Elevated Luteinizing Hormone Research Articles

Menopause and lipid profile; a comparative observational study

Introduction: Hormonal changes after menopause such as low plasma estrogen levels and elevated Luteinizing Hormone and Follicle Stimulating Hormone levels had a significant effect on plasma lipid metabolism. The incidence of atherosclerotic diseases is more in postmenopausal women compared to premenopausal women. The objective of this study was to find out the effect of menopause on lipid profile among apparently healthy postmenopausal women. Method: This was an unmatched comparative observational study carried out among apparently healthy pre and postmenopausal women aged between 35-65 years presented at the General Health Check-up OPD of Tribhuvan University Teaching Hospital, Nepal from May 2019 to June 2020.The sample size was 128 in each group and data were analyzed using an independent t-test to compare the mean between the two groups and were considered significant when the p-value is less than 0.05. Result: Among 128 postmenopausal women, mean total cholesterol 191.59±35.78 mg/dl, triglyceride 143.44±72.39 mg/dl, HDL-cholesterol 45.01±9.99 mg/dl, LDL-cholesterol116.43±31.79 mg/dl and VLDL cholesterol was found to 28.69±14.48 mg/dl. Similarly, among 128 premenopausal women, mean TC 164±35.03 mg/dl, TGs 125.52±65.84mg/dl, HDL cholesterol 41.66±7.66 mg/dl, LDL-cholesterol96.95 ±31.78 mg/dl and VLDL-cholesterol was found to 25.10 ± 13.17 mg/dl. Mean TC, TGs, LDL-cholesterol, and VLDL-cholesterol along with cardiac risk ratio (TC/HDL and LDL/HDL) were found to be statistically significantly higher in postmenopausal women compared to premenopausal women. We also observed significantly higher HDL cholesterol in the postmenopausal group. Conclusion: Menopause leads to an increase in mean TC, TGs, LDL-cholesterol, and VLDL-cholesterol along with an increased cardiac risk ratio among postmenopausal women compared to premenopausal women.

Bisphenol S stimulates Leydig cell proliferation but inhibits differentiation in pubertal male rats through multiple mechanisms.

Bisphenol S (BPS) is a novel bisphenol A (BPA) analogue, a ubiquitous environmental pollutant that disrupts male reproductive system. Whether BPS affects Leydig cell maturation in male puberty remains unclear. Male Sprague-Dawley rats (age of 35 days) were daily gavaged to 0, 1, 10, 100, and 200 mg/kg/day from postnatal days 35-56. BPS at 1-10 mg/kg/day and higher doses markedly reduced serum testosterone and progesterone levels but it at 200 mg/kg/day significantly increased estradiol level. BPS at 100 and 200 mg/kg/day significantly elevated serum luteinizing hormone (LH) levels. BPS at 1-10 mg/kg/day and higher doses significantly reduced inhibin A and inhibin B levels. BPS at 100 and 200 mg/kg/day markedly increased CYP11A1+ Leydig cell number, but did not affect HSD11B1+ (a mature Leydig cell marker) cell number. BPS at 10 mg/kg/day and higher doses significantly downregulated the expression of Cyp11a1 and at 100 and 200 mg/kg/d significantly lowered Cyp17a1, Hsd11b1, and Nr5a1 in the testes. BPS at 100 and/or 200 mg/kg/day significantly elevated Lhb in the pituitary. BPS at 100 and 200 mg/kg/day significantly increased the phosphorylation of AKT1, AKT2, and CREB without affecting total AKT1, AKT2, and CREB levels. BPS at 1-100 μM significantly suppressed testosterone production and induced proliferation of primary immature Leydig cells after 24 h of treatment and these actions were reversed by estrogen receptor α antagonist, ICI 182780, and partially reversed by vitamin E. BPS at 0.1-10 μM significantly increased oxidative stress of Leydig cells in vitro. BPS also directly inhibited 17β-hydroxysteroid dehydrogenase 3 activity at 10-100 μM. In conclusion, BPS causes hypergonadotropic androgen deficiency in male rats during pubertal exposure via activating ESR1 and inducing ROS in immature Leydig cells and directly inhibiting 17β-hydroxysteroid dehydrogenase 3 activity.

