Decrease In Follicle-stimulating Hormone Levels Research Articles

Laparoscopic orchidopexy for the treatment of cryptorchidism in adults: a description of the technique and outcomes

BackgroundThere are few studies on cryptorchidism in adults, and its treatment is still controversial.MethodsTo summarize the surgical strategy and clinical efficacy of laparoscopic orchidopexy for the treatment of cryptorchidism in adults, 37 adult cryptorchidism patients were retrospectively analyzed between September 2017 and February 2022. All 37 patients underwent laparoscopic orchidopexy, of whom 33 underwent inguinal hernia repair without tension. The intraoperative procedures and surgical techniques were recorded in detail. Preoperative examination and regular postoperative review of color Doppler ultrasound, and reproductive hormone, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase levels were performed.ResultsAll testes descended successfully into the scrotum, including 25 through the inguinal route and 12 through Hesselbach’s triangle route. No intraoperative or postoperative complications were observed. The follow-up time was 38.6 (± 19.4) months, and no evidence of testicular malignancy was found during the follow-up period. After analyzing the reproductive hormone levels at 1 year postoperatively in 28 patients with more than 1 year of follow-up, it was found that the patients had a significant increase in testosterone levels and a decrease in follicle-stimulating hormone levels after surgery. None of the patients showed any significant improvement in semen quality after surgery.ConclusionOur study suggests that laparoscopic orchidopexy is a safe and feasible surgical procedure for the treatment of cryptorchidism in adults, especially high cryptorchidism, which is difficult to treat. After comprehensive consideration, preserving the testis should be preferred for treating cryptorchidism in adults to maximize the protection of the patient’s reproductive hormone secretion function.

Kuntai capsule attenuates premature ovarian insufficiency by activating the FOXO3/SIRT5 signaling pathway in mice: A comprehensive study using UHPLC-LTQ-Orbitrap and integrated pharmacology

Ethnopharmacological relevanceClassical prescriptions are not only a primary method of clinical treatment in traditional Chinese medicine (TCM) but also represent breakthroughs in the inheritance and development of this field. Kuntai capsule (KTC), a formulation based on a classical prescription, comprises six TCMs: Rehmanniae Radix Praeparata, Coptidis Rhizoma, Paeoniae Radix Alba, Scutellariae Radix, Asini Corii Colla, and Poria. This formulation possesses various beneficial effects, such as nourishing yin and blood, clearing heat and purging fire, and calming the nerves and relieving annoyance. The investigation of the efficacy and mechanism of KTC in regulating anti-aging factors in the treatment of premature ovarian insufficiency (POI) is not only a prominent topic in classical prescription research but also a crucial issue in the treatment of female reproductive aging using TCM. Aim of the studyTo evaluate the therapeutic effect of KTC on POI and its underlying mechanism. Materials and methodsHealthy and specific pathogen-free (SPF) female Kunming mice aged 6–8 weeks were selected. After acclimatization, the mice were randomly divided into a control, model, and high, middle, and low dose groups of KTC (1.6, 0.8, and 0.4 mg/kg, respectively). Except for the control group, the animals in the other groups were administered a single intraperitoneal injection of 120 mg/kg cyclophosphamide and 30 mg/kg Busulfan to induce the model of POI. After modeling, the mice were treated with the corresponding drugs for 7 days. Serum and ovarian tissues were collected, and the levels of serum follicle-stimulating hormone (FSH), estradiol (E2), and superoxide dismutase 2 (SOD2) were determined using enzyme-linked immunosorbent assay (ELISA). The chemical composition of KTC was characterized and analyzed using ultra-high-pressure liquid chromatography-linear ion trap-Orbitrap tandem mass spectrometry. A “drug-component-target-pathway-disease” network was constructed using network pharmacology research methods to identify the key active components of KTC in treating POI and to elucidate its potential mechanism. The protein expression of the FOXO3/SIRT5 pathway was detected by western blotting. ResultsCompared to the model group, the high-dose group of KTC showed a significant increase in ovarian index, significant increase in levels of E2 and SOD2, and a significant decrease in FSH levels. Through systematic analysis of the chemical constituents of KTC, 69 compounds were identified, including 7 organic acids, 14 alkaloids, 28 flavonoids, 15 terpenoids, 2 lignans, 2 phenylpropanoids, and 1 sugar. Based on network pharmacology research methods, it was determined that KTC exerts its therapeutic effect on POI through multiple components (paeoniflorin and malic acid), multiple targets (FOXO3 and SIRT5), and multiple pathways (prolactin signaling pathway, longevity regulating pathway, and metabolic pathways). The accuracy of the network pharmacology prediction was further validated by detecting the protein expression of SIRT5 and FOXO3a, which showed a significant increase in the middle and high-dose groups of KTC compared to the model group. ConclusionsKTC may effectively treat POI through a multi-component, multi-target, multi-pathway approach, providing an experimental basis for using KTC based on classical prescriptions in the treatment of POI.

