Establishment and validation of a 5-factor diagnostic model for obstructive and non-obstructive azoospermia based on routine clinical parameters.

Azoospermia is a serious leading male-factor cause of infertility in couples of childbearing age. The two main azoospermia types, obstructive (OA) and non-obstructive (NOA) azoospermia, differ in their treatment approaches. Therefore, their clinical diagnosis is extremely important, requiring an accurate, efficient, and easy-to-use diagnostic model. This retrospective observational study included 707 patients with azoospermia treated between 2017 and 2021, 498 with OA, and 209 with NOA. Hematological and seminal plasma parameters, hormone levels, and testicular volume were used in logistic regression analysis to evaluate and compare their diagnostic performance, results showed that the optimal diagnostic model is constructed by five variables including semen volume, semen pH, seminal plasma neutral α-glucosidase activity, follicle-stimulating hormone in the serum, and testicular volume, compared with follicle-stimulating hormone-based and testicular volume-based models. The 5-factor diagnostic model had an accuracy of 90.4%, sensitivity of 96.4%, positive predictive value of 90.6%, negative predictive value of 89.8%, and area under the curve of 0.931, all higher than in the other two models. However, its specificity (76.1%) was slightly lower than in the other models. Meantime, the internal 5-fold cross-validation results indicated that the 5-factor diagnostic model had a good clinical application value. This study established an accurate, efficient, and relatively accessible 5-factor diagnostic model for OA and NOA, providing a reference for clinical decision-making when selecting an appropriate treatment.

Relationship between circulating FSH levels and body composition and bone health in patients with prostate cancer who undergo androgen deprivation therapy: The BLADE study.

Background: Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT. Methods: Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, t-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated. Results: At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (r = 0.36) and legs (r = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM (r = 0.52, p = 0.006), fat mass at arms (r = 0.54, p = 0.004), and fat mass at trunk (r = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed (r = -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation. Conclusions: FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT. Funding: This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript. Clinical trial number: clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.

Treatments given to cancer patients can cause negative side effects. For example, a treatment known as androgen deprivation therapy ­ which is used to reduce male sex hormone levels in prostate cancer patients ­ can lead to increased body fat percentage and decreased bone density. These adverse effects can have further negative impacts on patient health, such as increasing the risk of cardiovascular disease and fractures from falls from standing height or less, respectively. Understanding how androgen deprivation therapy contributes to these negative side effects may help clinicians better manage care and outcomes for patients with prostate cancer. Follicle stimulating hormone (or FSH for short) has roles in male and female reproduction but has also been linked to changes in body composition. For example, elevated FSH levels are associated with higher total fat body mass in post-menopausal women. While androgen deprivation therapy is known to alter FSH blood levels, the impact of this change in prostate cancer patients was not well understood. To investigate the effect of androgen deprivation therapy on FSH levels and body composition, Bergamini et al. used X-ray technology to measure total fat body mass in prostate cancer patients before and after undergoing 12 months of androgen deprivation therapy. The findings showed that patient FSH blood levels significantly decreased after 12 months of treatment. Higher FSH blood levels strongly correlated with increased total fat body mass after 12 months of treatment. The findings of this clinical trial suggest that FSH blood levels impact the body composition of patients undergoing androgen deprivation therapy. As a result, FSH blood levels may be a suitable biomarker for identifying patients that are more likely to develop obesity and are therefore at greater risk of complications such as cardiovascular disease.

Association of lipid profile and obesity in patients with polycystic ovary syndrome.

Objective. Abnormal lipid profile and obesity increase the risk of polycystic ovary syndrome (PCOS). PCOS patients may have a greater risk of infertility, metabolic syndrome (MetS) and cardiovascular disease (CVD) due to abnormal lipid profile and obesity. The aim of the study was to find the association between abnormal lipid profile and obesity in patients with PCOS. Methods. In this case-control study, a total of 102 female subjects (51 diagnosed PCOS and 51 age-matched healthy controls) were enrolled, aged between 20-40 years. Biochemical parameters such as total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), very low-density lipoprotein-cholesterol (VLDL-C), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were estimated. Anthropometric parameters such as body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were recorded. A p<0.05 was considered statistically significant. Results. Mean of BMI, WC, WHR, LH, FSH, TC, TG, LDL-C, and VLDL-C was found significantly elevated in patients with PCOS as compared to controls (p<0.01). However, the mean of HDL-C was found significantly reduced in patients with PCOS as compared to controls (p<0.01). BMI has shown a significant positive correlation with WC (r=0.562, p<0.01) and WHR (r=0.580, p<0.01) among PCOS patients. LH has shown a significant positive correlation with FSH (r=0.572, p<0.01) among PCOS patients. TC has shown a significant positive correlation with TG (r=0.687, p<0.01), LDL-C (r=0.917, p<0.01), and VLDL-C (r=0.726, p<0.01) among PCOS patients. Conclusion. The results showed that abnormal lipid profile and obesity have a significant association with PCOS patients. Regular monitoring and treatment of PCOS patients are required to reduce the risk of infertility, MetS, and CVD.

