Rise In Follicle-stimulating Hormone Research Articles

Neuroendocrinology of bone.

The past decade has witnessed significant advances in our understanding of skeletal homeostasis and the mechanisms that mediate the loss of bone in primary and secondary osteoporosis. Recent breakthroughs have primarily emerged from identifying disease-causing mutations and phenocopying human bone disease in rodents. Notably, using genetically-modified rodent models, disrupting the reciprocal relationship with tropic pituitary hormone and effector hormones, we have learned that pituitary hormones have independent roles in skeletal physiology, beyond their effects exerted through target endocrine glands. The rise of follicle-stimulating hormone (FSH) in the late perimenopause may account, at least in part, for the rapid bone loss when estrogen is normal, while low thyroid-stimulating hormone (TSH) levels may contribute to the bone loss in thyrotoxicosis. Admittedly speculative, suppressed levels of adrenocorticotropic hormone (ACTH) may directly exacerbate bone loss in the setting of glucocorticoid-induced osteoporosis. Furthermore, beyond their established roles in reproduction and lactation, oxytocin and prolactin may affect intergenerational calcium transfer and therefore fetal skeletal mineralization, whereas elevated vasopressin levels in chronic hyponatremic states may increase the risk of bone loss.. Here, we discuss the interaction of each pituitary hormone in relation to its role in bone physiology and pathophysiology.

O-192 Kisspeptin as a test of hypothalamic function in women presenting with oligo-amenorrhea

Abstract Study question Can kisspeptin be used as a novel tool to interrogate hypothalamic function in women presenting with oligo-amenorrhea? Summary answer The hormonal response to kisspeptin offers a novel approach for the assessment of hypothalamic function in patients presenting with oligo-amenorrhea of different aetiologies. What is known already Polycystic ovary syndrome (PCOS) and functional hypothalamic amenorrhea (FHA) are the two commonest causes of anovulation causing oligo-amenorrhea in pre-menopausal women. Additionally, congenital (CHH) and functional hypogonadotropic hypogonadism can present with similar endocrine profiles. Importantly, these conditions are caused and characterised by abnormal hypothalamic function. For instance, gonadotropin-releasing hormone (GnRH) pulsatility is increased in PCOS but reduced in FHA. Despite differences in pathophysiology, differentiating these diagnoses can be challenging in clinical practice. Kisspeptin is known to stimulate hypothalamic GnRH neurons. Thus, kisspeptin could represent a novel tool to interrogate hypothalamic function in women presenting with reproductive disorders causing oligo-amenorrhea. Study design, size, duration Single-centre, prospective, experimental study of healthy women (n = 33), women with PCOS (n = 30), FHA (n = 30), or CHH (n = 8), aged 18-35 years and not taking hormonal treatment. Participants were recruited for clinical studies between September 2019 and September 2023 and underwent two separate study visits. The visits assessed the gonadotropin response to hypothalamic stimulation with an intravenous bolus of kisspeptin-54 (9.6nmol/kg) and the pituitary response to an intravenous bolus of GnRH (100 mcg). Participants/materials, setting, methods All participants took part in two study visits. Serum luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels were measured every 15 minutes for 8 hours after administration of kisspeptin-54 and GnRH. The maximal rise in LH and FSH from baseline was compared between groups using an unpaired t-test. Receiver operator characteristic (ROC) analysis was used to assess the discriminatory potential of the hormone response to kisspeptin and GnRH. Main results and the role of chance The gonadotropin response to kisspeptin was increased in women with FHA compared to all other groups. The mean (SD) of the maximal rise in LH (IU/L) after kisspeptin was 9.7 (11.4) in healthy women, 9.7 (8.3) in women with PCOS, 17.6 (10.8) in women with FHA, and 1.0 (1.1) in women with CHH. The mean (SD) of the maximal rise in FSH (IU/L) after kisspeptin was 4.2 (3.4) in healthy women, 2.8 (2.1) in women with PCOS, 9.2 (5.6) in women with FHA, and 0.7 (0.5) in women with CHH. In lean women (BMI <25 kg/m2), the maximal rise in FSH after kisspeptin differentiated women with PCOS from those with FHA (area under ROC curve 0.91, p = 0.0001). Furthermore, the maximal rise in FSH after kisspeptin differentiated women with FHA from women with CHH (auROC 1.00, p < 0.0001), whereas the equivalent auROC for FSH rise after GnRH was 0.7 (p = 0.086). Limitations, reasons for caution Participants included in this study had clearcut diagnoses of PCOS, FHA, or CHH prior to inclusion, however this could increase the risk of spectrum bias. Whilst this study provides mechanistic insight into hypothalamic dysfunction in these conditions, further prospective validation of discriminatory thresholds in different settings is required. Wider implications of the findings The specific action of kisspeptin at hypothalamic GnRH neurons enables its use to assess hypothalamic function in patients with oligo-amenorrhea due to different anovulatory disorders. Our data suggests that the hormonal response to kisspeptin has promising diagnostic potential to aid in the evaluation of women with oligo-amenorrhea. Trial registration number ISRCTN21681316

