polygeia, London, UK
- London School of Economics and Political Science, London, UK
| | - Sonica Minhas
- Polygeia, London, UK
- Barts and the London School of Medicine and Dentistry, Queen Mary University, London, UK
| | - Natania Varshney
- Polygeia, London, UK
- Faculty of Medicine, Imperial College London, London, UK
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Prince C, Sharp GC, Howe LD, Fraser A, Richmond RC. The relationships between women's reproductive factors: a Mendelian randomisation analysis. BMC Med 2022; 20:103. [PMID: 35321746 PMCID: PMC8944090 DOI: 10.1186/s12916-022-02293-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 02/09/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Women's reproductive factors include their age at menarche and menopause, the age at which they start and stop having children and the number of children they have. Studies that have linked these factors with disease risk have largely investigated individual reproductive factors and have not considered the genetic correlation and total interplay that may occur between them. This study aimed to investigate the nature of the relationships between eight female reproductive factors. METHODS We used data from the UK Biobank and genetic consortia with data available for the following reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners. Linkage disequilibrium score regression (LDSC) was performed to investigate the genetic correlation between reproductive factors. We then applied Mendelian randomisation (MR) methods to estimate the causal relationships between these factors. Sensitivity analyses were used to investigate directionality of the effects, test for evidence of pleiotropy and account for sample overlap. RESULTS LDSC indicated that most reproductive factors are genetically correlated (rg range: |0.06-0.94|), though there was little evidence for genetic correlations between lifetime number of sexual partners and age at last birth, number of births and ever being parous (rg < 0.01). MR revealed potential causal relationships between many reproductive factors, including later age at menarche (1 SD increase) leading to a later age at first sexual intercourse (beta (B) = 0.09 SD, 95% confidence intervals (CI) = 0.06,0.11), age at first birth (B = 0.07 SD, CI = 0.04,0.10), age at last birth (B = 0.06 SD, CI = 0.04,0.09) and age at menopause (B = 0.06 SD, CI = 0.03,0.10). Later age at first birth was found to lead to a later age at menopause (B = 0.21 SD, CI = 0.13,0.29), age at last birth (B = 0.72 SD, CI = 0.67, 0.77) and a lower number of births (B = -0.38 SD, CI = -0.44, -0.32). CONCLUSION This study presents evidence that women's reproductive factors are genetically correlated and causally related. Future studies examining the health sequelae of reproductive factors should consider a woman's entire reproductive history, including the causal interplay between reproductive factors.
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Affiliation(s)
- Claire Prince
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
| | - Gemma C Sharp
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Laura D Howe
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Abigail Fraser
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Rebecca C Richmond
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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Wu P, Lv Q, Guan J, Shan W, Chen X, Zhu Q, Luo X. Clinical implications of morular metaplasia in fertility-preserving treatment for atypical endometrial hyperplasia and early endometrial carcinoma patients. Arch Gynecol Obstet 2022; 306:1135-1146. [PMID: 35246715 PMCID: PMC9470654 DOI: 10.1007/s00404-021-06382-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 12/27/2021] [Indexed: 11/28/2022]
Abstract
Objective Morular metaplasia (MM) is a benign epithelial metaplasia that sometimes appears in atypical endometrial hyperplasia (AEH) and endometrioid endometrial carcinoma (EEC). However, the clinical implications of MM for fertility-preserving treatment in AEH and EEC patients are unclear. This study investigated the clinical features and impact of MM on the efficacy of fertility-preserving treatment. Methods We retrospectively studied 427 AEH and EEC patients who received fertility-preserving treatment. Clinical features, treatment efficacy, and onco-fertility results were compared between patients with and without MM. Results MM appeared in 147 of 427 (34.4%) patients. Among them, 49 (33.3%) had MM only before treatment (BEF group), 32 (21.8%) had sustained MM before and during treatment (SUS group), and 66 (44.9%) had MM only during treatment (DUR group). The BEF group had a higher 12-month CR rate (98.0% vs 85.7%, p = 0.017) and shorter therapeutic duration to achieve CR (4.0 vs 5.7 months, p = 0.013) than the non-MM group had. In comparison with the non-MM group, the SUS and DUR groups had a lower CR rate after 7 months of treatment (SUS vs non-MM, 37.5% vs 61.1%, p = 0.010; DUR vs non-MM 33.3% vs. 61.1%, p < 0.001), and a longer median therapeutic duration to achieve CR (SUS vs non-MM, 7.6 vs. 4.0 months, p = 0.037; DUR vs non-MM, 7.9 vs. 4.0 months, p < 0.001). Conclusion Appearance of MM only before treatment was positively correlated with outcome of fertility-preserving treatment, while sustained MM or appearance of MM only during treatment implied poorer outcome of fertility-preserving treatment in AEH and EEC patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00404-021-06382-3.
