Decrease In Luteinizing Hormone Levels Research Articles

Key role of CYP17A1 in Leydig cell function and testicular development in Qianbei Ma goats

Reproductive traits are vital economic parameters in goat production, and boosting the reproductive capacity of breeding rams is crucial for enhancing the profitability of goat farming. Currently, research on the reproductive performance of Qianbei Ma goats mainly centers on investigating mechanisms associated with prolificacy and estrous ovulation in ewes, with limited emphasis on ram reproductive aspects. This study used scanning electron microscopy and enzyme-linked immunosorbent assay (ELISA) to profile the morphology of testis and the dynamic changes of Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), and Testosterone (T) in serum at different developmental stages of Qianbei Ma goats. Meanwhile, transcriptome sequencing technology was used to investigate the mRNA expression patterns in testicular tissues at different developmental stages: newborn (0 M), puberty (6 M), sexual maturity (12 M), and physical maturity (18 M). The results showed that the diameter, circumference, and area of the testicular seminiferous tubules gradually increased with age. The levels of T and LH in serum significantly increased from 0 to 6 months after birth (p < 0.05), followed by a stabilization of T levels and a significant decrease in LH levels (p < 0.05). Meanwhile, FSH shows a decreasing trend between 0 and 18 months after birth. A total of 26,437 differentially expressed genes were identified in 6 comparison groups, which involve various biological processes such as immunity, growth, metabolism, development, and reproduction, and are significantly enriched in signaling pathways related to testicular development and spermatogenesis. WGCNA analysis identified 6 regions significantly associated with testicular development and spermatogenesis, and selected 320 genes for constructing a PPI network. Ten candidate genes related to testicular development and spermatogenesis were identified, including TP53, PLK4, RPS9, PFN4, ACTB, CYP17A1, GPX4, CLDN1, AMH and DHH. Of these, the CYP17A1 gene promotes interstitial cell proliferation, and promotes T synthesis. This study provides a theoretical basis and data support for promoting efficient breeding of goats and early breeding of excellent male goats.

Therapeutic effects of Artocarpus communis J.R.Forst. & G.Forst. seeds on letrozole-induced polycystic ovary syndrome wistar rats

BackgroundHerbal extracts are an effective treatment for polycystic ovarian syndrome (PCOS) and have been shown to improve insulin resistance, hyperandrogenism, sex hormones, ovulation, and PCOS symptoms. Artocarpus communis seed's potential effects on polycystic ovary syndrome (PCOS) have not been studied. PurposeThis research aims to investigate the beneficial effects of Artocarpus communis seeds on PCOS induced by letrozole in Wistar rats. MethodsTo induce PCOS, female Wistar rats weighing between 160 g to 250 g were administered letrozole (1 mg/kg) for 21 days. Subsequently, for 12 days, the rats were given the Artocarpus communis seed methanol extract, and its hexane, DCM, ethyl acetate and aqueous fractions (100 mg/kg body weight) and Clomiphene citrate (1 mg/kg body weight), a standard medication. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels were assessed using ELISA, and the expression of P53, insulin receptor substrate (IRS), type 2 17-HSD (17-HSD), fat mass and obesity-associated (FTO), and 11a-hydroxylase/17,20-desmolase (CYP11a) genes were investigated. The data were analyzed using one-way ANOVA, and a significance threshold of p < 0.05 was set for Dunnett's Multiple Comparison Test. ResultsAdministration of the methanol extract of Artocarpus communis seed and its Hexane fraction led to a decrease in LH level and an increase in FSH and estradiol levels in the PCOS-induced animals. Furthermore, methanol extract, DCM, and ethyl acetate fraction normalize the expression of P53, insulin receptor substrate (IRS), type 2 17-HSD (17-HSD), fat mass and obesity-associated (FTO), and 11a-hydroxylase/17,20-desmolase (CYP11a) genes in PCOS rats cervix. ConclusionArtocarpus communis seed exhibited ameliorative effects on polycystic ovary conditions in Wistar rats, suggesting its potential use in the management of PCOS.

The impact of Apis dorsata forest honey administration on follicle-stimulating hormone and luteinizing hormone levels in rats (Rattus norvegicus) forced swim test as a chronic physical animal model.