DEALING WITH INSULIN RESISTANCE AMONG WOMEN WITH POLYCYSTIC OVARIAN SYNDROME

One of the most prevalent endocrine disorders in females, polycystic ovarian syndrome (PCOS), affects about 7-8% of women of reproductive age. Most females with PCOS also have increased cholesterol levels, insulin resistance, and BMI, leading to obesity. The study aimed to determine the effects of metformin and lifestyle modification (diet & exercise) on insulin resistance secondary to PCOS after 6 months of use. This RCT study was conducted at Arif Memorial Teaching Hospital from October 2022 to March 2023. The study compared the effects of metformin and lifestyle management, including only a diet plan with the use of metformin diet and exercise plan, on insulin resistance in 130 obese females aged between 20-40 years suffering from PCOS and had insulin resistance as diagnosed by HBA1C blood test. The main outcome measure was the reduction in the HBA1C level. The 130 participants were equally divided into two groups. Group A received metformin only, while Group B received metformin and an exercise plan. Baseline treatment included guidance to adopt a healthy diet. The results showed significant improvement in HBA1C level (P=0.00), BMI (P=0.02), and pregnancy rate. There was an overall improvement in the menstrual pattern but a significant improvement in Group B (P=0.00) than Group A (P=0.06). With a significant rise in follicle-stimulating hormone (FSH) levels in both groups [P=0.06 (A), P=0.01(B)], a statistically significant decrease in luteinizing hormone (LH) [P=0.02 (A), P=0.01(B)] was seen. A total drop in free testosterone level was also seen, but it wasn't significant [P=0.08 (A), P=0.06 (B)]. The study concluded that insulin resistance could be controlled effectively by acquiring a healthy lifestyle, including high protein and low carb, caloric deficient diet, and following an exercise plan and pharmacological treatment. Combining all three treatment options is more effective than using any one option as treatment.

Sleep symptoms signaling the menopausal transition.

To describe changes in sleep quality and associated sleep symptoms as women begin menopausal transition compared with premenopausal controls. In a repeated-measures design, we analyzed data collected every 2-6 months from a community-based sample of 223 women aged 40-50 (45.6 ± 2.3) years old over a 2-year period. Each 6-month visit included urinary follicle-stimulating hormone (FSH) as a marker of ovarian function and the Pittsburgh Sleep Quality Index (PSQI) and other questionnaires (Center for Epidemiological Studies-Depression Scale; Perceived Stress Scale). Menstrual cycle and vasomotor symptoms (Seattle Women's Health Symptom Checklist) were tracked every 2 months by phone. For women entering menopausal transition (n = 68) we used data from the two consecutive visits prior to their FSH rise and the next two visits. Data from the last four consecutive visits were used for controls remaining premenopausal (n = 155). The transition group did not differ from controls on age, vasomotor symptoms (hot flashes/night sweats), stress, or depression but did have a higher body mass index. Measures were stable over time for controls. However, the transition group experienced an increase in PSQI scores (initial PSQI = 5.7 ± 3.2 and final PSQI = 6.3 ± 3.8; P = .030) and frequency of trouble sleeping because of feeling too hot (P = .016), which lagged the FSH rise by 6 months with no notable change in report of hot flashes/night sweats. Trouble sleeping because of feeling too hot, distinct from awareness of vasomotor symptoms, was the only uniform contribution to higher PSQI scores after the initial FSH increase and may signal the onset of the menopausal transition. Zak R, Zitser J, Jones HJ, Gilliss CL, Lee KA. Sleep symptoms signaling the menopausal transition. J Clin Sleep Med. 2023;19(8):1513-1521.

