Impact of dehydroepiandrosterone sulfate and free androgen index on pregnancy and neonatal outcomes in PCOS patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder associated with infertility and pregnancy complications. The pathogenesis of PCOS and its impact on reproductive function may be influenced by the source of androgens, including testosterone, free androgen, dehydroepiandrosterone sulfate (DHEAS). However, the differential effects of these androgen on pregnancy and neonatal outcomes and the cut-off value of East Asian population with PCOS remain unclear. METHODS: A retrospective cohort study was conducted at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to November 2022, involving 636 cycles of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Subgroup analyses were performed using cut-off values of 6.4 for free androgen index (FAI), 9.5 µmol/L for DHEAS. Pregnancy and neonatal outcomes were compared between groups. Restricted cubic spline (RCS) was used to identify significant cut-off values affecting pregnancy. RESULTS: Higher FAI levels (> 6.4) were associated with decrease in clinical pregnancy rate (PR) (50.61% vs. 41.66%, p = 0.024), live birth rate (LBR) (42.42% vs. 32.35%, p = 0.011). When DHEAS levels exceeded 9.5 µmol/L, there was a significant decrease in clinical PR (51.27% vs. 42.73%, P = 0.039), LBR (42.73% vs. 32.73%, P = 0.012). Negative correlations were also observed between DHEAS levels and cumulative pregnancy rate (70.57% vs 56.62% p = 0.002) and cumulative live birth rate (CLBR) (59.35% vs 43.37%, p = 0.0007). Both FAI and DHEAS elevated is associated with the lowest clinical pregnancy rate (37.84%). Conversely, when solely FAI is elevated, the pregnancy rate increases to 52.38%, while an elevation in DHEAS alone is associated with a pregnancy rate of, both of which are lower than when neither FAI nor DHEAS are elevated (60.68%). The live birth rates exhibit a similar trend (30.00% vs 40.00% vs 41.83% vs 44.48%). RCS revealed a significant decrease in CPR and CLBR when DHEA levels exceeded 7.69 umol/L, while the cut-off value of FAI was 6.36 for CPR and CLBR. CONCLUSION: In conclusion, PCOS patients with biochemical hyperandrogenism show unsatisfactory clinical PR and CLBR when undergoing assisted reproductive technology (ART). This may be attributed to the influence of both adrenal-derived DHEAS and ovarian-derived FAI on the unfavorable pregnancy outcomes.

Metabolic disparities between obese and non-obese patients with polycystic ovary syndrome: implications for endometrial receptivity indicators.

OBJECTIVE: To investigate the differences in the metabolic indicators and sex hormones between obese and non-obese patients with polycystic ovary syndrome (PCOS), and their impacts on endometrial receptivity (ER). METHODS: We selected 255 individuals with PCOS, and categorized them into the obese groups, including the OP group (obese patients with PCOS) and the ON group (obese patients without PCOS), and selected 64 individuals who were categorized in the non-obese groups, namely, the control groups, which comprise the NP group (non-obese patients with PCOS) and the NN group(non-obese patients without PCOS). The one-way analysis of variance (ANOVA) and Mann-Whitney U tests were used to compare the metabolic indicators, and sex hormone-associated and ER-associated indicators between the groups. The correlation between the aforementioned clinical markers and ER was analyzed using the Pearson's correlation coefficient. RESULTS: (1) In comparison with the NP group, the OP group exhibited higher levels (p < .01) of free androgen index (FAI), anti-müllerian hormone (AMH), fasting insulin (FINS), insulin level within 60 min, 120 min, and 180 min-60minINS, 120minINS, and 180minINS, respectively, fasting blood glucose (FBG), blood glucose level within two hours (2hGlu), homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), waist-to-hip ratio (WHR), waist circumference, hip circumference, the ratio of the maximum blood flow velocity of the uterine artery during systole to the blood flow velocity of the uterine artery at the end of diastole (uterine artery S/D), and blood flow resistance index (RI) of the uterine artery. In comparison with the NP group, the OP group exhibited lower levels (p < .01) of sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), high molecular weight adiponectin (HMWA), and high-density lipoprotein cholesterol (HDL-C). (2) In the PCOS group, RI was significantly positively correlated with FAI, FINS, 120minINS, HOMA-IR, and WHR (p < .01), and significantly negatively correlated with SHBG, HDL-C, and HMWA (p < .01); uterine artery S/D was significantly positively correlated with FAI, FINS, 2hGlu, HOMA-IR, LDL-C, and WHR (p < .01), significantly positively correlated with 120minINS and FBG (p < .05), and significantly negatively correlated with SHBG and HMWA (p < .01). CONCLUSION: (1) The OP group exhibited obvious metabolic disorders and poor ER, which was manifested as low levels of SHBG and HMWA, and high levels of FAI, HOMA-IR, WHR, uterine artery S/D, and RI. (2) In patients with PCOS, there was a substantial correlation between ER-associated indicators RI and uterine artery S/D and FAI, FINS, 120minINS, HOMA-IR, WHR, SHBG, and HMWA.

