Kidney transplantation restores sex hormone profile and improves sexual function in ESRD patients with erectile dysfunction.

BACKGROUND: Erectile dysfunction (ED) and sex hormone profile disturbances are common in ESRD patients. OBJECTIVE: To assess the effect of kidney transplant (KT) and Hemodialysis/peritoneal dialysis (HD/PD) on the serum sex hormone profile and sexual functions in ESRD patients with ED. PATIENTS AND METHODS: A single-center, nonconcurrent cohort study included a hundred ESRD patients with ED, on regular HD/PD (group A, n = 50) and after KT (group B, n = 50) at Armed Forces Hospitals Southern Region, KSA. RESULTS: the mean age of patients was 47.3 ± 7.01 and 56.8 ± 9.6 years in groups A and B, respectively. The cohorts were comparable regarding patient demographics, apart from a higher incidence of comorbidities in group B. After KT the mean testosterone level was higher in Group B (13.64 ± 3.21 nmol/L vs 10.26 ± 3.26 nmol/L, p < 0.001). Similarly, LH and prolactin levels were lower in group B than in group A (p < 0.05). As regards sexual function, ED was reported in 92% of patients in group A compared to 42% in group B (p < 0.001). In groups A and B, mild ED was found in 48% and 14% of patients, while moderate ED was found in 16% and 8%, respectively. The mean total IIEF-15 score was 36.42 ± 9.33 and 43.87 ± 9.146 in groups A and B, respectively (p = 0.0001). Sexual desire and orgasm were significantly better in Group B. CONCLUSIONS: Our study showed that kidney transplantation could improve erectile function and restore normal sex hormone levels in ESRD male patients with ED, with better outcomes compared to HD/PD.

Lower serum LH level was related to poor embryo quality and adverse pregnancy outcomes in fixed GnRH antagonist protocol with estradiol pretreatment.

OBJECTIVE: To disclose the relationships between serum LH and reproductive outcomes in Gonadotropin-releasing hormone (GnRH) antagonist protocol pretreated with luteal estradiol. METHODS: 371 patients, pretreated with estradiol, followed the GnRH antagonist protocol. They were divided into four groups based on the quartiles of serum LH levels on the day of gonadotropin (Gn) initiation(LHGI) and trigger (LHtrigger). Data on various pregnancy outcomes were collected. RESULTS: As serum LHGI increased, anti-Müllerian hormone (AMH) level, antral follicle count (AFC), LHtrigger, estradiol (E2) and P on the trigger day, E2/oocytes, and oocyte numbers increased and peaked in Q4, while Gn dose decreased. Good-quality embryo and blast formation rates increased and peaked in Q3. LHGI <3.93 mIU/ml impaired ongoing pregnancy rate and LBR. After adjusting for AMH and AFC, the impacts were not significant. As LHtrigger increased, E2/oocytes and good-quality embryo rate increased and peaked in T4 and implantation rate increased and peaked in T3. LHtrigger <1.49 mIU/ml independently influenced clinical pregnancy rate (CPR) after adjusting for AMH and AFC. LHGI was positively related to AMH, AFC, LHtrigger, blast formation rate and negatively related to BMI, age and Gn dose. LHtrigger was positively related to E2/oocytes and good quality embryo rate. CONCLUSIONS: Lower serum LH represents as a potential indicator for embryo quality and reproductive outcomes in GnRH antagonist fixed protocol pretreated with estradiol. Early identification of excessive suppression of LH levels will benefit individuals with normal ovarian reserve more.

Frequency of Phenotypes and their Clinical and Hormonal Characteristics of Polycystic Ovarian Syndrome.