Serum Follicle-Stimulating Hormone and 5-Year Change in Adiposity in Healthy Postmenopausal Women.

Evidence from animal studies suggests that the gradual rise in follicle-stimulating hormone (FSH) during reproductive senescence may contribute to the change in adiposity distribution characteristic of menopause. The potential independent role the interrelationships of FSH and estradiol (E2) may play in postmenopausal adiposity changes are not well studied. Our objective was to evaluate the associations of FSH and dual x-ray absorptiometry (DXA)-derived adiposity measures, with consideration of estradiol and postmenopausal hormone therapy use. In a sample of 667 postmenopausal women from the Women's Health Initiative Buffalo OsteoPerio Ancillary Study, we studied the associations of serum FSH and E2 levels with dual x-ray absorptiometry (DXA)-derived adiposity measures via cross-sectional and longitudinal analyses (5-year follow-up). In cross-sectional analyses, FSH levels were inversely associated with all measures of adiposity in models adjusted for age, years since menopause, smoking status, pack-years, and hormone therapy (HT) use; these associations were not influenced by adjustment for serum E2. In longitudinal analyses, the subset of women who discontinued HT over follow-up (n = 242) experienced the largest increase in FSH (+33.9 mIU/mL) and decrease in E2 (-44.3 pg/mL) and gains in all adiposity measures in unadjusted analyses. In adjusted analyses, an increase in FSH was associated with a gain in percentage of total body fat, total body fat mass, and subcutaneous adipose tissue (SAT). While cross-sectional findings suggest that FSH is inversely associated with adiposity, our longitudinal findings suggest that greater increases in FSH were associated with greater increases in percentage of total body fat, total body fat mass, and SAT. Future studies are needed to provide additional insight into FSH-adiposity mechanisms in larger samples.

Assessment of Variations in Serum Testosterone, Follicle Stimulating Hormone, and Luteinizing Hormone Levels in Patients Receiving Radiotherapy for Rectal Cancer

Background: Testes being in close proximity to radiation fields in patients of rectal cancer treated with radiotherapy, inadvertently receive a part of the radiation dose. This study was conducted to evaluate the variation of male sex hormones during the course of radiotherapy in patients with rectal cancer. Method: In this single-institution prospective study, 20 patients with carcinoma rectum were included. The patients were treated with 3-dimensional conformal radiation therapy or intensity modulated radiation therapy technique to a dose of 50.4 Gy for five weeks. Serum testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels were obtained prior to and in the meantime of radiotherapy. The post treatment hormone levels were compared to the baseline values. The mean, percentage, standard deviation, and Paired t-test were used for statistical analysis. Results: The mean dose received by the testes was 2.65 Gy (1.96 Gy to 4.96 Gy), which accounted for 5.25% of the total dose. The baseline values of serum testosterone, FSH, and LH were 4.65±0.7 ng/ml, 7.57±1.2 mIU/ml, and 7.93±1.1 mIU/ml, respectively. There was a 32.1% drop in the post treatment testosterone levels compared to the baseline. There was a 77% rise in the post treatment FSH and 40.2% rise in the post treatment LH levels compared to the baseline. There was a significant difference in the rise of LH levels in the patients who received a testicular dose more than 2Gy compared to those who received a dose less than 2 Gy. Conclusion: Radiation therapy was found to have a significant acute impact on male sex hormones in patients receiving radiotherapy for rectal cancer.