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Affiliation(s)
- Pengfei Wu
- Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People's Republic of China
| | - Qiaoying Lv
- Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People's Republic of China
| | - Jun Guan
- Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People's Republic of China
| | - Weiwei Shan
- Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People's Republic of China
| | - Xiaojun Chen
- Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People's Republic of China.,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People's Republic of China
| | - Qin Zhu
- Department of Pathology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China
| | - Xuezhen Luo
- Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, No. 419, Fangxie Road, Shanghai, 200011, People's Republic of China. .,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People's Republic of China.
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Suen AA, Kenan AC, Williams CJ. Developmental exposure to phytoestrogens found in soy: New findings and clinical implications. Biochem Pharmacol 2022; 195:114848. [PMID: 34801523 PMCID: PMC8712417 DOI: 10.1016/j.bcp.2021.114848] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 11/13/2021] [Accepted: 11/16/2021] [Indexed: 01/03/2023]
Abstract
Exposure to naturally derived estrogen receptor activators, such as the phytoestrogen genistein, can occur at physiologically relevant concentrations in the human diet. Soy-based infant formulas are of particular concern because infants consuming these products have serum genistein levels almost 20 times greater than those seen in vegetarian adults. Comparable exposures in animal studies have adverse physiologic effects. The timing of exposure is particularly concerning because infants undergo a steroid hormone-sensitive period termed "minipuberty" during which estrogenic chemical exposure may alter normal reproductive tissue patterning and function. The delay between genistein exposure and reproductive outcomes poses a unique challenge to collecting epidemiological data. In 2010, the U.S. National Toxicology Program monograph on the safety of the use of soy formula stated that the use of soy-based infant formula posed minimal concern and emphasized a lack of data from human subjects. Since then, several new human and animal studies have advanced our epidemiological and mechanistic understanding of the risks and benefits of phytoestrogen exposure. Here we aim to identify clinically relevant findings regarding phytoestrogen exposure and female reproductive outcomes from the past 10 years, with a focus on the phytoestrogen genistein, and explore the implications of these findings for soy infant formula recommendations. Research presented in this review will inform clinical practice and dietary recommendations for infants based on evidence from both clinical epidemiology and basic research advances in endocrinology and developmental biology from mechanistic in vitro and animal studies.
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Affiliation(s)
- Alisa A Suen
- Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
| | - Anna C Kenan
- Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
| | - Carmen J Williams
- Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
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Grimes NP, Whitcomb BW, Reeves KW, Sievert LL, Purdue-Smithe A, Manson JE, Hankinson SE, Rosner BA, Bertone-Johnson ER. The association of parity and breastfeeding with anti-Müllerian hormone levels at two time points. Maturitas 2022; 155:1-7. [PMID: 34876244 PMCID: PMC8665225 DOI: 10.1016/j.maturitas.2021.09.006] [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: 06/25/2021] [Revised: 09/08/2021] [Accepted: 09/17/2021] [Indexed: 01/03/2023]
Abstract
OBJECTIVE To evaluate the association between parity and breastfeeding and anti-Müllerian hormone levels (AMH) and change in AMH levels over time. Furthermore, we examined whether AMH levels mediate the relation of parity and breastfeeding with age at menopause. STUDY DESIGN Observational, prospective cohort study. MAIN OUTCOME MEASURES AMH levels were assessed in a subset of premenopausal participants in the Nurses' Health Study II, including 1619 women who provided a blood sample in 1996-1999 and an additional 800 women who provided a second premenopausal sample in 2010-2012. RESULTS In multivariable linear regression models adjusted for parity, body mass index, smoking, and other factors, mean log AMH levels in 1996-1999 were 39% higher in women reporting ≥25 months of total breastfeeding vs. <1 month (P for trend = 0.009). Parity was not associated with AMH levels after adjustment for breastfeeding. Neither parity nor breastfeeding was associated with decline in AMH levels over 11 to 15 years. Breastfeeding duration was positively associated with age at menopause (P for trend = 0.01), with evidence that the association was mediated via AMH. CONCLUSIONS Our results suggest that breastfeeding is associated with higher AMH levels and later onset of menopause, and support the hypothesis that observed relations of parity with AMH levels and menopause timing may be largely attributable to breastfeeding.