Chronic physical stress has many effects on the nervous system and can cause structural changes in different parts of the brain and hemomodulatory, including hormonal. Current pharmacotherapeutic treatments have limited efficacy and are associated with many deleterious side effects. The aim of this research is to determine how Apis dorsata forest honey administration affects follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in rats who are subjected to forced swim tests as a model of chronic physical stress placed in a container filled with water from which it cannot escape. This was an experimental laboratory study with 32 rats divided into four treatment groups: control (C), Treatment 1 (T1) with a forced swim test + honey (2 g/rat/day), Treatment 2 (T2) with a forced swim test + honey (4 g/rat/day), and Treatment 3 (T3) with a forced swim test + honey (6 g/rat/day). All treatments were administered for 14 days. Then, blood was taken for FSH and LH serum tests, and a one-way ANOVA and Duncan test were used to statistically test the data analysis. The results of this study indicate that the administration of forest honey had no significant effect (p > 0.05) on the FSH parameter, but there was a significant decrease in LH levels in the T2 and T3 groups (p < 0.05). It can be concluded that giving forest honey to rats who were subjected to a 14-day forced swim test had no effect on FSH and LH levels. In rats given a forced swim test as a model of chronic stress, administration at doses of 4 and 6 g/rat/day reduced LH serum levels. Thus, giving forest honey could maintain reproductive health in rat that experience chronic stress.

#106 : The Efficacy of Intra-Ovarian Infusion of Autologous Platelet-Rich Plasma in Patients with Poor Ovarian Response: A Systematic Review and Meta-Analysis

Background and Aims: Poor ovarian response (POR) is a pathological condition characterized by a reduced ovarian response to gonadotropin stimulation. This condition presents with a low number of developed follicles during the ovulation induction cycle, low blood estradiol (E2) peak, high gonadotropin dosage, fewer retrieved oocytes, increased cycle cancellation rate, and low clinical pregnancy rate. POR is a significant challenge in assisted reproductive technology. Autologous platelet-rich plasma (PRP) has emerged as a potential therapy for POR, but its efficacy remains controversial. This meta-analysis aims to determine the effect of intraovarian infusion of PRP on ovarian reserve and pregnancy outcomes in patients with POR. Methods: This study was designed as a Meta-analysis. Women diagnosed with POR based on POSEIDON or Bologna criteria were included. Primary outcomes included anti-Müllerian hormone (AMH), antral follicle count (AFC), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and E2 levels, while secondary outcomes were the number of retrieved oocytes and embryo quality. Results: Seven prospective cohort studies involving 202 participants were included. Intra-ovarian infusion of autologous PRP significantly increased AMH (SMD: 0.20, 95% CI: 0.05–0.36; P=0.01), AFC (SMD: 0.92, 95% CI: 0.59–1.25, P&lt;0.05), and E2 (SMD: 3.46, 95% CI: 1.13–5.79; P=0.004) levels in patients with POR. PRP also decreased LH levels in POR (SMD: −1.17, 95% CI: −2.28 to −0.06; P=0.04). However, no statistically significant effect on FSH levels in POR was observed (SMD: −0.17, 95% CI: −0.78 to 0.44; P=0.59). Furthermore, PRP positively impacted the number of retrieved oocytes and embryo quality in IVF cycle patients. Conclusion: This meta-analysis indicates that intra-ovarian injection of autologous PRP can improve ovarian reserve and pregnancy outcomes in patients with POR.

Effects of Low Luteinizing Hormone Serum Levels on Oocyte Retrieval, Fertilization Rate, and Embryo Quality during Controlled Ovarian Stimulation: Results from a Prospective Cohort Analysis

