Higher Follicle Stimulating Hormone Concentrations Research Articles

Roles of Follicle-Stimulating Hormone on Bone Metabolism in Late Postmenopausal Women.

BackgroundThe effects of elevated follicle-stimulating hormone (FSH) levels on physiological changes in the bone remain unclear. This study aimed to clarify the association between FSH concentrations and bone mineral density (BMD) and bone turnover markers (BTM) in late postmenopausal women.MethodsA total of 169 Korean women were enrolled. The participants’ ages ranged from 60 to 84 years (mean age, 69.0±5.1) and reported a mean duration of 19.4±6.6 years since menopause (YSM). The participants showed an average body mass index (BMI) of 24.4±2.8 kg/m2. Age, YSM, estradiol, testosterone, and BMI were confounders in the Pearson’s partial correlation. A test for trends across the quartiles of FSH levels was performed for each variable.ResultsThe mean FSH and estradiol concentrations were 61.5 IU/L and 2.9 pg/mL, respectively. Serum FSH concentration was not significantly associated with BMD (lumbar, r=0.09, P=0.30; total hip, r=0.00, P=0.96; and femoral neck, r=0.05, P=0.62). BTM across the FSH quartiles did not show any trend association (bone-specific alkaline phosphate, P=0.31; cross-linked C-terminal telopeptide of type I collagen, P=0.90). Instead, FSH levels were negatively correlated with BMI (r=−0.34, P=0.00). In the multivariate regression model adjusted for age, testosterone, and estradiol, only BMI showed a negative value across the FSH quartiles (β coefficient −0.11, P=0.00).ConclusionsThis study identified that high FSH concentrations were not associated with bone loss or high bone turnover in women in the late postmenopausal period.

Parabens and Menopause-Related Health Outcomes in Midlife Women: A Pilot Study.

Background: Parabens are antimicrobial agents prevalently found in daily-use products that can interfere with the endocrine and reproductive systems. In this study, we examined the cross-sectional associations of parabens with hot flashes, hormone concentrations, and ovarian volume in a subsample of 101 nonsmoking, non-Hispanic 45- to 54-year-old women from the Midlife Women's Health Study. Materials and Methods: Women self-reported their hot flash history and underwent a transvaginal ultrasound to measure ovarian volume. Participants provided blood for quantification of serum hormones (by enzyme-linked immunosorbent assay or radioimmunoassay) and urine samples for measurements of urinary paraben biomarker levels (by high-performance liquid chromatography negative-ion electrospray ionization-tandem mass spectrometry). Linear or logistic regression models evaluated associations of specific gravity-adjusted paraben biomarker concentrations with hot flashes, hormone concentrations, and ovarian volume. Results: We observed marginal associations of propylparaben, methylparaben, and ∑parabens biomarkers (molar sum of four parabens) with hot flashes and follicle-stimulating hormone (FSH) concentrations, and of these paraben biomarkers and ethylparaben with ovarian volume. For example, women tended to have 32% (95% confidence intervals [CI]: 0.9 to 1.81), 40% (95% CI: 1.0 to 1.95), and 40% (95% CI: 0.98 to 2.01) higher odds of having recent, monthly, and mild hot flashes, respectively, for every two-fold increase in ∑parabens. Similarly, women tended to have 14.54% (95% CI: -0.10 to 31.32) higher FSH concentrations, but 5.67% (95% CI: -12.54 to 1.75) reduced ovarian volume for every two-fold increase in ∑parabens Conclusions: Overall, our preliminary findings suggest that urinary paraben biomarkers may be associated with menopause-related outcomes in midlife women. Additional studies in larger and diverse populations are needed to expand on these findings.

High doses of FSH induce autophagy in bovine ovarian granulosa cells via the AKT/mTOR pathway.

Follicle-stimulating hormone (FSH) plays a critical role in follicular growth and granulosa cell function; however, the mechanism by which the aggressive stimulation of FSH leads to poorer oocyte quality and embryo development potential is unclear. In this study, bovine ovarian granulosa cells (BGCs) were challenged with FSH doses (vehicle, 0.1, 1, 10 and 100ng/ml) to investigate the effects of FSH on BGCs. The results indicated that the relative viability of BGCs was significantly increased in cells challenged with 1ng/ml FSH, whereas the viability was significantly decreased with 100ng/ml FSH treatment. The mRNA abundance of FSHR, CYP19, StAR and BAX was significantly upregulated with 1, 10 and 100ng/ml of FSH, while the BCL-2 mRNA level was downregulated with higher concentrations of FSH (10 and 100ng/ml). Furthermore, BGC autophagy was detected in cells treated with 10 and 100ng/ml FSH by MDC staining, and the mRNA abundance of LC3, BECN1, BNIP3, ATG3 and ATG7 was upregulated with increasing FSH concentration. Meanwhile, the protein expression of LC3 was increased in cells treated with 10 and 100ng/ml FSH. 1 and 10ng/ml FSH significantly increased E2 production, whereas 10 and 100ng/ml FSH significantly increased P4 production. FSH significantly inhibited the phosphorylation of AKT in cells treated with higher concentrations (1, 10 and 100ng/ml), while activating mTOR phosphorylation at concentrations of 10 and 100ng/ml of FSH. In summary, we can conclude that higher doses of FSH (10 and 100ng/ml) induce BGC autophagy via the AKT/mTOR signalling pathway.

