Reproductive hormones in relation to white matter hyperintensity volumes among midlife women.

INTRODUCTION: Although reproductive hormones are implicated in cerebral small vessel disease in women, few studies consider measured hormones in relation to white matter hyperintensity volume (WMHV), a key indicator of cerebral small vessel disease. Even fewer studies consider estrone (E1), the primary postmenopausal estrogen, or follicle-stimulating hormone (FSH), an indicator of ovarian age. We tested associations of estradiol (E2), E1, and FSH to WMHV among women. METHODS: Two hundred twenty-two women (mean age = 59) underwent hormone assays (E1, E2, FSH) and 3T brain magnetic resonance imaging. Associations of hormones to WMHV were tested with linear regression. RESULTS: Higher E2 (B[standard error (SE)] = -0.17[0.06], P = 0.008) and E1 (B[SE] = -0.26[0.10], P = 0.007) were associated with lower whole-brain WMHV, and higher FSH (B[SE] = 0.26[0.07], P = 0.0005) with greater WMHV (covariates age, race, education). When additionally controlling for cardiovascular disease risk factors, associations of E1 and FSH to WMHV remained. DISCUSSION: Reproductive hormones, particularly E1 and FSH, are important to women's cerebrovascular health. HIGHLIGHTS: Despite widespread belief that sex hormones are important to women's brain health, little work has considered how these hormones in women relate to white matter hyperintensities (WMH), a major indicator of cerebral small vessel disease. We considered relations of estradiol (E2), estrone (E1), and follicle-stimulating hormone (FSH) to WMH in midlife women. Higher E2 and E1 were associated with lower whole-brain WMH volume (WMHV), and higher FSH with higher whole-brain WMHV. Associations of E1 and FSH, but not E2, to WMHV persisted with adjustment for cardiovascular disease risk factors. Findings underscore the importance of E2 and FSH to women's cerebrovascular health.

Effects of Aerobic Training on Sex Hormones in A Cuprizone Rat Model of Multiple Sclerosis.

BACKGROUND: Central nervous system damage in multiple sclerosis (MS) leads to severe physical disability and neurological defects. Sexual dysfunction and infertility in patients with MS have often been neglected in previous studies. Aerobic exercise is suggested to improve circulating testosterone levels and sexual function. Therefore, the purpose of this study was to investigate the effect of aerobic exercise on sex hormone levels in a cuprizone rat model of MS. MATERIALS AND METHODS: In this experimental study, 30 male rats (aged 70 days, 154.55 ± 18.1 g) were randomly divided into five groups: MS, exercise-MS (EX-MS), MS-EX, EX-MS-EX, and normal control (control). MS was induced by feeding cuprizone pellets (0.2%) to the rats for six weeks. The exercise groups performed an aerobic exercise protocol on a treadmill five days/week for six weeks before and during the induction of the MS model. Serum testosterone, follicle stimulating hormone (FSH), and luteinising hormone (LH) levels were measured using the ELISA method with standard kits (ZellBio Germany). Luxol fast blue staining (LFB) of the corpora collosa were performed. RESULTS: The results showed a significant decrease in the serum levels of testosterone, FSH, and LH in the MS groups compared to the control group (P<0.05). There was a significant increase in the serum levels of testosterone, FSH, and LH in the EX-MS-EX, and EX-MS groups compared to the MS group (P<0.05). CONCLUSION: Aerobic exercise could improve the level of sex hormones in the cuprizone rat model of MS and may be used to attenuate sexual dysfunction in patients with MS.

The relationship between male and female endogenous reproductive hormones levels and subjective cognitive decline score: A cross-sectional analysis of the Pingyin cohort study.

