This study aimed to investigate the association between low basal total testosterone (TT) levels and the risk of recurrent pregnancy loss (RPL) in women with infertility.

The study included women under 40 years with infertility, normal ovarian reserve, and regular ovulation. Participants were categorized into two groups: those with a history of recurrent pregnancy loss (RPL group) and those without a history of miscarriage (control group). All participants underwent in vitro fertilization (IVF) treatment. Serum TT and other sex hormone levels were measured on day 2 of spontaneous menstrual cycles and subsequently evaluated. Endocrine and coagulation conditions were also assessed.

A total of 561 women were enrolled, into either the RPL group (n = 364) or the control group (n = 197) between January 2012 and December 2020. The RPL group demonstrated significantly lower median TT levels and were older compared with the control group (1.21 vs. 1.37 nmol/L, P = 0.001; 34 vs. 33 years, P = 0.010). Additionally, fasting plasma insulin levels were higher in the RPL group (10.67 vs. 8.84 mU/L, P < 0.001). A negative correlation between basal TT levels and pregnancy loss frequency was observed. Low basal TT levels were significantly associated with RPL (OR: 1.58, 95 % CI: 1.04 - 2.41), with TT cut-off value of <1.33 nmol/L indicating an increased likelihood of RPL (P < 0.001).

Low basal serum TT levels are associated with an increased risk of RPL. However, further studies are required to evaluate the predictive value of basal TT levels in RPL risk.

The menopause transition is a period of accelerated cardiovascular disease (CVD) development in women, and sex differences in CVD incidence are reduced after menopause. Higher plasma cyclic guanosine monophosphate (cGMP) levels are also associated with greater CVD risk. Thus, we examined the changes in cGMP levels associated with the menopause transition.

We measured plasma cGMP levels in 511 women and 283 men in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Over a 20-year follow-up period, women who completed the menopause transition had smaller reductions in cGMP relative to women who remained premenopausal (P < 0.05) but had similar changes compared to men (P = 0.3) after adjusting for demographic variables.

Plasma cGMP changes through the menopause transition may reflect the underlying mechanisms associated with greater cardiovascular disease risk.

As China's population continues to age, addressing cognitive decline related to aging has become increasingly important. Simultaneously, rapid economic development has led to rising concerns about lipid metabolism disorders, particularly those involving blood lipids. Identifying modifiable risk factors early is critical to enhancing cognitive function in older adults. Thus, this study focuses on the relationship between triglycerides (TG), high-density lipoprotein (HDL), and cognitive performance to investigate potential mechanisms. A cross-sectional study was conducted using data from the 2015 China Health and Retirement Longitudinal Study (CHARLS) survey. Cognitive function was assessed across three domains: global cognition, episodic memory, and mental status. Fasting blood samples were analyzed for triglycerides and high-density lipoprotein (HDL) levels. The relationship between triglycerides, HDL, and cognitive function was examined using restricted cubic spline (RCS) analysis, multivariate linear regression, and mediation analysis. The analysis identifies a non-linear, inverse U-shaped relationship between triglycerides and both global cognition and episodic memory, with significant inflection points at a triglyceride (TG) level of 202.65 for global cognition and 115.04 for episodic memory. No non-linear relationship was observed between High-Density Lipoprotein (HDL) and cognitive outcomes, including global cognition, episodic memory, or mental status (p > 0.05). Linear mixed models indicate that HDL has a positive association with episodic memory, as shown by HDLQ1 (B = 0.0033, 95% CI: 0, 0.569), HDLQ2 (B = 0.039, 95% CI: 0.051, 0.594), and HDLQ3 (B = 0.033, 95% CI: 0.004, 0.556) compared to HDLQ4. A combined analysis of TG and HDL on episodic memory further demonstrated that the ''High-TG-low-HDL'' group (B = 0.036, 95% CI: 0.043, 0.578) had a significantly positive effect compared to the "High-HDL-low-TG" group. Mediation analysis revealed that Body Mass Index (BMI) indirectly mediated the HDL-episodic memory relationship, with a mediation effect size of 22.2%. In conclusion, this study explored the interplay between triglyceride levels, high-density lipoprotein cholesterol (HDL-C) levels, and cognitive function among middle-aged and elderly individuals in China. The findings reveal a U-shaped inverse relationship between triglyceride concentrations and cognitive ability, underscoring the need to maintain optimal triglyceride levels for cognitive health. Additionally, lower HDL levels (HDLQ1-Q3) were found to positively affect cognitive function, particularly in overall cognition and episodic memory, compared to higher HDL levels (HDLQ4). Importantly, body mass index (BMI) mediated the influence of HDL on episodic memory, with an effect size of 22.2%.

The impact of endogenous estrogen exposure (EEE) on hypertension (HTN) incidence has not been investigated yet.

This study aimed to evaluate HTN incidence in women with different endogenous estrogen durations.

Information was gathered from the Tehran Lipid and Glucose Study to conduct current research. At the initiation of the study, 4463 postmenarche normotensive women, including 3599 premenopausal and 864 menopausal women, were included. EEE was calculated for each woman, and they were followed up for the HTN event. According to the EEE, the hazard ratios and 95% confidence intervals (CI) for the HTN event were presented using Cox proportional hazards regression models (unadjusted and adjusted).

The median (interquartile range) of follow-up (between menarche and the date of HTN incidence or last follow-up) was 33.2 (25.1, 42.3) years. The event of menopause occurred in 31.8% of participants. The unadjusted model's findings illustrated that the EEE z-score was inversely associated with HTN incidence in postmenarcheal women [unadjusted hazard ratio (HR) .47, 95% CI .44-.50], meaning that the risk of HTN decreased by 53% for every 1-SD rise in the EEE z-score. After adjusting for potential confounders, the results showed no statistically significant changes (adjusted HR .46, 95% CI .43-.49). In participants with prehypertension at baseline, the hazard of HTN decreased by 56% per 1-SD rise in the EEE z-score.

This longitudinal study demonstrated the protective effect of a longer EEE duration on HTN risk, even among those with prehypertension status.

In this review, we discuss recent developments in our understanding of frontal fibrosing alopecia, a disease that has become increasingly common and widespread since its first description in 1994. An inherited predisposition to frontal fibrosing alopecia, previously suspected from the occurrence of familial cases, has been confirmed through genetic studies. Nevertheless, the epidemiology continues to implicate environmental factors in the aetiology. The search has focussed mainly on personal skin care products such as facial moisturisers and UV filters, and there is also some evidence implicating exogenous oestrogens, but confirmation of direct causal links has so far proved elusive. The pathologic mechanisms underlying follicular deletion are being clarified, including the nature of the inflammatory component, the loss of follicular immune privilege in the bulge region and the role of epithelial-mesenchymal transition in the scarring process. Lichen planus pigmentosus, a common accompaniment to frontal fibrosing alopecia in those with darker skin, is probably a feature of the same pathology affecting interfollicular epidermis, rather than a co-morbidity, and may offer new clues to the aetiology. Treatment is still based largely on retrospective case series and variable endpoints. However, methods for assessing frontal fibrosing alopecia and monitoring treatment responses have been strengthened and randomised controlled trials with novel agents (e.g. Janus kinase inhibitors) are in progress. As the main aim of effective treatment is to prevent disease progression, early diagnosis will remain an important target, as will prevention in the longer term.

