Preconceptional maternal hyperandrogenism and metabolic syndrome risk in male offspring: a long-term population-based study.

PURPOSE: There is limited research on the effects of maternal hyperandrogenism (MHA) on cardiometabolic risk factors in male offspring. We aimed to compare the risk of metabolic syndrome (MetS) in sons of women with preconceptional hyperandrogenism (HA) to those of non-HA women in later life. METHODS: Using data obtained from the Tehran Lipid and Glucose Cohort Study, with an average of 20 years follow-up, 1913 sons were divided into two groups based on their MHA status, sons with MHA (n = 523) and sons without MHA (controls n = 1390). The study groups were monitored from the baseline until either the incidence of events, censoring, or the end of the study period, depending on which occurred first. Age-scaled unadjusted and adjusted Cox regression models were utilized to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in their sons. RESULTS: There was no significant association between MHA and HR of MetS in sons with MHA compared to controls, even after adjustment (unadjusted HR (95% CI) 0.94 (0.80-1.11), P = 0.5) and (adjusted HR (95% CI) 0.98 (0.81-1.18), P = 0.8). Sons with MHA showed a HR of 1.35 for developing high fasting blood sugar compared to controls (unadjusted HR (95% CI) 1.35 (1.01-1.81), P = 0.04), however, after adjustment this association did not remain significant (adjusted HR (95% CI) 1.25 (0.90-1.74), P = 0.1). CONCLUSION: The results suggest that preconceptional MHA doesn't increase the risk of developing MetS in sons in later life. According to this suggestion, preconceptional MHA may not have long-term metabolic consequences in male offspring.

Maternal androgen excess increases the risk of pre-diabetes mellitus in male offspring in later life: a long-term population-based follow-up study.

PURPOSE: Prenatal androgen exposure could be a source of early programming, leading to the development of cardiometabolic diseases in later life. In this study, we aimed to examine cardiometabolic disturbances in males exposed to maternal androgen excess during their prenatal life. METHODS: In this prospective population-based study, 409 male offspring with maternal hyperandrogenism (MHA), and 954 male offspring without MHA, as controls, were included. Both groups of male offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. Age-scaled unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association between MHA with pre-diabetes mellitus (Pre-DM), type 2 diabetes mellitus (T2DM), pre-hypertension (Pre-HTN), hypertension (HTN), dyslipidemia, overweight, and obesity in the offspring of both groups. Statistical analysis was performed using the STATA software package; the significance level was set at P < 0.05. RESULTS: A higher risk of Pre-DM (adjusted HR: 1.46 (1.20, 1.78)) was observed in male offspring with MHA after adjustment for potential confounders, including body mass index, education, and physical activity. However, no significant differences were observed in the risk of T2DM, Pre-HTN, HTN, dyslipidemia, overweight, and obesity in males with MHA compared to controls in both the unadjusted and adjusted models. CONCLUSION: Maternal androgen excess increases the risk of Pre-DM in male offspring in later life. More longitudinal studies with long enough follow-up are needed to clarify the effects of MHA on the cardiometabolic risk factors of male offspring in later life.

Maternal hyperandrogenism is associated with a higher risk of type 2 diabetes mellitus and overweight in adolescent and adult female offspring: a long-term population-based follow-up study.

PURPOSE: Adverse intrauterine environment may predispose offspring to cardio-metabolic dysfunction in later life. In this study, we aimed to investigate the effects of maternal hyperandrogenism (MH) on cardio-metabolic risk factors in female offspring in later life. METHODS: This prospective population-based study included 211 female offspring with MH and 757 female offspring without MH (controls). Both groups were followed from baseline to the date of incidence of events, censoring, or end of the study period, whichever came first. Age scaled unadjusted and adjusted cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association of MH with pre-diabetes (pre-DM), type 2 diabetes mellitus (T2DM), overweight and obesity in offspring of both groups. Statistical analysis was performed using the software package STATA; significance level was set at P < 0.05. RESULTS: This study revealed a higher risk of T2DM (unadjusted HR 2.67, 95% CI 1.33-5.36) and overweight (unadjusted HR 1.41, 95% CI 1.06-1.88) in female offspring with MH, compared to controls. Results remained unchanged after adjustment for potential confounders including body mass index, education, physical activity, mother's age at delivery, birth weight, and childhood obesity. However, no significant difference was observed in the risk of pre-DM and obesity in females with MH, compared to controls in both unadjusted and adjusted models. CONCLUSION: This pioneer study with a long-term follow-up demonstrated that MH increases the risk of developing T2DM and being overweight in female offspring in later life. Further long-term population-based studies are needed to confirm these findings.

The association between polycystic ovary syndrome, obesity, and the serum concentration of adipokines.