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Affiliation(s)
- Nydjie P Grimes
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA 01003, USA.
| | - Brian W Whitcomb
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA 01003, USA
| | - Katherine W Reeves
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA 01003, USA
| | - Lynnette L Sievert
- Department of Anthropology, University of Massachusetts Amherst, Amherst, MA 01003, USA
| | - Alexandra Purdue-Smithe
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
| | - JoAnn E Manson
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA
| | - Susan E Hankinson
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA 01003, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Bernard A Rosner
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Elizabeth R Bertone-Johnson
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA 01003, USA; Department of Health Promotion and Policy, University of Massachusetts Amherst, Amherst, MA 01003, USA
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Lindseth LRS, de Lange AMG, van der Meer D, Agartz I, Westlye LT, Tamnes CK, Barth C. Associations between reproductive history, hormone use, APOE ε4 genotype and cognition in middle- to older-aged women from the UK Biobank. Front Aging Neurosci 2022; 14:1014605. [PMID: 36760712 PMCID: PMC9907169 DOI: 10.3389/fnagi.2022.1014605] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 12/20/2022] [Indexed: 01/26/2023] Open
Abstract
Introduction Relative to men, women are at a higher risk of developing age-related neurocognitive disorders including Alzheimer's disease. While women's health has historically been understudied, emerging evidence suggests that reproductive life events such as pregnancy and hormone use may influence women's cognition later in life. Methods We investigated the associations between reproductive history, exogenous hormone use, apolipoprotein (APOE) ε4 genotype and cognition in 221,124 middle- to older-aged (mean age 56.2 ± 8.0 years) women from the UK Biobank. Performance on six cognitive tasks was assessed, covering four cognitive domains: episodic visual memory, numeric working memory, processing speed, and executive function. Results A longer reproductive span, older age at menopause, older age at first and last birth, and use of hormonal contraceptives were positively associated with cognitive performance later in life. Number of live births, hysterectomy without oophorectomy and use of hormone therapy showed mixed findings, with task-specific positive and negative associations. Effect sizes were generally small (Cohen's d < 0.1). While APOE ε4 genotype was associated with reduced processing speed and executive functioning, in a dose-dependent manner, it did not influence the observed associations between female-specific factors and cognition. Discussion Our findings support previous evidence of associations between a broad range of female-specific factors and cognition. The positive association between a history of hormonal contraceptive use and cognition later in life showed the largest effect sizes (max. d = 0.1). More research targeting the long-term effects of female-specific factors on cognition and age-related neurocognitive disorders including Alzheimer's disease is crucial for a better understanding of women's brain health and to support women's health care.
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Affiliation(s)
| | - Ann-Marie G. de Lange
- LREN, Department of Clinical Neurosciences, Centre for Research in Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
- Department of Psychology, University of Oslo, Oslo, Norway
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Dennis van der Meer
- NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
| | - Ingrid Agartz
- NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
- Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm Health Care Services, Karolinska Institute, Stockholm County Council, Stockholm, Sweden
| | - Lars T. Westlye
- Department of Psychology, University of Oslo, Oslo, Norway
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Christian K. Tamnes
- Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Psychology, PROMENTA Research Center, University of Oslo, Oslo, Norway
| | - Claudia Barth
- NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
- *Correspondence: Claudia Barth, ✉
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Louwers YV, Visser JA. Shared Genetics Between Age at Menopause, Early Menopause, POI and Other Traits. Front Genet 2021; 12:676546. [PMID: 34691139 PMCID: PMC8529948 DOI: 10.3389/fgene.2021.676546] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 09/14/2021] [Indexed: 12/12/2022] Open
Abstract
Reproductive ageing leading to menopause is characterized by depletion of follicles and its regulating mechanisms are only partly understood. Early age at menopause and premature ovarian insufficiency (POI) are associated with several other traits such as cardiovascular disease, dyslipidemia, osteoporosis and diabetes. In large cohorts of Northern European women hundreds of Single Nucleotide Polymorphisms (SNPs) have been identified to be associated with age at menopause. These SNPs are located in genes enriched for immune and mitochondrial function as well as DNA repair and maintenance processes. Genetic predisposition to earlier menopause might also increase the risk of other associated traits. Increased risk for cardiovascular disease in women has been associated with age at menopause lowering SNPs. Pleiotropy between early age at menopause and increased mortality from coronary artery disease has been observed, implicating that genetic variants affecting age at menopause also affect the risk for coronary deaths. This review will discuss the shared genetics of age at menopause with other traits. Mendelian Randomization studies implicate causal genetic association between age at menopause and age at menarche, breast cancer, ovarian cancer, BMD and type 2 diabetes. Although the shared biological pathways remain to be determined, mechanisms that regulate duration of estrogen exposure remain an important focus.