Serum gonadal hormones levels and hypogonadism in ART naïve newly diagnosed HIV infected adult males in Mwanza, Tanzania.

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is an endemic chronic disease which is characterized with progressive depletion of CD4 T cells and increased susceptibility to opportunistic infections. Previous studies have associated HIV infection with increased hypogonadism. However, the prevalence of hypogonadism remained poorly defined and widely ranging in various studies. This study aims to evaluate the serum gonadal hormonal levels and hypogonadism in antiretroviral therapy (ART) naïve newly diagnosed HIV infected-males in Mwanza, Tanzania. METHODS: This was a comparison study involving 81 ART naïve newly diagnosed HIV-infected adult males as study group and 81 apparently healthy HIV-negative males as comparison group. The participants in the study group and comparison group were matched by body mass index and age. Serum hormones [Total testosterone (TT), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E) were estimated. Serum testosterone < 300 ng/dl, or testosterone > 300 ng/dl with high LH and FSH (compensatory hypogonadism) were taken as markers of hypogonadism. Data were analyzed using STATA version 15. RESULTS: The median serum testosterone level among ART naïve newly diagnosed HIV-infected adult males was significantly lower as compared to their comparison group (447 [259-534] versus 517 [396-605]; p = 0.0074) and shown to decrease with decreasing CD4 level. The median [IQR] serum FSH level among ART naïve newly diagnosed HIV-infected adult males was significantly higher than among their comparison group (3.8 [2.1-6.5] versus 2.6 [1.8-4.2]; p = 0.0086). The differences in serum LH and Estradiol were not statistically significant. Furthermore, the proportion of hypogonadism was significantly higher among ART naïve newly diagnosed HIV-infected adult males than in their comparison group (37.0% [30/81] versus 14.8% [12/81]; p = 0.0006). Out of these 30, 24 HIV-infected males had secondary hypogonadism, one had primary, and the remaining five had compensatory hypogonadism. CONCLUSION: Serum testosterone was lower and follicle stimulating hormone was higher among ART naïve HIV-infected males as compared to the HIV negative controls. Hypogonadism, mainly secondary, is common endocrine abnormality among ART naïve HIV-infected male patients in this study. HIV is associated with variations in gonadal hormones which may lead to sexual dysfunction in infected individuals.

The role of anti-Mullerian hormone and other correlates in patients with polycystic ovary syndrome.

BACKGROUND: Anti-Müllerian hormone (AMH) has recently emerged as a promising biomarker for the detection of polycystic ovarian morphology. In polycystic ovary syndrome (PCOS), an elevated level of AMH has been suggested to add value to the Rotterdam criteria in cases of diagnostic uncertainty. In this study, we evaluated the correlation between AMH and PCOS, and the potential role of AMH in PCOS diagnosis. METHODS: A case-control study was performed on a total of 200 females, 100 of which were diagnosed with PCOS as per Rotterdam revised criteria (2003) and 100 as the control (non-PCOS group). Patient medical records were therefore retrieved for clinical, biochemical and ultrasound markers for PCOS diagnosis. Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and multivariate linear regression models were applied to analyze our data. RESULTS: Mean serum levels of LH and AMH, and LH/FSH ratio were significantly different between compared groups. In the PCOS group, the mean serum AMH level was 6.78 ng/mL and LH/FSH ratio was 1.53 while those of controls were 2.73 ng/mL and 0.53, respectively (p < .001). The most suitable compromise between 81% specificity and 79% sensitivity was obtained with a cutoff value of 3.75 ng/mL (26.78 pmol/L) serum AMH concentration for PCOS prediction, with an AUROC curve of 0.9691. CONCLUSION: Serum AMH cutoff level of 3.75 ng/mL was identified as a convenient gauge for the prediction of PCOS and an adjuvant to the Rotterdam criteria.

Follicle-stimulating hormone is negatively associated with nonalcoholic fatty liver disease in a Chinese elderly population: a retrospective observational study.