FSH promotes fat accumulation by activating PPARγ signaling in surgically castrated, but not immunocastrated, male pigs

Follicle-stimulating hormone (FSH) was recently implicated as a novel regulator of fat accumulation. Surgical castration causes high FSH concentrations and increases fat accumulation, whereas immunocastration results in low FSH concentrations and less fat in immunocastrated boars versus barrows. However, detailed information regarding the role of FSH in regulation of fat accumulation in male pigs is unclear. First, expression of FSH receptor was confirmed (real-time quantitative PCR) in subcutaneous and visceral adipose tissues (SAT and VAT, respectively) of boars. Then, surgical castration (high FSH model) was compared to immunocastration (low FSH model) to investigate potential roles of FSH in adipogenesis and fat accumulation. High FSH concentrations after surgical castration activated PPARγ signaling by upregulating expression of CREB (P<0.05), and then recruited an array of PPARγ target adipogenic genes, including transcription factor (C/EBPα), long-chain fatty acid uptake (LPL), fatty acid de novo synthesis (FASN, ACACA) and lipid droplet formation (PLIN1) in both SAT and VAT, promoting fat accumulation in barrows. In contrast, much lower serum FSH concentrations in immunocastrates attenuated (P<0.05) expressions of PPARγ and PPARγ target genes in both SAT and VAT, resulting in less fat accumulation in immunocastrated boars versus barrows. We concluded that the substantially elevated FSH concentrations in barrows promoted fat accumulation by activating the PPARγ signaling pathway in adipose tissues, whereas immunocastrates accumulated less fat due to low FSH.

In vitro growth of bovine oocytes in oocyte-cumulus cell complexes and the effect of follicle stimulating hormone on the growth of oocytes.

Several successful in vitro culture experiments have used oocyte-cumulus cell-mural granulosa cell complexes (OCGCs) from early antral follicles (0.5–0.7 mm) for the growth of bovine oocytes. However, in studies related to in vitro oocyte maturation and in vitro embryo production, oocyte-cumulus cell complexes (OCCs) that have no mural granulosa cells have been widely used instead of OCGCs. The purpose of this study was to determine whether cumulus cells alone support oocyte growth. First, OCCs and OCGCs were cultured in vitro for 14 days to compare the integrity of the complexes as well as antrum formation. After 14 days, the diameter and meiotic competence of oocytes in OCCs and OCGCs were examined. Oocytes in OCCs grew fully and acquired meiotic competence similar to OCGCs, whereas antrum formation occurred later in OCCs as compared to OCGCs. Subsequently, the effects of follicle stimulating hormone (FSH) on in vitro growth of OCCs were examined for 14 days. When FSH was added to the culture medium, OCCs formed antrum-like structures one day earlier than those cultured without FSH. Oocytes cultured with 1 mIU/ml FSH grew fully and acquired meiotic competence. In contrast, when oocytes were cultured in media containing high concentrations of FSH, some of the OCCs collapsed and the number of degenerated oocytes increased. In conclusion, bovine oocytes in OCCs grow and acquire meiotic competence similar to OCGCs and, 1 mIU/ml FSH supports the development of OCCs and oocyte growth as observed in our culture system.

Per- and Polyfluoroalkyl Substances (PFAS) and Hormone Levels during the Menopausal Transition: Study of Women’s Health Across the Nation (SWAN)

Background: PFAS are endocrine disrupting chemicals that have been associated with an earlier age at menopause. However, information on their association with serum hormone concentrations is limited and inconsistent. We examined longitudinal associations between serum PFAS concentrations at baseline and serial serum concentrations of follicle stimulating hormone (FSH), estradiol (E2), testosterone (T) and sex hormone-binding globulin (SHBG) in the Study of Women’s Health Across the Nation (SWAN), a multi-racial/ethnic, community-based cohort of women transitioning through menopause. Methods: We assayed serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), 2-(N-ethyl-perfluorooctane sulfonamide) acetate (EtFOSAA), 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) in 1,398 women eligible for the SWAN Multi-Pollutant Study in 1999-2000 who were followed approximately annually to 2016. Serum PFAS concentrations were quantified by online solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry. Hormone and PFAS concentrations were log-transformed. Linear mixed regression with random intercepts was used to analyze longitudinal associations, adjusting for menopausal status, smoking, parity, race/ethnicity, site and body mass index (BMI). Results: At baseline, women had a mean age of 49.5 years, a mean BMI of 28.0 and included white (50.5%), black (22.0%), Chinese (12.7%) and Japanese (14.8%) women. PFAS were not associated with E2. In adjusted models including BMI, FSH was positively associated with total PFOS (β=0.041, 95% CI=0.000, 0.0092), branched-PFOS, (β=0.044, 95% CI=0.006, 0.0083), and n-PFOA (β=0.055, 95% CI=0.008, 0.0103) but not with EtFOSAA, MeFOSAA, PFHxS, or PFNA. T and SHBG were negatively associated with PFOS, n-PFOA and EtFOSAA, but these associations were greatly attenuated and not significant after adjustment for BMI. Conclusions: The results of this prospective study suggest that PFAS, especially PFOS and its precursors (MeFOSAA and EtFOSAA), and PFOA are associated with higher FSH concentrations in women during the menopausal transition, consistent with findings that PFAS affects reproductive aging.