OBJECTIVE: Reproductive hormones might impact disease course in cognitive decline. We examined the association between male and female endogenous reproductive hormones and subjective cognitive decline (SCD) score. DESIGN, PATIENTS AND MEASUREMENTS: A cross-sectional study design was used with baseline data from the Pingyin cohort study, involving 1943 participants aged 45-70 years. Oestrogen (E2), testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured in females and E2 and testosterone were measured in males. We categorised hormones into three levels of low, intermediate and high level. The 9-item subjective cognitive decline questionnaire (SCD-Q9) scores were collected to assess the symptoms of SCD. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) between categorised hormone levels and SCD status. Multivariable linear regression models were also used. RESULTS: Overall, 1943 participants were involved and 1285 (66.1%) were female. The mean age at baseline was 59.1 (standard deviation 7.1) years. Women with high testosterone levels had a higher probability of having SCD compared with those with low testosterone levels (OR 1.43, 95% CI 1.01-2.05). Men with a high level of testosterone (0.59, 0.35-0.98) and high testosterone/E2 ratio (0.55, 0.33-0.90) were related to decreased chances of having SCD. Each one-unit increase of testosterone was linked to reduced SCD score in males [(ß: -.029, 95% CI (-0.052, -0.007)]. CONCLUSION: There was sex-specific relationship between hormone levels and SCD abnormal. Those with higher testosterone levels in females may increase likelihood of experiencing SCD. Males with higher testosterone levels and higher testosterone/E2 ratio may be associated with reduced likelihood of SCD. The roles of endogenous reproductive hormone levels and their dynamic changes in cognitive function need further investigation.

Peroxiredoxin 4 deficiency induces accelerated ovarian aging through destroyed proteostasis in granulosa cells.

Ovarian aging, a complex and challenging concern within the realm of reproductive medicine, is associated with reduced fertility, menopausal symptoms and long-term health risks. Our previous investigation revealed a correlation between Peroxiredoxin 4 (PRDX4) and human ovarian aging. The purpose of this research was to substantiate the protective role of PRDX4 against ovarian aging and elucidate the underlying molecular mechanism in mice. In this study, a Prdx4-/- mouse model was established and it was observed that the deficiency of PRDX4 led to only an accelerated decline of ovarian function in comparison to wild-type (WT) mice. The impaired ovarian function observed in this study can be attributed to an imbalance in protein homeostasis, an exacerbation of endoplasmic reticulum stress (ER stress), and ultimately an increase in apoptosis of granulosa cells. Furthermore, our research reveals a noteworthy decline in the expression of Follicle-stimulating hormone receptor (FSHR) in aging Prdx4-/- mice, especially the functional trimer, due to impaired disulfide bond formation. Contrarily, the overexpression of PRDX4 facilitated the maintenance of protein homeostasis, mitigated ER stress, and consequently elevated E2 levels in a simulated KGN cell aging model. Additionally, the overexpression of PRDX4 restored the expression of the correct spatial conformation of FSHR, the functional trimer. In summary, our research reveals the significant contribution of PRDX4 in delaying ovarian aging, presenting a novel and promising therapeutic target for ovarian aging from the perspective of endoplasmic reticulum protein homeostasis.

Development and characterization of a novel variant of long-acting bovine follicle-stimulating hormone (brscFSH).

Assisted reproduction is a key aspect of modern animal breeding, providing valuable assistance in improving breeding programs. In this field, the administration of exogenous hormones, such as follicle-stimulating hormone (FSH), plays a crucial role in the induction of multiple ovulations. However, commercial FSH used in veterinary practice has been derived primarily from pituitary glands, obtained mostly from pigs for nearly four decades. Although these hormones have contributed significantly to the advancement of assisted reproductive techniques, they have certain limitations that warrant further improvements. These limitations include contamination with luteinizing hormone (LH), the potential risk of pathogen contamination, the potential to trigger an immune response in non-pig species, and the short half-life in circulation, requiring the implementation of complex 8-dose superovulation schedules. Our research team has developed and characterized a new variant of bovine follicle-stimulating hormone (bscrFSH) to address these limitations. The new hormone is produced recombinantly in CHO cell cultures, with a specific productivity of about 30 pg/cell/day. The bscrFSH can be purified to a high purity of 97 % using a single step of immobilized metal affinity chromatography (IMAC). N-glycan analysis of bscrFSH showed that approximately 74 % of the glycans corresponded to charged structures, including mono-, di-, tri-, and tetra-sialylated glycans. Superovulation trials conducted in cattle revealed that bscrFSH, administered at a total dose of about 0.5 µg per kg of body weight, using a decrescent schedule of 4 doses with 24-h intervals, resulted in an average yield of 8-12 transferable embryos per animal. Further research is required; however, the preliminary findings indicate that bscrFSH, currently packaged under the provisional brand name of Cebitropin B, holds potential as a commercial product for assisted reproduction in ruminants.