BACKGROUND: Several studies have explored the connection between follicle-stimulating hormone (FSH) and nonalcoholic fatty liver disease (NAFLD). However, the impact of FSH elevation on NAFLD remains a topic of debate. Hence, this investigation aimed to evaluate the potential correlation between FSH levels and NAFLD in the aging population. METHODS: This was a retrospective observational cross-sectional study between July 2017 and August 2018 in our hospital. We used data obtained from 455 patients over 60 years old. Anthropometrics and laboratory tests were performed for each patient. NAFLD was diagnosed by sonographic features and the fatty liver index (LFI). RESULTS: Of the 455 patients, 200 (43.96%) had NAFLD on their ultrasound and 169 (37.14%) had NAFLD according to the LFI. An intraclass correlation coefficient of the two methods was 80.4% (P < 0.001). People with NAFLD on their ultrasound showed lower FSH levels (52.68 vs. 61.39 IU/L) and more unfavorable metabolic profiles. FSH was negatively correlated with age, alanine aminotransferase, estradiol, testosterone, systolic blood pressure, waist, body mass index, fasting blood glucose, postload plasma glucose and positive associated with total cholesterol, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol by Spearman correlation analysis (all P < 0.05). By controlling for all confounding factors, the odds ratios (OR) of FSH for NAFLD were determined in elderly individuals, both men and women, aged 60-70 years and over 70 years. These ORs were found to be 0.937, 0.982, 0.983, and 0.973, respectively, with corresponding 95% confidence intervals (CI) of 0.892-0.984 (P = 0.009), 0.971-0.993 (P = 0.002), 0.967-0.999 (P = 0.033), and 0.958-0.989 (P = 0.001). In addition, our findings demonstrated no significant correlation between FSH and advanced fibrosis when adjusting for potential covariates. The OR for advanced fibrosis was 0.979 (95% CI, 0.938-1.022, P = 0.339). Additionally, ROC curve analysis showed an optimal cut-off value of 66.91 for women and 15.25 for men for NAFLD diagnosis. CONCLUSIONS: There was an inverse relationship observed between levels of FSH in the blood serum and NAFLD in the elderly population. These findings suggest that reduced FSH levels might serve as a potential risk factor or biomarker for NAFLD in the elderly.

Serum organophosphate flame retardants and plasticizers in Chinese females of childbearing age: Association with serum reproductive and thyroid hormones.

Organophosphate flame retardants (OPFRs) are extensively used as flame retardants and plasticizers, but their endocrine disrupting potentials have raised concerns. However, the impacts of OPFR exposures on reproductive and thyroid hormones in females remains unclear. In this study, serum concentrations of OPFRs were investigated, and levels of reproductive and thyroid hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, anti-Müllerian hormone, prolactin (PRL), testosterone (T), and thyroid stimulating hormone, were analyzed in childbearing-age females undergoing in-vitro fertilization treatment from Tianjin, a coastal city in China (n = 319). Tris (2-chloroethyl) phosphate (TCEP) was the predominant OPFR, with a median concentration of 0.33 ng/mL and a detection frequency of 96.6%. In the whole population, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP) were positively associated with T (p < 0.05), while triethyl phosphate (TEP) was negatively associated with LH (p < 0.05) and LH/FSH (p < 0.01). Particularly, TCIPP was negatively associated with PRL in the younger subgroup (age≤30, p < 0.05). Moreover, TCIPP was negatively associated with diagnostic antral follicle counting (AFC) in the mediation analysis by a dominating direct effect (p < 0.01). In conclusion, serum levels of OPFRs were significantly associated with reproductive and thyroid hormone levels and a risk of decreased ovarian reserve in childbearing-age females, with age and body mass index being significant influencing factors.

The serum follicle stimulating hormone-to-luteinizing hormone ratios can predict assisted reproductive technology outcomes in women undergoing gonadotropin releasing hormone antagonist protocol.