Microglia: Sculptors of the polycystic ovary syndrome (PCOS)-like brain?

Several lines of evidence support a role for the brain in both the development and maintenance of polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility worldwide. Persistently elevated luteinizing hormone secretion and impaired gonadal steroid hormone feedback in PCOS patients suggests impairments within the neuronal networks that regulate the reproductive axis. Evidence from preclinical models has linked androgen excess during prenatal life with altered structure and function of the developing female brain that might underpin disease development in adulthood. Studies investigating the mechanisms by which excess androgens program changes in the female brain have highlighted an important role for microglia. This review discusses how these non-neuronal cells shape the developing female brain in response to excess androgens and focuses on how microglia may be involved in the development of the neuroendocrine dysfunctions associated with PCOS.

Immune checkpoint inhibitor effects on male reproduction.

e16528 Background: Immune checkpoint inhibitors (ICI) have been shown to improve overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) as compared to previous therapy with multi-kinase inhibitors (MKI). However, little is known about the effects of these drugs on male reproductive capacity and the current data regarding effects of MKI and ICI therapies on gonadal function and fertility are both limited and conflicting. We sought to evaluate effects of MKI and ICI on male reproductive function in patients with RCC. Methods: Male patients with RCC receiving MKI or ICI for a period of at least 3 months were identified. Inclusion criteria included age ≤ 50 years, no prior history of chemotherapy, and no prior history of medical or surgical conditions that would affect spermatogenesis such as hypogonadism, Klinefelter syndrome, or vasectomies. Patients were instructed to abstain from ejaculation 2 to 7 days prior to study collection. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), morning testosterone, and a semen analysis was obtained for each patient and analyzed. Results: Of 10 patients, 5 (50%) were on ICI and 5 (50%) were on MKI. Of the patients on ICI, 2 (40%) exhibited abnormal semen morphology, motility, and sperm concentration. Of the patients on ICI, one exhibited elevated LH and FSH levels and one exhibited elevated LH levels only. Of the patients on MKI, 2 (40%) exhibited abnormal semen morphology, motility, and sperm concentration. One patient on MKI exhibited elevated LH and FSH levels. All patients had normal testosterone levels. Conclusions: Our preliminary descriptive data analysis suggests that both ICI and MKI may affect semen morphology and motility, sperm concentration, and LH and FSH levels, but does not affect testosterone levels. Due to the currently limited sample size, abnormal semen analysis and hormone levels may be attributable to confounding factors, such as performance status, the metastatic disease itself, comorbidities, etc. Study recruitment and analysis are ongoing.

Effect of 12-months testosterone replacement therapy on bone mineral density and markers of bone turnover in testicular cancer survivors – results from a randomized double-blind trial

Background Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. Methodology In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). Results After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): −0.01 − 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: −0.01–0.03), BMD of the left femoral neck: 0.00, (95% CI: −0.01–0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. Conclusion 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort.

Ovulatory-cycle frozen embryo transfer: spontaneous or triggered ovulation and the impact of LH elevation at hCG triggering

The effect of the luteinizing hormone (LH) elevation before the human chorionic gonadotropin (hCG) trigger in ovulatory frozen-thawed embryo transfer (Ovu-FET) cycles has not been determined. We aimed to investigate whether triggering ovulation in Ovu-FET cycles affects the live birth rate (LBR), and the contribution of elevated LH at the time of hCG trigger. This retrospective study included Ovu-FET cycles performed in our center from August 2016 to April 2021. Modified Ovu-FET (hCG trigger) and true Ovu-FET (without hCG trigger) were compared. The modified group was divided according to whether hCG was administered, before or after LH increased to > 15 IU/L and was twice the baseline value. The modified (n = 100) and true (n = 246) Ovu-FET groups and both subgroups of the modified Ovu-FET, those who were triggered before (n = 67) or after (n = 33) LH elevation, had comparable characteristics at baseline. Comparison of true vs. modified Ovu-FET outcomes revealed similar LBR (35.4% vs. 32.0%; P = 0.62), respectively. LBR were similar between the modified Ovu-FET subgroups regardless of the hCG trigger timing (31.3% before vs. 33.3% after LH elevation; P = 0.84). In conclusion, LBR of Ovu-FET were not affected by hCG trigger or whether LH was elevated at the time of hCG trigger. These results add reassurance regarding hCG triggering even after LH elevation.

