Maternal androgen excess increases the risk of metabolic syndrome in female offspring in their later life: A long-term population-based follow-up study.

PURPOSE: Hyperandrogenic intrauterine environment may lead to the development of metabolic disorders in offspring in their later life. In this study, we aimed to determine the impact of maternal hyperandrogenism (MHA) on metabolic syndrome (MetS) risk in female offspring in their later life. METHODS: In this cohort study conducted in Tehran, Iran, female offspring with MHA (n = 323) and without MHA (controls) (n = 1125) were selected. Both groups of female offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. We used age-scaled unadjusted and adjusted Cox regression models to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in female offspring. The software package STATA was used for statistical analysis, and the significance level was set at P < 0.05. RESULTS: We observed a higher risk of MetS (unadjusted HR (95% CI), 1.36 (1.05-1.77)), (P = 0.02) and (adjusted HR (95% CI), 1.34 (1.00-1.80)), (P = 0.05, borderline)), in female offspring with MHA, compared to controls. The results were adjusted for the potential confounders including body mass index (BMI) at baseline, net changes of BMI, physical activity, education status, and birth weight. CONCLUSION: Our results suggest that MHA increases the risk of developing MetS in female offspring in their later life. Screening of these female offspring for MetS may be recommended.

Bone Health in Women With Polycystic Ovary Syndrome: A Narrative Review.

Bone as an active connective and endocrine tissue is influenced by hormones, physical activity, inflammatory factors, minerals, dietary components, and body weight. Bone fractures are a major cause of decreased quality of life and mortality in humans. Polycystic ovary syndrome (PCOS), is one of the most common endocrine disorders in women of reproductive age worldwide. PCOS is associated with disturbances in androgen and estrogen levels, insulin resistance (IR), obesity, as well as low-grade chronic inflammation, and gut microbiota (GM) dysbiosis, all of which may negatively or positively affect bone metabolism. However, it has not yet been well clarified whether PCOS is bone-protective or bone-destructive. This study aimed to review the association between bone health and PCOS, and summarize its related factors. PubMed, Scopus, and Web of Science databases were searched to retrieve relevant English publications investigating the relationship between bone health and PCOS. Several disorders associated with PCOS can negatively or positively affect bone metabolism. Despite some positive effects of insulin, androgens, estrogens, and obesity on bone, IR, estrogen deficiency, low-grade chronic inflammation, and GM dysbiosis may adversely affect the bone metabolism in PCOS women. Studies comparing bone mineral density or bone metabolism and the risk of bone fractures in women with PCOS have controversial results. Further studies are required to understand the mechanisms underlying bone metabolism in PCOS subjects. Moreover, prospective studies are needed to estimate the risk of bone fractures and osteoporosis in PCOS subjects.

Follicle-Stimulating Hormone and Diabetes in Postmenopausal Women: A Systematic Review and Meta-Analysis.

CONTEXT: The co-occurrence of hormonal changes during menopause and the risk of cardio-metabolic disorders has been well studied. OBJECTIVE: We explored the association of circulating levels of follicle-stimulating hormone (FSH) with diabetes (DM) among postmenopausal women. METHOD: In this systematic review and meta-analysis, the search was performed in PubMed, Scopus, Web of Sciences, Epistemonikos, and Cochrane Library up to September 2023. Risk of bias was assessed by Newcastle-Ottawa Quality Assessment Scale. Pooled estimates of mean differences in FSH levels were compared between postmenopausal women with and without DM. Correlations between FSH and fasting blood glucose (FBG)/insulin/homeostatic model assessment for insulin resistance (HOMA-IR) as well as pooled effect sizes with their 95% CIs for risk of DM were calculated. RESULTS: In this study, 14 articles, including 7878 postmenopausal women, met eligibility criteria. Most of the included studies had a low/moderate risk of bias. Women with DM had significantly lower FSH levels than those without DM (standardized mean difference [SMD] -0.751 [95% CI, -1.129 to -.372], I2 = 82.46%, n = 1416). The pooled effect size for diabetes was 0.861 (95% CI, 0.740-1.001; I2 = 80.11%). The pooled risk estimate for DM based on the categorical FSH levels (high vs low) was (HR = 0.550; 95% CI, 0.356-0.850, I2 = 0). The significant inverse correlation was found between FSH levels and glycemic parameters: FBG (r= -0.285 [95% CI -0.441 to -0.113]; n = 1229), HOMA-IR (r = -0.241[-0.378 to -0.0924]; n = 1229) and insulin (r = -0.337 [-0.434 to -0.232]; n = 959)]. There were no statistically significant differences between estradiol levels among diabetic and nondiabetic groups; however, the SMD for luteinizing hormone was similar to that reported for FSH. CONCLUSION: The available data indicated an indirect association between FSH levels and glucose disturbances among postmenopausal women, notwithstanding heterogeneity among included studies, and the complexity of various influential factors needs to be considered. Further efforts should be made to clarify the underlying mechanisms.