Background: The basal follicle stimulating hormone (FSH)/luteinizing hormone (LH) ratio is a useful predictor of ovarian response. In this study, we investigated whether the FSH/LH ratios during the entire controlled ovarian stimulation (COS) can be used as effective predictors of outcomes in women undergoing in vitro fertilization (IVF) treatment using the gonadotropin releasing hormone antagonist (GnRH-ant) protocol. Methods: A total of 1,681 women undergoing their first GnRH-ant protocol were enrolled in this retrospective cohort study. A Poisson regression model was used to analyze the association between the FSH/LH ratios during COS and embryological outcomes. Receiver operating characteristic analysis was performed to determine the optimal cutoff values for poor responders (≤ 5 oocytes) or poor reproductive potential (≤ 3 available embryos). A nomogram model was constructed to provide a tool for predicting the cycle outcomes of individual IVF treatments. Results: The FSH/LH ratios (at the basal day, stimulation day 6 (SD6) and trigger day) were significantly correlated with the embryological outcomes. The basal FSH/LH ratio was the most reliable predictor of poor responders with a cutoff value of 1.875 (area under the curve (AUC) = 72.3%, P < 0.05), or of poor reproductive potential with a cutoff value of 2.515 (AUC = 66.3%, P < 0.05). The SD6 FSH/LH ratio predicted poor reproductive potential with a cutoff value of 4.14 (AUC = 63.8%, P < 0.05). The trigger day FSH/LH ratio predicted poor responders with a cutoff value of 9.665 (AUC = 63.1%, P < 0.05). The basal FSH/LH ratio, combined with the SD6 and trigger day FSH/LH ratios, slightly increased these AUC values and improved the prediction sensitivity. The nomogram provides a reliable model with which to assess the risk of poor response or poor reproductive potential directly based on the combined indicators. Conclusions: FSH/LH ratios are useful predictors of poor ovarian response or reproductive potential throughout the entire COS with the GnRH antagonist protocol. Our findings also provide insights into the potential for LH supplementation and regimen adjustment during COS to achieve improved outcomes.

The diagnostic value of transvaginal color Doppler ultrasonography plus serum ß-HCG dynamic monitoring in intrauterine residue after medical abortion.

To probe the diagnostic value of transvaginal color Doppler ultrasonography plus serum ß-human chorionic gonadotropin (ß-HCG) dynamic monitoring in intrauterine residue after medical abortion.In total, 200 pregnant women undergoing medical abortion in our institution from January 2017 to December 2019 were picked, and assigned to either group A (n = 75, with residue) or group B (n = 125, without residue). We detected serum ß-HCG, progesterone (P), follicle stimulating estrogen (FSH) levels and ultrasonic indicators endometrial thickness (ET), peak systolic velocity (PSV), resistance index (RI) values, dissected correlation of indicators using logistic linear regression analysis, and prospected the diagnostic value of relevant indicators in intrauterine residue after medical abortion utilizingreceiver operating characteristic curve.At 7 days after abortion (T3), total vaginal bleeding and visual analogue scalescore in group A were saliently higher in contrast to group B ( P < .05). At 72 hours after abortion (T2) and T3, serum ß-HCG, P and FSH levels declined strikingly in both groups, but group B held plainly higher decrease rate than group A ( P HC.05). At T3, ET and PSV levels in both groups considerably waned, whereas RI levels notedly waxed, and group B owned markedly higher decrease/increase than group A ( P wa.05). At T3, serum ß-HCG in group A possessed positive association with serum P, FSH, intrauterine ET, PSV levels separately ( P HC.05), whereas negative link with RI levels ( P , .05). The specificity and sensitivity of ß-HCG, P, FSH, ß-HCG/ET, ß-HCG/PSV and ß-HCG/RI in the diagnosis of intrauterine residue after medical abortion were high ( P < .05).Serum ß-HCG dynamic monitoring plus transvaginal color Doppler ultrasonography is of great value in diagnosing intrauterine residue after medical abortion. Serum ß-HCG, P, FSH levels can be combined with the results of intrauterine ET, PSV, RI values, so as to boost the diagnostic accuracy of the intrauterine residue after medical abortion.

The effects of different physiologic concentrations of prolactin in association with reproductive hormones on the incidence of type 2 diabetes mellitus in men: Tehran Lipid and Glucose Study.

BACKGROUND: Data is inconsistent and, for the most part, not sufficient to demonstrate the association between serum Prolactin (PRL) concentration within the physiologic range and the incidence rate of type 2 Diabetes Mellitus (DM) among men. Moreover, since both PRL and type 2 DM are associated with reproductive hormones, investigating these hormones might improve our understanding of how PRL might impose its effect on the incidence rate of type 2 DM. METHODS: For the present study, 652 eligible men aged 29-70 with a normal baseline PRL concentration were selected from the Tehran Lipid and Glucose Study (TLGS). Participants were sub-classified into three groups (tertiles) according to the serum concentration of PRL and were followed for 15.8 years. The incidence of type 2 DM and PRL, LH, FSH, testosterone, and AMH concentrations were measured. The effect of hormonal variables on the incidence of type 2 DM was estimated using the log-binomial model, adjusted for major confounding factors. The correlations between PRL and the indicators of glucose and lipid metabolism and other hormonal variables were also explored. RESULTS: In the unadjusted model, PRL was not significantly associated with the incidence rate of type 2 DM (RR = 0.98, 95% CI: 0.94 - 1.03). After adjusting for potential confounders, the inverse effect of AMH on the incidence rate of type 2 DM was the only significant association. The analyses also indicated a significant positive association between PRL and LH/FSH ratio (r = 0.1, P = 0.01). CONCLUSION: No significant association was found between serum PRL concentrations within the physiologic range and the incidence rate of type 2 diabetes mellitus among middle-aged men. Men with higher concentrations of PRL within the physiologic range tended to show higher levels of LH and LH/FSH. AMH was the only variable significantly linked to the incidence rate of type 2 DM in men.