Bushen Huoxue formula for the treatment of diminished ovarian reserve: A combined metabolomics and integrated network pharmacology analysis

ObjectiveThis study aimed to explore the mechanism of the Bushen Huoxue Formula (BHF) in treating diminished ovarian reserve (DOR) through the use of metabolomics and integrated network pharmacology. MethodsThe study involved 24 non-pregnant female Sprague-Dawley rats, divided into four groups of six rats each: control, model, BHF, and DHEA (n = 6 per group). The model group was induced with DOR by administering Tripterygium glycosides orally [50 mg (kg·d)−1] for 14 days. Subsequently, BHF and Dehydroepiandrosterone (DHEA) treatments were given to the respective groups. Ovarian reserve function was assessed by measuring anti-Müllerian hormone (AMH), estradiol (E2), and follicle-stimulating hormone (FSH) levels and conducting hematoxylin-eosin staining. In addition, UHPLC-QTOF-MS analysis was performed to identify differential metabolites and pathways in DOR rats treated with BHF. In this study, LC-MS was utilized to identify the active ingredients of BHF, while network pharmacology was employed to investigate the correlations between BHF-related genes and DOR-related genes. An integrated analysis of metabonomics and network pharmacology was conducted to elucidate the mechanisms underlying the efficacy of BHF in treating DOR. ResultsThe model group exhibited a poor general condition and a significant decrease in the number of primordial, primary, and secondary follicles (P < 0.05) when compared to the control group. However, BHF intervention resulted in an increase in the number of primordial, primary, and secondary follicles (P < 0.05), along with elevated levels of AMH and E2 (P < 0.05), and a decrease in FSH levels (P < 0.05) in DOR rats. The modeling process identified eleven classes of metabolites, including cholesterol esters (CE), diacylglycerols (DAG), hexosylceramides (HCER), lysophosphatidylcholines (LPC), phosphatidylcholines (PC), phosphatidylethanolamines (PE), sphingomyelins (SM), ceramides (CER), free fatty acids (FFA), triacylglycerols (TAG), and lysophosphatidylethanolamines (LPE). The study found that PC, CE, DAG, and TAG are important metabolites in the treatment of DOR with BHF. LC-MS analysis showed that there were 183 active ingredients in ESI(+) mode and 51 in ESI(−) mode. Network pharmacology analysis identified 285 potential genes associated with BHF treatment for DOR in ESI(+) mode and 177 in ESI(−) mode. The combined analysis indicated that linoleic acid metabolism is the primary pathway in treating DOR with BHF. ConclusionBHF was found to improve ovarian function in rats with DOR induced by Tripterygium glycosides. The study identified key metabolites such as phosphatidylcholine (PC), cholesteryl ester (CE), diacylglycerol (DAG), triacylglycerol (TAG), and the linoleic acid metabolism pathway, which were crucial in improving ovarian function in DOR rats treated with BHF.

Ginsenoside Rg1 Attenuates Premature Ovarian Failure of D-gal Induced POF Mice Through Downregulating p16INK4a and Upregulating SIRT1 Expression.