OBJECTIVE: To determine the frequency of phenotypes of polycystic ovarian syndrome (PCOS) in patients presenting with sub-fertility, and to compare the clinical and hormonal characteristics among them. STUDY DESIGN: Descriptive cross-sectional study. Place and Duration of the Study: Department of Obstetrics and Gynaecology, Forest View Specialist Clinic, Peshawar, Pakistan, from August 2022 to January 2023. METHODOLOGY: The study included 662 female patients presenting with menstrual irregularities, hyperandrogenism, and infertility to the clinic. PCOS was diagnosed on the basis of the Rotterdam criterion and clinical features and classified into different phenotypes on the basis of the National Institute of Health (NIH) panel criteria. Data were entered and analysed by IBM SPSS VERSION 23.0. The frequency of four phenotypes was calculated and phenotypes were compared for age, weight, hormonal profiles, and history of miscarriages. A p <0.05 was considered statistically significant. RESULTS: Frequency of PCOS in patients with infertility was 59.76%. Phenotype A was seen in 58.2%, phenotype D in 23.3%, phenotype C in 16.9%, and phenotype B in 1.7% of cases. The LH/FSH ratio was statistically significant in phenotype A as compared to other phenotypes, while other parameters were non-significant. CONCLUSION: The frequency of PCOS is high in patients with infertility. Phenotype A is the most common variant and is associated with significant impairment of the LH/FSH ratio. KEY WORDS: Polycystic ovarian syndrome, Subfertility, Phenotypes of PCOS, Hyperandrogenism, Anovulation, R-C1.

Acetate attenuates hypothalamic pyroptosis in experimentally induced polycystic ovarian syndrome.

This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.

Assessment of parenteral estradiol and dihydroxyprogesterone use among other feminizing regimens for transgender women: insights on satisfaction with breast development from community-based healthcare services.

The practice of hormone therapy is crucial in aligning secondary sex characteristics with the gender identity of transgender adults. This study examines the effects of a commonly used injectable hormone combination, specifically estradiol enanthate with dihydroxyprogesterone acetophenide (EEn/DHPA), on serum hormonal levels and self-reported satisfaction with breast development in transwomen. Our research focused on a retrospective longitudinal study involving a large cohort of transwomen evaluated between 2020 and 2022, comprising 101 participants. We assessed serum levels of estradiol (E2), testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), comparing the EEn/DHPA hormonal regimen with other combined estrogen-progestogen (CEP) therapies. Additionally, a subset of 43 transwomen completed a 5-question survey to evaluate self-reported satisfaction with breast development using Tanner scales. Our findings indicated that participants using the EEn/DHPA regimen exhibited significantly higher serum E2 levels (mean: 186 pg/mL ± 32 pg/mL) than those using other therapies (62 ± 7 pg/mL), along with lower FSH levels, but no significant differences in T and LH levels. Concerning satisfaction with breast development, 76% reported increased fulfillment with breast augmentation while using EEn/DHPA. These results suggest that an injectable, low-cost EEn/DHPA administered every three weeks could serve as an alternative feminizing regimen, particularly considering the extensive long-term experience of the local transgender community. Further longitudinal studies on the efficacy of feminizing-body effects and endovascular risks of various parenteral CEP types are warranted to improve primary healthcare provision for transgender persons.

[Clinical case of plurihormonal pituitary adenoma (STH/ACTH/TSH/FSH/LH-secreting), diagnostic pitfalls].

According to numerous studies, the most common pituitary tumors are prolactinomas, reaching 60% of all clinically significant adenomas, the next in order are non-functional pituitary adenomas, somatotropinomas, corticotropinomas and thyrotropinomas. Plurigormonal tumors occur in less than 1% of all pituitary adenomas. The most common form of mixed secretion adenoma in this patient population, derived from the Pit-1 cell line, produces various combinations of hormones: growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH). This article presents a patient with a plurihormonal two-component pituitary macroadenoma with a rare and exceptional combination of secreted hormones - GH / adrenocorticotropic hormone (ACTH) / TSH / follicle-stimulating hormone (FSH) / luteinizing hormone (LH) with minimal nonspecific clinical manifestations such as diabetes mellitus and poorly controlled arterial hypertension.

SARS-CoV-2 impairs male fertility by targeting semen quality and testosterone level: A systematic review and meta-analysis.

BACKGROUND: Since the discovery of COVID-19 in December 2019, the novel virus has spread globally causing significant medical and socio-economic burden. Although the pandemic has been curtailed, the virus and its attendant complication live on. A major global concern is its adverse impact on male fertility. AIM: This study was aimed to give an up to date and robust data regarding the effect of COVID-19 on semen variables and male reproductive hormones. MATERIALS AND METHODS: Literature search was performed according to the recommendations of PRISMA. Out of the 852 studies collected, only 40 were eligible for inclusion in assessing the effect SARS-CoV-2 exerts on semen quality and androgens. More so, a SWOT analysis was conducted. RESULTS: The present study demonstrated that SARS-CoV-2 significantly reduced ejaculate volume, sperm count, concentration, viability, normal morphology, and total and progressive motility. Furthermore, SARS-CoV-2 led to a reduction in circulating testosterone level, but a rise in oestrogen, prolactin, and luteinizing hormone levels. These findings were associated with a decline in testosterone/luteinizing hormone ratio. CONCLUSIONS: The current study provides compelling evidence that SARS-CoV-2 may lower male fertility by reducing semen quality through a hormone-dependent mechanism; reduction in testosterone level and increase in oestrogen and prolactin levels.