[Lycium barbarum polysaccharides regulate AMPK/Sirt autophagy pathway to delay D-gal-induced premature ovarian failure].

This study aims to explore the molecular mechanism of Lycium barbarum polysaccharides(LBP) in alleviating premature ovarian failure(POF) in mice via the 5'-adenosine monophosphate activated protein kinase(AMPK)/silent information regulator 1(Sirt1) signaling pathway. The POF mouse model was established by D-galactose(D-gal) injection at the back. Six groups were set up, including a normal control group, a model group, a LBP group, a 3-MA(autophagy inhibitor 3-methyladenine) group, an AMPK inhibitor group, and a LBPAMPK inhibitor group, with 15 mice in each group. After 28 continuous days of administration, enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of sex hormones [estradiol(E_2), luteinizing hormone(LH), and follicle-stimulating hormone(FSH)] in serum. The ovarian mass coefficient was measured. Senescence-associated ß-Galactosidase(SA-ß-Gal) staining and hematoxylin-eosin(HE) staining were performed for observing the state of ovarian senescence and the morphological changes of the ovary. Immunohistochemical method was used to measure the expression of the autophagy marker LC3-Ⅱ in ovarian tissue. Western blot was employed to measure the expression levels of the senescence marker p16~(INK4 a), autophagy markers(LC3-Ⅱ and Beclin-1), the autophagy substrate p62, lysosome-associated membrane protein 2(LAMP2), and the proteins in the AMPK/Sirt1 pathway and mammalian target of rapamycin complex 1(mTORC1)/UNC-51-like kinase 1 Ser757 site(Ulk1 Ser757) pathway. Compared with the normal control group, the modeling of POF decreased the ovarian granulosa cells and follicles, led to the ovarian aging and severe sex hormone secretion disorders, weakened ovarian autophagy activity, and down-regulated the expression of proteins in the AMPK/Sirt1 pathway(P<0.05). Compared with the model group, the treatment with LBP increased ovarian granulosa cells and follicles, alleviated aging and sex hormone disorders, increased autophagy activity, and activated the AMPK/Sirt1 pathway(P<0.05). Both 3-MA and AMPK inhibitor can inhibit autophagy and aggravate ovarian damage and aging in mice. AMPK inhibitor can partially attenuate the role of LBP in promoting autophagy activation and alleviating aging and ovarian tissue damage(P<0.05). LBP can alleviate the symptoms of POF induced by D-gal by promoting the activation of AMPK/Sirt1 pathway.

Does COVID-19 cause testicular damage? A cross-sectional study comparing hormonal parameters.

OBJECTIVE: We aimed to predict the potential testicular damage of COVID-19 by comparing the hormones FSH, LH, and TT before COVID-19 with values measured after COVID-19. PATIENTS AND METHODS: A total of 348 patients - who were followed up in our urology clinic for varicocele, premature ejaculation, erectile dysfunction and infertility, had FSH, LH and TT levels measured one year before COVID-19 and were positive for COVID-19 after a Polymerase Chain Reaction (RT-PCR) tests - were included in the study. Presence of pneumonia compatible with COVID-19, hospitalization in the intensive care unit and FSH, LH and TT values before and after COVID-19 were recorded, along with lung computed tomography (CT). RESULTS: The post-COVID-19 LH value (9.72±3.27 mIU/mL) of the patients was significantly higher than the pre-COVID-19 LH value (5.72±2.50 mIU/mL) (p<0.001). The post-COVID-19 TT (253.85±88.03 ng/dl) value was significantly lower than the pre-COVID-19 TT value (351.08±106.19 ng/dl) (p<.001). In addition, while there was a mean decrease of 127.8 ng/dl in TT level in patients with pneumonia, a decrease of 39.03 ng/dl was observed in patients without pneumonia (p<.001). CONCLUSIONS: COVID-19 may cause an increase in serum LH levels while decreasing TT levels. Additionally, those with COVID-19 pneumonia may experience a greater decrease in serum TT levels than those with COVID-19 without pneumonia.