Premature ovarian failure (POF) refers to pathological amenorrhea before 40 years. To explore the regulatory effect of Rg1 on POF and clarify associated mechanisms. POF mice were induced by injecting with D-galactose (D-gal, 200 mg/kg/- day). Mice were divided into phosphate buffered saline (PBS), D-gal (POF mice), D-gal/Rg1 group (POF mice administrating D-gal/Rg1). Weight growth rate and ovarian weight coefficient were measured. Serum estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), catalase (CAT) levels were examined using ELISA. The status of follicle and corpus luteum was determined using hematoxylin-eosin (HE) staining. P16INK4a and silent- mating type information regulation-2 homolog-1 (SIRT1) were determined using western blotting and RT-PCR. Weight growth rate and ovarian weight coefficient of mice in D-gal group were significantly decreased than PBS group (p<0.05). Serum E2, LH, SOD, CAT levels were significantly decreased, FSH levels were remarkably increased in D-gal group than PBS group (p<0.05). Rg1 (D-- gal/Rg1 group) significantly increased weight growth rate and ovarian weight coefficient, enhanced E2, LH, SOD, CAT levels and decreased FSH levels than D-gal group (p<0.05). HE staining demonstrated normal follicle morphology/structure of mice in PBS group and decreased the number of follicles, obvious vacuolation of corpus luteum and increased atretic follicles of mice in D-gal group. Compared with D-gal group, the number of follicles was increased, luteal follicles were decreased in mice in D-gal/Rg1 group (p<0.05). Rg1 significantly (D-gal/Rg1) downregulated p16INK4a and upregulated SIRT1 expression in ovarian tissues of mice compared to the D-gal group (p<0.05). Rg1 could delay premature ovarian failure in D-gal induced POF mouse model through downregulating p16INK4a and upregulating SIRT1 expression.

Clinical and epidemiological characteristics and hormonal profile of adult females with acne vulgaris: a cross-sectional study from a tertiary care hospital

&lt;p class="abstract"&gt;&lt;strong&gt;Background: &lt;/strong&gt;To study clinical and epidemiological characteristics and hormonal profile of adult females with acne&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Adult female patients of &amp;gt;25 years of age with acne were enrolled. Demographic profile, habits, location of acne lesions, associated disease and acne flare association with menstrual cycle were noted. Prevalence of abnormalities in testosterone, dihydroepiandrosterone-sulfate (DHEAS), prolactin, luteinizing hormone (LH), follicle stimulating hormone (FSH), LH:FSH ratio, anti-mullerian hormone (AMH), and serum insulin were noted. Ultrasound (abdomen and pelvis) was performed for screening the presence of any abnormality.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Fifty one patients [mean (SD) age 30.96 (4.93) years] were included in the study. Thirty six (70.59%) patients had persistent type of acne. Grade 2 acne was present in 40 (78.43%) patients. Oily skin was seen in 27 (52.94%) patients. Hirsuitism and menstrual irregularity was present in 24 (47.06%) and 13 (25.49%) patients respectively. Pigmentation and scarring was present in 27 (52.94%) and 35 (68.63%) patients respectively. Acne lesions were seen on cheeks in 36 (70.59%) patients. Eight (15.69%) patients had elevated testosterone. DHEAS and prolactin levels were normal in all patients. Elevation of LH and decreased FSH levels were seen in five (9.80%) and three (5.88%) patients respectively. Five (9.80%) patients had elevated LH:FSH level. Raised insulin level was seen in 8 (15.69%) patients.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Derangement of hormonal profile is not very common among adult female patients with acne. However, in some patients laboratory markers of hyperandrogenism are seen. &lt;/p&gt;

Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis

Aims/hypothesisVariants close to the VPS13C/C2CD4A/C2CD4B locus are associated with altered risk of type 2 diabetes in genome-wide association studies. While previous functional work has suggested roles for VPS13C and C2CD4A in disease development, none has explored the role of C2CD4B.MethodsCRISPR/Cas9-induced global C2cd4b-knockout mice and zebrafish larvae with c2cd4a deletion were used to study the role of this gene in glucose homeostasis. C2 calcium dependent domain containing protein (C2CD)4A and C2CD4B constructs tagged with FLAG or green fluorescent protein were generated to investigate subcellular dynamics using confocal or near-field microscopy and to identify interacting partners by mass spectrometry.ResultsSystemic inactivation of C2cd4b in mice led to marked, but highly sexually dimorphic changes in body weight and glucose homeostasis. Female C2cd4b mice displayed unchanged body weight compared with control littermates, but abnormal glucose tolerance (AUC, p = 0.01) and defective in vivo, but not in vitro, insulin secretion (p = 0.02). This was associated with a marked decrease in follicle-stimulating hormone levels as compared with wild-type (WT) littermates (p = 0.003). In sharp contrast, male C2cd4b null mice displayed essentially normal glucose tolerance but an increase in body weight (p < 0.001) and fasting blood glucose (p = 0.003) after maintenance on a high-fat and -sucrose diet vs WT littermates. No metabolic disturbances were observed after global inactivation of C2cd4a in mice, or in pancreatic beta cell function at larval stages in C2cd4a null zebrafish. Fasting blood glucose levels were also unaltered in adult C2cd4a-null fish. C2CD4B and C2CD4A were partially localised to the plasma membrane, with the latter under the control of intracellular Ca2+. Binding partners for both included secretory-granule-localised PTPRN2/phogrin.Conclusions/interpretationOur studies suggest that C2cd4b may act centrally in the pituitary to influence sex-dependent circuits that control pancreatic beta cell function and glucose tolerance in rodents. However, the absence of sexual dimorphism in the impact of diabetes risk variants argues for additional roles for C2CD4A or VPS13C in the control of glucose homeostasis in humans.Data availabilityThe datasets generated and/or analysed during the current study are available in the Biorxiv repository (www.biorxiv.org/content/10.1101/2020.05.18.099200v1). RNA-Seq (GSE152576) and proteomics (PXD021597) data have been deposited to GEO (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152576) and ProteomeXchange (www.ebi.ac.uk/pride/archive/projects/PXD021597) repositories, respectively.Graphical abstract