Effects of dietary supplementation with benthic diatom Amphora coffeaeformis on blood biochemistry, steroid hormone levels and seed production efficiency of Nile tilapia Oreochromis niloticus broodstock.

Aquafeed additive quality and quantity remain pivotal factors that constrain the sustainability and progress of aquaculture feed development. This study investigates the impact of incorporating the benthic diatom Amphora coffeaeformis into the diet of Nile tilapia (Oreochromis niloticus) broodstock, on the blood biochemistry, steroid hormone (SH) levels and seed production efficiency. Broodstock females displaying mature ovary indications were initially combined with males at a ratio of three females to one male. A total of 384 adult Nile tilapia (288 females and 96 males) were used, with 32 fish (24 females and eight males) assigned to each of 12 concrete tanks (8 m³; 2 m × 4 m × 1 m), with three replicate tanks for each dietary treatment, throughout a 14-day spawning cycle until egg harvest. Fish were fed one of four different dietary treatments: AM0% (control diet), and AM2%, AM4% and AM6% enriched with the diatom A. coffeaeformis at levels of 20, 40 and 60 g/kg of diet respectively. At the trial's conclusion, total protein, albumin, triglyceride and creatinine), SHs (follicle-stimulating hormone, luteinizing hormone, free testosterone, total testosterone, progesterone and prolactin) and seeds production efficiency of Nile tilapia improved significantly (p < 0.05) in alignment with the increment of A. coffeaeformis supplementation. The findings propose that including A. coffeaeformis at levels ranging from 4% to 6% could be effectively employed as a feed additive during the Nile tilapia broodstock's spawning season.

Follicle-Stimulating Hormone Receptor and Estrogen Receptor Gene Polymorphisms in Women With Discordant Follicle-Stimulating Hormone and Anti-Mullerian Hormone Levels.

Objective This study aimed to investigate follicle-stimulating hormone receptor (FSHR) polymorphisms (Thr307Ala and Asn680Ser), estrogen receptor 1 (ESR1) polymorphisms (PvuII and XbaI), and ESR2 polymorphisms (RsaI and AluI) in Turkish women with follicle-stimulating hormone (FSH) and anti-Mullerian hormone (AMH) discordance. Method Genotyping was performed in 60 patients aged 21-35 with FSH-AMH discordance and/or low ovarian reserve and 20 age-matched controls with normal FSH and AMH levels. The patients were investigated in four groups of 20 women according to their FSH and AMH levels. Groups 1, 2, 3, and 4 were as follows: normal FSH and low AMH levels, normal AMH and high FSH levels, high FSH and low AMH levels, and normal FSH and AMH levels. Genomic DNA was obtained from 3 cc peripheral blood, and polymorphisms were analyzed using TaqMan genotyping assays. Relations between groups of categorical variables were analyzed with a chi-square test. Differences between the groups were assessed using a student's t-test or Mann-Whitney U test. Results Women with discordant FSH and AMH levels (group 1 and group 2) were not statistically different from women with concordant FSH and AMH levels (group 3 and group 4) in terms of FSHR, ESR1, and ER2 single nucleotide polymorphisms (SNPs). Body mass index (BMI) was statistically significant between groups 1 and 2 as well as groups 2 and 3 (p = 0.004). Conclusions This study showed that FSHR, ESR1, and ESR2 SNPs have not had any effect on AMH-FSH discordance in reproductive age Turkish women.

The Effect of Salpingectomy on Ovarian Reserve Using Two Different Electrosurgical Instruments: Ultrasonic Shears Versus Bipolar Electrocautery.