Transcription factor GATA2 may potentiate follicle-stimulating hormone production in mice via induction of the BMP antagonist gremlin in gonadotrope cells.

Mammalian reproduction depends on the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription factor GATA2 was previously implicated in FSH production in male mice; however, its mechanisms of action and role in females were not determined. To directly address GATA2 function in gonadotropes, we generated and analyzed gonadotrope-specific Gata2 KO mice using the Cre-lox system. We found that while conditional KO (cKO) males exhibited ∼50% reductions in serum FSH levels and pituitary FSHß subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. In addition, RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. We show Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Furthermore, Gata2, Grem1, and Fshb mRNA levels were significantly higher in the pituitaries of WT males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Finally, we found that recombinant gremlin stimulated Fshb expression in pituitary cultures from WT mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, facilitating induction of Fshb transcription by activins or related ligands.

High Follicle-Stimulating Hormone Level Associated With Risk of Rheumatoid Arthritis and Disease Activity.

Background: The prevalence of rheumatoid arthritis (RA) has significant gender and age difference. The peak age of RA is consistent with the age of menopause, which is accompanied by a sharp increase in serum follicle-stimulating hormone (FSH) level. This study aims to identify the FSH levels in female RA patients and the relationship with diseases activity. Methods: In total, 79 female RA patients and 50 age-matched controls were included in our study. Serum sex hormones levels were measured using chemiluminescence. RA patients were grouped by FSH quartile. Disease activity and inflammatory marks were analyzed among groups. Results: Lower sex hormones and higher gonadotropin were found in RA patients. Serum FSH level was significantly higher in RA patients than in the age-match controls (57.58 ± 15.94 vs. 43.11 ± 19.46, p=0.025). Even after adjusting for age (OR: 1.071; 95%CI: 1.006-1.139; p = 0.031), luteinizing hormone (LH), estradiol (E), and testosterone (T) OR: 1.066; 95%CI: 1.003-1.133; p = 0.039), the OR were still more than one. RA patients in the higher quartiles had higher ESR, DAS28-ESR and DAS28-CRP (p<0.05) than the lowest quartile. Besides, menopause age was significantly related with onset age in post-menopause RA patients (r = 0.432, p =0.008). Conclusion: High FSH appears to be a risk factor for RA and is positively associated with their disease activity. Early menopause might be an essential factor of RA.

Effects of Different Ovulation Induction Regimens on Sex Hormone Levels and Serum CTRP3 and CTRP15 Levels in Patients with Polycystic Ovary Syndrome (PCOS).

Objective: A retrospective cohort study aimed to explore the effects of different ovulation induction regimens on the levels of sex hormones and serum C1q/TNF-related protein-3 (CTRP3) and C1q/TNF-related protein-15 (CTRP15) in patients with PCOS. Methods: A total of 100 patients with PCOS treated in the department of gynecology and obstetrics from February 2019 to April 2021 in our hospital were enrolled. The patients were arbitrarily assigned into control group and study group. The treatment effect, pregnancy rate, ovulation rate, follicle size, thickness of endometrium, number of mature follicles and ovulation, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), serum CTRP3, CTRP15 and menstrual score were compared. Results: There exhibited no statistical difference in baseline clinical data between the two kinds of patients. The therapeutic effects were compared, the effective rate was 98.00% in the study group, 13 cases in the control group, 20 cases in the effective group and 7 cases in the control group, and the effective rate was 86.00%. The effective rate in the study group was higher (P <0.05). The size of follicles and the thickness of endometrium in the two groups were compared before and after intervention. There exhibited no significant difference in the size of follicles and the thickness of endometrium before and after intervention (P >0.05). The size of follicles and the thickness of endometrium in the study group were significantly higher (P <0.05). The size of follicles and the thickness of endometrium in the study group were significantly higher (P <0.05). There exhibited no significant difference in the number of mature follicles and ovulation before and after intervention (P >0.05). After intervention, the number of mature follicles and ovulation in the two groups increased. The number of mature follicles and ovulation in the study group were (4.76 ± 0.90) and (4.48 ± 0.73), respectively, which were higher compared to the control group (2.45 ± 0.86) and (2.82 ± 0.84), respectively (P <0.05). The levels of serum LH, FSH, E2 and T were not significantly different before and after intervention. After the intervention of different ways of ovulation induction, the levels of serum LH, FSH, E2 and T in the two groups continued to decrease, and the levels of the above sex hormones in the study group were significantly lower (P <0.05). The menstrual score and the levels of serum CTRP3 and CTRP15 were compared before and after intervention. After intervention, the menstrual score of patients in both groups decreased, and the menstrual score of the study group was lower. In addition, the levels of serum CTRP3 and CTRP15 in the two groups decreased after intervention. Compared with the control group, the levels of CTRP3 and CTRP15 in the study group were lower after intervention (P <0.05). The ovulation rate and pregnancy rate of the two groups were compared. In the study group, there were 45 ovulation cases, the ovulation rate was 90.00% (45/50), the pregnancy rate was 33 cases, the pregnancy rate was 66.00% (33/50), and the ovulation rate in the control group was 31 cases, the ovulation rate was 62.00% (31/50), the pregnancy rate was 20 cases, and the pregnancy rate was 40.00% (20/50). The ovulation rate and pregnancy rate in the study group were higher (P <0.05). Conclusion: Different ovulation induction regimens have different effects on the levels of sex hormones and serum CTRP3 and CTRP15 in patients with PCOS. Long-acting follicular phase regimens can effectively promote the therapeutic effect of patients and increase the ovulation rate and pregnancy rate. In addition, it can also reduce the levels of serum LH, follicle stimulating FSH, E2 and testosterone T, and help to promote the levels of serum CTRP3 and CTRP15, which is worth popularizing and applying in clinic.