The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rising due to rapid lifestyle changes. Although females may be less prone to MASLD than males, specific studies on MASLD in females should still be conducted. Previous research has shown that sex hormone levels are strongly linked to MASLD in females. By reviewing a large number of experimental and clinical studies, we summarized the pathophysiological mechanisms of estrogen, androgen, sex hormone-binding globulin, follicle-stimulating hormone, and prolactin involved in the development of MASLD. We also analyzed the role of these hormones in female MASLD patients with polycystic ovarian syndrome or menopause, and explored the potential of targeting sex hormones for the treatment of MASLD. We hope this will provide a reference for further exploration of mechanisms and treatments for female MASLD from the perspective of sex hormones.

Sexual health is multidimensional across the lifespan. At midlife, women may face challenges to sexuality, often requiring intervention. Menopause-related and age-related hormonal changes intermingle with common medical conditions and contribute to biological substrates less favorable to a healthy sexual response. Psychological, sociocultural, and relational factors modulate the impact of such changes positively or negatively, contributing to adaptation or manifestation of sexually related distress. A comprehensive diagnostic approach and multidimensional management are needed to address sexual symptoms due to both menopause and aging, individualizing non-pharmacological and pharmacological evidence-based treatment options according to personal goals and expectations in the woman/couple.

This study aimed to examine the effects of exercise on pulse wave velocity (PWV) in hypertensive and prehypertensive patients.

A comprehensive search was performed in PubMed, Cochrane, Embase, Scopus, and Web of Science, covering data up to August 31, 2023. A meta-analysis was conducted to determine the weighted mean difference (WMD) and 95% confidence interval for the effects of exercise on PWV in hypertensive and prehypertensive patients.

A total of 17 studies met the inclusion criteria. Exercise had a significant effect on improving PWV in hypertensive and prehypertensive patients (WMD, -0.93, P = 0.0001). Subgroup analysis showed that aerobic exercise (WMD, -1.29, P = 0.0004) significantly improved PWV in hypertensive and prehypertensive patients. Moreover, aerobic exercise, specifically moderate-intensity aerobic exercise (WMD, -1.69, P = 0.03), conducted for ≥12 weeks (WMD, -1.54, P = 0.002), ≥3 times per week (WMD, -1.44, P = 0.002), ≤60 min per session (WMD, -1.50, P = 0.02), and ≥180 min per week (WMD, -0.57, P = 0.005), was more effective in improving PWV in hypertensive and prehypertensive patients, especially in middle-aged individuals (WMD, -1.78, P < 0.0001).

To improve arterial stiffness, hypertensive and prehypertensive patients, particularly middle-aged individuals, are recommended to participate in a minimum of 12 weeks of moderate-intensity aerobic exercise at least 3 times per week for less than 60 min per session, with a goal of 180 min per week being achieved by increasing the frequency of exercise.

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=458981, identifier: CRD42023458981.

Studies in animals have shown that androgens promote early follicular development and granulosa cell proliferation by augmenting follicle-stimulating hormone (FSH) receptor expression in granulosa cells. Inconsistency exists regarding the association between basal serum androgen levels and follicular development in low responders undergoing in vitro fertilization (IVF), although the number of studies is limited. The aim of the current study was to assess the association between basal serum androgen concentrations and the number of follicles ≥ 11 mm on the day of triggering final oocyte maturation in low responders undergoing IVF. This prospective study was performed from June 2020 to September 2024 in 96 low responders, categorized according to the Bologna criteria. Total testosterone, dehydroepiandrosterone sulfate (DHEAS), 17-OH progesterone (17-OH-P), Δ4-androstenedione (Δ4-A), and sex hormone-binding globulin (SHBG) were measured on the day of initiation of ovarian stimulation. No association was found between basal serum testosterone (coef.: -0.002, p = 0.98), DHEAS (coef.: -0.096, p = 0.35), 17-OH-P (coef.: +0.086, p = 0.40), Δ4-A (coef.: -0.028, p = 0.79), and SHBG (coef.: +0.160, p = 0.12) concentrations and the number of follicles ≥ 11 mm on the day of triggering final oocyte maturation. The results of the current study challenge the usefulness of basal serum androgen measurements prior to ovarian stimulation in low responders as predictors of ovarian response.

Fluctuation in sex hormones and the occurrence of sleep disturbance are 2 major health challenges among midlife women. However, the temporal relationship between them remains unclear.

This study included 2488 females (mean ± SD age, 49.0 ± 2.70 years) with an average follow-up of 6.95 years. We constructed a composite score by summing items related to sleep problems to reflect the comprehensive sleep status of the participants in the Study of Women's Health Across the Nation. Cross-lagged path analysis was used to examine the temporal relationship between sex hormones and sleep status. Sensitivity analyses were conducted in nonoverweight and overweight groups and adjusted for vasomotor symptoms in the main model.

In this study, we aimed to examine the temporal relationship between sex hormones and sleep status in midlife women using cross-lagged path analysis.

The primary outcomes included results of the cross-lagged path analysis between sex hormones and sleep status.

After adjusting for age, race, income, menopausal status, body mass index, hormone therapy use, smoking, and drinking, the cross-lagged path coefficients from baseline follicle-stimulating hormone (FSH) and estradiol (E2) to follow-up sleep status were 0.054 (P = .017) and -0.054 (P = .016), respectively. The path coefficient from baseline sleep to follow-up dehydroepiandrosterone sulfate (DHAS) was 0.042 (P = .017). The path coefficients between testosterone and sleep were not statistically significant. In the nonoverweight group, the patterns of the temporal relationship between sex hormones and sleep were the same as the total sample, and the point estimates were larger. However, the temporal relationships in the overweight group were nonsignificant. After adjustment for vasomotor symptoms in the main model, results were basically consistent.

Given the temporal relationship between sex hormones and sleep, our findings will provide scientific perspectives to benefit health management in the transition of menopause.

This study used a longitudinal theoretical model to distinguish the temporal relationship between sex hormones and sleep status in midlife women. Limitations include limited causal evidence in observational studies, unknown confounders, and careful extrapolation.

There were distinct patterns in the unidirectional temporal relationship between (1) FSH, E2, and DHAS and (2) sleep. Changes in FSH and E2 occurred earlier than the change of sleep, while the change of DHAS was later. In contrast, there was no temporal relationship between testosterone and sleep.