Background Salpingectomy is a common surgical procedure in gynecology performed for various indications. Given its proximity to the ovaries and shared vascular supply, concerns have arisen regarding compromised ovarian reserve post-salpingectomy. Objective We aim to study the effect of two different energy sources (group 1: salpingectomy using bipolar electrocautery followed by division with scissors versus group 2: salpingectomy with ultrasonic shears) on residual ovarian reserve. The effect on ovarian reserve was assessed using serum levels of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), antral follicle count (AFC), and ovarian size pre- and postoperatively. Materials and methods According to the inclusion criteria, 68 women were included in the study and randomized into the bipolar electrocautery group and the ultrasonic shear group. The final analysis included 34 women in the bipolar electrocautery group and 32 in the ultrasonic shear group. Preoperatively, the ovarian reserve of all women was assessed using FSH, AMH, AFC, and ovarian size. These parameters were then reassessed at three months postoperatively, and the percentage change was analyzed. Results The mean baseline serum AMH and serum FSH values in the bipolar electrocautery group were 3.9 ± 2.9 ng/ml and 6.6 ± 2.1 IU/L, respectively, comparable with the values in the ultrasonic shear group, where serum AMH was 3.2 ± 2.9 ng/ml and serum FSH was 7.3 ± 3.9 IU/L. AFC and ovarian size were comparable between the two groups preoperatively (bipolar electrocautery group AFC was 8 ± 2.2, ovarian size on the right side was 3.3 ± 0.7 cm and on the left was 3.2 ± 0.6 cm; ultrasonic shear group AFC was 5.7 ± 2.3, ovarian size on the right side was 3.4 ± 0.8 cm and on the left was 3.2 ± 0.8 cm). After three months of postoperative analysis, AFC showed a significant fall from the preoperative value in the bipolar electrocautery group compared to the ultrasonic shear group (AFC reduced from 8 ± 2.2 to 5.5 ± 2.3 vs. 8.6 ± 0.5 to 7.9 ± 2.3; p=0.002). The other parameters showed no statistically significant change. Conclusion Our study suggests that ultrasonic shear is safer than bipolar electrocautery for preserving ovarian reserve after salpingectomy. However, further research is needed to confirm these findings.

Associations of sex-related and thyroid-related hormones with risk of metabolic dysfunction-associated fatty liver disease in T2DM patients.

BACKGROUND: We aimed to examine sex-specific associations between sex- and thyroid-related hormones and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Cross-sectional analyses of baseline information from an ongoing cohort of 432 T2DM patients (185 women and 247 men) in Xiamen, China were conducted. Plasma sex-related hormones, including estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone, and total testosterone (TT), and thyroid-related hormones, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and parathyroid hormone (PTH), were measured using chemiluminescent immunoassays. MAFLD was defined as the presence of hepatic steatosis (diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score > 60) since all subjects had T2DM in the present study. RESULTS: Prevalence of MAFLD was 65.6% in men and 61.1% in women with T2DM (P = 0.335). For men, those with MAFLD showed significantly decreased levels of FSH (median (interquartile range (IQR)):7.2 (4.9-11.1) vs. 9.8 (7.1-12.4) mIU/ml) and TT (13.2 (10.4-16.5) vs. 16.7 (12.8-21.6) nmol/L) as well as increased level of FT3 (mean ± standard deviation (SD):4.63 ± 0.68 vs. 4.39 ± 0.85 pmol/L) than those without MAFLD (all p-values < 0.05). After adjusting for potential confounding factors, FSH and LH were negative, while progesterone was positively associated with the risk of MAFLD in men, and the adjusted odds ratios (ORs) (95% confidence intervals (CIs)) were 0.919 (0.856-0.986), 0.888 (0.802-0.983), and 8.069 (2.019-32.258) (all p-values < 0.05), respectively. In women, there was no statistically significant association between sex- or thyroid-related hormones and the risk of MAFLD. CONCLUSION: FSH and LH levels were negative, whereas progesterone was positively associated with the risk of MAFLD in men with T2DM. Screening for MAFLD and monitoring sex-related hormones are important for T2DM patients, especially in men.