Objectives: Luteinizing hormone (LH) plays a key role in normal follicular development and oocyte maturation in controlled ovarian stimulation. LH stimulates the proliferation and differentiation of theca cells for the secretion of androgens, synergistically increasing estrogen production. This study aimed to investigate the effects of low LH concentrations on oocyte retrieval, fertilization, and embryo development in patients undergoing in vitro fertilization/intracytoplasmic sperm injection. Design: We prospectively (ClinicalTrials ID: NCT05755529) analyzed patients undergoing in vitro fertilization/intracytoplasmic sperm injection, subdividing them into three groups according to their age. Serum LH levels were evaluated on day 3, during stimulation (day 10) and before ovulation induction (day 12). Participants/Materials, Setting, Methods: Forty-three consecutive women were scheduled for IVF and received ovarian stimulation with follitropin alfa (Gonal F, Merck Serono, Germany) and ganirelix (Fyremaldel, Sun Pharma, Italy). Statistical analysis was performed with InStat 3.10, GraphPad software, San Diego, CA, USA. Normal distribution was tested by the Shapiro-Wilk test. Continuous variables were expressed as the mean and standard deviation. Categorical variables are expressed as frequencies and percentages. Results: Our data analysis suggests that serum LH levels progressively decrease during controlled ovarian stimulation, and this effect is more evident in the early phase of this procedure. From this perspective, circulating LH levels may significantly decrease during the late follicular phase due to the negative feedback of ovarian hormones from multiple follicular developments or after the suppressive effects of gonadotropin-releasing hormone antagonists. Limitations: Although our study confirms that exogenous LH can be considered a strategy in women with reduced LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome, the generalizability of the results is limited by the low number of participants enrolled. Conclusions: Exogenous LH may be considered a strategy in women with a decrease in LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome.

Association between LH level decrease on the triggering day and pregnancy outcome for IVF/ICSI patients following GnRH antagonist protocol: a retrospective cohort study

Objective: Optimal luteinizing hormone (LH) levels for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients following the GnRH antagonist protocol remain controversial. This study aimed to estimate the association between serum LH levels on the triggering day (LHLOT) and clinical pregnancy outcomes in IVF/ICSI patients following the GnRH antagonist protocol. Methods: We enrolled 4743 IVF/ICSI cycles using flexible or fixed GnRH antagonist protocols between January 2017 and June 2021. The patients were stratified into four groups according to the LHLOT quartiles (Q1-Q4). Each group was further divided into two subgroups according to the median basal LH/LHLOT. The main outcomes were clinical pregnancy, birth, and miscarriage rates. Secondary outcomes were oocyte yield, number of MII, 2PN, and high-quality embryos. Results: Serum LHLOT levels were negatively correlated with oocyte yield and the numbers of MII, 2PN, and high-quality embryos. Reproductive outcomes were compared among the different quartiles and subgroups. The absolute difference in the clinical pregnancy rates between the Q4 and Q1 groups was 6.4% (47.2% vs. 40.8%, P˂0.05). Clinical pregnancy rates between the subgroups with basal LH/LHLOT˃ 3.04 and ≤ 3.04 were 32.7% and 48.6% (P˂0.01), respectively, in Q1. Within Q3, the clinical pregnancy rates between the subgroups with basal LH/LHLOT ˃2.14 and ≤2.14 were 50.2% and 41.9%, respectively (P˂0.05). The greater the decrease in LH levels, the lower the oocyte maturation rate across all quartiles. Conclusions: According to the LHLOT quartiles, the Q1 of serum LHLOT ˂ 1.43 IU/L may result in a higher number of oocytes but reduced oocyte maturation and lower clinical pregnancy rates. A decrease in LH levels by approximately 2.14–3.04 times compared to basal LH levels may lead to higher clinical pregnancy rates in IVF/ICSI patients following the GnRH antagonist protocol.

Sperm abnormality and infertility in male mice treated with the recommended dose of dimethoate and its double.

Dimethoate (DM) is one of the most important organophosphate insecticides used for controlling many pests which affect vegetables, fruits, and agricultural crops, its persistence in soils and crops could cause a health hazard to humans as well as other non-target organisms. This study was conducted to evaluate the effect of the recommended dose and its double of DM on sex hormones, sperm morphology, and fertility of adult male mice. Twenty-seven Swiss albino adult male mice were divided into three groups of nine animals each: control group received distilled water only, while other groups received DM orally at doses (0.1 and 0.2 ml DM/100 ml distilled water) for 20 days, at the end of the treatment, six mice from each group were sacrificed. The sperm morphology was evaluated and sex hormones were measured. Three mice from each group were allowed to mate with untreated females (1:2). The results revealed a decrease in luteinizing hormone levels in mice treated with (0.2 ml DM/100 ml distilled water) compared with the control group while the levels of follicle-stimulating hormone and testosterone did not record any significant differences. Also, the results demonstrated a significant increase in abnormal sperm morphology such as head and tail. The fertility was reduced and the average number of dead embryos increased while the average number of live embryos decreased. This current study confirmed that DM has detrimental effects on sperm morphology, fertility, and the embryos; therefore, more efforts should be exerted to protect ourselves and our environment from the harmful effects of this pesticide.