The increase in age-related comorbidities, such as cardiometabolic diseases, has become a global health priority. There is a growing need to find new parameters capable of improving the detection of cardiometabolic risk factors, and circulating endocannabinoids (eCBs) are a promising tool in this context. Here, we aimed to investigate the relationship between plasma levels of eCBs and their analogues with body composition and cardiometabolic risk factors in middle-aged adults. Seventy-two individuals (54% women; 53.6 ± 5.1 years old) were included in this study. Plasma levels of eCBs and analogues were determined using liquid chromatography-tandem mass spectrometry. Body composition was measured by dual-energy X-ray absorptiometry. Cardiometabolic risk factors (i.e., glucose and lipid profile, blood pressure, liver and renal parameters, and gonadal hormones) were also assessed. The plasma levels of 1- and 2-arachidonylglycerol (1-AG&2-AG) were positively correlated with adiposity (all r ≥ 0.23, P < 0.05). Interestingly, the plasma levels of 1-AG&2-AG, arachidonoylethanolamide, and palmitoyl-ethanolamide were positively correlated with the homeostatic model assessment index - Insulin Resistance (HOMA-IR) (all r ≥ 0.32, P < 0.01). Our results also showed that high levels of 1-AG&2-AG, arachidonoylethanolamide, linoleoyl ethanolamide, and palmitoleoyl ethanolamide were correlated with poorer liver (all r ≥ 0.27, P < 0.05), kidney (all r ≥ 0.24, P < 0.05), and gonadal function parameters (testosterone: all r > 0.26, P < 0.05, SHBG: 1-AG&2-AG r=-0.33, P < 0.01). The plasma levels of some eCBs and analogues are correlated with a worse cardiometabolic profile in middle-aged adults.

The decrease in serum estrogens after menopause is associated with a shift from a gynoid to an android adipose tissue (AT) distribution. Menopausal hormone therapy (HT) mitigates this change and accompanying metabolic dysfunction, but its effects on AT sex steroid metabolism have not been characterized.

We studied effects of HT on subcutaneous and visceral AT estrogen and androgen concentrations and metabolism in postmenopausal women.

Serum and subcutaneous and visceral AT from 63 postmenopausal women with (n = 50) and without (n = 13) per oral HT were analyzed for estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and serum estrone sulfate using liquid chromatography-tandem mass spectrometry. Steroid sulfatase activity was measured using radiolabeled precursors. mRNA expression of genes encoding sex steroid-metabolizing enzymes and receptors was performed using real-time reverse transcription quantitative polymerase chain reaction.

HT users had 4- to 7-fold higher concentrations of estrone and estradiol in subcutaneous and visceral AT, and 30% lower testosterone in visceral AT compared to nonusers. Estrogen-to-androgen ratios were 4- to 12-fold higher in AT of users compared to nonusers of HT. In visceral AT, estrogen-to-androgen ratios increased with HT estradiol dose. AT to serum ratios of estrone and estradiol remained high in HT users.

Higher local estrogen to androgen ratios and high AT to serum ratios of estrogen concentrations in HT users suggest that HT may significantly influence intracrine sex steroid metabolism in AT; these local changes could be involved in the preventive effect of HT on menopause-associated abdominal adiposity.

Testosterone, an essential sex steroid hormone, influences brain health by impacting neurophysiology and neuropathology throughout the lifespan in both genders. However, human research in this area is limited, particularly in women. This study examines the associations between testosterone levels, gray matter volume (GMV) and cerebral blood flow (CBF) in midlife individuals at risk for Alzheimer's disease (AD), according to sex and menopausal status. A cohort of 294 cognitively normal midlife participants, 83% female, ages 35-65 years, with an AD family history and/or Apolipoprotein E epsilon 4 (APOE-4) genotype, underwent volumetric Magnetic Resonance Imaging (MRI) to measure GMV and MR-Arterial Spin Labeling (ASL) for measurement of CBF. We used voxel-based analysis and volumes of interest to test for associations between testosterone (both total and free testosterone) and brain imaging outcomes, stratified by sex and menopausal status. Higher total and free testosterone levels were associated with larger GMV in men, with peak effects in frontal and temporal regions. Conversely, in women, higher testosterone levels correlated with higher CBF, with peak effects in frontal and limbic regions, subcortical areas and hypothalamus. Among women, associations between testosterone and GMV were observed at the premenopausal and perimenopausal stages, but not postmenopause, whereas associations of testosterone with CBF were significant starting at the perimenopausal stage and were more pronounced among hormone therapy non-users. Results were independent of age, APOE-4 status, midlife health indicators, and sex hormone-binding globulin levels. These findings indicate sex-specific neurophysiological effects of testosterone in AD-vulnerable regions in midlife individuals at risk for AD, with variations observed across sex and menopausal status. This underscores the need for further research focusing on the neuroprotective potential of testosterone in both sexes.

In a global effort to assess expert perspectives on the use of recombinant gonadotropins, recombinant human luteinizing hormone (r-hLH) and recombinant human follicle-stimulating hormone (r-hFSH), a consensus meeting was held in Dubai. The key aim was to address three critical questions: What are the factors that influence follicle response to gonadotropins? Which categories of patients are most likely to benefit from LH supplementation? And what are the optimal management strategies for these patients?

A panel of thirty-six experts reviewed and refined the initial statements and references proposed by the Scientific Coordinator. Consensus was defined as agreement or disagreement by more than two-thirds (66%) of the panel members for each statement.

Thirty-five statements were formulated, of which thirty-one reached consensus. For patients with Hypo-Response to Gonadotropin Stimulation (20 statements), all identified risk factors, including advanced age, high BMI, and chronic conditions, achieved unanimous agreement. Diagnostic approaches, such as the inclusion of POSEIDON criteria and hormone level monitoring, were endorsed by the majority, with over 90% agreement. Management strategies, particularly individualized stimulation protocols and optimized scheduling, garnered broad consensus, with only one statement falling short of the threshold. Additionally, in cases of severe FSH and LH deficiency, combining r-hFSH with r-hLH was found to improve pregnancy rates and cost efficiency compared to human menopausal gonadotropin (hMG). For patients with Advanced Maternal Age (AMA) (15 statements), there was strong agreement on the use of oral contraceptive pills and estrogen priming. Recommendations concerning antagonist protocols and dosing of r-hLH and r-hFSH also achieved high levels of consensus. Significant agreement supported r-hLH supplementation and a tailored approach to luteal phase support. However, there were mixed opinions on the route of progesterone administration, with some experts expressing neutral or disagreeing views. Despite these differences, unanimous consensus was reached on markers of treatment success, particularly live birth rates, pregnancy rates, and embryo development, underscoring the importance of these outcomes in evaluating treatment efficacy.

This consensus provides a practical clinical perspective to a wide range of global professionals on the strategies employed during key phases of Assisted Reproductive Technology (ART) treatment. To further improve outcomes, incorporating additional clinical insights on ART approaches, alongside existing guidelines and policies, may offer valuable guidance for optimizing patient care.