AYURVED APPROACH TO DIMINISHING OVARIAN RESERVE (DOR) IN FEMALE INFERTILITY - CASE STUDY

According to Ayurveda Having no Baby is described as Vandhyatva and Infertility in Modern science. In-fertility is a main issue in today’s era. Many couples go for IVF, Surrogacy and many more with very little benefits. Nearly 10-14% of individuals are belonging to the reproductive age group are affected by Infertil-ity. Infertility caused by Diminished Ovarian Reserve (DOR) results from an endocrinological imbalance. The rise in follicle stimulating hormone (FSH), decrease in Anti Mullerian hormone (AMH) and Antral fol-licle count (AFC) etc. for women age more than 35 years can lower pregnancy rates to less than 5 % and increases miscarriage rates to more than 75%. Ayurveda explained wide range of protocols and medicines for the management of Vandhyatva. In Ayurveda its appropriate correlation can be done with Dhatukshaya Vandhya explained in Harita Samhita. Ayurveda states four factors are mentioned Rutu, Kshetra, Ambu, Beeja should be in proper state in order to achieve conception and complete the pregnancy successfully. Aim & Objectives: To evaluate the efficacy of Shamana Aushadhi, Yog Basti, Uttarbasti in the manage-ment of Diminishing Ovarian Reserve (DOR) induced Female Infertility. Materials & Methods: It is the single arm, open labelled case study of the subject of 35 yrs age with pri-mary infertility of Diminishing Ovarian Reserve (DOR) from Ayurveda College who has been treated with Shodhana Chikitsa as Yog Basti, Uttarbasti and Shamana Chikitsa simultaneously. Results & Discussion: There was improvement in hormonal assay with increase in Anti Mullerian hormone (AMH) and Antral follicle count (AFC) followed by conception later on. The Patient delivered with full term normal healthy female baby. Samshodhana and Shamana Aushadha helped to pacify Vata Dosha by Dhatukshaya Vandhya Chikitsa thus restored the fertility. Conclusion: The selected treatment protocol i.e. Samshodhana and Shamana Aushadha is very effective in the management of Diminishing Ovarian Reserve (DOR) induced Female Infertility.

MiR-7 mediates the signaling pathway of NE affecting FSH and LH synthesis in pig pituitary.

MicroRNA-7 (miR-7) is an important modulator of a plenty of gene expressions and the interrelated biological processes, highly expressed in porcine pituitary. Norepinephrine (NE), acting as an important neurotransmitter or/and a hormone secreted excessively under stress, affects the synthesis and secretion of various hormones, including pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which are the key hormones which regulate sexual maturation and reproductive functions. However, the relationship among NE, miR-7 and gonadotropin needs to be elucidated. The aim of this study was to identify whether miR-7 involved in the NE-adrenoceptor signaling pathway affects the synthesis and secretion of FSH and LH in porcine pituitary. Our results showed that the NE intracerebroventricular injection increased pituitary miR-7 level and the synthesis and secretion of FSH and LH in porcine, whereas the inhibition of either endogenous miR-7 or β-adrenergic receptors hindered the rise of FSH and LH synthesis induced by NE in cultured primary porcine anterior pituitary cells. Further, we identified the molecular type of β-adrenergic receptors and the signaling pathway in porcine pituitary, and we found that NE played its roles relying on adrenoceptor beta 2 (β2AR) and the RAF/MEK/ERK1/2 signaling pathway. The phosphorylation of ERK1/2 upregulated miR-7 level which subsequently enhanced FSH and LH synthesis by targeting to Golgi glycoprotein 1 (GLG1). These suggest that miR-7 mediates NE's effect on promoting FSH and LH synthesis in porcine pituitary.

Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.

Female reproductive aging is characterized by a rise in follicle-stimulating hormone (FSH) levels during peri-menopause. N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit. Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24). The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women. Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities. However, the direct effects of FSH glycoforms on the mouse ovarian follicle have not yet been determined. In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose. Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function. Our results, therefore, indicate that FSH glycoforms are bioactive in isolated murine follicles.

SAT-417 The Gonadotrope Leptin Signal Is Critical for the Early-Morning Estrus Rise in FSH in Female Mice