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Affiliation(s)
- Yvonne V Louwers
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Jenny A Visser
- Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
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Menopausal hormone therapy: Characterising users in an Australian national cross-sectional study. PLoS One 2021; 16:e0253725. [PMID: 34379634 PMCID: PMC8357145 DOI: 10.1371/journal.pone.0253725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 06/05/2021] [Indexed: 11/19/2022] Open
Abstract
Menopausal hormone therapy (MHT) is effective for menopausal symptoms, however, its use is also associated with risks of serious health conditions including breast, ovarian and endometrial cancer, stroke and venous thromboembolism. MHT-related health risks increase with longer durations of use. In Australia, while overall MHT use fell when risk-related findings were published in 2002, a significant number of women continue using MHT long-term. We aimed to examine socio-demographic, health-related and lifestyle characteristics in relation to post-2002 MHT use, and to compare use for <5 and ≥5 years. Data from 1,561 participants from an Australian, national, cross-sectional survey of women aged 50–69 in 2013 were analysed. Odds ratios (ORs) were calculated using logistic regression for characteristics related to overall MHT use post-2002 and multinomial logistic regression for associations between MHT duration of use [never/<5 years/≥5 years] and personal characteristics, adjusting for sociodemographic, reproductive, health and lifestyle factors. Post-2002 MHT use was associated with increasing age (p-trend<0.001), hysterectomy versus no hysterectomy (OR:2.55, 95%CI = 1.85–3.51), bilateral oophorectomy vs no oophorectomy (OR:1.66, 95%CI = 1.09–2.53), and ever- versus never-use of therapies other than MHT for menopausal symptoms (OR:1.93, 95%CI = 1.48–2.57). Women with prior breast cancer (OR:0.35, 95%CI = 0.17–0.74) and with more children (p-trend = 0.034) were less likely than other women to use MHT. Prior hysterectomy was more strongly associated with MHT use for ≥5 years than for <5 years (p = 0.004). Ever-use of non-MHT menopausal therapies was associated with MHT use for <5 years but not with longer-term use (p = 0.004). This study reinforces the need for MHT users and their clinicians to re-evaluate continued MHT use on an ongoing basis.
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Searching for female reproductive aging and longevity biomarkers. Aging (Albany NY) 2021; 13:16873-16894. [PMID: 34156973 PMCID: PMC8266318 DOI: 10.18632/aging.203206] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 05/31/2021] [Indexed: 12/21/2022]
Abstract
Female reproductive aging is, in a way, a biological phenomenon that develops along canonical molecular pathways; however, it has particular features. Recent studies revealed complexity of the interconnections between reproductive aging and aging of other systems, and even suggested a cause-effect uncertainty between them. It was also shown that reproductive aging can impact aging processes in an organism at the level of cells, tissues, organs, and systems. Women at the end of their reproductive lives are characterized by the accelerated incidence of age-related diseases. Timing of the onset of menarche and menopause and variability in the duration of reproductive life carry a latent social risk: not having enough information about the reproductive potential, women keep on postponing childbirth. Identification and use of the most accurate and sensitive aging biomarkers enable the prediction of menopause timing and quantification of the true biological and reproductive ages of an organism. We discuss current views on reproductive aging and peculiarities of using available biomarkers of aging. We also consider latest advances in the search for potential genetic markers of reproductive aging. Finally, we posit the importance of determining the female biological age and highlight potential research directions in this area.