Effect of short-term gavage of ethanolic extract of cogon grass (Imperata cylindrica L) root on the ovarian activity and estrus behavior of female mice

Objective: To assess the effect of short-term gavage of ethanolic extract of Imperata cylindrica L root on the ovarian activity and estrus behavior of female mice. Methods: Eighteen virgin female ddY mice, 8 to 10 weeks of age, weighing 22–25 g with regular estrus cycle, were divided into three groups. Group 1 received 0.5% carboxymethylcellulose, whereas Groups 2 and 3 received the ethanolic extract of Imperata cylindrica L root at 90 and 115 mg/kg body weight (b.w.) per day by gavage for 20 days, respectively. All of the groups were checked before 9 a.m. daily for vaginal cytology to determine the estrus phase. On day 21, the mice were sacrificed to collect serum samples to quantify the concentrations of reproductive hormones using enzyme-linked immunosorbent assay and to determine changes in the reproductive organs based on their reproductive organ weight, histomorphology, and histomorphometry of ovarium and uterus. Results: The reproductive organ weight in the treatment groups was similar compared with that in the control group. The 90 mg/kg b.w. treatment group showed an increase in corpus luteum number when compared with the control group, with few degenerated follicles and diminished oocytes. Moreover, the 115 mg/kg b.w. treatment group showed fewer primordial and primary follicles and an increase in corpus luteum number and a prolonged diestrus phase compared to the control and 90 mg/kg b.w. treatment groups. The histomorphology examination of the uterus showed that the thickness of myometrium and epithelium in the treated animals was similar to the control group. In addition, there was a significant decrease in follicle-stimulating hormone level in the 115 mg/kg b.w. treatment group (P Conclusions: Short-term gavage of ethanolic extract of Imperata cylindrica L root reduces the follicle-stimulating hormone serum level and folliculogenesis.

Effects of Co-Administration of Bone Marrow Stromal Cells and L-Carnitine on The Recovery of Damaged Ovaries by Performing Chemotherapy Model in Rat.

BackgroundL-carnitine (Lc) as a type of flavonoid antioxidants and bone marrow stromal cells (BMSCs) as a type of mesenchymal stem cells may recover damaged ovaries. It seems that Lc has favorable effects on differentiation, increasing lifespan and decreasing apoptosis in BMSCs. The aim of this study was to investigate effects of co-ad- ministration of BMSC+Lc on damaged ovaries after creating a chemotherapy model with cyclophosphamide in rats.Materials and MethodsIn this experimental study, cyclophosphamide was intraperitoneally (IP) injected to forty female wistar rats for 14 days, in terms of chemotherapy-induced ovarian destruction. The rats were then randomly divided into four groups: control, Lc, BMSCs and co-administration of BMSC+Lc. Injection of BMSCs into bilateral ovaries and intraperitoneal injection of Lc were performed individually and together. Four weeks later, levels of se- rum estradiol (E2) and follicle-stimulating hormone (FSH) using enzyme-linked immunosorbent assay (ELISA) kit, number of ovarian follicles at different stages using hematoxylin and eosin (H&E) staining and expression of ovarian Bcl-2 and Bax proteins using western blot were assessed.ResultsCo-administration of BMSC+Lc increased E2 and decreased FSH levels compared to the control group (P<0.001). The number of follicles was higher in the co-administrated group compared to the control group (P<0.001). Co-administration of BMSC+Lc increased Bcl-2 protein level, decreased Bax protein level and increased Bcl-2/Bax ratio (P<0.001).ConclusionThe effect of co-administration of BMSC+Lc is probably more effective than the effect of their separate administration on the recovery of damaged ovaries by chemotherapy.