The importance of peripheral nutritional signals to the functioning of the reproductive axis is appreciated, but the mechanisms are not well understood. The three tiers of the hypothalamic-pituitary-gonadal axis are receptive to many of these nutritional signals, including leptin. We have previously shown that leptin communicates with pituitary gonadotropes to maintain numbers of gonadotropin-releasing-hormone receptors (GnRHrs), and that loss of the leptin signal (LEPR) in gonadotropes results in subfertility in females. Using our current model of gonadotrope leptin resistance (GnRHR-cre, floxed Lepr exon 1) which targets the deletion of all LEPRs specifically to gonadotropes expressing Gnrhr, we investigated the role of leptin in the follicle-stimulating hormone (FSH) surge in female mice. Pituitaries and serum from 2-3 month-old control (CTL) and gonadotrope-Lepr-null (MUT) females were collected at midnight between proestrus and estrus, and at 0400 and 0900 on the morning of estrus. The samples were assayed for LH and FSH, and pituitaries were also used to determine GnRHr levels (ELISA) and Lh, Fsh, and Gnrhr mRNA levels (qPCR). Our gonadotrope-Lepr-null females showed a dramatic decrease in serum FSH during the peak of FSH secretion (0400 estrus, CTL: 25.8 ng/mL ± 5.7, n=6, MUT: 6.9 ng/mL ± 0.8, n=5, p<0.03). This result is significant, despite the large natural variability in gonadotropin surges. MUT FSH secretion also trended down at midnight by about 40%, although this effect was not significant. Interestingly, stores of FSH at 0400 were significantly increased in MUT pituitaries compared to controls. Control FSH stores dropped by ~74% from midnight to 0400, whereas mutant stores only dropped about 14% in the same time period, suggesting that the mutants have insufficient FSH secretion beginning at midnight. Analyses of ovarian sections from diestrous or proestrous MUT females showed a significant 38-43% decline in the average number of antral follicles (ANOVA, p<0.05 n=7-8), which correlates with the low FSH secretion. We also discovered a major drop in Fsh mRNA in our MUT pituitaries at 0400 (CTL RQ: 0.68 ± 0.14, n=5; MUT RQ: 0.10 ± 0.04, n=6, p<0.02). MUT Fsh mRNA remained low at 0900 (NS), at about 40% of control mRNA. Importantly, despite finding GnRHR proteins decreased at other stages in the cycle, no differences were seen between controls and mutants with regards to GnRHR (protein or mRNA) during these specific FSH surge time points. Our study indicates that leptin signals to the reproductive axis through control of FSH secretion specifically during the time of the FSH surge in female mice. We hypothesize that leptin may also be able to regulate Fsh transcription. Future studies will test the ability of leptin to stimulate Fsh transcription and secretion from normal, early AM estrous pituitaries and will investigate the pathways that mediate these effects.

The etiology of menopause: not just ovarian dysfunction but also a role for the central nervous system

Background: The hormonal changes which occur leading up to menopause have been described in multiple cross-sectional and longitudinal studies. Results from these studies document the occurrence of marked alterations in pituitary-hypothalamic function, along with the changes in the ovary, which play a role in the etiology of menopause. However, the role of pituitary-hypothalamic function in the menopausal transition (MT) has been generally overlooked. Methods: Literature searches were performed using PubMed, Scopus, and Medline, for articles with content related to menopause and the MT. The searches were restricted to English language observational studies and reviews of human studies and clinical trials. Results: During the MT, in addition to a reduction in the number of ovarian follicles, there is a marked reduction in the sensitivity of the central nervous system to both the positive and negative feedback effects of estrogen. These changes in sensitivity explain menstrual irregularities and systemic systems which are present in the time before the final menstrual period. Although the timing of menopause is difficult to predict, broad patterns in hormonal changes are seen, including a slow drop in inhibin B levels, followed by a monotropic rise in follicle-stimulating hormone during the late reproductive period. The MT is marked by irregular cycles with unpredictable luteinizing hormone levels and unpredictable ovulation. The levels of estrogen remain stable, or are even elevated through most of the MT, and levels of estrogen do not begin to decrease until late in the MT. The Stages of Reproductive Aging Workshop guidelines have improved the homogeneity of classifications in studies. Conclusions: On the basis of longitudinal hormone studies, it is clear that desensitization of the hypothalamic-pituitary-ovarian feedback loop plays an important role, in addition to a decrease in follicle number and insensitivity of remaining follicles to the positive feedback of estrogen, to trigger ovulation. Further studies in humans are needed to elucidate the mechanisms responsible for these perimenopausal changes if proper therapeutic modalities for the symptoms associated with menopause can be developed.