Effect of methylphenidate on the onset of puberty and reproductive organ development in rats

Methylphenidate (MPH) is the first-line therapy for attention deficit hyperactivity disorder (ADHD) in children and adolescents. The aim of this study was to investigate the effects chronic MPH administration on reproductive parameters in both male and female pre-pubertal rats and reversibility of these effects. Sprague-Dawley rats were administered with 5 mg/kg MPH or saline orally from postnatal day (PND) 21 to PND60 and from PND21 to PND90. In addition, recovery groups from both sexes, in which MPH administration was stopped from PND60 to PND90 were included. Puberty onset, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol levels were determined. Histopathology of male and female reproductive organs was examined. Puberty onset was significantly early in the males (p<0.01), but late in females (p<0.05). In males, serum LH and FSH levels were similar. Testosterone levels tended to decrease in MPH-treated animals. Morphology of testes, epididymis and vas deferens was disrupted in MPH-treated animals, while it was improved in the recovery group. In females, estradiol levels decreased in MPH-treated group compared to controls, and elevated LH levels were detected in recovery group. Similar to the males, disruption in the reproductive organ histology was seen with morphological deterioration in basement membrane of the ovaries of MPH-treated groups. These adverse effects of MPH were recovered after drug cessation for 30 days. The present results demonstrate that MPH could affect the reproductive functions in both male and female rats. However, our findings also suggest that those effects are transient.

Role of luteinizing hormone elevation in outcomes of ovulation induction with letrozole for polycystic ovary syndrome.

The effect of elevated luteinizing hormone (LH) on the clinical outcomes of ovulation induction (OI) in infertile anovulatory patients with polycystic ovary syndrome (PCOS) remains controversial. This retrospective study included PCOS patients undergoing intrauterine insemination (IUI) following letrozole (LE) stimulation without OC pretreatment. A retrospective cohort analysis was conducted in a single, academic ART center from January 2013 to May 2019. In total, 835 IUI cycles of PCOS patients treated with letrozole were collected for the analysis. Cohorts were separated based on the level of basal LH (bLH) and LH level after letrozole administration (LHle) during OI. OI response and reproductive outcomes were evaluated for each cohort. No adverse effects of dysregulated levels of either bLH or LHle on ovulation rate or reproductive outcomes were observed. Furthermore, the cohort of individuals with normal bLH and high LHle levels, exclusive of LH surge, exhibited significantly higher rates of clinical pregnancy (30.3% vs. 17.3%, p = 0.002) and live birth (24.2% vs. 15.2%, p = 0.024) than those with normal bLH and normal LHle. These results indicated that high LH levels in PCOS are not solid evidence of poor prognosis of letrozole-induced ovulation, while elevated LHle may be a prospective predictor for better OI outcomes. It seems that preinhibition of LH secretion is not needed.

Identifying risk factors for polycystic ovary syndrome in women with epilepsy: A comprehensive analysis of 248 patients.