Evaluation of Dehydroepiandrosterone Supplementation on Diminished Ovarian Reserve: A Randomized, Double-Blinded, Placebo-Controlled Study.

We conducted a randomized, double-blinded, placebo-controlled study, to evaluate the effect of dehydroepiandrosterone (DHEA), on diminished ovarian reserve (DOR). Twenty patients with DOR received DHEA (oral 25mg three times a day). Post-supplementation 12weeks, D2/3 age-specific follicle-stimulating hormone (FSH), anti-mullerian hormone (AMH) levels, and antral follicle count (AFC), were repeated to evaluate response. Spontaneous pregnancy rates and regularization of menstrual cycles were also studied as secondary outcome. Predominant risk factors were age >35years (28%) and poor responders to ovarian stimulation (23%). There was significant improvement of AMH levels (1.15±1.49 vs. 1.53±1.62) found before and after supplementation in the DHEA group. When the AMH values between DHEA and placebo group were compared, pre- and post-supplementation, no significant difference was found. There was decrease in FSH levels and increase in AFC value post-supplementation in both DHEA and placebo groups which was not statically significant. DHEA supplementation benefited clinically, as evidenced by the improvement in the menstrual abnormality spontaneous conception in two cases each. A significant improvement in AMH levels pre- and post-supplementation of DHEA was noted. The same was not seen for FSH and AFC values.

The extracts of Pacific oyster (Crassostrea gigas) alleviate ovarian functional disorders of female rats with exposure to bisphenol a through decreasing FSHR expression in ovarian tissues.

Bisphenol-A (BPA) is one of the widespread industrial compounds, which has adverse effects on animal and human health. The study was aimed to explore the effects of Crassostrea gigas extracts (CGE) in alleviating ovarian functional disorders of female rats with exposure to BPA and the underlying possible mechanism. Eighteen four-week-old female Sprague-Dawley (SD) rats were randomly divided into BPA group (50mg/kg BPA), BPA+CGE group (50mg/kg BPA+50mg/kg CGE), and control group (equivalent dosage of vehicle) with 6 rats in each group. After a 6-week treatment ended, the serum levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH) were measured by using commercial standard assay kits. The expression levels of FSH receptor (FSHR) in the rat ovarian tissues were respectively detected by immunohistochemistry and Real-time PCR. CGE treatment markedly increased E2 levels and decreased FSH levels in the serum (P<0.05), however, the alterations of serum LH levels were not significant (P>0.05). The protein and mRNA expression levels of FSHR were the lowest in the ovaries of control rats and the highest in BPA rats (P<0.05). CGE treatment markedly decreased the expression levels of FSHR in the ovarian tissues (P<0.05). Crassostrea gigas successfully alleviates ovarian functional disorders of female rats with exposure to BPA partly through decreasing FSHR expression levels in the ovarian tissues.

The correlation between thyroid hormones, reproductive hormones, body mass index (BMI) and hirsute in Iraqi women with polycystic ovary syndrome (PCOS).

This research was conducted to study the relationship between the polycystic ovarysyndrome (PCOS) and thyroid disorders. The study includes 50 infertile Iraqi women with polycystic ovary syndrome (PCOS) and 20 healthy women. Blood samples were collected from the Infertility Center of AL-Yarmok Teaching Hospital in Baghdad, during the period from November, 2010 to May, 2011. The age of infertile and fertile women was ranged from 16 to 45 years. Hormonal study of Estradiol (E2), Luteinizing hormone (LH), Follicle stimulating hormone (FSH), Testosterone (T),Thyroid stimulating hormone (TSH) , Triiodothyronine (T3) and Thyroxin(T4) was done for each patient. The results showed that there is a significant (P <0.05) decrease in E2 and FSH levels in PCOS women comparing with fertile women. Also a significant (P <0.05) increase in LHFSH was detected in PCOS women and fertile women and non-significant (P <0.05) differences in testosterone,TSH,T3 and T4 levels between infertile and fertile women.The hormonal profile according to Body mass index -BMI was showed to be significantly (P <0.05) decreased in testosterone in obese and overweight PCOS women, significant (P <0.05) decrease in FSH level in obese PCOS women and no significant differences in E2 and LH levels.According to the hirsute in PCOS women the hormonal profile showed a significant (P <0.05) decrease in E2 and FSH levels in hirsute PCOS women, no significant differences in LH levels and elevated in testosterone levels but without significance in hirsute PCOS

Degarelix as a new antiangiogenic agent for metastatic colon cancer?