In vivo effect of recombinant Fsh and Lh administered to meagre (Argyrosomus regius) at the initial stages of sex differentiation.

Recombinant gonadotropins, follicle stimulating (rFsh) and luteinizing hormone (rLh), offer the potential to induce gametogenesis in prepubertal fish. This study aimed to determine the in vivo effect of the administration of Argyrosomus regius rFsh and rLh on the reproductive development of prepubertal meagre juveniles at the initial stages of sexual differentiation. Juvenile meagre, 9-months old with mean weight of 219 ± 3.9 g (mean ± SEM) were randomly distributed into nine groups (n = 8 per group). Experimental groups were treated weekly with an acute injection of either rFsh or rLh. Control groups were injected with saline solution. In a 3-week experiment, different groups were administered with different doses 6, 12 or 18 µg kg-1 of rFsh or rLh or saline solution. In a 6-week experiment a group was administered with 12 µg kg-1 of rFsh and a second group with saline solution. The fish were held in a single 10 m3 tank with natural photoperiod (Feb. - March) and temperature 16.1 ± 0.4 °C. At the start of the experiment (n = 8) and at the end of the 3-week experiment, fish were blood sampled and sacrificed. Blood was analysed for 17ß-estradiol (E2) and 11-ketotestosterone (11-KT). Gonads and liver were dissected and weighed. Gonads were fixed in Bouins solution and processed for histological analysis. Juvenile meagre at the start of the experiment were in the initial stages of sexual differentiation, indicated by the presence of the ovarian cavity or testes duct that was surrounded by undifferentiated embryonic germ stem cells and somatic cells. At the end of the 3-week experiment, there was no significant difference in gonadosomatic index (GSI) amongst control (initial and saline treated) and the experimental groups. After three weeks of application of rFsh, rLh or saline all fish presented a similar gonadal structure as at the start of the experiment. However, the incidence of sporadic developing germ cells (principally spermatogonia, spermatocytes, spermatids, but also perinucleolar stage oocytes) generally increased in rGth treated meagre. A mean of 44 % of meagre treated with rFsh or rLh presented sporadic isolated developing germ cells, mainly male cells. Plasma steroid levels of E2 decreased significantly from the start of the experiments to the end. At the end of the experiments there were no differences in plasma E2 amongst Control fish and rGth treated fish. Plasma 11-KT showed no change from the start of the experiment to week 3. However, a significant increase was observed in a proportion of the rFsh group after six weeks of treatment compared to the start of the experiment and the saline control group on week 6. The application of rFsh or rLh to meagre at the initial stages of sex differentiation did not stimulate steroid production until week six (11-KT) and had a limited, but evident effect on the development of sporadic isolated germ cells. However, we conclude that rGth, rFsh or rLh did not stimulate large developmental changes in sexually undifferentiated meagre gonads.

Recombinant Human Follicle-Stimulating Hormone in Controlled Ovarian Hyperstimulation with Assisted Reproductive Technology in China: A Cost-Effectiveness Analysis.

Background: To compare the cost-effectiveness of originator (reference) recombinant human follicle stimulating hormone alfa (rhFSH-α) (follitropin alfa, GONAL-f) and its biosimilar (rhFSH, JinSaiHeng) in assisted reproductive technology (ART) from a Chinese patient perspective. Methods: A decision tree model was developed to simulate the treatment pathway of infertile women undergoing ART using GONAL-f or JinSaiHeng. Published clinical and cost data were used to evaluate the cost-effectiveness of the rhFSH-α. The cumulative live birth rate (CLBR), direct medical costs and costs per cumulative live birth were estimated via an analytic decision-tree model. Results: CLBR of GONAL-f was higher than JinSaiHeng preparation (88.3% vs 84.4%), while the cost per cumulative live birth was lower (51,475 vs 52,095 CNY). Conclusion: The originator rhFSH-α was associated with higher CLBR and lower cost per cumulative live birth, with incremental cost per additional live birth of 38,096 CNY (Chinese Yuan).