To assess the risk factors for polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) and develop a practical approach for PCOS screening based on clinical characteristic, blood indicator, and anti-seizure medication (ASM) profiles. This cross-sectional study was conducted with 248 WWE who were consecutively enrolled from the Epilepsy Center of West China Hospital between April 2021 and March 2022. The epilepsy characteristics, blood indicators, and use of ASMs were compared between WWE with and without PCOS. Multivariate logistic regression was used to identify the factors independently associated with PCOS. The differential analysis showed that younger age at onset of epilepsy (<13 years), a history of birth hypoxia, obesity (BMI ≥25 kg/m2 ), use of levetiracetam (LEV) (≥1 year), higher levels of cholesterol, luteinizing hormone (LH) and anti-Müllerian hormone (AMH), and lower levels of sex hormone-binding globulin were associated with PCOS (p < .05). Multivariate logistic regression identified that obesity (BMI ≥25 kg/m2 ), use of LEV (≥1year), and higher levels of AMH and LH were independently associated with PCOS in WWE (p < .05). Obesity (BMI ≥25 kg/m2 ), LEV use (≥1year), and elevated AMH and LH levels suggest an increased in the probability of occurrence of PCOS in WWE. The combination of these profiles provides a practical approach for screening PCOS in WWE.

Effects of time-restricted feeding on letrozole-induced mouse model of polycystic ovary syndrome

The present study aimed to investigate whether time-restricted feeding (TRF) ameliorates metabolic and reproductive phenotypes in a letrozole-induced mouse model of polycystic ovary syndrome (PCOS). Sixty female C57BL/6 N mice were randomly divided into two groups according to the type of food received: either a chow or a 60% high-fat diet. Those mice were subcutaneously implanted with letrozole or placebo pellets at four weeks of age. Then, letrozole-treated mice were randomly assigned to different feeding regimens: (1) TRF for 4 h (ZT12–ZT16) or (2) ad libitum diet. After 4 weeks of dietary intervention, estrous cycles were determined with daily vaginal smear examination, and serial tail-tip blood sampling was performed at 5-min intervals for 2 h to measure the luteinizing hormone (LH) pulse frequency, amplitude, and mean LH levels in the diestrus cycle stage. Letrozole-treated mice in the ad libitum group demonstrated multiple PCOS-like phenotypes including ovulatory dysfunction, polycystic ovaries, and increased body weight, parametrial fat weight, adipocyte size and inflammation, and higher expression of Cyp17, Cyp19, and Fshr in the ovary, and Kiss1r and Gnrh in the hypothalamus, elevated serum testosterone levels, and more rapid and elevated LH pulsatility, with increased pulse frequency, amplitude, and mean levels in the diestrus stage, compared with the controls. After TRF for 4 weeks, those phenotypes reverted to normal levels in letrozole-treated mice, except the percentage of diestrus cycles indicating the arrest of estrous cycling which did not differ between the TRF and ad libitum groups. Our results demonstrate that TRF has therapeutic effects on the reproductive and metabolic phenotypes of a letrozole-induced mouse model of PCOS.

Ultrasonographic Evaluation and Clinicobiochemical Association in Patients with Polycystic Ovarian Disease in a Tertiary Care Hospital: A Cross-sectional Study

Introduction: Polycystic Ovarian Syndrome (PCOS) is an endocrinological disorder characterised by a combination of polycystic ovarian morphology, diverse clinical features, and abnormal biochemical indices that affects women of reproductive age. Aim: To assess the sonographic appearance of ovaries and endometrium in clinically suspected cases of PCOS and to determine the association between the sonographic appearance of ovaries and endometrium with the clinical and hormonal profile of the patient. Materials and Methods: This cross-sectional study included 53 female patients in the reproductive age group (18-35 years) who were referred to the Department of Radiology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India for pelvic ultrasonography in clinical suspicion of PCOS from September 2020 to September 2022. All patients underwent transabdominal sonography, only married individuals with abdominal obesity underwent transvaginal ultrasonography. Complete biochemical hormonal analysis was performed. Association between volume, size of the ovary, number of follicles, and stromal thickness with hormones like Follicle Stimulating Hormone (FSH), Luteinising Hormone (LH), testosterone, prolactin, Thyroid Stimulating Hormone (TSH) was analysed. All continuous variables were expressed as mean±standard deviation and categorical variables as percentages. Chi-square test was used for statistical analysis. Results: The mean age was 25.60±4.09 years and the majority 26 (49.1%) were between 18 to 25 years and presented with menstrual abnormalities. Volume of ovary was ≥10 cc in 41 (93.18%) patients with LH &gt;6.7 IU/mL which was statistically significant (p=0.03) and LH/FSH ratio was &gt;2:1 in 30 patients of which 28 (93.3%) had ovarian volume ≥10 cc which was statistically significant (p=0.03). A number of follicles &gt;12 showed a significant association with LH (p=0.04), LH/FSH (p=0.01), testosterone (p=0.002). Stromal thickness also showed significant association with LH (p=0.018), LH/FSH (p=0.001), testosterone (p=0.04). Conclusion: Predominant patients with PCOS had enlarged ovaries with multiple (&gt;12), small-sized (&lt;9 mm) peripherally arranged follicles and low FSH and elevated LH, LH/FSH ratio, testosterone, TSH, and prolactin levels.