Recently, follicle stimulating hormone receptor was found to be selectively expressed by endothelial cells on tumor-associated blood vessels in a wide range of human cancers. In this context, we hypothesized that degarelix, a new gonadotropin-releasing hormone receptor antagonist developed for patients with prostate cancer, may have antiangiogenic effects via its capacity to block follicle stimulating hormone (FSH) production. We report the case of a patient with metastatic colon cancer exhibiting tumor progression after failure of all conventional chemotherapeutic regimens. The addition of degarelix to the last chemotherapeutic regimen was proposed as compassionate treatment. Degarelix induced a rapid decrease in FSH level. This treatment induced radiological stabilization and carcinoembryonic antigen stabilization during 1 year. Contrast-enhanced ultrasonography demonstrated reduction of tumor vasculature. This case represents the first report of an antitumoral effect of degarelix in metastatic colon cancer and suggests an antiangiogenic property of this drug.

Clinical Comparison of Conventional Testicular Sperm Extraction and Microdissection Techniques for Non-Obstructive Azoospermia

BackgroundWe compared the efficacy of microdissection testicular sperm extraction (microdissection TESE) and conventional TESE in patients with non-obstructive azoospermia (NOA) and related the positive sperm recovery to certain variables: follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, testicular volume and histology.MethodsSperm retrieval rates (SRR) in patients with NOA who underwent microdissection TESE (n = 65) or conventional TESE (n = 68) were compared and related to the different variables.ResultsSRR by microdissection TESE (56.9%) was significantly higher than conventional TESE (38.2%). There was a positive relation between the SRR and increased testicular volume or decreased FSH levels. No effect of Testosterone or Prolactin levels on SRR by using either technique was observed. Sperm were recovered from those with hypospermatogenesis in 84% and 92.9% by conventional and microdissection TESE, respectively (P = 0.3). In cases of maturation arrest the SRR was 27.3% and 36.4%, respectively (P = 0.6). In cases of Sertoli-cell-only syndrome (SCOS) the SRR was 6.2% and 26.9%, respectively (P = 0.03). No major operative complications occurred in any patient in either group, and no patient required post-operative hormone replacement to treat hypogonadism.ConclusionsMicrodissection TESE significantly had twice better probability of success of SRR when compared to conventional TESE. No secure pre-operative prognostic elements of sperm recovery exist for NOA patients. Microdissection TESE appears to be recommendable in cases of atrophied testicles, high FSH concentration, or when SCOS with high FSH concentration can be predicted.KeywordsMicrodissection TESE; Sperm retrieval; Non-obstructive azoospermia; Histopathology; FSH concentration; Orchidometry

Mild ovarian stimulation for IVF

Mild ovarian stimulation for in vitro fertilization (IVF) aims to achieve cost-effective, patient-friendly regimens which optimize the balance between outcomes and risks of treatment. Pubmed and Medline were searched up to end of January 2008 for papers on ovarian stimulation protocols for IVF. Additionally, references to related studies were selected wherever possible. Studies show that mild interference with the decrease in follicle-stimulating hormone levels in the mid-follicular phase was sufficient to override the selection of a single dominant follicle. Gonadotrophin-releasing hormone antagonists compared with agonists reduce length and dosage of gonadotrophin treatment without a significant reduction in the probability of live birth (OR 0.86, 95% CI 0.72-1.02). Mild ovarian stimulation may be achieved with limited gonadotrophins or with alternatives such as anti-estrogens or aromatase inhibitors. Another option is luteinizing hormone or human chorionic gonadotrophin administration during the late follicular phase. Studies regarding these approaches are discussed individually; small sample size of single studies along with heterogeneity in patient inclusion criteria as well as outcomes analysed does not allow a meta-analysis to be performed. Additionally, the implications of mild ovarian stimulation for embryo quality, endometrial receptivity, cost and the psychological impact of IVF treatment are discussed. Evidence in favour of mild ovarian stimulation for IVF is accumulating in recent literature. However, further, sufficiently powered prospective studies applying novel mild treatment regimens are required and structured reporting of the incidence and severity of complications, the number of treatment days, medication used, cost, patient discomfort and number of patient drop-outs in studies on IVF is encouraged.