Effects of Rosa damascena on reproductive improvement, metabolic parameters, liver function and insulin-like growth factor-1 gene expression in estradiol valerate induced polycystic ovarian syndrome in Wistar rats.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. The present study aimed to evaluate the effects of Rosa damascena (RD) extract in estradiol valerate (EV) induced polycystic ovary syndrome rats. METHODS: Adult female Wistar rats were divided into control (n = 12) and PCOS groups (n = 36). The PCOS model was induced using EV (4 mg/kg/day), which was confirmed in 6 rats in each control and PCOS group by observation of irregular estrous cycles in vaginal smears and ovarian multiple cystic. Then, the rest of the control group (n = 6) and PCOS rats (n = 30 in 5 divided groups) were treated orally for 28 days with metformin (MET) as a positive control (200 mg/kg/day) and RD extract (400, 800, and 1200 mg/kg/day, respectively). Body and ovary weights, biochemical and histological parameters, and expression of the IGF-1 gene were measured. RESULTS: Compared to the PCOS group, metformin and higher doses of RD extract (800 and 1200 mg/kg/day) significantly reduced BW, HOMA-IR, FBS, FINS, TG, LDL, TT, E2, LH, TC, and liver enzymes, and increased HDL and FSH levels. In addition, ovarian weight and CFs decreased, and the findings showed an increment in PFs, CLs, PAFs, AFs, and GFs. IGF-1 gene expression levels were significantly decreased (p < 0.001). CONCLUSION: RD extract seems to have the potential therapeutic effect of alleviating PCOS complications, and IGF-1 signaling may be involved in the beneficial effects of RD on PCOS.

Self-reported Male Infertility and Metabolic Disturbance: A Cross-Sectional Study.

Background: Male infertility is a growing health problem. It is proposed that infertility is associated with some metabolic abnormalities. Objectives: This study aimed to examine the prevalence of self-reported male infertility and related metabolic disturbances. Methods: This is a cross-sectional analysis of the Tehran Lipid and Glucose Study (TLGS). A total of 1526 males participated in the study. Logistic regression was used to examine metabolic factors associated with self-reported male infertility. Results: The total prevalence of self-reported male infertility was 6.42%. The mean (SD) body mass index (BMI) of participants among fertile and infertile males was 26.80 (3.93) and 26.92 (4.36), respectively. The majority of participants in both groups were in the age group of 40-50 years old. In the fully adjusted model, the odds of infertility were significantly increased by each unit increase in total cholesterol [TC; odds ratio (OR), 1.01; 95% CI, 1.01 - 1.01; P = 0.03] and hip circumference (HC; OR, 1.06; 95% CI, 1.00 - 1.12; P = 0.02), respectively. Conclusions: The prevalence of self-reported male infertility was 6.42%. Male infertility was positively associated with TC and HC, indicating that knowledge about these risks might assist health care professionals and governments in developing and executing measures to change the status quo.

The Prevalence of Polycystic Ovary Syndrome, Its Phenotypes and Cardio-Metabolic Features in a Community Sample of Iranian Population: Tehran Lipid and Glucose Study.