Effects of aging and the body mass index on male sex hormones: a cross-sectional study in 701 Brazilian men

Background: Some studies indicated that body mass index (BMI) is inversely proportional to serum testosterone concentrations in men. Purposes: This study aimed to analyze the effects of aging and obesity on total testosterone (TT), free testosterone (FT), bioavailable testosterone (BT), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels. Methods: A cross-sectional study was performed to assess the clinical and laboratory profiles of 701 patients treated at a private urology clinic in Ponta Grossa, Brazil, from January 2016 to December 2018. Results: Patients’ age ranged from 16 to 88 years (mean, 56.9 ± 13.62 years). Age did not significantly influence serum TT concentrations, except compared to patients aged &gt;70 years. However, changes were observed in FT and BT (p &lt; 0.05). The mean SHBG increased with age (p &lt; 0.05). A tendency toward LH elevation was observed in older patients, but it was not statistically significant. An inverse proportional relationship between TT, FT, and BT and the testosterone deficiency rate (TT &lt; 300 ng/dL) was observed within BMI groups (p &lt; 0.05). The testosterone deficiency rate was 21.5% in individuals with normal BMI, 29% in overweight individuals, and 37% in obese individuals. Conclusions: Aging affected the testosterone concentrations in men and became increasingly evident using FT and BT instead of TT. SHBG increased with age. Obesity was associated with a decrease in TT, FT, and BT but also increased the rate of hypogonadism.

Comparison of characteristics between Chinese diabetes mellitus-induced erectile dysfunction populations and non-diabetes mellitus-induced erectile dysfunction populations: A cross-sectional study.

Erectile dysfunction (ED) is a common disease in adult men, and diabetes is an independent risk factor for ED. However, there are few reports on the distinction between diabetes mellitus-induced erectile dysfunction (DMED) and non-DMED features, as well as ED features of varying severity in the two groups. A total of 365 ED patients treated at two clinics in China from 2019 to 2022 were included. Questionnaires of the International Index of Erectile Function (IIEF-5), Erectile Hardness Score (EHS), Premature Ejaculation Diagnostic Tool (PEDT), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) were administered to the patients. They were divided into three groups according to the IIEF-5 score: 5-7 for severe ED, 8-11 for moderate ED, and 12-21 for mild ED. In addition, the patient's age, weight, height, fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), total testosterone (TT) and other indicators were also collected. Statistical analysis was performed using SPSS 26, comparing all parameters between groups. Age (P<0.001), height (P=0.009), body mass index (BMI) (P=0.002), PEDT (P<0.001), FBG (P<0.001), FSH (P<0.001), TG (P<0.001), TT (P<0.001) and triglyceride-glucose index (TyG) (P<0.001) were significantly different between diabetic ED and nondiabetic ED subjects. The trend test in the nondiabetic ED population found a negative correlation between the IIEF-5 score and PHQ-9 (P for trend=0.15). Multivariate ordinal logistic regression in the diabetic ED population showed that elevated LH OR=11.37 (95% CI: 0.966, 3.897) and elevated PRL OR=4.10 (95% CI: 0.410, 2.411) were associated with an increased risk of more severe ED. The aetiology, demographic parameters, degree of premature ejaculation, and related biochemical tests were significantly different between the DMED and non-DMED populations.