Analytical Investigation of the Profile of Human Chorionic Gonadotropin in Highly Purified Human Menopausal Gonadotrophin Preparations.

Highly purified human menopausal gonadotropin (HP-hMG [Menopur®, Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur® and two of Menogon® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid®) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.

Luteinizing hormone supplementation with human menopausal gonadotropin versus low dose human chorionic gonadotropin during ovarian stimulation does not affect live birth rates after fresh and frozen embryo transfer.

AIM: Luteinizing hormone (LH) plays an important role in ovarian follicle maturation. Human menopausal gonadotropin (hMG) or low dose human chorionic gonadotropin (hCG) can provide LH supplementation during in vitro fertilization (IVF) ovarian stimulation, though studies directly comparing their impact on IVF outcomes are limited. The aim of the study was to determine whether LH supplementation with hMG versus low dose hCG during IVF stimulation affects live birth rate. METHODS: Fresh and frozen embryo transfers (ET) from 2017 to 2021 after standard long or antagonist protocols supplemented with hMG (75-250 IU) or low dose hCG (50-100 IU) during stimulation cycles in our academic center were included. Statistical analysis was performed with T-tests, Mann-Whitney U tests, Chi-square, and multiple linear and logistic regression. RESULTS: Four hundred and sixty eight unique stimulation cycles resulting in 213 fresh and 412 frozen embryo transfers were analyzed. There was a lower mature oocyte yield (10.9 vs. 11.8, p = 0.044) but similar high-quality blastocyst yield (3.6 vs. 3.9, p = 0.11) for hMG vs low dose hCG. Live birth rates per transfer were comparable for fresh (42% vs. 49%, p = 0.24) and frozen (46% vs. 53%, p = 0.45) embryo transfers. Multiple logistic regressions showed no association between supplemental gonadotropin and live birth for both fresh and frozen embryo transfers. CONCLUSION: Fresh and frozen IVF-ET pregnancy outcomes were comparable after hMG versus low dose hCG supplementation, suggesting flexibility in supplemental LH dosing regimens that may address patient or physician preference or cost concerns.

The Transcriptome Characterization of the Hypothalamus and the Identification of Key Genes during Sexual Maturation in Goats.

Sexual maturation in goats is a dynamic process regulated precisely by the hypothalamic-pituitary-gonadal axis and is essential for reproduction. The hypothalamus plays a crucial role in this process and is the control center of the reproductive activity. It is significant to study the molecular mechanisms in the hypothalamus regulating sexual maturation in goats. We analyzed the serum hormone profiles and hypothalamic mRNA expression profiles of female goats during sexual development (1 day old (neonatal, D1, n = 5), 2 months old (prepuberty, M2, n = 5), 4 months old (sexual maturity, M4, n = 5), and 6 months old (breeding period, M6, n = 5)). The results indicated that from D1 to M6, serum hormone levels, including FSH, LH, progesterone, estradiol, IGF1, and leptin, exhibited an initial increase followed by a decline, peaking at M4. Furthermore, we identified a total of 508 differentially expressed genes in the hypothalamus, with a total of four distinct expression patterns. Nuclear receptor subfamily 1, group D, member 1 (NR1D1), glucagon-like peptide 1 receptor (GLP1R), and gonadotropin-releasing hormone 1 (GnRH-1) may contribute to hormone secretion, energy metabolism, and signal transduction during goat sexual maturation via circadian rhythm regulation, ECM receptor interactions, neuroactive ligand-receptor interactions, and Wnt signaling pathways. This investigation offers novel insights into the molecular mechanisms governing the hypothalamic regulation of goat sexual maturation.

Prevalence of adrenal rest tumors and course of gonadal dysfunction in a clinical sample of men with congenital adrenal hyperplasia: a longitudinal analysis over 10 years.