Serum Follicle-Stimulating Hormone and 5-Year Change in Adiposity in Healthy Postmenopausal Women.

CONTEXT: Evidence from animal studies suggests that the gradual rise in follicle-stimulating hormone (FSH) during reproductive senescence may contribute to the change in adiposity distribution characteristic of menopause. The potential independent role the interrelationships of FSH and estradiol (E2) may play in postmenopausal adiposity changes are not well studied. OBJECTIVE: Our objective was to evaluate the associations of FSH and dual x-ray absorptiometry (DXA)-derived adiposity measures, with consideration of estradiol and postmenopausal hormone therapy use. METHODS: In a sample of 667 postmenopausal women from the Women's Health Initiative Buffalo OsteoPerio Ancillary Study, we studied the associations of serum FSH and E2 levels with dual x-ray absorptiometry (DXA)-derived adiposity measures via cross-sectional and longitudinal analyses (5-year follow-up). RESULTS: In cross-sectional analyses, FSH levels were inversely associated with all measures of adiposity in models adjusted for age, years since menopause, smoking status, pack-years, and hormone therapy (HT) use; these associations were not influenced by adjustment for serum E2. In longitudinal analyses, the subset of women who discontinued HT over follow-up (n = 242) experienced the largest increase in FSH (+33.9 mIU/mL) and decrease in E2 (-44.3 pg/mL) and gains in all adiposity measures in unadjusted analyses. In adjusted analyses, an increase in FSH was associated with a gain in percentage of total body fat, total body fat mass, and subcutaneous adipose tissue (SAT). CONCLUSION: While cross-sectional findings suggest that FSH is inversely associated with adiposity, our longitudinal findings suggest that greater increases in FSH were associated with greater increases in percentage of total body fat, total body fat mass, and SAT. Future studies are needed to provide additional insight into FSH-adiposity mechanisms in larger samples.

Per- and polyfluoroalkyl substances (PFAS) and male reproductive function in young adulthood; a cross-sectional study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a large family of persistent industrial chemicals with endocrine disrupting properties. OBJECTIVES: To examine biomarkers of reproductive function in young adult males according to current environmental exposure to single and combined PFAS. METHODS: The study population consisted of young men (n = 1041, age 18-21) from the Fetal Programming of Semen Quality (FEPOS) cohort. These men were recruited from pregnancies included in the Danish National Birth Cohort (DNBC) between 1996 and 2002. From 2017 to 2019, participants answered an online questionnaire, completed a clinical examination and provided a blood and a semen sample. Exposure to 15 PFAS was measured in plasma. Six compounds were quantified above the limit of detection in at least 80% of the participants. We applied negative binomial regression and weighted quantile sum (WQS) regression models to assess associations between single and combined exposure to PFAS and measures of semen quality, testicular volume and reproductive hormones among the young men. RESULTS: We found no consistent associations between plasma concentrations of PFAS, semen quality and testicular volume. Higher levels of single and combined PFAS were associated with slightly higher levels of follicle-stimulating hormone (FSH) (WQS 4% difference, 95% confidence interval: 0, 9). Perfluorooctanoic acid (PFOA) was the main contributor to this finding with positive signals also from perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS). DISCUSSION: We examined exposure to a range of common PFAS in relation to biomarkers of male reproductive function and found an association with higher levels of FSH among young men from the general population in Denmark. Further studies on especially combined exposure to PFAS are needed to expand our understanding of potential endocrine disruption from both legacy and emerging compounds in relation to male reproductive function.