Burning Fat and Building Bone by FSH Blockade

The rise of follicle-stimulating hormone (FSH) is a hallmark of menopause associated with osteoporosis and visceral adiposity. In Nature, Zaidi and colleagues (Liu etal., 2017) report that blocking FSH action reduces body fat by promoting brown/beige fat thermogenesis, potentially providing a new intervention for the treatment of menopause-related metabolic diseases.

Plasma anti-Müllerian hormone profile in heifers from birth through puberty and relationship with puberty onset.

The current study aimed to define the plasma profile of anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH) in heifers during postnatal life until achieving puberty, as defined by plasma progesterone (P4) profile, to demonstrate a relationship between AMH and age of puberty onset. Blood samples collected from 11 Japanese Black female calves within 1 week after birth (W0) and then biweekly until the sixth week after puberty (WP 6) were assayed for AMH, FSH, and P4. The heifers were classified into two groups based on age of puberty onset: ≤42 weeks (early puberty group; EP, n =4) and ≥44 weeks (late puberty group; LP, n =7). Minimal plasma AMH concentration occurring at W 0 gradually increased to its peak level by W 10 (fourfold higher than W 0; P<0.01) before gradually declining to a steady plateau 6 weeks before puberty (WP -6). The AMH peak was preceded by a significant rise in plasma FSH at W 4, W 6, and W 8 compared with W0. Plasma AMH at W 16 positively correlated with WP 4 and WP 6 (r =0.69 and 0.71, respectively; P<0.05). Overall plasma AMH and FSH was significantly higher and lower in EP compared with LP, respectively. In conclusion, heifers exhibit a characteristic plasma AMH profile during postnatal life, such that plasma AMH at an early prepubertal age could be a biomarker for precocious puberty and postpubertal AMH levels.

Bayesian estimation of associations between identified longitudinal hormone subgroups and age at final menstrual period.

BackgroundAlthough follicle stimulating hormone (FSH) is known to be predictive of age at final menstrual period (FMP), previous methods use FSH levels measured at time points that are defined relative to the age at FMP, and hence are not useful for prospective prediction purposes in clinical settings where age at FMP is an unknown outcome. This study is aimed at assessing whether FSH trajectory feature subgroups identified relative to chronological age can be used to improve the prediction of age at FMP.MethodsWe develop a Bayesian model to identify latent subgroups in longitudinal FSH trajectories, and study the relationship between subgroup membership and age at FMP. Data for our study is taken from the Penn Ovarian Aging study, 1996–2010. The proposed model utilizes mixture modeling and nonparametric smoothing methods to capture hypothesized latent subgroup features of the FSH longitudinal trajectory; and simultaneously studies the prognostic value of these latent subgroup features to predict age at FMP.ResultsThe analysis identified two FSH trajectory subgroups that were significantly associated with FMP age: 1) early FSH class (15 %), which displayed initial increases in FSH shortly after age 40; and 2) late FSH class (85 %), which did not have a rise in FSH until after age 45. The use of FSH subgroup memberships, along with class-specific characteristics, i.e., level and rate of FSH change at class-specific pre-specified ages, improved prediction of FMP age by 20–22 % in comparison to the prediction based on previously identified risk factors (BMI, smoking and pre-menopausal levels of anti-mullerian hormone (AMH)).ConclusionsTo the best of our knowledge, this work is the first in the area to demonstrate the existence of subgroups in FSH trajectory patterns relative to chronological age and the fact that such a subgroup membership possesses prediction power for age at FMP. Earlier ages at FMP were found in a subgroup of women with rise in FSH levels commencing shortly after age 40, in comparison to women who did not exhibit an increase in FSH until after 45 years of age. Periodic evaluations of FSH in these age ranges are potentially useful for predicting age at FMP.Electronic supplementary materialThe online version of this article (doi:10.1186/s12874-015-0101-3) contains supplementary material, which is available to authorized users.