BACKGROUND: Subfertility is prevalent in men with classic 21-hydroxylase deficiency (21OHD). We sought to characterize the long-term evolution of their gonadal function. METHODS: Retrospective longitudinal single-center study in 27 men (11 with testicular adrenal rest tissue [TART]), median observation period 12 years, testosterone (T), 11-oxygenated androgens, gonadotropins, and inhibin B measurement at each time point. RESULTS: T concentrations were below the normal range (n.s.) in 43.2% (no TART) and 54.6% (TART) per patient. After accounting for body mass index, sex hormone-binding globulin, and age, men with TART exhibited higher T (14.0 ± 0.80 nmol/L) than those without (11.9 ± 0.71 nmol/L). During the observation period, T levels rose in both groups but more in men with TART (from 10.1 ± 1.1 to 17.3 ± 1.9 nmol/L vs 10.3 ± 1.0 to 12.8 ± 1.9 nmol/L); this was accompanied by rising luteinizing hormone and diminishing hydrocortisone equivalent dosages (TART: from 38.1 ± 3.2 to 35.1 ± 1.8 mg/d; vs no TART: 28.8 ± 2.7 to 28.1 ± 1.6 mg/d) without correlation with any markers of adrenal androgen control. Inhibin B declined in men with large TART over time while TART status remained stable. CONCLUSION: T levels below the normal range are frequent in men with 21OHD, regardless of TART, but change little over time. Besides adrenal androgen control gonadal axis suppression from supraphysiological glucocorticoid dosages needs to be considered. While our results do not endorse regular screening for alterations in TART status among adults, Sertoli cell function should be monitored in men with large TART.

ZEB1 Inhibits LHß Subunit Transcription When Overexpressed, but Is Dispensable for LH Synthesis in Mice.

Luteinizing hormone (LH), a heterodimeric glycoprotein produced by pituitary gonadotrope cells, regulates gonadal function. Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates LH synthesis and secretion. GnRH induces LHß subunit (Lhb) expression via the transcription factor, early growth response 1 (EGR1), acting on the Lhb promoter. In contrast, overexpression of zinc finger E-box binding homeobox 1 (ZEB1) represses LH production in mice, but the underlying mechanism was not previously elucidated. Here, we observed that ZEB1 inhibited GnRH-stimulated but not basal Lhb mRNA expression in homologous murine LßT2 cells. Moreover, ZEB1 blocked GnRH and/or EGR1 induction of murine Lhb but not human LHB promoter-reporter activity in these cells. Using chimeric reporters, we mapped the species-specific ZEB1 sensitivity to sequence differences, including in Z- and E-boxes, in the proximal Lhb/LHB promoters, immediately upstream of the transcription start sites. ZEB1 bound to the murine Lhb promoter with higher affinity than to the human LHB promoter in this region. To examine ZEB1's physiological role in LH synthesis, we characterized gonadotrope-specific Zeb1 knockout mice. Loss of ZEB1 in gonadotropes did not affect LH production or secretion. Collectively, the data suggest that ZEB1, when overexpressed, can inhibit GnRH/EGR1 induction of murine Lhb transcription but does not play a necessary role in LH synthesis in mice.

In vivo evaluation of medicinal effects of Myristica fragrans, Cinnamomum zeylanicum, Mucuna pruriens on male murine fertility.

Herbal remedies are used for managing different ailments including male sexual abnormalities. Mucuna pruriens, Cinnamomum zeylanicum and Myristica fragrans, are some of the important herbs of these remedies for male sexual disorders. This study has been conducted to evaluate the effects of these drugs, individually and in combination on fertility parameters in mice. The study was carried out on male and female albino mice of BALB/c strain bearing weight of 20-25 g and age 12 to 13 weeks. Animals were divided into control and test batches (n=10). Drugs were given to the male mice test groups daily for 52 days by oral route and on 53rd day the fertility parameters were measured. Afterwards, histopathological analysis was also done. One-way analysis of variance (ANOVA) followed by post hoc was applied for statistical analysis. Important contrast was found in fertility parameters, including pregnancy outcome, serum testosterone, luteinizing hormone, follicle stimulating hormone and histological examination of tested batches as compared to control. The fertility enhancing effect of the drugs were found in the tested doses used in this study in male albino mice of BALB/c strain. However further preclinical and clinical studies are necessary to determine the safety of these drugs.