A GWAS in Idiopathic/Unexplained Infertile Men Detects a Genomic Region Determining Follicle-Stimulating Hormone Levels.

CONTEXT: Approximately 70% of infertile men are diagnosed with idiopathic (abnormal semen parameters) or unexplained (normozoospermia) infertility, with the common feature of lacking etiologic factors. Follicle-stimulating hormone (FSH) is essential for initiation and maintenance of spermatogenesis. Certain single-nucleotide variations (SNVs; formerly single-nucleotide polymorphisms [SNPs]) (ie, FSHB c.-211G > T, FSHR c.2039A > G) are associated with FSH, testicular volume, and spermatogenesis. It is unknown to what extent other variants are associated with FSH levels and therewith resemble causative factors for infertility. OBJECTIVE: We aimed to identify further genetic determinants modulating FSH levels in a cohort of men presenting with idiopathic or unexplained infertility. METHODS: We retrospectively (2010-2018) selected 1900 men with idiopathic/unexplained infertility. In the discovery study (n = 760), a genome-wide association study (GWAS) was performed (Infinium PsychArrays) in association with FSH values (Illumina GenomeStudio, v2.0). Minor allele frequencies (MAFs) were analyzed for the discovery and an independent normozoospermic cohort. In the validation study (n = 1140), TaqMan SNV polymerase chain reaction was conducted for rs11031005 and rs10835638 in association with andrological parameters. RESULTS: Imputation revealed 9 SNVs in high linkage disequilibrium, with genome-wide significance (P < 4.28e-07) at the FSHB locus 11p.14.1 being associated with FSH. The 9 SNVs accounted for up to a 4.65% variance in FSH level. In the oligozoospermic subgroup, this was increased up to 6.95% and the MAF was enhanced compared to an independent cohort of normozoospermic men. By validation, a significant association for rs11031005/rs10835638 with FSH (P = 4.71e-06/5.55e-07) and FSH/luteinizing hormone ratio (P = 2.08e-12/6.4e-12) was evident. CONCLUSIONS: This GWAS delineates the polymorphic FSHB genomic region as the main determinant of FSH levels in men with unexplained or idiopathic infertility. Given the essential role of FSH, molecular detection of one of the identified SNVs that causes lowered FSH and therewith decreases spermatogenesis could resolve the idiopathic/unexplained origin by this etiologic factor.

Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter?

BACKGROUND: Whether changes in blood pressure (BP) over women's midlife are more driven by chronological aging or the menopause transition has been debated. We sought to determine whether women can be classified into distinct trajectory groups based on pattern and level of systolic BP (SBP), diastolic BP, pulse pressure (PP), and mean arterial pressure (MAP) over the menopause transition, and to assess whether menopause-related factors predict the group and level of BP measures. METHODS: Participants were from the SWAN (Study of Women's Health Across the Nation). Group-based trajectory modeling was used to identify women who shared distinct BP trajectories over time relative to menopause onset and to assess associations of menopause-related factors with trajectory group and level of BP measures. An accelerated rise relative to menopause onset suggests a menopause contribution. RESULTS: The study included 3302 multiracial and multiethnic women with BP measures over 17 follow-up visits (baseline age [SD]: 46.3 [2.7]). Women were classified into either low, medium, or high trajectory group in each BP measure. The low SBP, PP, and MAP trajectories (in 35%, 53%, and 28% of the cohort, respectively) were rising slowly before menopause but showed a significant accelerated rise 1 year after menopause, indicating a menopause contribution. The remaining BP trajectories were rising up until menopause and either continued with the same rise or declined after menopause. A younger menopause age predicted the low SBP, PP, and MAP trajectories. A greater follicle-stimulating hormone level predicted lower SBP and PP levels, while vasomotor symptoms occurrence predicted higher SBP, PP, and MAP levels over time. Estradiol did not predict trajectory or level of any BP measure. CONCLUSIONS: Distinct BP trajectories over the menopause transition exist that revealed a group of women whose SBP, PP, and MAP trajectories are consistent with a menopause contribution. Our findings support frequent monitoring of BP during the menopause transition.