Клініко-діагностичні аспекти дефіциту тестостерону в жінок фертильного віку

Актуальність. До сьогодні роль андрогенів в організмі жінки не отримала належної оцінки. Поки не існує чіткого і загальноприйнятого визначення поняття «андрогенний дефіцит у жінок» за аналогією з таким у чоловіків. Мета дослідження: вивчити клініко-діагностичні аспекти дефіциту тестостерону в жінок репродуктивного віку. Матеріали та методи. Під наглядом перебувало 60 жінок із дефіцитом тестостерону без супутньої патології. Середній вік пацієнток становив 28,3 року. Контрольну групу становили 20 здорових жінок. Пацієнтки були розподілені за показником індексу маси тіла (ІМТ) на три групи. Першу групу становили 20 жінок із надмірною масою тіла (ІМТ 25–29,9 кг/м2), другу групу— 20 жінок з ожирінням I ступеня і третю групу— 20 жінок з ожирінням II ступеня. Результати. Для пацієнток із групи з ожирінням I ступеня була характерна на 14-й день оваріально-менструального циклу тенденція до зниження базальних рівнів лютеїнізуючого гормона (ЛГ), фолікулостимулюючого гормона (ФСГ), естрадіолу і прогестерону на тлі вірогідної гіпоандрогенемії. У пацієнток із групи з ожирінням II ступеня відзначалося вірогідне зниження базальних рівнів ЛГ, ФСГ, естрадіолу, прогестерону на тлі вірогідної гіпоандрогенемії. При проведенні кореляційного аналізу виявлений прямий зв’язок дефіциту тестостерону зі ступенем ожиріння. Так, найнижчі значення тестостерону виявлені в пацієнток третьої групи (&lt;0,05нмоль/л). Водночас у пацієнток першої і другої груп рівень тестостерону також був значно знижений— від 0,02 до 0,05 нмоль/л відповідно. Вірогідно зниженими виявилися рівні дегідроепіандростерону и 17-оксипрогестерону, особливо в третій групі— 0,3 мкг/мл і 0,1 нмоль/л відповідно. Висновки. У більшості жінок репродуктивного віку з дефіцитом тестостерону спостерігається гіпоменорея з низьким вмістом вільного тестостерону. Встановлено пряму кореляційну залежність дефіциту тестостерону від ступеня ожиріння в жінок з андрогенною недостатністю.

A single dose of allopregnanolone affects the ovarian morphology and steroidogenesis.

Allopregnanolone, a progesterone metabolite, is one of the best characterized neurosteroids. In a dose that mimics serum levels during stress, allopregnanolone inhibits sexual receptivity and ovulation and induces a decrease in luteinizing hormone levels. The aim of this work was to examine the effect of an intracerebroventricular administration of allopregnanolone on ovarian morphophysiology, serum and tissue levels of progesterone and estrogen, and enzymatic activity of 3β-hydroxysteroid dehydrogenase, 20α-hydroxysteroid dehydrogenase and 3α-hydroxysteroid oxido-reductase in the ovary and in the medial basal hypothalamus on the morning of estrus. Ovarian morphology was analyzed under light microscopy. The hormone assays were performed by radioimmunoassay. The enzymatic activities were measured by spectrophotometric analysis. The morphometric analysis revealed that, in allopregnanolone-treated animals, the number of secondary and Graafian follicles was decreased while that of atretic follicles and cysts was significantly increased. Some cysts showed luteinized unruptured follicles. There were no differences in the number of tertiary follicles or corpora lutea in comparison with the corresponding control groups. In allopregnanolone-treated animals, progesterone serum levels were increased, while ovarian progesterone levels were decreased. Moreover, 3β-HSD and 3α-HSOR enzymatic activities were increased in the medial basal hypothalamus while ovarian levels were decreased. The enzyme 20α-hydroxysteroid dehydrogenase showed the opposite profile. The results of this study showed that allopregnanolone interferes on ovarian steroidogenesis and ovarian morphophysiology in rats, providing a clear evidence for the role of this neurosteroid in the control of reproductive function under stress situations.