Role of Follicle-stimulating Hormone, Inhibin B, and Anti-Müllerian Hormone in Predicting Sperm Retrieval from Men with Nonobstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: A Systematic Review and Meta-analysis.

Background and objective: No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE. Methods: We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis. Key findings and limitations: Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and -SR groups, with lower FSH (SMD -0.30), higher InhB (SMD 0.54), and lower AMH (SMD -0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00-1.06) or InhB (OR 1.01, 95% CI 1.00-1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73-0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend. Conclusions and clinical implications: Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE. Patient summary: We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.

Single-chain human follicle-stimulating hormone with a di-N-glycosylated linker.

The classic way to produce single-chain (sc) glycoprotein hormones is to fuse their two subunits through the carboxy-terminal peptide (CTP) from human Choriogonadotropin (hCG). The CTP confers a longer half-life to single-chain hormones thanks to its four O-glycosyl side chains. However, unlike syncytiotrophoblastic cells, most cells used for recombinant protein production do not transfer O-glycosyl chains efficiently. We thus choose to fuse the hFSH subunits with a linker comprising two N-glycosyl side chains (sc-hFSH LNN) or none (sc-hFSH L0N), that were generated using two expression systems, HEK293 and CHO K1 cells. Their production levels and biological activities were tested and compared. Both expression systems successfully produced biologically active sc-hFSH, but, in our hands, CHO K1 cells yielded about 30-fold higher amounts of recombinant protein than HEK293 cells. Moreover, sc-hFSH L0N was considerably less expressed than sc-hFSH LNN in both cell types. Our data show that sc-hFSH L0N and sc-hFSH LNN produced from both cell lines stimulate cAMP and progesterone production in mLTC cells expressing hFSH receptors and exhibit similar B/I (in vitro Bioactivity/Immuno activity) ratios. Finally, the ratio of in vivo/in vitro bioactivities for sc-hFSH LNN relative to natural pituitary heterodimeric hFSH increased 8-fold, most likely because of a longer half-life in the blood.

A Dose-Response Study on Functional and Transcriptomic Effects of FSH on Ex Vivo Mouse Folliculogenesis.

Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation-related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.

Low Serum Testosterone as a Poor Prognostic Marker in Urethral Stricture: A Single-Center Prospective Longitudinal Study.

Introduction Androgens play a key role in modulating periurethral and preputial vascularity, cavernosal smooth muscle integrity, and penile growth. As a result, low testosterone may adversely affect the severity and outcome of urethral stricture patients. So, to find out the hormonal influence on the clinical outcome of urethral stricture we conducted a prospective longitudinal study at our institute. Methods The study was conducted at the Department of Urology, Institute of Post Graduate Medical Education & Research (IPGMER), Kolkata, India, from February 2023 to September 2023. This study was approved by the Institutional Ethics Committee at IPGMER, Kolkata with the approval number IPGMER/IEC/2023/436. Hormonal levels in patients with diagnosed non-traumatic urethral stricture were compared with patients without stricture. Patients with any overt hormonal abnormality or androgen-secreting tumor were excluded. A morning 10 cc blood sample was collected for testosterone, follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone. The association of hormonal levels was measured in both groups and compared statistically. Any association of hypogonadism (testosterone <300 ng/dL) with respect to length, severity, and recurrence of urethral stricture was also studied. Results Forty patients with urethral stricture and same number of patients without stricture were included in the study. The mean testosterone level was found to be significantly low in patients with stricture (386 ng/dL vs 660 ng/dL). The age-wise distribution also showed low mean testosterone compared to patients without stricture. The incidence of hypogonadism is also found to be higher in stricture patients (47.5% vs 27.5%). It was also observed low testosterone is more prevalent in pan-anterior stricture (10/40) and long-segment stricture(>2 cm). Patients with stricture were also followed up for 6 months for recurrence of symptoms. Thirteen patients had recurrence. Patients with recurrence had significantly low serum testosterone (272 ng/dL vs 440 ng/dL). Conclusion Our study documented stricture patients with low serum testosterone have poor outcomes. Low testosterone level is strongly associated with longer stricture and increased risk of stricture recurrence.