Inferences from the ADMET analysis of predicted inhibitors to Follicle Stimulating Hormone in the context of infertility

Follicle stimulating hormone (FSH) is a glycoprotein secreted by gonadotrophs of the anterior pituitary gland that regulates reproduction in mammals. FSH targets its receptor (FSHR) expressed only on grannulosa cells and induce the maturation of ovarian follicles in females. The levels of both FSH and FSHR rise until the middle of estrus cycle and then falls on level at the time of ovulation. It is associated with stimulated sertoli cell proliferation in testes and supports spermatogenesis in males. The interaction between the polypeptide FSH hormone and its corresponding receptor is highly selective. Therefore, it is of interest to inhibit FSH in the context of infertility. The structure of FSH (PDB ID: 1XWD) is screened using molecular docking techniques against the ZINC database (a database of 2.7 million compounds) with reference to known standard compounds. This exercise identifies compounds with better binding and ADMET (Absorption, Digestion, Metabolism, Excretion and Toxicity) properties compared to known standard compounds. These observations find application for the consideration of such compounds for further validation towards inhibiting the FSH.

Serum hormonal levels in HIV/AIDS infected male subjects on antiretroviral therapy (ART) in Nnewi, Nigeria

This study was designed to assess the serum hormonal levels (Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Testosterone, Estrogen, Progesterone, Prolactin and Cortisol) in symptomatic HIV/AIDS male subjects on ART. A total of 411 participants aged between 17 and 58 (43 ±10) years were randomly recruited for the study. The participants were staged and grouped as follows: symptomatic HIV/AIDS male subjects on ART (n= 139), symptomatic HIV/AIDS male subjects not on ART (n= 136) and HIV seronegative subjects (n= 136). Blood samples were collected from the participants for the determination of HIV status by immunochromatography and HIV confirmation by Western Blot. Enzyme Linked Immunosorbent assay (ELISA) was used to assay for FSH, LH, Testosterone, Estrogen, Progesterone, Prolactin and Cortisol levels. Their results showed significant rise in FSH, LH in HIV seropositive participants on ART compared respectively to those not on ART and the HIV seropositive subjects (p< 0.05). On the other hand, the Estrogen, Progesterone, Prolactin and Cortisol were all raised in symptomatic HIV seropositive participants not on ART compared respectively to the symptomatic HIV seroposive on ART and the HIV seronegative groups (p< 0.05). The testosterone levels significantly decreased in both symptomatic HIV infected subjects on ART and those not on ART compared with the HIV seronegative controls (p< 0.05). The relevance of HIV infection on the serum hormonal status is that HIV infection causes hypogonadism as well as primary testicular failure in symptomatic HIV participants not on ART. Also, HIV infection causes hyperprolactinaemia, hyperprogesteronaemia and hypercortisolism in symptomatic HIV participants not on ART.

Diminished Ovarian Reserve, Clomid, and Traditional Chinese Medicine: A Case Study.

Infertility caused by diminished ovarian reserve (DOR) can result from an endocrinological imbalance. A rise in follicle stimulating hormone (FSH) and decrease in antral follicle count (AFC) for women age ≤35 can lower pregnancy rates to <5%, and increase miscarriage rates to >75%. Chinese medicine may improve FSH and AFC levels in patients with DOR. It is common for women to seek adjunctive Traditional Chinese Medicine (TCM) treatment with biomedical clomid treatment. This article reports the case of a female with DOR who had completed three multiple, serial clomid cycles from September to December 2005, and for whom clomid failed. This is a case study of a 34-year-old patient with a 5-year history of infertility caused by DOR. She was treated in a private practice in Bellevue, WA. TCM treatment-including acupuncture and herbal therapy-lasted from from January 2007 to April 2007. The main outcomes sought were improvements in this patient's reproductive hormone panel, including tests for FSH, estradiol, and AFC levels; in addition a pregnancy outcome was desired. After 4 months of TCM treatment, the patient returned to biomedical care. Pregnancy was not achieved during three more clomid cycles, although she had improvements her levels of FSH (from 14.5 mIU/mL to 8.7 mIU/mL) and AFC (from 10-12 to 16-18 total). After 3 more cycles with clomid, her FSH level increased to 16.8 mIU/mL and her AFC level was <10. After three failed clomid cycles, a patient with DOR had improved FSH and AFC levels when she received TCM treatment. However, this patient was still unable to conceive although three more clomid cycles were attempted. More research is needed to discern demographically which patients benefit best from multiple, serial clomid interventions. In addition, it is important to investigate more-integrative treatments for patients with DOR, including assisted reproductive techniques, acupuncture, and Chinese herbs.