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Reynolds ML, Poulton CJ, Blazek LN, Hogan SL, Falk RJ, Derebail VK. Subfertility and early menopause in women with glomerular disease. Nephrol Dial Transplant 2021; 36:948-950. [PMID: 33508104 DOI: 10.1093/ndt/gfab005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 01/06/2021] [Indexed: 11/12/2022] Open
Affiliation(s)
- Monica L Reynolds
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Caroline J Poulton
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Lauren N Blazek
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Susan L Hogan
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Ronald J Falk
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Vimal K Derebail
- UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Pubertal Growth, IGF-1, and Windows of Susceptibility: Puberty and Future Breast Cancer Risk. J Adolesc Health 2021; 68:517-522. [PMID: 32888770 PMCID: PMC7902462 DOI: 10.1016/j.jadohealth.2020.07.016] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 07/08/2020] [Accepted: 07/09/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE Risk markers for breast cancer include earlier onset of menarche (age at menarche [AAM]) and peak height velocity (PHV). Insulin-like growth factor-1 (IGF-1) is associated with pubertal milestones, as well as cancer risk. This study examined the relationships between pubertal milestones associated with breast cancer risk and hormone changes in puberty. METHODS This is a longitudinal study of pubertal maturation in 183 girls, recruited at ages 6-7, followed up between 2004 and 2018. Measures included age at onset of puberty, and adult height attained; PHV; AAM; adult height, and serum IGF-1, and estrone-to-androstenedione (E:A) ratio. RESULTS PHV was greatest in early, and least in late maturing girls; length of the pubertal growth spurt was longest in early, and shortest in late maturing girls. Earlier AAM was related to greater PHV. IGF-1 concentrations tracked significantly during puberty; higher IGF-1 was related to earlier age of PHV, earlier AAM, greater PHV, and taller adult height. Greater E:A ratio was associated with earlier AAM. CONCLUSIONS Factors driving the association of earlier menarche and pubertal growth with breast cancer risk may be explained through a unifying concept relating higher IGF-1 concentrations, greater lifelong estrogen exposure, and longer pubertal growth period, with an expanded pubertal window of susceptibility.
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50
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Rostami Dovom M, Bidhendi-Yarandi R, Mohammad K, Farahmand M, Azizi F, Ramezani Tehrani F. Prevalence of premature ovarian insufficiency and its determinants in Iranian populations: Tehran lipid and glucose study. BMC Womens Health 2021; 21:79. [PMID: 33622308 PMCID: PMC7903639 DOI: 10.1186/s12905-021-01228-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 02/17/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Premature ovarian insufficiency (POI) considered as a concerning health issue for women of reproductive age. In this study we aim to estimate the prevalence of POI and assessing the influential factors. METHODS Data was obtained from Tehran lipid and glucose study (TLGS). All eligible post-menarcheal female participants of the TLGS, ages 20-65, were recruited (n = 6521). Participants were followed for the event of menopause, and age at menopause was recorded. Kaplan Meier analysis was applied to estimate mean and median for age at menopause. Weibull accelerated failure time survival regression model (AFT), was applied to assess influential determinants of POI. Conditional probability approach was used to provide estimation for prevalence of POI. RESULTS In this population-based study, the prevalence of POI (menopause age < 40 years) and early menopause (menopause age < 45 years) were estimated 3.5% and 24.6%, respectively. AFT model showed that in comparison to normal weight women, time to menopause was decreased by - 0.09 year (95% CI - 0.27, - 0.01, p = 0.023) and - 0.03 year (95% CI - 0.05, - 0.02, p = 0.000) in underweight and overweight women, respectively. Moreover, time to natural menopause was increased by 0.12 year (95% CI 0.07 to 0.17, p = 0.000) in women used oral contraceptives for > 6 months. CONCLUSION About one quartile of Iranian women experienced menopause at an age less than 45, especially the non-normal weight ones; this high prevalence is a critical public health concerns that needs to be addressed by health policy makers.
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Affiliation(s)
- Marzieh Rostami Dovom
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Shahid Arabi St., Yaman Ave, Velenjak, P.O.Box, 19395-4763, Tehran, Iran
| | - Razieh Bidhendi-Yarandi
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Shahid Arabi St., Yaman Ave, Velenjak, P.O.Box, 19395-4763, Tehran, Iran.
| | - Kazem Mohammad
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Farahmand
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Shahid Arabi St., Yaman Ave, Velenjak, P.O.Box, 19395-4763, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No 24, Shahid Arabi St., Yaman Ave, Velenjak, P.O.Box, 19395-4763, Tehran, Iran
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