Pesticide chlorpyrifos acts as an endocrine disruptor in adult rats causing changes in mammary gland and hormonal balance

Endocrine disruptors (EDs) are compounds that interfere with hormone regulation and influence mammary carcinogenesis. We have previously demonstrated that the pesticide chlorpyrifos (CPF) acts as an ED in vitro, since it induces human breast cancer cells proliferation through estrogen receptor alpha (ERα) pathway. In this work, we studied the effects of CPF at environmental doses (0.01 and 1mg/kg/day) on mammary gland, steroid hormone receptors expression and serum steroid hormone levels. It was carried out using female Sprague-Dawley 40-days-old rats exposed to the pesticide during 100 days. We observed a proliferating ductal network with a higher number of ducts and alveolar structures. We also found an increased number of benign breast diseases, such as hyperplasia and adenosis. CPF enhanced progesterone receptor (PgR) along with the proliferating cell nuclear antigen (PCNA) in epithelial ductal cells. On the other hand, the pesticide reduced the expression of co-repressors of estrogen receptor activity REA and SMRT and it decreased serum estradiol (E2), progesterone (Pg) and luteinizing hormone (LH) levels. Finally, we found a persistent decrease in LH levels among ovariectomized rats exposed to CPF. Therefore, CPF alters the endocrine balance acting as an ED in vivo. These findings warn about the harmful effects that CPF exerts on mammary gland, suggesting that this compound may act as a risk factor for breast cancer.

Testosterone replacement therapy in older male subjective memory complainers: double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety.

Testosterone replacement therapy (TRT) has been investigated in older men as a preventative treatment against Alzheimer's disease and dementia. However, previous studies have been contradictory. We assessed TRT physiological effects in 44 older men (aged 61 ± 7.7 years) with subjective memory complaints using a double blind, randomized, crossover, placebo-controlled study. Participants were randomized into 2 groups, one group received transdermal testosterone (50 mg) daily for 24 weeks, followed by a 4 week wash-out period, then 24 weeks of placebo; the other group received the reverse treatment. Blood evaluation revealed significant increases in total testosterone, free (calculated) testosterone, dihydrotestosterone, and a decrease in luteinizing hormone levels (p<0.001) following TRT. Although there were significant increases in red blood cell counts, hemoglobin and prostate specific antigen levels following TRT, they remained within normal ranges. No significant differences in plasma amyloid beta, estradiol, sex hormone binding globulin, insulin levels, body fat percentage, or body mass index were detected. This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men on blood biomarkers linked to dementia risk. Our study suggests TRT is safe and well-tolerated in this Indonesian cohort, yet longitudinal studies with larger cohorts are needed to assess TRT further, and to establish whether TRT reduces dementia risk.

Effect of aromatase inhibitors on the endometrium and ovary with their possible role in ovulation in adult albino rats