Associations of Serum Follicle-Stimulating Hormone and Luteinizing Hormone Levels with Fat and Lean Mass during Menopausal Transition

Introduction: The association of serum follicle-stimulating hormone (FSH) levels with body fat mass remains inconclusive. Furthermore, little was known about the association of luteinizing hormone (LH) with body fat. This study aimed to investigate the associations of serum FSH and LH levels with fat and lean mass in women during menopausal transition. Methods: The data analyzed in this study were derived from the National Health and Nutrition Examination Survey from 1999 to 2002. Women aged from 35 to 60 years were eligible. Serum FSH and LH levels were assayed using the microparticle enzyme immunoassay technology. A dual energy X-ray absorptiometry was used to measure body fat mass and lean mass. Fat mass index (FMI) and fat-free mass index (FFMI) were respectively used to assess fat and lean mass. General linear regression was employed to examine the associations of serum FSH and LH levels with FMI and FFMI. Results: This study included 1,329 women. For the total participants, elevated serum FSH and LH levels were associated with an increased FMI (β = 0.004 and 0.007; 95% CI: 0.002, 0.006 and 0.004, 0.010, respectively) and a decreased FFMI (β = −0.004 and −0.007; 95% CI: −0.006, −0.002 and −0.010, −0.004, respectively). Furthermore, the significant associations of serum FSH and LH levels with FMI and FFMI were fully observed in postmenopausal women, especially in a certain range of higher serum FSH and LH quartiles. Conclusion: Elevated serum FSH and LH levels were associated with increased body fat mass but decreased lean mass in postmenopausal women but not in premenopausal women. Furthermore, only higher serum FSH and LH percentiles were associated with fat and lean mass in postmenopausal women.

Aging and androgens: Physiology and clinical implications.

In men > ~35years, aging is associated with perturbations in the hypothalamus-pituitary-testicular axis and declining serum testosterone concentrations. The major changes are decreased gonadotropin-releasing hormone (GnRH) outflow and decreased Leydig cell responsivity to stimulation by luteinizing hormone (LH). These physiologic changes increase the prevalence of biochemical secondary hypogonadism-a low serum testosterone concentration without an elevated serum LH concentration. Obesity, medications such as opioids or corticosteroids, and systemic disease further reduce GnRH and LH secretion and might result in biochemical or clinical secondary hypogonadism. Biochemical secondary hypogonadism related to aging often remits with weight reduction and avoidance or treatment of other factors that suppress GnRH and LH secretion. Starting at age ~65-70, progressive Leydig cell dysfunction increases the prevalence of biochemical primary hypogonadism-a low serum testosterone concentration with an elevated serum LH concentration. Unlike biochemical secondary hypogonadism in older men, biochemical primary hypogonadism is generally irreversible. The evaluation of low serum testosterone concentrations in older men requires a careful assessment for symptoms, signs and causes of male hypogonadism. In older men with a body mass index (BMI) ≥ 30, biochemical secondary hypogonadism and without an identifiable cause of hypothalamus or pituitary pathology, weight reduction and improvement of overall health might reverse biochemical hypogonadism. For older men with biochemical primary hypogonadism, testosterone replacement therapy might be beneficial. Because aging is associated with decreased metabolism of testosterone and increased tissue-specific androgen sensitivity, lower dosages of testosterone replacement therapy are often effective and safer in older men.

Adverse impact of elevated serum progesterone and luteinizing hormone levels on the hCG trigger day on clinical pregnancy outcomes of modified natural frozen-thawed embryo transfer cycles.