Although the deleterious impact of chemotherapy regimen used to treat women of reproductive age with breast cancer on ovarian reserve has been extensively studied, hardly anything has been reported on the effect of these protocols on theca cell function and ovarian androgen secretion. The aim of this prospective multicentric cohort study was to describe serum levels of total testosterone and androstenedione during chemotherapy and 24-month follow-up in 250 patients <40 years treated for breast cancer. Mean basal levels of androstenedione and total testosterone at diagnosis were 1.68 ng/mL and 0.20 ng/mL respectively. No correlation with age was found. Serum levels of androstenedione and total testosterone rapidly decreased after chemotherapy completion, before slowly increasing and almost returning to basal levels in all patients during 2-year follow-up. In conclusion our study demonstrates a chemotherapy-induced alteration of ovarian thecal function, resulting in a significant decrease in serum androgen levels. This alteration of theca cell function adds to the well-known alteration of granulosa cell function, resulting in a global, but partly transient, ovarian failure in young women treated for breast cancer. These data bring new insight into ovarian physiology and emphasize the need for pre and post-treatment ovarian follow-up. Trial registration: ClinicalTrial.gov identifier NCT01114464.

The increasing prevalence of Anabolic-androgenic steroids (AAS) among women, driven by the pursuit of improved body aesthetics, characterized by higher lean mass and reduced adipose tissue, raises significant health concerns, particularly due to the limited knowledge regarding their effects on the female organism. Prolonged use and/or high doses of AAS are linked to various harmful side effects, including mood changes, psychiatric disorders, voice deepening, clitoromegaly, menstrual irregularities, and cardiovascular complications, prompting medical societies to discourage their widespread use due to insufficient evidence supporting their safety and efficacy. Studies in female rodents have shown that AAS can lead to increased aggression, inflammation, reduced neuronal density, and negative impacts on the myocardium and blood vessels. Additionally, maternal administration of androgens during pregnancy can adversely affect offspring's reproductive, neuronal, and metabolic health, resulting in long-term impairments. The complexity of the mechanisms underlying AAS effects, and their potential genotoxicity remains poorly understood. This review aims to elucidate the various ways in which AAS can impact female physiology and that of their offspring, highlight commonly used anabolic substances, and discuss the positions of medical societies regarding AAS use.

Hyperandrogenemia in patients with Cushing's syndrome (CS) presents a diagnostic pitfall due to its rare occurrence and overlapping symptoms with more common conditions like polycystic ovary syndrome (PCOS). This review explores the significance of androgen dysregulation in CS, focusing on both classical and 11-oxygenated androgens. While classical androgens contribute to hyperandrogenism in CS, their levels alone do not fully account for clinical symptoms. Recent research highlights the overlooked role of 11oxC19 androgens, particularly 11OHA4 and 11KT, in driving hyperandrogenic manifestations across all CS subtypes. These adrenal-specific and highly potent androgens offer stable expression throughout the lifespan of a woman, serving as valuable diagnostic biomarkers. Understanding their prominence not only aids in subtype differentiation but also provides insights into the complex nature of androgen dysregulation in CS. Recognizing the diagnostic potential of 11oxC19 androgens promises to refine diagnostic approaches and improve clinical management strategies for patients with CS.

Sex differences exist in type 2 diabetes (T2D), and androgens have been implicated in the etiology of T2D in a sex-specific manner. We therefore aimed to investigate whether androgens play a role in explaining sex differences in glucose homeostasis and incidence of T2D.

We used observational data from the German population-based KORA F4 study (n = 1975, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1412). T2D was determined through self-reporting and confirmed by contacting the physicians and/or reviewing the medical charts. Multivariable linear and logistic regression models were employed to explore associations. Mediation analyses were performed to assess direct effects (DE) and indirect effects (IE), and the mediating role of androgens (total testosterone (TT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAs)) in the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis).

After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower levels of TT, DHEAs, fasting glucose levels, fasting insulin levels, 2 h-glucose levels and HOMA-IR, compared to men. An inverse association was observed for TT and glucose- and insulin-related traits in men, while a positive association was observed for TT and fasting glucose levels in women. We found a mediatory role of TT on the association of sex with fasting glucose levels (IE: β = 3.08, 95% CI: 2.04, 4.30), fasting insulin levels (IE: β = 0.39, 95% CI:0.30, 0.47), 2 h-glucose levels (IE: β = 12.77, 95% CI: 9.01, 16.03) and HOMA-IR (IE: β = 0.41, 95% CI: 0.33, 0.50). Also, the inconsistent mediatory role of TT was seen on the association of sex with incidence of T2D (DE: 0.12, 95% CI: 0.06, 0.20 and IE: OR = 7.60, 95% CI: 3.43, 24.54). The opposing DE and IE estimates suggest that the association between sex and either glucose homeostasis or the incidence of T2D may differ when TT is considered as a potential mediator, with higher TT levels being beneficial for glucose metabolism or incidence of T2D in men, while in women, detrimental. No mediatory role was observed for either DHEA or DHEAs on glucose homeostasis or the incidence of T2D.

The dimorphic mediatory role of TT highlights its complex role in metabolic health, contributing differently to the glucose dysregulation and risk of T2D in men and women.

Transgender is a term for people whose gender identity or expression differs from their natal sex. These individuals often seek cross-hormonal therapy to simulate the individual´s desired gender. However, the use of estrogens and testosterone has side effects such as a higher propensity to cancer, weight changes and cardiovascular diseases. Testosterone has also been linked with hypertension. Still, little is known about the outcomes and prevalence of metabolic perturbations in the trans community. Here we aim to analyze if cross-administering sexual hormones affects heart mitochondrial function. Mitochondria produces the ATP needed for heart function. In fact, different studies show that mitochondrial dysfunction precedes cardiac damage. In this work we used either female rats castrated and injected with testosterone or male rats castrated and injected with estrogens for 4 months. We performed an electrocardiogram, and then we isolated heart mitochondria to measure the rate of oxygen consumption, calcium fluxes, membrane potential, superoxide dismutase activity, lipoperoxidation and cytokines. We detected wide modifications in all parameters associated to cross-hormonal administration.

Androgen excess (AE)-related symptoms can vary widely and may appear across the life course.

We assessed the prevalence of signs of potential AE and heterogeneity by demographic/health characteristics.

We used data of 24 435 participants who consented and enrolled during November 2019 to December 2022 in a US digital cohort to evaluate the prevalence and heterogeneity of self-reported signs of potential AE: possible hirsutism (having thick coarse hair on ≥4 of 8 body locations), hair level on the chin, hair loss on top of the head, and moderate to severe acne.