Introduction Aromatase inhibitors act by inhibiting estrogen synthesis and depletion of its concentrations in the circulation. Aim The aim of the study was to investigate the effect of exemestane and letrozole on the endometrium and ovary with their possible role in ovulation in adult albino rats. Materials and methods Thirty adult female albino rats were used and divided into control and experimental groups. Rats in the experimental group were further divided into subgroup IIA and subgroup IIB. In subgroup IIA each rat was given exemestane at 1 mg/kg/day and in subgroup IIB each rat was given letrozole at 5 mg/kg/day by means of a gastric tube for five consecutive ovarian cycles. Specimens from their ovaries and endometrium were taken and prepared for H&E staining and for immunohistochemical staining for vascular endothelial growth factor study. Morphometric study of endometrial thickness and surface area percentage of immunoreaction in the endometrium was evaluated. Hormonal assay of luteinizing hormone and follicular stimulating hormone was carried out. Results Significant decrease in endometrial thickness was observed in the exemestane-treated group. The letrozole-treated group revealed significantly thickened endometrium. The exemestane-treated group showed markedly disturbed ovarian architecture in the form of thickened germinal epithelial cell layer and multiple corpora lutea with atretic follicles. The letrozole-treated group revealed an ovarian cortex with multiple stages of follicular development. The vascular endothelial growth factor immunoreaction of the letrozole-treated group showed significant highly positive cytoplasmic reaction. Significant decrease in luteinizing hormone level in the exemestane group and significant increase in the letrozole group were detected. Conclusion It is concluded that letrozole improved the endometrial thickness and may have a role in ovulation induction. In contrast, exemestane led to disruption of the endometrium and ovary. Therefore, not all aromatase inhibitors help in ovulation.

Endocrine Response to a Single Injection of Goserelin 3.6 mg or Leuprolide 3.75 mg in Men with Prostate Cancer

Hormonal responses were assessed in men with prostate cancer (T2-4, Nx, Mx) who were randomized to receive either a single injection of goserelin 3.6 mg or leuprolide 3.75 mg. Testosterone increased over the first week, with a significantly higher mean rate of change of total testosterone (day 3) and free testosterone (days 3 and 7) with leuprolide. Following the initial rise in luteinizing hormone (LH), the rate of decrease in LH levels was significantly greater with goserelin by day 28. There are significant differences in endocrine response to goserelin and leuprolide in the 4 weeks following administration.

Endocrine Response to a Single Injection of Goserelin 3.6 mg or Leuprolide 3.75 mg in Men with Prostate Cancer

Hormonal responses were assessed in men with prostate cancer (T2-4, Nx, Mx) who were randomized to receive either a single injection of goserelin 3.6 mg or leuprolide 3.75 mg. Testosterone increased over the first week, with a significantly higher mean rate of change of total testosterone (day 3) and free testosterone (days 3 and 7) with leuprolide. Following the initial rise in luteinizing hormone (LH), the rate of decrease in LH levels was significantly greater with goserelin by day 28. There are significant differences in endocrine response to goserelin and leuprolide in the 4 weeks following administration.

The Estrogenic Effect of Pueraria mirifica on Gonadotrophin Levels in Aged Monkeys

We investigated the effect of Pueraria mirifica (PM) on gonadotrophin and estradiol levels in aged animals; nine menopausal cynomolgus monkeys were divided into three groups. Each group (n = 3) was fed with 10, 100, and 1000 mg/d of PM for 90 d. PM-10 induced the decrease of follicle stimulating hormone (FSH) levels on d 15-90 in one out of three monkeys. PM-100 and PM-1000 decreased FSH levels of all monkeys throughout the treatment period. After the treatment period, FSH levels continued to decrease for 5 and 10-20 d in PM-100 and PM-1000, respectively, and the levels rebounded in all groups thereafter. PM-10 decreased luteinizing hormone (LH) levels throughout the treatment period in one out of three monkeys and returned to the pretreatment levels immediately after stopping treatment. PM-100 and PM-1000 prominently decreased LH levels between d 10 and 90 during treatment and persisted until d 15-25 and d 20-30 for PM-100 and PM-1000, respectively, during the post-treatment period. Serum LH levels rebounded after returning to pre-treatment levels in a dose-dependent manner. Estradiol levels tended to decrease during the treatment period in all groups. The daily feeding of PM suppressed gonadotrophin levels in aged menopausal monkeys based on dose. Moreover, they can be recovered, and there is a direct correlation between dosage and recovery time. PM may be effective as an alternative medicine in menopausal women because the effects are not permanent.