Inhibin B and antiMüllerian hormone as surrogate markers of fertility in male and female Crohn's disease patients: a case-control study.

Background: Several studies suggest that women with Crohn disease (CD) have reduced fertility due to decreased ovarian reserve, among other causes. On the other hand, male CD patients could have difficulties conceiving. The present study aimed to test the effect of CD on both male and female fertility potential, Sertoli cell function and ovarian reserve, assessed by inhibin-B (IB) plus IB:FSH ratio (IFR) and antiMüllerian hormone (AMH), respectively. Sexual dysfunction (SD) was studied as secondary endpoint. Methods: We performed a cross-sectional, case-control study. Serum IB levels plus IFR were measured in 58 men with CD and compared to 25 age-matched healthy controls (HC). Serum AMH levels were measured in 50 women with CD and in 30 HC matched by age. SD was assessed by means of the International Index of Erectile Function (IIFE-15) in males and the Index of Female Sexual Function (IFSF) in women. Results: A total of 108 CD patients and 55 HC were included. IB serum levels were significantly lower in CD men than in HC (177 ± 58 vs. 234 ± 75 pg./mL, p = 0.001). IFR was also decreased in CD patients compared to HC (58.27 ± 59.5 vs. 91.35 ± 60.04, p = 0.014). Women with CD > 30 years had lower serum AMH levels compared to HC (1.15 ± 0.74 vs. 2.14 ± 1.68 ng/mL, p = 0.033). In addition, CD women >30 years presented a serum AMH < 2 ng/mL more frequently than HC (90% vs. 40%, p = 0.004). The prevalence of SD was significantly higher among both male and female CD patients compared to HC, without association to fertility potential. Age was the only predictor of low ovarian reserve. Conclusion: Testicular Sertoli cell function assessed through serum IB levels and IFR is decreased in CD male patients compared to HC, regardless of age. Age > 30 years is the single independent predictor of reduced ovarian reserve in women with CD. These results should be confirmed in further studies in order to properly counsel patients with CD and desire for offspring.

Diagnostic Value of Single LH and LH/FSH Ratio at 60-minute after GnRHa Stimulation Test for Central Precocious Puberty.

OBJECTIVES: To evaluate the diagnostic value of luteinizing hormone (LH) and LH/follicle stimulating hormone (FSH) ratio at 60 min after gonadotropin-releasing hormone analogs (GnRHa) stimulation test for central precocious puberty (CPP) in girls. METHODS: Two hundred and fifty-seven girls, aged 3 to 7.5 y, suspected of precocious puberty at authors' hospital from April 2020 through November 2023 were enrolled in the study. The blood was taken at 0, 30, 60 min after GnRHa stimulation test, and LH and LH/FSH were detected by chemiluminescence assay. The diagnostic efficacy was analysed by Mann-Whitney U test, spearman's correlation analysis and receiver operating characteristic (ROC) analysis. The proportion of obesity was analysed by Chi-square test. RESULTS: LH and LH/FSH at different times were statistically significantly different (P <0.05) between the CPP and non-CPP groups. Spearman's correlation analysis showed that the level of LH and LH/FSH at 60 min had the strongest consistency with the peak of LH (r = 0.9988, P <0.001) and LH/FSH (r = 0.9981, P <0.001). ROC curve analysis showed that the area under the ROC curves at 60 min of LH and LH/FSH were 0.975 and 0.997 with a cut-off value of 5.70 IU/L and 0.609, respectively. CONCLUSIONS: The peak of LH and LH/FSH in the diagnosis of CPP can be determined by LH and LH/FSH at 60 min after the triptorelin acetate is injected. This will reduce the number of blood draws required compared with the traditional stimulation test, which is more effective and acceptable for children.

Long-Term Ovarian Function Assessment After Haematopoietic Stem Cell Transplantation in Female Sickle Cell Anaemia Survivors.