Hormonal and Allosteric Regulation of the Luteinizing Hormone/Chorionic Gonadotropin Receptor.

Luteinizing hormone (LH) and human chorionic gonadotropin (CG), like follicle-stimulating hormone, are the most important regulators of the reproductive system. They exert their effect on the cell through the LH/CG receptor (LHCGR), which belongs to the family of G protein-coupled receptors. Binding to gonadotropin induces the interaction of LHCGR with various types of heterotrimeric G proteins (Gs, Gq/11, Gi) and ß-arrestins, which leads to stimulation (Gs) or inhibition (Gi) of cyclic adenosine monophosphate-dependent cascades, activation of the phospholipase pathway (Gq/11), and also to the formation of signalosomes that mediate the stimulation of mitogen-activated protein kinases (ß-arrestins). The efficiency and selectivity of activation of intracellular cascades by different gonadotropins varies, which is due to differences in their interaction with the ligand-binding site of LHCGR. Gonadotropin signaling largely depends on the status of N- and O-glycosylation of LH and CG, on the formation of homo- and heterodimeric receptor complexes, on the cell-specific microenvironment of LHCGR and the presence of autoantibodies to it, and allosteric mechanisms are important in the implementation of these influences, which is due to the multiplicity of allosteric sites in different loci of the LHCGR. The development of low-molecular-weight allosteric regulators of LHCGR with different profiles of pharmacological activity, which can be used in medicine for the correction of reproductive disorders and in assisted reproductive technologies, is promising. These and other issues regarding the hormonal and allosteric regulation of LHCGR are summarized and discussed in this review.

Influence of Menstrual Phase and Symptoms on Match Running in Professional Footballers.

This study examined the effects of menstrual cycle phases and symptoms on match running performance in football (soccer) players. Twenty-one nonhormonal contraceptive using football players from four professional teams were monitored for up to four menstrual cycles during a domestic league season. Menstrual phases, classified as early-follicular phase (EFP), mid-late follicular phase (MFP), and luteal phase (LP), were determined by self-reporting of menstruation and urinary hormone tests (luteinizing hormone and pregnanediol-3-glucuronide). On match day, players completed a menstrual symptom severity questionnaire. In repeated matches, players wore 10 Hz Global Positioning Satellite (GPS) devices to measure relative (/min) total distance, high-speed running distance, very high-speed distance, peak speed, acceleration count, and deceleration count. Linear mixed models were performed for each GPS measure to determine the relationship with phase or symptoms. Data for 7 and 10 players were included for menstrual phase and menstrual symptoms analyses, respectively. A significantly higher total distance was reported during MFP compared to EFP (Δ 5.1 m min-1; p = 0.04) and LP (Δ 5.8 m min-1; p = 0.007). Significantly greater high-speed running was reported during MFP compared to EFP (Δ 1.2 m min-1; p = 0.012) and LP (Δ 1.1 m min-1; p = 0.007). No significant effect of menstrual phase was found for any other GPS measures (p > 0.05). Accelerations declined with increasing symptom severity (p = 0.021, estimate = -0.01count.min-1). Menstrual symptom severity did not affect any other GPS measures (p > 0.05). In conclusion, greater total distance and high-speed running occurred during the MFP. Additionally, accelerations minimally decreased with increasing menstrual symptom severity. Large intra- and inter-variability existed, suggesting individualized monitoring and management of menstrual effects on performance would be beneficial.

Characteristics of the hormonal background in women with abnormal uterine bleeding and extragenital disorders.