Organophosphorus insecticides exposure and sex hormones in general U.S. population: A cross-sectional study.

BACKGROUND: Evidence showed organophosphorus (OPs) insecticide exposure is common in general population with endocrine-disrupting effects. However, the association between OPs metabolites and sex hormones remains unclear. OBJECTIVE: To investigate the association between OPs metabolites and sex hormones. METHODS: Data of 1438 participants from NHANES 2015-2016 was applied. Urinary OPs metabolites, dialkyl phosphates (DAPs), and serum sex hormones (total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG)) were measured. Free androgen index (FAI) and TT/E2 ratio were also calculated. The generalized linear regression model and restricted cubic spline (RCS) model were employed to evaluate the association and exposure-response curve of DAPs and sex hormones in males and females. The modulation effect of age on their associations in female participants was also explored. RESULTS: After adjusting for confounding factors, DETP was negatively associated with E2 (ß = -0.03; 95% CI: -0.05, -0.01) and FAI (ß = -0.03; 95% CI: -0.06, -0.001) in males. In females, all the four DAP metabolites (DMP, DEP, DMTP, and DETP) were negatively associated with FAI (DMP: ß = -0.06, 95% CI: -0.11, -0.01; DEP: ß = -0.06, 95% CI: -0.12, -0.01; DMTP: -0.05, 95% CI: -0.09, -0.02; DETP: -0.09, 95% CI: -0.14, -0.04). DETP was also found negatively associated with TT and TT/E2 ratio in females. The associations between DETP and TT, FAI, and TT/E2 ratio were modified by gender (Pinteraction<0.05). RCS analysis found these associations were in linear decreased exposure-response curves. For females of different age groups, the inverse associations of DETP with TT and FAI remained stable. Decreased FAI with DMP and DMTP was also found in females ≤50 years old. CONCLUSIONS: Our study indicates OPs metabolites had negative associations with androgen indicators, which was characterized as decreased FAI and E2 in males and decreased TT, FAI, and TT/E2 ratio in females, particularly among females ≤50 years old. Further studies are warranted in larger-scale populations.

Dehydroepiandrosterone sulfate/free androgen index ratio predicts a favorable metabolic profile in patients with polycystic ovary syndrome.