The prevalence of possible hirsutism, having several/a lot of hair on the chin, significantly reduced hair/visible scalp on top of the head, and moderate to severe acne were 6.9%, 12.6%, 1.7%, and 31.8%, respectively. While possible hirsutism and moderate to severe acne decreased with age (range: 18-86 years), hair on the chin and hair loss on the head increased with age. Participants who self-identified as Hispanic or South Asian reported a higher prevalence of possible hirsutism (11.2%, 16.9%, vs 6.3% among non-Hispanic White participants). Participants with higher body mass index had a higher prevalence of possible hirsutism. Moderate to severe acne was more common among those with polycystic ovary syndrome. Possible hirsutism and hair loss were less common among participants using hormones for contraception.

In this large cohort, signs of potential AE varied by demographic and health factors. These results could provide a new understanding of how potential AE may appear differently in diverse groups, informing future work to develop more inclusive evaluation at a population level.

Currently, there is no consensus on the optimal management of women with low prognosis in ART. In this Delphi consensus, a panel of international experts provided real-world clinical perspectives on a series of literature-supported consensus statements regarding the overall relevance of the POSEIDON criteria for women with low prognosis in ART.

Using a Delphi-consensus framework, twelve experts plus two Scientific Coordinators discussed and amended statements and supporting references proposed by the Scientific Coordinators (Round 1). Statements were distributed via an online survey to an extended panel of 53 experts, of whom 36 who voted anonymously on their level of agreement or disagreement with each statement using a six-point Likert-type scale (1 = Absolutely agree; 2 = More than agree; 3 = Agree; 4 = Disagree; 5 = More than disagree; 6 = Absolutely disagree) (Round 2). Consensus was reached if > 66% of participants agreed or disagreed.

The extended panel voted on seventeen statements and subcategorized them according to relevance. All but one statement reached consensus during the first round; the remaining statement reached consensus after rewording. Statements were categorized according to impact, low-prognosis validation, outcomes and patient management. The POSEIDON criteria are timely and clinically sound. The preferred success measure is cumulative live birth and key management strategies include the use of recombinant FSH preparations, supplementation with r-hLH, dose increases and oocyte/embryo accumulation through vitrification. Tools such as the ART Calculator and Follicle-to-Oocyte Index may be considered. Validation data from large, prospective studies in each POSEIDON group are now needed to corroborate existing retrospective data.

This Delphi consensus provides an overview of expert opinion on the clinical implications of the POSEIDON criteria for women with low prognosis to ovarian stimulation.

Increased access to and indications for genetic testing will lead to more women undergoing risk-reducing salpingo-oophorectomy (RRSO), with a potential impact on sexual function.

Our objective was to prospectively investigate (1) sexual function in women with pathogenic variant (PV) in BRCA1/2 genes, before and 1 year after RRSO, and to compare with a healthy age-matched control group and (2) to study if testosterone levels correlate with sexual functioning after RRSO.

A prospective observational follow-up study of 43 BRCA1/2-PV carriers planned for RRSO and 73 healthy-age matched controls. Data including personal medical history, the Female Sexual Function Index (FSFI) and blood samples for analysis of testosterone by tandem mass spectrometry and free androgen index (FAI) were collected before and 1 year after surgery or at inclusion (controls).

Sexual function and testosterone levels following RRSO.

Median age in the RRSO group was 42 years at baseline, 55.8% were premenopausal and 53.5% had a history of breast cancer. The RRSO group had significantly lower median FSFI total score (P < .001), lower scores of all 6 FSFI domains (P < .001), as well as a higher proportion of female sexual dysfunction (FSD) (P < .001) compared to the control group at 1 year after surgery. In the RRSO group, users of menopausal hormone therapy (MHT) had a significantly higher median FSFI total score compared with the nonusers both at baseline (P = .023) and follow-up (P = .010). The proportion of FSD was significantly higher in the non-MHT group at both baseline (P = .041) and follow-up (P = .009). FAI was significantly lower in the RRSO group when compared to the controls at 1-year follow-up (P = .041); however, no significant correlations between testosterone levels and FSFI scores were found.

The results highlight the need to counsel BRCA1/2-PV carriers before RRSO and offer a structured follow-up and support addressing sexual function and impact of MHT use.

The main strength of this study is its prospective design with age-matched controls. Limitation is a small sample size.

Our findings show that sexual function deteriorated 1 year after RRSO independent of testosterone levels, and the proportion with impaired sexual function was higher compared to healthy age-matched controls.

Hormones are linked to cardiometabolic diseases and may be impacted by acculturation though multiple mechanisms. We evaluated associations of Hispanic/Latino background and acculturation with levels of sex- and thyroid-related hormones and the potential mediating effect of adiposity, lifestyle factors, and sleep apnea syndrome on these associations.

We studied 1789 adults, aged 45-74, from a sub-cohort of the Hispanic Community Health Survey/Study of Latinos. Peri/pre-menopausal women and individuals on medications related to hormones were excluded. Our study assessed eleven sex- and thyroid-related hormones, Hispanic/Latino background, and five acculturation measures. Associations were assessed using multivariable linear and logistic regression adjusted for survey design and confounding variables. We explored potential mediation using a path analysis.

In postmenopausal women, acculturation score-MESA was associated with decreased thyroid-stimulating hormone (β = - 0.13;95%CI = - 0.22, - 0.03) while age at immigration greater than the median (vs US-born) was associated with decreased (β = - 14.6; 95%CI = - 28.2, - 0.99) triiodothyronine (T3). In men, language acculturation and acculturation score-MESA were associated with increased estradiol and sex hormone-binding globulin (SHBG) while age at immigration greater and lesser than the median (vs US-born) was associated with decreased SHBG. Hispanic/Latino background (Mexicans as reference) were selectively associated with sex- and thyroid-related hormone levels in both sexes. Current smoking and sleep apnea syndrome partially mediated the association of Cuban and Puerto Rican heritage (vs Mexican) with T3 levels in men and postmenopausal women, respectively.

Selected acculturation measures were associated with thyroid-related hormones in postmenopausal women and sex-related hormones in men. Understanding the mechanisms involved in the relationship of acculturation and Hispanic/Latino background with hormones warrants additional investigation.

The present study aimed to clarify the conflicting association of premenopausal hyperandrogenaemia (HA) with the development of hypertension and cardiovascular disease (CVDs) in women.

A population-based cohort study including 5889 women.

The association of serum testosterone (T), sex hormone-binding globulin (SHBG), and free androgen index (FAI) at age 31 with blood pressure (BP) and hypertension (BP ≥ 140/90 mmHg and/or use of antihypertensive medication) at ages 31 and 46 and with CVDs (angina pectoris [AP] and/or acute myocardial infarction [AMI] n = 74, transitory cerebral ischaemia and/or stroke n = 150) and combined CVD events (AP, AMI, stroke, heart failure, or CVD mortality n = 160) by age 53 was investigated.