PURPOSE: This study aimed to investigate the interactive effect of polycystic ovary syndrome (PCOS) status and obesity status on the serum levels of adipokines. METHODS: In this comparative case-control cross-sectional study, 58 women with PCOS and 104 eumenorrheic non-hirsute women as the control group were recruited. They were further divided into two subgroups of overweight/obese and normal weight. The interactive effect of the PCOS status and obesity status on the circulating levels of adipokines was assessed using general linear model with the adjustment of age. RESULTS: A statistically significant negative interaction was reported between obesity status and PCOS status in the determination of serum adiponectin and resistin concentrations (effect size = -0.14, interaction P = 0.001, effect size = -0.15, P = 0.016). It indicated that adiponectin and resistin were significantly decreased in overweight/obese patients with PCOS compared with other subgroups. Statistically significant positive interactive effects were found between PCOS status obesity status and leptin (effect size = 0.321, interaction P = 0.036), indicating that the overweight/obese women with PCOS had the higher levels of leptin compared with the control group. Also, no interaction was reported between PCOS status and obesity status with regard to the serum levels of other adipokines. CONCLUSIONS: While no sufficient evidence is available with regard to the causal association between adipokines and PCOS, they may contribute to the development of PCOS and regarded as the novel biomarkers of PCOS.

Sexual function and hormonal profiles in women with and without polycystic ovary syndrome: a population-based study.

There is no consensus regarding the impact of polycystic ovary syndrome (PCOS) and its hormonal profile on sexual function of affected women; majority of data documented are not population based and there is a lack of studies investigating the association between hormonal profiles with sexual function in women with PCOS. We aimed to compare the sexual function of PCOS women with controls in a population-based study based on their hormonal profiles. In this cross-sectional study, sexual function (using the Female Sexual Function Index (FSFI) questionnaire) and hormonal profiles were determined in 63 PCOS subjects and 216 healthy women (controls); aged 18-45 years. A comparison of PCOS women and controls showed no statistically significant difference in total FSFI and each of its specific domain scores. There were significant positive correlations between dehydroepiandrosterone sulfate and total FSFI, orgasm and satisfaction domains in controls (r=0.156, r=0.206, r=0.275, respectively). No significant correlations between hormonal profiles and FSFI scores were found in the PCOS group, except for prolactin and orgasm (r=-0.250). In conclusion, sexual function did not differ between PCOS women and controls. High levels of androgens in women with PCOS were not associated with an improvement in sexual function.

Surgical menopause versus natural menopause and cardio-metabolic disturbances: A 12-year population-based cohort study.

PURPOSE: Menopausal status exposes women to increased risk of cardiovascular disease. This study was performed to compare the effect of menopausal types, including surgical and natural, on metabolic syndrome and other metabolic disorders 3 years before and after menopause. METHODS: Of 437 postmenopausal women, who participated in the Tehran Lipid and Glucose Study, 13 women with surgical menopause and 39 age-matched controls with natural menopause were selected. During the follow-up period, changes in metabolic and biochemical profiles were compared between surgical and natural menopause women. RESULTS: Odds of incidence of metabolic syndrome in surgical menopause women, compared to natural menopause women, was 9.7 (95 % CI 1.8-51.8). CONCLUSIONS: Metabolic disturbances after menopause are highly influenced by type of menopause and are more prevalent in those undergoing surgical menopause.

The impact of prenatal exposure to a single dose of testosterone on insulin resistance, glucose tolerance and lipid profile of female rat's offspring in adulthood.

PURPOSE: In our previous study, we introduced a rat model of polycystic ovary syndrome (PCOS) induced by prenatal exposure to a single dose of testosterone on embryonic day 20. In the current study, we aimed to investigate whether prenatal exposure to a single dose of testosterone could also induce metabolic disturbances, especially insulin resistance in adulthood (100-110 days of age) and also to make it as an appropriate rat model of PCOS (exhibiting both reproductive and metabolic disturbances with minimum morphological disorders in reproductive system) for further studies in PCOS. METHODS: Pregnant rats in the experimental group were subcutaneously injected with 5 mg free testosterone on the gestational day 20, while controls received only the solvent. Female offspring of both groups, prenatally androgenized (PNA) rats (PCOS models of rats) and controls were examined. RESULTS: Body weight measures showed significant increase in the PNA rats compared to controls on days 30, 45, 60 of age and in adulthood (P < 0.05). PNA rats showed insulin resistance compared to controls. Impaired glucose tolerance was not observed in the PNA rats compared to controls. There were no significant differences in lipid profile between the PNA and control rats (P > 0.05). CONCLUSION: Our study suggests that metabolic disturbances in PCOS and their severity during adult life probably depend on the particular time and levels of prenatal androgen exposure.