Potential effect of hyperandrogenemia on metabolic disturbances in polycystic ovary syndrome (PCOS) has always been a matter of interest. We analyzed the records of 125 patients with PCOS and 54 age-matched healthy women. All participants underwent biochemical and hormonal assessment and a 75 g oral glucose tolerance test was performed. PCOS and control groups were comparable in terms of age. Dehydroepiandrosterone sulfate/free androgen index (DHEAS/FAI) ratio was negatively correlated with body mass index (BMI) (p < .001), fasting glucose (p = .02), area under the curve (AUC) of glucose (p = .03), AUC of insulin (p = .001), homeostasis model assessment-estimated insulin resistance (HOMA-IR) (p < .001), and triglycerides (TG) (p = .009), and positively correlated with insulin sensitivity index (ISI) (p < .001) and high-density lipoprotein cholesterol (HDL-C) (p < .001) among PCOS patients. In logistic regression analysis, higher DHEAS/FAI ratio levels were associated with lower risk of low HDL-C [RR(95%CI); 0.97(0.95-0.98); p < .001] as well as atherogenic dyslipidemia (TG/HDL-C) [RR(95%CI); 0.97(0.94-0.99); p = .035] even after adjustment for BMI in the PCOS group. Androgens, DHEAS and FAI act differently on metabolic parameters. Our results demonstrate that high DHEA-S/FAI ratio levels are associated with a more favorable metabolic profile.

Comparison Of Free Androgen Index In Polycystic Ovary Syndrome And Non-Polycystic Ovary Syndrome Infertile Patients.

BACKGROUND: One of the leading causes of infertility in child bearing age females is polycystic ovary syndrome. It is characterized by altered hormonal profile causing androgen excess and insulin resistance which eventually leads to decreased ovulation rate. METHODS: This was a crosssectional study that included 40 polycystic ovary syndrome (PCOS) patients and 40 infertility patients that did not have polycystic ovary syndrome determined by sonography and clinical features through quota sampling technique. Serum Total Testosterone and Sex Hormone Binding Globulin Levels were assayed. Using these two parameters, Free Androgen Index was calculated. Body Mass Index and central obesity was also determined. RESULTS: Total Testosterone, Free Androgen Index and Body Mass Index were raised in PCOS group as indicated by p-value <0.05. Hirsutism was present in PCOS group (p-value <0.05). Sex Hormone Binding Globulin Levels were decreased in PCOS patients (p-value <0.05) but were within the lower half of normal range. CONCLUSIONS: Levels of Sex Hormone Binding Globulin were decreased in PCOS cases and Free Androgen Index can help in better determining hyperandrogenaemia than total testosterone alone.

Correlation of biochemical markers and clinical signs of hyperandrogenism in women with polycystic ovary syndrome (PCOS) and women with non-classic congenital adrenal hyperplasia (NCAH).

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of hyperandrogenism in women. Non-classic congenital adrenal hyperplasia (NCAH) is very close to PCOS. The diagnosis of hyperandrogenism is not based on the finding of decreased or increased levels of a single hormone. OBJECTIVE: In our paper, we are going to test correlation between clinical signs and biochemical markers of hyperandrogenism. MATERIALS AND METHODS: In this prospective study, we calculated free testosterone (cFT), bioavailable testosterone (cBT), free androgen index (FAI), free estrogen index (FEI), total testosterone (TT), sex-hormone binding globulin (SHBG), estradiol (E2), dehydroepiandrosterone-sulfat (DHEA-S), 17α -hydroxyprogesterone (17α -OHP), prolactin (P), C-peptid and homeostasis model assessment for insulin resistance (Homa-IR) were measured in two groups of young untreated women with PCOS and NCAH. RESULTS: In our research, we did not find any significant differences between PCOS and NCAH groups by age, hormonal and calculated parameters of androgens. Waist to hip ratio (WHP) and body mass index (BMI) values were higher in the group of patients with PCOS than NCAH group. But in all patients we found positive correlation between hirsutism score and FAI, cFT, cBT, as well as we found negative correlation between hirsutism score and SHBG. We also tested hormonal and calculated parameters of androgens between PCOS patients by upper body and lower body obesity, but we did not find any significant differences. There was not any difference by the hirsutism score in these groups either. CONCLUSION: In our research we found that the calculated values of cFT, cBT and FAI are helpful for determinate hirsutism score in all hirsute patients, despite of ovarian or adrenal hyperandrogenemia.