T and FAI were positively associated with systolic and diastolic BP at ages 31 and 46 in the multivariable model. Compared to their lowest quartile, the highest quartiles of T and FAI were positively associated with hypertension at age 31 in the multivariable model. During the 22-year follow-up, FAI was positively associated with increased risk of AP/AMI (hazard ratio [HR]: 2.02, 95% CI: 1.06-3.85) and overall CVD events or mortality (HR: 1.54, 95% CI: 1.02-2.33) in the unadjusted models. However, the significance disappeared after adjusting for body mass index (BMI).

Women with HA at premenopausal age had an elevated risk of hypertension, and together with BMI, increased risk of CVD events and CVD mortality during the 22-year follow-up. However, because of several study limitations regarding ethnicity and BMI characteristics, a longer follow-up of this cohort and future studies in ethnically diverse populations are needed to verify the results.

It is challenging for clinicians to distinguish adrenocortical carcinoma (ACC) from benign adrenocortical adenomas (ACA) in their early stages. This study explored the value of serum steroid profiling as a complementary biomarker for malignancy diagnosis of ACC other than diameter and explored the influence of sex and functional status.

In this retrospective study, a matched cohort of patients diagnosed with either ACC or ACA based on histopathology was meticulously paired in a 1:1 ratio according to sex, age, and functional status. Eight serum steroids including 11-deoxycortisol, 11-deoxycorticosterone, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and estradiol, were quantified by liquid chromatography tandem mass spectrometry. We conducted a comparative analysis of the clinical characteristics and serum steroid profiles of patients with ACC and ACA, with further subgroup analysis.

The study included 31 patients with ACC and 31 matched patients with ACA. Patients with ACC exhibited significantly larger tumor diameters, lower body mass index (BMI), and higher levels of 11-deoxycortisol, progesterone, and androstenedione than those with ACA. 11-deoxycortisol was the only valuable index for discriminating ACC from ACA, regardless of functional status and sex. Progesterone, DHEA, and DHEAS levels were higher in the functional ACC group than in the non-functional ACC group. Female ACC patients, especially in postmenopausal female exhibited higher levels of androstenedione than male patients. The area under the curve of tumor diameter, 11-deoxycortisol, and BMI was 0.947 (95% CI 0.889-1.000), with a sensitivity of 96.8% and specificity of 90.3%.

Serum steroid profiling serves as a helpful discriminative marker for ACC and ACA, with 11-deoxycortisol being the most valuable marker. For other steroid hormones, consideration of sex differences and functional status is crucial.

Does luteal estradiol (E2) pretreatment give a similar number of retrieved oocytes compared to no-pretreatment in advanced-aged women stimulated with corifollitropin alfa in an antagonist protocol?

Programming antagonist cycles with luteal E2 gave similar number of retrieved oocytes compared to no-pretreatment in women aged 38-42 years.

Programming antagonist cycles with luteal E2 pretreatment is a valuable tool to organize the IVF procedure better and is safe without any known impact on cycle outcome. However, variable effects were observed on the number of retrieved oocytes depending on the treated population. In advanced-age women, recruitable follicles tend to decrease in number and to be more heterogeneous in size but it remains unclear if estradiol pretreatment could change the oocyte yield through its negative feed-back effect on FSH intercycle rise.

This non-blinded randomized controlled non-inferiority trial was conducted between 2016 and 2022 with centrally computerized randomization and concealed allocation. Participants were 324 women aged 38-42 years undergoing IVF treatment. The primary endpoint was the total number of retrieved oocytes. Statistical analysis was performed with one-sided alpha risk of 2.5% and 95% confidence interval (CI) with the non-inferiority of E2 pretreatment proved by a P value <0.025 and a lower delta margin of the CI within two oocytes compared to no pretreatment. Secondary endpoints were duration and total dosage of recombinant FSH, cancellation rate, percentage of oocyte pick-up (OPU) on working days, total number of metaphase II oocytes and obtained embryos, fresh transfer live birth rate, and cumulative live birth rate.

This multicentric study enrolled women with regular cycles, weight >50 kg and body mass index <32, IVF cycle 1-2. According to randomization, micronized estradiol 2 mg twice a day was started on days 20-24 and continued until Wednesday beyond the onset of menses followed by administration of corifollitropin alfa on Friday, i.e. stimulation (S)1 or from D1-3 of a natural cycle in unpretreated patients. GnRH antagonist was started at S6 and additional FSH at S8.

Basal characteristics were similar in patients randomized in E2 pretreated (n = 164) and non-pretreated (n = 160) groups (intended to treat (ITT) population). A total of 291 patients started treatment (per protocol (PP) population), 147 in E2 pretreated group with a mean number [SD] of pre-treatment days 9.8 [2.6] and 144 in the non-pretreated group. Despite advanced age, oocyte yields ranged from 0 to 29 in both groups with a median number of 6 retrieved oocytes in accordance with a mean anti-Müllerian hormone (AMH) level above 1.2 ng/ml. We demonstrated the non-inferiority of E2 pretreatment with a mean difference of -0.1 oocyte 95% CI [-1.5; 1.3] P = 0.004 in the PP population and a mean difference of -0.44 oocyte [-1.84; 0.97] P = 0.014 in the ITT population. Oocyte retrieval was more often on working days in E2 pretreated patients (91.9 versus 74.2%, P < 0.001). In patients reaching OPU, the duration of stimulation was statistically significantly longer (11.7 [1.7] versus 10.8 [1.8] days, P < 0.001) and the extra FSH dosage in addition to corifollitropin alfa was statistically significantly higher (1040 [548] versus 778 [504] IU, P < 0.001) in E2 pretreated than non-pretreated patients. We did not observe any significant differences in the number of retrieved oocytes (8.4 [6.1] versus 9.1 [6.0]), in the number of Metaphase 2 oocytes (7 [5.5] versus 7.3 [5.2]) nor in the number of obtained embryos (5 [4.6] versus 5.2 [4.2]) in E2 pretreated patients compared to non-pretreated patients. The live birth rate after fresh transfer (16.2% versus 18.5%, respectively), and the cumulative live birth rate per patient (17.7% versus 22.9%, respectively) were similar in both groups. Among the PP population, 31.6% of patients fulfilled the criteria for group 4 of Poseïdon classification (AMH <1.2 ng/ml and/or antral follicle count <5). In this sub-group of patients, we observed in contrast a statistically higher number of retrieved oocytes in E2 pretreated patients compared to non-pretreated (5.1 [3.8] versus 3.4 [2.7], respectively, the mean difference of +1.7 oocyte [0.2; 3.2] P = 0.022) but without significant difference in the cumulative live birth rate per patient (15.7% versus 7.3%, respectively).

Our stimulated women older than 38 years obtained a wide range of collected oocytes suggesting very different stages of ovarian aging in both groups. E2 pretreatment is more likely to increase oocyte yield at the stage of ovarian aging characterized by asynchrony of a reduced follicular cohort. Another limitation is the sample size in sub-group analysis of patients with AMH <1.2 ng/ml. Finally, the absence of placebo for pretreatment could also introduce possible bias.