New evidence for the selective, long-lasting central effects of the brain-targeted estradiol, Estredox

The present study examined the dose- and time-dependent central effects of an estradiol chemical delivery system cyclodextrin complex (E 2-CDS–CD) on the reestablishment of copulatory behavior of castrated male and ovariectomized female rats with concomitant determination of the blood luteinizing hormone (LH) and E 2 levels. In orchidectomized males, Estredox, after single doses of 0.3 and 3.0 mg/kg iv, reestablished the mounting and intromission up to 4 weeks. The LH suppressive effect lasted to Day 7 and 28, respectively. After repeated administration for 10 days at a dose of 0.01mg/kg iv, significant effect was obtained by Day 14. Ovariectomized females were treated iv daily for 5 days either with E 2-CDS–CD, estradiol benzoate (EB) or vehicle, and the lordosis quotient was determined. At a dose of 0.03 mg/kg the duration of EB's effect was 10 days shorter and only one-third of that of E 2-CDS–CD. The LH suppression lasted to Day 18. On the other hand, after EB treatment there was no significant decrease in LH levels. The low plasma E 2 levels indicated fast rate of peripheral elimination in both males and females. The brain-targeting E 2 indicates better efficacy and increased safety in replacement therapies because of the reduced peripheral side effects.

Cytogenetic and molecular analysis of the Y chromosome: absence of a significant relationship between CAG repeat length in exon 1 of the androgen receptor gene and infertility in Indian men

The genetic basis of male infertility remains unclear in the majority of cases. Recent studies have indicated an association between microdeletions of the azoospermia factor a (AZFa)-AZFc regions of Yq and severe oligospermia or azoospermia. Increased (CAG)n repeat lengths in the androgen receptor (AR) gene have also been reported in infertile men. Therefore, in order to assess the prevalence of these genetic defects to male infertility, 183 men with non-obstructive azoospermia (n = 70), obstructive azoospermia (n = 33), severe oligospermia (n = 80) and 59 fertile men were examined cytogenetically and at molecular level for Yq deletions, microdeletions, and AR-CAG repeat lengths along with hormonal profiles [luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T)]. We used high resolution cytogenetics to detect chromosome deletions and multiplex polymerase chain reaction (PCR) involving 27 sequence-tagged site (STS) markers on Yq to determine the rate and extent of Yq microdeletions. PCR amplification with primers flanking exon 1 of AR gene was used to determine the AR-(CAG)n repeat lengths. Hormonal profiles (LH, FSH and T levels) were also analysed in infertile and fertile men. Testicular biopsies showed Sertoli cell only (SCO) morphology, maturation arrests (MA) and hypospermatogenesis. No chromosome aberrations were found in infertile men but there was a significant increase (p < 0.001) in the association of acrocentric chromosomes including the Y chromosome. Yq microdeletions were found in 16 non-obstructive azoospermic men (16 of 70; 22%) and seven severe oligospermic individuals (seven of 80; 8.7%) and most of them had deletions in the sY240 locus. No Yq microdeletions were detected in patients with obstructive azoospermia. No statistically significant difference in the mean length of CAG repeats in AR gene was observed between infertile and fertile men (22.2 +/- 1.5 and 21.5 +/- 1.4 respectively). No significant increase or decrease in levels of LH, FSH and T was observed in infertile and fertile men. In some infertile men, significantly elevated levels of FSH alone or in combination with LH were found to be indicative of failure of spermatogenesis and/or suggestive of testicular failure. Y-chromosome microdeletions contribute to infertility in some patients but no relationship could be established with the (CAG)n repeat lengths in exon 1 of the AR gene in infertile Indian men.

Effects of acute alcohol intoxication on pituitary-gonadal axis hormones, pituitary-adrenal axis hormones, beta-endorphin and prolactin in human adults of both sexes.

- The effects of acute alcohol intoxication (AAI) on the pituitary-gonadal axis hormones, and the possible contribution of pituitary-adrenal axis hormones, beta-endorphin and prolactin to alcohol-induced dysfunction of pituitary-gonadal axis hormones were studied in adult men and women. Blood samples were drawn from adults of both sexes who arrived at the emergency department with evident behavioural symptoms of drunkenness (AAI) or from adult volunteers with nil consumption of alcohol (controls). Our results demonstrated that AAI produces a high increase in plasma prolactin, corticotropin (adrenocorticotropic hormone, ACTH), and cortisol in adults of both sexes, a decrease in luteinizing hormone levels only in men, an increase in dehydroepiandrosterone-sulphate (DHEAS) and a contradictory behaviour of testosterone according to gender, with increased plasma testosterone in women and a decrease in men. ACTH and prolactin correlated positively with cortisol, DHEAS and testosterone in women, which suggests that prolactin and ACTH could contribute to stimulated adrenal androgen production. In contrast, the decrease in testosterone and increase in beta-endorphin in men suggests that AAI could have an inhibitory effect on testicular testosterone, perhaps mediated by beta-endorphin. Our results suggest that the effect of alcohol on pituitary-gonadal axis hormones in humans could depend on the gender and degree of sexual maturity of the individual.