OBJECTIVE: Aim: To establish the peculiarities of the hormonal background in women with abnormal uterine bleeding and extragenital disorders. PATIENTS AND METHODS: Materials and Methods: The study involved examination of 100 women of reproductive age with concomitant ED and AUB (MG). CG included 50 healthy women. MG women were additionally divided into subgroups depending on the detected pathological changes in the uterine cavity. When examining the hormonal status, concentrations of FSH, LH, estradiol, progesterone, and leptin in BS were determined. Additionally, the level of 25-hydroxyvitamin D ((25-OH) D) was determined. RESULTS: Results: The decrease in FSH level in subgroups of GP, PSL, EH, EHL was 1.8-2.4 times (KWT, p<0.01). LH in BS of MG patients was statistically lower than that of CG patients (MWT, p=0.0083). The lowest level of LH was registered in patients with EHL, which was 2 times lower than this indicator in CG. A statistically significant increase in the level of estradiol was registered in 73% of MG patients (MWT, p=0.044). The lowest level of progesterone was registered in patients with EHL - 8.40, which is 4.7 times lower than in CG (MWT, p=0.0021). A statistically significant increase in the level of leptin in BS was observed in MG patients (KWT, p=0.0021). The highest level of leptin was found in women with AFP, 2.3 times higher than CG indicators. A statistically significant correlation between the level of leptin and BMI (r=0.86, p=0.011) and a statistically significant (p=0.023) correlation between the level of leptin and estradiol in BS of patients of the examined groups (r=0.42) were revealed. In 87% of MG women, vitamin D deficiency was observed in BS (KWT, p=0.03). A statistically significant (p=0.01) negative correlation between the level of estradiol and vitamin D in the BS of female patients was revealed (r=-0.61, p=0.01). CONCLUSION: Conclusions: Women of reproductive age with AUB and ED were found to have disorders in the hypothalamic-pituitary-ovarian system. Most patients are characterized by an elevated level of leptin, the concentration of which is closely correlated with BMI, and an elevated level of estradiol is correlated with the level of vitamin D.

Deletion of Nuclear Progesterone Receptors From Kisspeptin Cells Does Not Impair Negative Feedback in Female Mice.

Reproductive function in mammals depends on the ability of progesterone (P4) to suppress pulsatile gonadotrophin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion in a homeostatic-negative feedback loop. Previous research identified that cells upstream from GnRH neurons expressing the nuclear progesterone receptor (PGR) are required for P4-negative feedback. However, the identity of these cells and the mechanism by which they reduce GnRH/LH pulsatile secretion is unknown. We aimed to address the hypothesis that PGR expressed by a neural population in the arcuate nucleus recently identified as the GnRH pulse generator, cells expressing kisspeptin, neurokinin B, and dynorphin (KNDy cells), mediate P4-negative feedback. To achieve this, we used female mice with the PGR gene conditionally deleted from kisspeptin cells (KPRKO mice) and observed a substantial decrease in the percentage of KNDy neurons coexpressing PGR messenger RNA (mRNA) (11% in KPRKO mice vs 86% in wild-type [WT] mice). However, KPRKO mice did not display changes in the frequency or amplitude of LH pulses in diestrus or estrus, nor in the ability of exogenous P4 to blunt a postcastration increase in LH. Further, mRNA expression of arcuate kisspeptin and dynorphin, which are excitatory and inhibitory to GnRH secretion, respectively, remained unaltered in KPRKO mice compared to WT controls. Together, these findings show that the near-complete loss of PGR signaling from KNDy cells does not affect negative feedback regulation of GnRH pulse generation in mice, suggesting that feedback through this receptor can occur via a small number of KNDy cells or a yet unidentified cell population.

Effects of the glucagon-like peptide-1 receptor agonist dulaglutide on sexuality in healthy men: a randomised, double-blind, placebo-controlled crossover study.

BACKGROUND: The reward-regulatory properties of GLP-1 are attracting increasing interest. Animal studies show that GLP-1 receptor agonists not only reduce consumption of addictive substances, but also influence sexual behaviour. We aimed to investigate the effect of dulaglutide versus placebo on sexual desire in humans. METHODS: In this randomised, double-blind, placebo-controlled crossover trial, healthy eugonadal men of normal weight, aged 18-50 years with active and satisfactory sex lifes were (1:1) randomly allocated to dulaglutide or placebo for four weeks. We assessed sexual desire (Massachusetts General Hospital-Sexual Functioning Questionnaire [MGH-SFQ]), hormones of the hypothalamic-pituitary-gonadal axis (total testosterone, follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and sperm parameters. Changes in these parameters were compared under dulaglutide versus placebo using paired t-tests. FINDINGS: 24 out of 26 randomised participants completed the study (13 participants randomised to dulaglutide first and 13 to placebo first). No change in the MGH-SFQ was observed after four weeks of dulaglutide versus placebo (estimated difference 0.58 [95% CI -0.83 to 2.00], p-value = 0.402). Hormones of the hypothalamic-pituitary-gonadal axis (estimated differences: total testosterone (nmol/l) 0.9 [95% CI -1.5 to 3.3], FSH (IU/l) -0.2 [95% CI -0.3 to 0.0] and LH (IU/l) -0.8 [95% CI -1.5 to 0.0]) as well as sperm parameters all remained in the normal range without significant differences between the treatments. No severe adverse events occurred. INTERPRETATION: In this study of healthy men, we found no evidence of negative impacts of a four-week treatment with the widely used GLP-1 receptor agonist dulaglutide on sexual desire, hypothalamic-pituitary-gonadal axis hormones or sperm parameters. FUNDING: Swiss National Science Foundation (PZ00P3_193206), Gottfried and Julia Bangerter-Rhyner Foundation, Goldschmidt-Jacobson Foundation, Swiss Academy of Medical Sciences.