Evaluation of pituitary–ovarian axis suppression with three oral contraceptive regimens

Background The study was conducted to evaluate follicular development and hormone patterns with three oral contraceptive (OC) regimens before, during and after the 7-day hormone-free interval (HFI) or 7-day ethinyl estradiol (EE)-supplemented interval. Study Design The study is a single-center, open-label, prospective, randomized trial to evaluate pituitary–ovarian suppression with three OC regimens containing identical hormones: 30 mcg of EE and 150 mcg of levonorgestrel (LNG). Methods After a standard 21/7 OC baseline cycle, subjects were randomized to one of three treatment groups: (1) three 21/7-day cycles of 150 mcg LNG/30 mcg EE for 21 days followed by 7 days of placebo (n=10); (2) one 84/7-day cycle of 150 mcg LNG/30 mcg EE for 84 days followed by 7 days of placebo (n=12) and (3) one 84/7EE-day cycle of 150 mcg LNG/30 mcg EE for 84 days followed by 7 days of 10 mcg EE (n=11). Estradiol; follicle-stimulating hormone (FSH); luteinizing hormone and inhibin-B levels, ovarian follicles and daily symptom diaries were collected. Results Compared to subjects receiving placebo during the 7-day HFI, those receiving EE demonstrated reductions (p<.05) in both FSH and estradiol. Number of developing follicles was less after the 7-day EE interval compared to that after 7-day HFI. Subjects on the 84/7 and 84/7EE regimens reported less (p=.03) daily menstrual flow than those on the 21/7-day regimen. A trend (p=.06) toward reduced headaches during the 7-day EE-supplemented interval was noted. Conclusions Supplementation of the standard 7-day HFI with 10 mcg EE after 84 days of an extended OC decreased FSH levels and decreased the number of developing follicles.

Long‐term effects of a short course of neoadjuvant luteinizing hormone‐releasing hormone analogue and radical radiotherapy on the hormonal profile in patients with localized prostate cancer

To assess whether a long-term follow-up shows any reduction in the level of luteinizing hormone (LH) secretion, which could result in declining testosterone levels in men with localized prostate cancer, as most (96%) men have testosterone levels within the normal range by 1 year after treatment with a short course of LH-releasing hormone analogue (LHRHa) and radiotherapy, and LH and follicle stimulating hormone (FSH) remain high at 1 year after treatment, maintaining the testosterone levels. We prospectively evaluated 55 patients who previously had a short course of LHRHa (median 97 days, range 28-167) and radiotherapy for localized prostate cancer. Eligible patients had documented normal testosterone, LH and FSH levels at baseline and at 1-3 years after radiotherapy. LH, FSH and testosterone were then measured at 5 years after treatment. The mean hormone levels before, at 1-3 years and at 5 years after treatment, respectively, were: testosterone (nmol/L), 15.33, 13.98, 12.97; LH (U/L), 5.51, 9.95, 6.95; and FSH (U/L), 7.95, 22.40, 17.00. The decrease in testosterone level at 5 years vs 1-3 years was not statistically significant and was of little clinical relevance (P = 0.057). LH and FSH levels were higher at 1-3 years than at baseline and decreased significantly (P < 0.001) at 5 years towards the baseline value. The decrease in FSH level was less marked than for LH. After a short course of LHRHa and radiotherapy, the testosterone level was maintained at 5 years. LH levels decreased towards the baseline value, suggesting recovery of Leydig cell function. FSH levels remained high, suggesting persistent Sertoli cell damage from treatment.

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.

Effects of oral raloxifene on serum estradiol levels and other markers of estrogenicity

Objective: To determine the effects of raloxifene hydrochloride, 60 mg/d, on serum levels of E 2, estrone, sex steroid-binding globulin, thyroxine-binding globulin, and follicle-stimulating hormone (FSH) in postmenopausal women. Design: Randomized placebo-controlled study at 16 centers in the United States. Patient(s): Ninety three women 42 to 80 years of age who were at least 2 years postmenopausal. Intervention(s): Raloxifene (n = 47) or placebo (n = 46) for 3 months. Main Outcome Measure(s): Levels of E 2, estrone, sex steroid-binding globulin, thyroxine-binding globulin, and FSH were measured at baseline and after 3 months of therapy. Result(s): Raloxifene increased serum levels of sex steroid-binding globulin and thyroxine-binding globulin and decreased FSH levels compared with placebo. Levels of E 2 and estrone were unaffected. Conclusion(s): In postmenopausal women, raloxifene (60 mg/d) did not increase serum estrogen levels; however, it increased levels of sex steroid-binding globulin and thyroxine-binding globulin and decreased FSH levels.