The relationship between serum progesterone (P) and luteinizing hormone (LH) levels on the human chorionic gonadotropin (hCG) trigger day and the clinical pregnancy outcomes in modified natural frozen-thawed embryo transfer (mNC-FET) cycles are controversial. This was a retrospective study of 788 mNC-FET cycles. A smooth fitting curve and threshold effect analysis was performed to identify the effect of serum P and LH levels measured on the hCG day on the clinical pregnancy rate (CPR) and live birth rate (LBR) of mNC-FET cycles. The CPR and LBR decreased significantly when the LH level on the hCG day was greater than or equal to 32 IU/L. Further subgroup analysis showed that the CPR decreased significantly when the P level on the hCG day was equal to or greater than 1 ng/mL. When the P level was lower (< 1 ng/mL), the patients with an LH level greater than or equal to 32 IU/L had reduced CPR and LBR in mNC-FET cycles. Applying the hCG trigger on a day with a higher P level (≥ 1 ng/mL) leads to a decreased CPR and LBR. hCG administration with a higher LH level (≥ 32 IU/L) also leads to a decreased CPR and LBR in mNC-FET cycles when the P level is less than 1 ng/mL.

Socially Induced Infertility in Naked and Damaraland Mole-Rats: A Tale of Two Mechanisms of Social Suppression.

The naked mole-rat (Heterocephalus glaber) and the Damaraland mole-rat (Fukomys damarensis) possess extreme reproductive skew with a single reproductive female responsible for reproduction. In this review, we synthesize advances made into African mole-rat reproductive patterns and physiology within the context of the social control of reproduction. Non-reproductive female colony members have low concentrations of luteinising hormone (LH) and a reduced response of the pituitary to a challenge with gonadotropin releasing hormone (GnRH). If the reproductive female is removed from the colony, an increase in the basal plasma LH and increased pituitary response to a GnRH challenge arises in the non-reproductive females, suggesting the reproductive female controls reproduction. Non-reproductive male Damaraland mole-rats have basal LH concentrations and elevated LH concentrations in response to a GnRH challenge comparable to the breeding male, but in non-breeding male naked mole-rats, the basal LH concentrations are low and there is a muted response to a GnRH challenge. This renders these two species ideal models to investigate physiological, behavioural and neuroendocrine mechanisms regulating the hypothalamic-pituitary-gonadal axis. The recently discovered neuropeptides kisspeptin and RFamide-related peptide-3 are likely candidates to play an important role in the regulation of reproductive functions in the two mole-rat species.

Reduced-Intensity Conditioning Mitigates Risk for Primary Ovarian Insufficiency but Does Not Decrease Risk for Infertility in Pediatric and Young Adult Survivors of Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for many pediatric malignant and nonmalignant conditions. Gonadal insufficiency or infertility is present in almost all HSCT survivors who received a myeloablative conditioning (MAC) regimen. Reduced-intensity conditioning (RIC) regimens are being increasingly used in medically fragile patients or in patients with nonmalignant diagnoses to limit the toxicities associated with HSCT; however, the short-term and long-term gonadal toxicity of RIC regimens in pediatric and young adult survivors remains unknown. In this study, we compared the prevalence of gonadal insufficiency and infertility among pubertal and postpubertal pediatric and young adult survivors of HSCT who received a RIC regimen versus those who received a MAC regimen. Twenty-three females (RIC, n=8; MAC, n=15) and 35 males (RIC, n=19; MAC, n=16) were included in this single-center, retrospective cross-sectional study. Eligible patients were those with available laboratory results who were ≥1 year post-HSCT, age <40 years, and pubertal or postpubertal as assessed by an endocrinologist. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) levels were measured in females, and FSH, LH, total testosterone, and inhibin B (InhB) levels were measured in males. Twenty-one males (RIC, n=11; MAC, n=10) underwent semen analysis through a separate consent. Parametric and nonparametric analyses were undertaken to compare the RIC and MAC groups. Female patients who received RIC were less likely than those who received MAC to develop primary ovarian insufficiency, as demonstrated by elevated FSH (P=.02) and low estradiol (P=.01) or elevated LH (P=.09). Most females in the RIC (75%) and MAC (93%) groups had low AMH levels, indicating low or absent ovarian reserve, with no significant difference between the groups (P=.53). In males, there were no significant differences between the 2 groups in the prevalence of abnormal FSH, LH, testosterone, or InhB levels. Ten of 11 RIC males (91%) and 10 of 10 MAC males (100%) had azoospermia or oligospermia, at a median time to semen analysis from HSCT of 3.7 years (range, 1.3 to 12.2 years). RIC may pose less risk than MAC for primary ovarian insufficiency among female survivors of HSCT; however, both female and male recipients of either RIC or MAC regimens are at high risk for infertility. In the largest reported series of semen analyses of pediatric and young adult male recipients of RIC, azoospermia or oligospermia was found in nearly all (91%) RIC survivors. All patients undergoing HSCT should receive counseling about the high risk of gonadal toxicity, and efforts should be made to preserve fertility in patients undergoing either RIC or MAC.