BACKGROUND: Haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for sickle cell anaemia (SCA). While HSCT offers the possibility of disease remission, it can also lead to long-term complications, including gonadal dysfunction and premature menopause. METHODS: We conducted a retrospective cohort study of female survivors who had hydroxyurea therapy and those who underwent post-HSCT follow-up for SCA at a teaching hospital in Lagos, Nigeria, between January 2019 and December 2022. Participants were eligible if they were at least five years post-HSCT or hydroxyurea treatment and had available serum samples for markers of ovarian function measurement. Demographic and clinical data were collected from the hospital register and patients' medical records. Serum levels of oestradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) were measured using the Abbott Architect i1000SR chemiluminescent immunoassay analyzer (Abbott Diagnostics, Abbott Park, IL). Descriptive statistics and inferential analyses were used to assess the relationship between markers of ovarian function (FSH and AMH) and clinical parameters. RESULTS: There were statistically significant differences in the median serum levels of all the assessed endocrine hormones between the HSCT and non-HSCT (hydroxyurea) groups of SCA survivors. Up to 82.6% of the SCA survivors experienced ovarian dysfunction after HSCT treatment. Impaired ovarian function in SCA survivors was associated with a longer median follow-up duration than in SCA survivors who had normal ovarian function (12.0 vs. 7.5 years, p = 0.048). There were higher odds of impaired ovarian function in the SCA survivors who had myeloablative regimens than in those who had reduced intensity conditioning regimens (94.1% vs. 50.0%, p = 0.040). CONCLUSION: Our study highlights the significant impact of HSCT on long-term ovarian function in female SCA survivors. However, further prospective studies with larger sample sizes and longer follow-up periods are required to confirm our findings and elucidate the factors influencing ovarian function in SCA survivors of HSCT. In addition, studies are also needed to further elucidate the optimal transplant protocols and fertility preservation strategies to minimize gonadal toxicity and preserve reproductive potential in female SCA patients undergoing HSCT.

The Reproductive Lifespan of Ovarian Follicle.

The functional unit within mammalian ovaries is the ovarian follicle. The development of the ovarian follicle is a lengthy process beginning from the time of embryogenesis, passing through multiple different stages of maturation. The purpose of this review is to describe the most basic events in the journey of ovarian follicle development, discussing the importance of ovarian reserve and highlighting the role of several factors that affect oocyte quality and quantity during aging including hormonal, genetic and epigenetic factors. Novel, promising anti-aging strategies are also discussed.

Distribution and Positive Predictive Value of Follicle Stimulating Hormone Among Nonazoospermic Men.

PURPOSE: Our goal was to characterize the distribution of follicle stimulating hormone (FSH) in fertile and subfertile nonazoospermic men, and to determine the ability of various FSH thresholds to predict fertility status. MATERIALS AND METHODS: We performed a retrospective cohort study of 1389 nonazoospermic men who presented for fertility evaluation. Men with at least 2 semen analyses and 1 FSH level were included. Men were dichotomized into fertile and subfertile groups based on total motile sperm count. FSH was evaluated within a multivariable model, and positive predictive values (PPVs) for subfertility were used to assess the clinical utility of various FSH thresholds. RESULTS: One thousand fifteen (80%) men were classified as fertile and 274 (20%) as subfertile. Age, presence of varicocele, and testosterone levels were not statistically different between the groups. Median FSH was 4.0 vs 6.0 (P < .001) among fertile vs subfertile men. Multiple FSH thresholds ranging from 2.9 to 9.3 performed similarly in predicting fertility status (PPV 0.49-0.59). Only FSH thresholds above the 95th percentile (12.1) had PPVs greater than 0.7. The highest PPV (0.84) was seen at an FSH of 20.8 (99th percentile). CONCLUSIONS: While there were significant differences in FSH levels among fertile and subfertile nonazoospermic men, multiple FSH cutoffs between 2.2 and 9.3 performed poorly for prediction of fertility status as determined by total motile sperm count. It was not until the 95th percentile FSH value that a clinically useful level of predictability for subfertility was reached, indicating that FSH should not be used as a standalone test of fertility status. Nonetheless, FSH testing remains clinically useful and may be most informative in the setting of extreme values or discordant FSH and semen analysis results.