A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men.

Testosterone undecanoate (TU) provides testosterone (T) replacement for hypogonadal men when administered orally but requires multiple doses per day and produces widely variable serum T levels. We investigated the pharmacokinetics of a newly available TU preparation administered by intramuscular injection to hypogonadal men. Eight patients with Klinefelter's syndrome received either 500 mg or 1,000 mg of TU by intramuscular injection; 3 months later, the other dose was given to each man (except to one, who did not receive the 1,000-mg dose). Serum levels of reproductive hormones were measured at regular intervals before and after the injections. Mean serum T levels increased significantly at the end of the first week, from less than 10 nmol/L to 47.8+/-10.1 and 54.2+/-4.8 nmol/ L for the lower and higher doses, respectively. Thereafter, serum T levels decreased progressively and reached the lower-normal limit for adult men by day 50 to 60. Pharmacokinetic analysis showed a terminal elimination half-life of 18.3+/-2.3 and 23.7+/-2.7 days and showed a mean residence time of 21.7+/-1.1 and 23.0+/-0.8 days for the lower and higher doses, respectively. The area under the serum T concentration-time curve and the T-distribution value related to serum T concentration were significantly higher following the 1,000-mg dose than following the 500-mg dose. The 500-mg dose, when given as the second injection, yielded optimal pharmacokinetics (defined as mean peak T values not exceeding the normal range and persistence of normal levels for at least 7 weeks), suggesting that repeated injections of 500 mg at 6-8-week intervals may provide optimal T replacement. The mean serum levels of estradiol were normalized following the injections, and prolactin levels were normal throughout the study. Significant decrease of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels was observed, with the decrease in LH levels being more pronounced. There were no significant differences in serum LH and FSH levels between the two doses. Sex hormone-binding globulin (SHBG) levels before any T therapy were near the upper limit of normal for adult men and were reduced by approximately 50% just prior to the second dose of TU. The decreased SHBG levels produced by the first TU injection could have led to lower peak total T levels and to a more rapid clearance of T following the second TU injection. We conclude that single-dose injections of TU to hypogonadal men can maintain serum T concentration within the normal range for at least 7 weeks without immediately apparent side effects. It is likely that this form of T would require injections only at 6-8-week or longer intervals, not at the 2-week intervals necessary with currently used T esters (enanthate and cypionate). This injectable TU preparation may provide improved substitution therapy for male hypogonadism and, in addition, may be developed as an androgen component of male contraceptives.

Inhibition of ovarian follicular development associated with a decrease in luteinizing hormone levels during the estrous cycle of the rat.

To examine the importance of tonic LH secretion in ovarian follicular development, plasma concentrations of LH were lowered by administering antiserum to GnRH (GnRH AS). At 1100 h on metestrus or diestrus of the 4-day estrous cycle, rats were injected with GnRH AS, and blood samples were collected at 6 h intervals until 1100 h on the next metestrus. Separately, rats were injected with hCG after the administration of GnRH AS to examine the effect of lowered LH on the number of ovulatory follicles. Treatment with GnRH AS on either metestrus or diestrus lowered plasma concentrations of LH, inhibin, and estradiol. In contrast, the plasma concentrations of FSH increased after the GnRH AS treatment, probably due to a decrease in plasma levels of inhibin associated with suppression of ovarian follicular development. Administration of GnRH AS on metestrus noticeably reduced the number of ovulatory follicles in spite of the high FSH secretion. Such a reduction in the number of ovulatory follicles was blocked by replacing rat LH with ovine LH. These data indicate that tonic secretion of LH plays an important role in the regulation of follicular development during the estrous cycle of the rat.