A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention).

Elevated luteinizing hormone (LH) in combination with low-normal testosterone (mild Leydig cell insufficiency) is common in testicular cancer (TC) survivors and is associated with impaired insulin sensitivity and metabolic syndrome. The aim was to evaluate if testosterone replacement therapy (TRT) improves metabolic health in this subgroup of TC survivors. This was a single-center, double-blind, randomized, controlled trial. The main eligibility criterion was LH above the age-adjusted upper limit of normal in combination with free testosterone in the lower half of the age-adjusted normal range (mild Leydig cell insufficiency) >1 year after TC treatment. Eligible patients were randomly assigned (1:1) to 12 months transdermal TRT (Tostran, gel, 2%) or placebo with a maximum daily dose of 40 mg. The primary outcome was difference in Δ2 hour glucose measured with oral glucose tolerance test between groups assessed at 12 months. Outcomes were assessed after 6-, 12- and 3 months post-treatment. The study was registered at www. gov (NCT02991209) and ended June 2019. Between October 2016 and February 2018, 140 patients were screened for eligibility and 69 were randomized to testosterone (n=35, 51%) or placebo (n=34, 49%). TRT was not associated with a statistically significant difference in Δ2 hour glucose compared to placebo after 12 months of treatment (0.04 mmol/L (95% CI: -0.53, 0.60)). There was no statistically significant difference in Δ2 hour insulin between the groups after 12 months of treatment (28.23 pmol/L (95% CI: -34.40, 90.86)). Similarly, TRT was not associated with significant improvement in components of metabolic syndrome. TRT was associated with a decrease in fat mass after 12 months compared to placebo (-1.35 kg, (95% CI: -2.53, -0.18)). In TC survivors with mild Leydig cell insufficiency, TRT was not associated with improvement of metabolic health. These findings do no not support routine use of TRT in these patients.

Effects of Secretoneurin and Gonadotropin-Releasing Hormone Agonist on the Spawning of Captive Greater Amberjack (Seriola dumerili).

The greater amberjack (Seriola dumerili), a pelagic marine species with a global distribution, has considerable worldwide potential as an aquaculture species. However, difficulties have been encountered in inducing spontaneous spawning in cultured fish stocks. In this study, we analysed the key regulatory factors, secretoneurin (SN) and gonadotropin-releasing hormone (GnRH), in greater amberjack. Active peptides of SN and GnRH, SdSNa, and SdGnRH, respectively, were obtained by comparative analysis of homologous proteins from different species. Amino acid substitutions of the SdGnRH decapeptide at position 6 with a dextrorotatory (D) amino acid and at position 10 with an ethylamide group yielded a super-active agonist (SdGnRHa). The injection of SdSNa and SdGnRHa elevated luteinizing hormone, thyroid-stimulating hormone, and oxytocin levels in the sera of sexually mature fish, whereas it reduced the level of follicle-stimulating hormone. Furthermore, in response to the SdSNa and SdGnRHa injections, we detected an increase in the expression of genes associated with oocyte development and spermatogenesis. We established that the greater amberjack cultured along the southern coast of China reached sexual maturity at three years of age, and its reproductive season extended from February to April. Spawning of the cultured greater amberjack was successfully induced with a single injection of SdGnRHa/SdSN/DOM/HCG. Our findings indicate that similar to GnRHa, SNa is a potential stimulator of reproduction that can be used to artificially induce spawning in marine fish.