Programming antagonist cycles with luteal E2 pretreatment seems a useful tool in advanced age women to better schedule oocyte retrievals on working days. However, the potential benefit of the number of collected oocytes remains to be demonstrated in a larger population displaying the characteristics of decreased ovarian reserve encountered in Poseïdon classification.

Research grant from (MSD) Organon, France. I.C., S.D., B.B., X.M., S.G., and C.J. have no conflict of interest with this study. I.C.D. declares fees as speaker from Merck KGaA, Gedeon Richter, MSD (Organon, France), Ferring, Theramex, and IBSA and participation on advisory board from Merck KGaA. I.C.D. also declares consulting fees, and travel and meeting support from Merck KGaA. N.M. declares grants paid to their institution from MSD (Organon, France); consulting fees from MSD (Organon, France), Ferring, and Merck KGaA; honoraria from Merck KGaA, General Electrics, Genevrier (IBSA Pharma), and Theramex; support for travel and meetings from Theramex, Merck KGaG, and Gedeon Richter; and equipment paid to their institution from Goodlife Pharma. N.C. declares grants from IBSA Pharma, Merck KGaA, Ferring, and Gedeon Richter; support for travel and meetings from IBSA Pharma, Merck KGaG, MSD (Organon, France), Gedeon Richter, and Theramex; and participation on advisory board from Merck KGaA. A.G.L. declares fees as speaker from Merck KGaA, Gedeon Richter, MSD (Organon, France), Ferring, Theramex, and IBSA.

ClinicalTrials.gov NCT02884245.

29 August 2016.

4 November 2016.

This study aimed to translate and validate the Estro-Androgenic-Symptom Questionnaire in Women (EASQ-W) into Brazilian Portuguese language, as we hypothesized that this tool would be consistent for addressing the specific context of hormonal symptoms in menopause.

In a cross-sectional study, a total of 119 women with Genitourinary Syndrome of Menopause (GSM) and 119 climacteric women without GSM were included. The EASQ-W was translated, and its psychometric properties were rigorously examined. Participants completed questionnaires covering sociodemographic details, the EASQ-W, and the Menopause Rating Scale (MRS). A subgroup of 173 women was re-invited after 4 weeks for test-retest analysis of the EASQ-W. Additionally, the responsiveness of the questionnaire was evaluated in 30 women who underwent oral hormonal treatment.

The internal consistency of the EASQ-W was found to be satisfactory in both GSM and control groups (Cronbach's alpha ≥ 0.70). Notably, a floor effect was observed in both groups; however, a ceiling effect was only evident in the sexual domain of the GSM group. Construct validity was established by comparing the EASQ-W with the MRS, yielding statistically significant correlations (0.33831-0.64580, p < 0.001). The test-retest reliability over a 4-week period was demonstrated to be satisfactory in both the GSM and control groups (ICC 0.787-0.977). Furthermore, the EASQ-W exhibited appropriate responsiveness to oral hormonal treatment (p < 0.001).

This study successfully translated and validated the Estro-Androgenic-Symptom Questionnaire in Women (EASQ-W) into Brazilian Portuguese, with satisfactory internal consistency, test-retest reliability, and construct validity.

Hypoestrogenism related to the cessation of ovarian function increases the risk of metabolic disorders in postmenopausal women. Women with primary ovarian insufficiency (POI) are exposed to longer period of estrogen deficiency together with a subsequently higher risk of long-term comorbidities.

To compare metabolic along with hormonal status among newly diagnosed women with POI with pre- and postmenopausal women. To investigate the impact of POI etiology on both metabolic and hormonal profiles.

A case-control study with women assigned to one of the groups: 1) POI (n = 216), 2) age-matched premenopausal (n = 216), 3) postmenopausal (n = 227). Lipid profile, fasting glucose and insulin levels together with insulin resistance were determined among all participants.

POI women exhibited increased both total cholesterol (TC, p = 0.04) and low-density lipoprotein cholesterol (LDL-C, p < 0.01) compared to the premenopausal women and higher triglycerides (TG, p < 0.001) than postmenopausal women. POI group showed higher fasting glucose level (p = 0.04) differently to premenopausal women. The idiopathic POI group showed both lower sex hormone binding globulin (p = 0.02) and dehydroepiandrosterone sulfate (p = 0.04) along with reduced TC (p = 0.03) and TG (p = 0.01) together with increased high-density lipoprotein cholesterol (p = 0.04) levels than non-idiopathic POI women.

Women with newly diagnosed POI exhibited less favorable lipid profile than pre- or postmenopausal women. The association of negatively changed lipid profile in POI women is mostly mediated by women with unknown cause of premature ovarian cessation.

In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages.

Bulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures.

RNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11β-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11β-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17), whilst 11β-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11β-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes.

This study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.

The purpose of this study was to investigate the presence of sex-steroid receptors in human choroidal tissue across different ages and sex, aiming to better understand the pronounced sex difference in central serous chorioretinopathy (CSC) occurrence.

Paraffin-embedded enucleated eyes of 14 premenopausal women, 15 postmenopausal women, 10 young men (<45 years), and 10 older men (>60 years) were used. A clinically certified immunostaining was performed to detect the presence of the androgen receptor (AR), progesterone receptor (PR; isoform A and B), and estrogen receptor (ERα). The stained slides were scored in a blinded manner for positive endothelial cells and stromal cells in consecutive sections of the same choroidal region.

Our analysis revealed the presence of AR, PR, and ERα in endothelial cells and stromal cells of choroidal tissue. The mean proportion of AR-positive endothelial cells was higher in young men (46% ± 0.15) compared to aged-matched women (29% ± 0.12; P < 0.05, 95% confidence interval [CI]). Premenopausal women showed markedly lower mean proportion of ERα (5% ± 0.02) and PR-positive endothelial cells (2% ± 0.01) compared to postmenopausal women (15% ± 0.07 and 19% ± 0.13; both P < 0.05, 95% CI), young men (13% ± 0.04 and 21% ± 0.10; both P < 0.05, 95% CI), and older men (18% ± 0.09 and 27% ± 0.14; both P < 0.05, 95% CI). Mean PR-positive stromal cells were also less present in premenopausal women (12% ± 0.07) than in other groups.

The number of sex-steroid receptors in the choroidal tissue differs between men and women across different ages, which aligns with the prevalence patterns of CSC in men and postmenopausal women.