Evaluation of the primary humoral immune response following exposure of male rats to 17beta-estradiol or flutamide for 15 days.

There is a concern that certain industrial chemicals found in the environment may mimic or antagonize endogenous hormones and adversely affect the endocrine as well as the immune system. The objective of this study was to determine if exposure of Crl:CD (SD)BR male rats to 17beta-estradiol (17beta-E2), an estrogen receptor agonist, or flutamide (FLUT), an androgen receptor antagonist, would significantly alter the primary IgM humoral immune response to sheep red blood cells (SRBC). This study was conducted in the context of a male in vivo Tier I battery designed to identify endocrine-active compounds (EACs). The Tier I male battery consists of organ weights coupled with a comprehensive hormonal assessment. Rats were dosed by the intraperitoneal route for 15 days with vehicle or 0.001, 0.0025, 0.0075, or 0.050 mg/kg/day 17beta-E2 or 0.25, 1, 5, or 20 mg/kg/day FLUT. Six days prior to termination, selected rats were injected intravenously with SRBC for assessment of humoral immune function. Spleen cell number and spleen and thymus weights were obtained. Serum was analyzed for anti-SRBC IgM antibody by using an enzyme-linked immunosorbent assay. At 0.050 mg/kg/day 17beta-E2, mean final body and absolute thymus weights were significantly decreased to 84 and 65% of control, respectively. 17beta-E2 did not significantly alter spleen weight, spleen cell number, or the primary IgM humoral immune response to SRBC. The no-observed-adverse-effect level (NOAEL) for immune system alteration was 0.050 mg/kg/day 17beta-E2 since the decrease in absolute thymus weight was judged to be secondary to the decrements in body weight. In the Tier I male battery, responses to 17beta-E2 included decreased absolute testis and epididymis weights, decreased relative accessory sex gland unit weights, hormonal alterations (decreased serum testosterone (T), dihydrotestosterone (DHT), and luteinizing hormone (LH), and increased serum prolactin and E2 levels). The lowest-observed-adverse-effect level (LOAEL) for the reproductive indices was 0.001 mg/kg/day 17beta-E2 based on the hormonal alterations seen at this level; no NOAEL was established. Exposure to FLUT did not significantly alter mean final body, spleen, or absolute thymus weights, spleen cell number, or the primary IgM humoral immune response to SRBC. A significant increase (118% of control) in relative thymus weight was observed at 20 mg/kg/day FLUT. The NOAEL for immune system alteration was 5 mg/kg/day FLUT based on the increased relative thymus weights that were judged to be compound-related. In the Tier I male battery, responses to FLUT included decreased absolute epididymis and relative accessory sex gland unit weights and hormonal alterations (increased serum T, DHT, E2, and LH, and decreased follicle stimulating hormone levels). The LOAEL for the reproductive indices was 0.25 mg/kg/day FLUT based on the hormonal alterations seen at this level; no NOAEL was established. Based on these data, the reproductive and not the immune system appears to be the primary target organ of toxicity in young adult male rats treated with either 17beta-E2 or FLUT.

Effect of pinealectomy and melatonin treatment during pregnancy on the sexual development of the female and male rat offspring

Sexual development of female and male rat offspring of control, pinealectomized (PIN-X) or melatonin (MEL 250 micrograms/100 g body wt)-treated mother rats during pregnancy was studied. Newborns were studied at the following phases of sexual development: neonate (5 days old), infantile (15 days old), juvenile (25 and 30 days old) and pubertal phase (55 days). In female offspring, MEL treatment during pregnancy significantly increased plasma luteinizing hormone (LH) in 15- and 25-day-old rats; however, at the end of the prepubertal period (30 days) the concentration of plasma LH decreased significantly as compared to control rats. This hormonal pattern was different from that observed in offspring of control and PIN-X rats, which had low LH levels at 25 days of age and higher LH levels at 30 days of age. Follicle-stimulating hormone (FSH) did not vary significantly among the three groups. Plasma prolactin levels were affected by PIN-X of the mother, showing significantly higher levels in the 5-day-old offspring than in the controls; plasma prolactin levels were also affected by MEL treatment of the mother, producing hyperprolactinemia in the 30-day-old female offspring. In male offspring, sexual development in control male rats progressed rapidly with significantly increased LH and FSH levels at 25 and 30 days compared to those measured during the neonatal and infantile periods.(ABSTRACT TRUNCATED AT 250 WORDS)