Modeling Follicle Stimulating Hormone Levels in Serum for Controlled Ovarian Hyperstimulation III: Improved Gonadotropin Administration

A numerical model with two pharmacokinetic parameters (the rate of diffusion into the blood (τin) and the rate of disappearance from the blood (τout)) mimicks the slow changes of follicle stimulating hormone (FSH) seen in serum. It is often desired to change serum FSH levels more rapidly. Since the pharmacokinetic parameters cannot be changed in patients, we used the model to investigate changing the amount and timing of gonadotropin administration to change FSH levels in serum more rapidly. Parameters defining the model were obtained as described previously [1]. The doses administered, and the timing of administration were individually specified. The rise of serum FSH was made more rapid by administering an initial injection larger than the subsequent injections. When a rapid decrease of serum FSH was desired, administration of the new, lower dose was delayed. Use of a model that simulates the serum levels of FSH during gonadotropin administration provided a framework for learning how to achieve the desired serum FSH levels more rapidly in patients. With knowledge of a particular patient's τin and τout, optimal FSH administration for that patient can be determined through modeling.

Role of serum FSH measurement on bone resorption in postmenopausal women

In vitro and animals models have shown follicle-stimulating hormone (FSH) effects on osteoclastic function, and FSH levels seem to influence bone loss independently of estrogen concentrations in humans. Our aim was to evaluate the role of serum FSH measurement in the assessment of bone resorption in postmenopausal women. We conducted a cross-sectional study including 92 postmenopausal healthy women aged 56.2 (3.6) and 7.2 (4) years since menopause. Serum FSH, luteinizing hormone (LH), estradiol (E2) and bone turnover markers as osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) were measured. We analyzed the relationship between serum levels of gonadotropins, E2, and bone turnover markers. Serum levels of OC and CTX were positively related to FSH (r = 0.234, P = 0.047 and r=0.384, P=0.003) and LH (r=0.319, P=0.012 and r=0.273, P=0.038). There was no relationship with E2 levels. When gonadotropins levels were divided into quartiles, we found significant differences in bone turnover markers between the first and the fourth quartile. OC levels were higher in the highest quartile of FSH (P=0.024) and LH (P=0.001). Serum CTX was also higher in the highest quartile of FSH (P=0.004) and LH (P=0.039). FSH levels could explain approximately 14.7% of the chances in CTX. In summary, gonadotropins were related to bone turnover in postmenopausal healthy women. Moreover, the rise in FSH appears to contribute to higher bone resorption. Our results suggest that the measurement of FSH could be usefulness to perform a more comprehensive assessment of bone loss in these women.

PACAP, an Autocrine/Paracrine Regulator of Gonadotrophs1

Hypothalamic-hypophysiotropic peptides are the proximate regulators of pituitary cells, but they cannot fully account for the complex functioning of these cells. Accordingly, awareness is growing that an array of peptides produced in the pituitary exert paracrine/autocrine functions. One such peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), was originally identified as a hypothalamic activator of cAMP production in pituitary cells. Gonadotrophs and folliculostellate cells are the main source of pituitary PACAP, and each pituitary cell type expresses a PACAP receptor. PACAP increases alpha-subunit (Cga) and Lhb mRNAs, and it stimulates the transcription of follistatin (Fst) that, in turn, restrains activin signaling to repress Fshb and gonadotropin-releasing hormone-receptor (Gnrhr) expression as well as other activin-responsive genes. The PACAP (Adcyap1) promoter is activated by cAMP, and pituitary cells may communicate by a feed-forward, cAMP-dependent mechanism to maintain a high level of PACAP in the fetal pituitary. At birth, pituitary PACAP declines and pituitary follistatin levels decrease, which together with increased gonadotropin-releasing hormone secretion allow Gnrhr and Fshb to increase and facilitate activation of the newborn gonads. Changes in Adcyap1 expression levels in the adult pituitary may contribute to the selective rise in follicle-stimulating hormone (FSH) from age 20-30 days to the midcycle surge and to the secondary increase in FSH that occurs before estrus. These results provide further support for the notion that PACAP is a key player in reproduction through its actions as a pituitary autocrine/paracrine hormone.