Migraine affects ∼12 % of the worldwide population and is more prevalent in females, which suggests a role of sex hormones in migraine pathophysiology. Most studies have focused on estrogen and progesterone, and the involvement of androgens has been less studied. However, due to the recent advances in androgen interventions, which could advance new androgen-based migraine treatments, it is critical to better understand the role of androgens in migraine. Testosterone, the most studied androgen, was found to have an antinociceptive effect in various animal and human pain studies. Thus, it could also have a protective effect related to lower migraine severity and prevalence. In this review, we discuss studies examining the role of androgens on migraine-related symptoms in migraine animal models. Additionally, we summarize the results of human studies comparing androgen levels between patients with migraine and healthy controls, studies assessing the relationships between androgen levels and migraine severity, and intervention studies examining the impact of testosterone treatment on migraine severity. Many of the studies have limitations, however, the results suggest that androgens may have a minor effect on migraine. Still, it is possible that androgens are involved in migraine pathophysiology in a sub-group of patients such as in adolescents or postmenopausal women. We discuss potential mechanisms in which testosterone, as the main androgen tested, can impact migraine. These mechanisms range from the cellular level to systems and behavior and include the effect of testosterone on sensory neurons, the immune and vascular systems, the stress response, brain function, and mood. Lastly, we suggest future directions to advance this line of research.

Depressive symptoms and sarcopenia, often observed among middle-aged and elderly individuals, are significant health concerns in China, particularly given the country's rapidly aging population. Depressive symptoms, characterized by persistent feelings of sadness and loss of interest, can significantly impact quality of life. Little is known about the underlying pathway connecting these two conditions.

The data for this study were derived from the China Health and Retirement Longitudinal Study (CHARLS). Depressive symptoms were evaluated using the Centre for Epidemiological Studies Depression (CSED) scale. Logistic regression analyses were employed to investigate the association between depressive symptoms, activities of daily living (ADL) disability, and sarcopenia, while adjusting for potential confounding factors. The selection of predictor variables, including social activity, chronic diseases, demographic factors, and lifestyle habits, was based on their known associations with mental health, physical functioning and sarcopenia. These variables were included to ensure a comprehensive adjustment for potential confounding factors and to provide a more accurate estimation of the relationship between depressive symptoms and sarcopenia. Additionally, mediation analysis was conducted to assess the mediating role of ADL disability in the relationship between depressive symptoms and sarcopenia.

A comprehensive study was conducted on a total of 8,238 participants aged 45 years and older, comprising 3,358 men and 4,880 women. Logistic regression analyses were conducted to identify significant associations between depressive symptoms (OR = 1.30, P = 0.0269,95%CI = 1.03-1.63), ADL disability (OR = 1.94, P < 0.001,95%CI = 1.37-2.75) and sarcopenia. The results revealed significant relationships among these variables. Furthermore, mediation effect analyses demonstrated that ADL disability partially mediated the association between depressive symptoms and sarcopenia (estimated indirect effect: 0.006, 95% CI: 0.003, 0.008, proportion of mediation effect: 20.00%).

The study underscores a significant association between depressive symptoms and sarcopenia among middle-aged and elderly individuals in China, with ADL disability acting as a mediator. These findings offer novel insights for targeted health interventions. Future interventions should effectively combat sarcopenia by integrating psychological support with muscle-strengthening exercise programs. By addressing both depressive symptoms and ADL disability, clinicians and public health professionals can enhance outcomes for this demographic. Collaborative efforts across disciplines are essential for providing comprehensive health management tailored to the needs of middle-aged and elderly individuals. Future research should longitudinally assess the impact of such integrated interventions on sarcopenia prevention and depressive symptom alleviation. Additionally, investigating the role of social and environmental factors in mediating this relationship is crucial for developing more effective health strategies for this vulnerable population.

Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy.

To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction.

We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions.

Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction.

Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods.

We included 28 RCTs. There were 1533 women in the intervention groups and 1469 in the control groups. Apart from three trials, trial participants were women identified as 'poor responders' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus estradiol or T versus estradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor.

Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.

Androgens are produced in both sexes. In females produced by the adrenal gland and the ovaries they play a crucial role in regulating ovarian function, estrogen synthesis and follicular growth. Age leads to a reduction in androgen concentrations, although, at present, these mechanisms are not elucidated in mares. The objective of this study was to evaluate the concentrations of testosterone (T), androstenedione (A4) and dehydroepiandrosterone (DHEA) in mares of different ages. Blood samples were drawn from seventy cyclic Spanish Purebred mares belonging to five age groups: 3-5 years, 6-9 years, 10-13 years, 14-16 years and > 16 years. The concentrations of T, A4 and DHEA were determined by EIA, validated specifically for horses. Mares aged 3-5, 6-9 and 10-13 years had higher T concentrations (P < 0.05) than mares aged >16 years, and mares aged 6-9 years had also higher concentrations than those 14-16 years old (P < 0.05). A4 concentrations were lower (P < 0.05) in mares >16 years old when compared with those of other age groups. DHEA concentrations were lower (P < 0.05) in mares 14-16 years and > 16 years old when compared with those of other age groups. DHEA was positively correlated with T (r = 0.61; P < 0.05) and A4 (r = 0.51; P < 0.05). Age induces reduction in androgens' synthesis in physiologically cyclic Spanish Purebred mares. These physiological variations must be duly considered for a correct and objective interpretation of the analytical data.

Female sexual desire is a complex interplay of neurotransmitters and hormones. Diagnosis is based on clinical features and sexual distress. Treatments that affect neurotransmitters and hormones that may be out of balance can help improve sexual desire in women with hypoactive sexual desire disorder.

According to real-world data, is recombinant human FSH (r-hFSH) combined with recombinant human LH (r-hLH) or r-hFSH alone more effective for women of advanced maternal age (AMA) in terms of live birth?

Non-interventional study comparing the effectiveness of r-hFSH and recombinant r-hLH (2:1 ratio) versus r-hFSH alone for ovarian stimulation during ART treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register.

Overall clinical pregnancy (29.8%, 95% CI 28.2 to 31.6 versus 27.8%, 95% CI 26.5 to 29.2) and live birth (20.3%, 95% CI 18.7 to 21.8 versus 18.0%, 95% CI 16.6 to 19.4) rates were not significantly different between the combined r-hFSH and r-hLH group and the r-hFSH alone group (P = 0.269 and P = 0.092, respectively). Treatment effect was significantly higher for combined r-hFSH and r-hLH compared with r-hFSH alone for clinical pregnancy (33.1%, 95% CI 31.0 to 35.0 versus 28.5%, 95% CI 26.6 to 30.4; P = 0.001, not adjusted for multiplicity) and live birth (22.5%, 95% CI 20.5 to 24.2 versus 19.4%, 95% CI 17.6 to 20.9; P = 0.014, not adjusted for multiplicity) in a post-hoc analysis of women with five to 14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of combined r-hFSH and r-hLH for ovarian stimulation in women aged 35-40 years with normal ovarian reserve.

Women of AMA with normal ovarian response benefit from treatment with combined r-hFSH and r-hLH in a 2:1 ratio versus r-hFSH alone in terms of live birth rate. The effectiveness of treatments is best assessed by RCTs; however, real-world data are valuable for examining the effectiveness of fertility treatment, especially among patient groups that are not well represented in clinical trials.