Objectives: The aim of the present study was to evaluate the prevalence of polycystic ovary syndrome (PCOS), its phenotypical and cardio-metabolic features in a community sample of the Iranian population in comparison to healthy eumenorrheic, non-hirsute women without polycystic ovaries. The second aim was to assess the cardio-metabolic characteristics of women who suffered from one criteria of PCOS compared to those healthy eumenorrheic, non-hirsute women. Methods: In this cross-sectional population-based study, a total of 1,960 eligible women, aged (18-45 years) were recruited from the Tehran-Lipid and Glucose-Study participants and were classified as the three groups of (i) women with PCOS by the Rotterdam criteria, (ii) non-PCOS women with one criteria of PCOS and (iii) healthy eumenorrheic, non-hirsute women without polycystic ovaries morphology (PCOM) as the control group. Further PCOS women were extended to four phenotypes of hyperandrogenism, oligo-anovulation, polycystic ovaries (phenotype A), hyperandrogenism, oligo/anovulation (phenotype B), hyperandrogenism, polycystic ovaries (phenotype C) and oligo-anovulation, polycystic ovaries (phenotype D). Cardio-metabolic profiles and the prevalence of comorbidities of metabolic syndrome (MetS) and lipid abnormalities were compared among these groups linear, and the median regression models adjusted for age and body mass index. Results: The prevalence of PCOS according to the diagnostic criteria of the NIH, Rotterdam and AE-PCOS Society were 13.6, 19.4, and 17.8, respectively. Among those who met the Rotterdam criteria, 23.9, 46.3, 21.6, and 8.2% had phenotypes A, B, C, and D, respectively. Among the remaining 1,580 women who did not fulfil the PCOS criteria, 108 (6.8%) suffered from only oligo/anovulation, 332 (21%) only hyperandrogenism/hyperandrogenemia, 159 (16.2%) only PCOM in ultrasound and 981 (62%) were healthy eumenorrheic, non-hirsute women without PCOM. The study revealed that some adiposity indices and lipid abnormalities in PCOS phenotypes with hyperandrogenism (A, B, and C) were worse than in healthy women. By contrast, women with phenotype D did not differ from the healthy ones in terms of adiposity and lipid abnormalities. However, the respective values for other cardio-metabolic profiles and MetS rates in different phenotypes of PCOS were similar to the healthy women. Only the prevalence of MetS in phenotype A was significantly higher than in the healthy women. There were no statistically significant differences between participants with one criteria of PCOS and healthy counterparts in terms of most adiposity indexes, cardio-metabolic factors, and comorbidity of MetS and its components. However, women with hyperandrogenism had a significantly higher level of the waist to height ratio (WHtR) and hypertriglyceridemia than their healthy counterparts. Conclusion: PCOS, mainly classical phenotypes A and B, are common among Iranian women of reproductive age. Women with PCOS who had androgen excess exhibited the worst lipid profile, and those who had full three criteria of the syndrome exhibited the higher rate of MetS. However, women with only ovulatory dysfunction and only PCOM had similar cardio-metabolic characteristics, compared to healthy subjects. These data suggest that routine screening for metabolic disturbances may be needed in the prevention of cardio-metabolic disorders in patients with more serious phenotypes of PCOS.

Maternal Exposure to D-galactose Reduces Ovarian Reserve in Female Rat Offspring Later in Life.

Background: Embryonic life is critical for the formation of ovaries in mammals, and the intrauterine environment may affect ovarian reserve. Objectives: The present study aimed to investigate the impact of prenatal D-galactose exposure on ovarian reserve in female rat offspring in their later lives. Methods: Ten pregnant Wistar rats were randomly divided into two groups. In one group, rats were fed with 35% D-galactose-enriched food from the third day to the end of pregnancy, and in the other group, rats were fed with a standard diet throughout pregnancy. Female offspring (prenatally galactose-exposed rats and non-exposed control rats) were examined in terms of hormonal levels [anti-Mullerian hormones (AMH), follicle-stimulating hormone (FSH), and estradiol (E2)] and ovarian histology at 45 - 50, 105 - 110, and 180 - 185 days of their age. Results: The number of primordial follicles significantly decreased time-dependently in prenatally galactose-exposed rats compared to controls (P-value = 0.002). In addition, decreases in AMH (3.25 vs. 7.5 ng/mL; P = 0.000) and E2 (7.9 vs. 19.5 pg/mL; P = 0.000) and increases in FSH (6.5 vs. 0.8 mIU/mL; P < 0.007) were observed in galactose-exposed rats compared to controls at 45 - 50 days of age. Conclusions: Prenatal exposure to D-galactose negatively affects ovarian reserve in female rats in their later lives. However, further investigation is needed to confirm our findings and explore underlying mechanisms.