Menstrual Cycle Variations in Wearable-Detected Finger Temperature and Heart Rate, But Not in Sleep Metrics, in Young and Midlife Individuals.

Most studies about the menstrual cycle are laboratory-based, in small samples, with infrequent sampling, and limited to young individuals. Here, we use wearable and diary-based data to investigate menstrual phase and age effects on finger temperature, sleep, heart rate (HR), physical activity, physical symptoms, and mood. A total of 116 healthy females, without menstrual disorders, were enrolled: 67 young (18-35 years, reproductive stage) and 53 midlife (42-55 years, late reproductive to menopause transition). Over one menstrual cycle, participants wore Oura ring Gen2 to detect finger temperature, HR, heart rate variability (root mean square of successive differences between normal heartbeats [RMSSD]), steps, and sleep. They used luteinizing hormone (LH) kits and daily rated sleep, mood, and physical symptoms. A cosinor rhythm analysis was applied to detect menstrual oscillations in temperature. The effect of menstrual cycle phase and group on all other variables was assessed using hierarchical linear models. Finger temperature followed an oscillatory trend indicative of ovulatory cycles in 96 participants. In the midlife group, the temperature rhythm's mesor was higher, but period, amplitude, and number of days between menses and acrophase were similar in both groups. In those with oscillatory temperatures, HR was lowest during menses in both groups. In the young group only, RMSSD was lower in the late-luteal phase than during menses. Overall, RMSSD was lower, and number of daily steps was higher, in the midlife group. No significant menstrual cycle changes were detected in wearable-derived or self-reported measures of sleep efficiency, duration, wake-after-sleep onset, sleep onset latency, or sleep quality. Mood positivity was higher around ovulation, and physical symptoms manifested during menses. Temperature and HR changed across the menstrual cycle; however, sleep measures remained stable in these healthy young and midlife individuals. Further work should investigate over longer periods whether individual- or cluster-specific sleep changes exist, and if a buffering mechanism protects sleep from physiological changes across the menstrual cycle.

Central δ/κ opioid receptor signaling pathways mediate chronic and/or acute suckling-induced LH suppression in rats during late lactation.

In mammals, secretion of tonic (pulsatile) gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) is often suppressed during lactation. Suppression of GnRH/LH pulses in lactating dams is assumed to be caused by suckling stimuli and a chronic negative energy balance due to milk production. The present study aimed to investigate whether the central enkephalin-δ opioid receptor (DOR) signaling mediated the suppression of LH secretion by acute suckling stimuli and/or chronic negative energy balance due to milk production in rats during late lactation when dams were under a heavy energy demand. On postpartum day 16, the number of Penk (enkephalin mRNA)-expressing cells in the arcuate nucleus was significantly higher in lactating rats than in non-lactating control rats. Pulsatile LH secretion was suppressed in rats with chronic suckling or acute 1-h suckling stimuli 6 h after pup removal on day 16 of lactation. Central DOR antagonism significantly increased the mean LH concentrations and the baseline of LH pulses in rats with chronic suckling but not with acute suckling stimuli on day 16 of lactation. Besides, central κ opioid receptor (KOR) antagonism increased the amplitude of LH pulses in rats with the acute suckling stimuli on day 16 of lactation. These results suggest that central DOR signaling mediates the suppression of LH secretion caused by a negative energy balance in rats receiving chronic suckling during late lactation. On the other hand, central KOR signaling likely mediates acute suckling stimuli-induced suppression of LH secretion in rats during late lactation.