Serum 25-hydroxyvitamin D levels and its relationship with sex hormones, puberty and obesity degree in children and adolescents

ABSTRACT Background/objectives Puberty and obesity have been associated with vitamin D deficiency but there is a lack of studies assessing this triple relationship at once. Thus, the aim of this study was to evaluate, under a cross-sectional design, the relationship between sex hormone levels and serum 25-hydroxyvitamin D (25(OH)D), taking into account pubertal status and obesity degree. Subjects/methods A total of 460 participants from the GENOBOX study (241 females), aged 6–18 years were included in the analysis. Children were divided in groups according to their pubertal stage (prepubertal (n = 225) and pubertal (n = 235)) and obesity degree (normal weight children (n = 100) and children with overweight/obesity (n = 360)). Serum 25(OH)D, Follicle-Stimulating Hormone (FSH) and Luteinizing hormone (LH), estradiol and testosterone were measured. 25(OH)D levels were categorized and the hormones concentration wasadjusted by sex and converted into tertiles. Mann Whitney and Kruskal–Wallis tests, and quantile regression were performed. Results Pubertal children showed lower serum concentrations of 25(OH)D than prepubertal children (median: 20 ng/mL vs. 24 ng/mL, respectively; p = 0.006). Moreover, within normal weight children, differences were found for 25(OH)D levels according to tertiles of testosterone (I: 27 ng/mL; II: 30 ng/mL; III: 19 ng/mL, p = 0.008). Among overweight/obese, differences were found according to the tertiles of FSH (I: 25 ng/mL; II: 21 ng/mL; III: 19 ng/mL, p = 0.010), LH (I: 24 ng/mL; II: 21 ng/mL; III: 20 ng/mL, p = 0.004) and estradiol (I: 24 ng/mL; II: 21 ng/mL; III: 19.5 ng/mL, p = 0.043). Finally, higher concentrations of FSH were associated with a reduction of 25(OH)D levels in children with overweight/obesity (coefficient: −1.092, p = 0.022). Conclusion Higher concentrations of sex hormones (FSH, LH, and estradiol) were associated with lower 25(OH)D levels in children with overweight or obesity. Thus, pubertal status and obesity degree need to be considered to achieve an optimal status of vitamin D in children.

Relationships between the antral follicle count, steroidogenesis, and secretion of follicle-stimulating hormone and anti-M\xfcllerian hormone during follicular growth in cattle

BackgroundThe antral follicle count (AFC) in mammalian ovaries positively correlates with female fertility. To clarify the causes of differences in fertility between low and high AFC cows, we investigated follicular growth dynamics and hormone concentrations in plasma, follicular fluid, and in vitro growth (IVG) media at different stages of follicular growth.MethodsSeven cows were divided into high AFC (n = 4, > 30 follicles) and low AFC (n = 3, < 30 follicles) groups based on the peak AFC detected by ultrasonography. These cows were subjected to estrous synchronization, daily ovarian ultrasonography, and blood collection. Their follicular fluid was collected from dominant follicles at different stages (selection, luteal, and ovulatory phases). In another experiment, we cultured oocyte-cumulus-granulosa cell complexes collected from early antral follicles (< 1 mm) for 12 days. Estradiol-17β (E2), testosterone (T), progesterone (P4), and anti-Müllerian hormone (AMH) concentrations in follicular fluids and plasma were measured. Plasma follicle-stimulating hormone (FSH) concentrations were examined. E2, P4, and AMH concentrations were also measured in IVG media.ResultsThe numbers of small (< 4 mm) and intermediate (4–8 mm) follicles were larger in the high AFC group than in the low AFC group (P < 0.05). The number of intermediate follicles was stable in the low AFC group, indicating consistent development. However, the number of these follicles fluctuated in the high AFC group. Plasma FSH concentrations were higher, whereas E2 and T concentrations were lower in the low AFC group (P < 0.05). E2 concentrations and the E2/P4 ratio in ovulatory follicles and IVG media on day 8 were higher in the high AFC group (P < 0.05). AMH concentrations in plasma and IVG media (P < 0.01) were higher in the high AFC group.ConclusionsThe weaker response to FSH of granulosa cells caused low E2 production in the low AFC group, resulting in high FSH concentrations and the consistent development of intermediate follicles. Conversely, higher E2 concentrations suppressed FSH secretion in the high AFC group. Granulosa cells in the high AFC group had the ability to produce more AMH than those in the low AFC group throughout IVG culture.

New Insights Into the Role of Follicle-Stimulating Hormone in Sex Differentiation of the Protogynous Orange-Spotted Grouper, Epinephelus coioides.

Follicle-stimulating hormone (FSH) signaling is considered to be essential for early gametogenesis in teleosts, but its functional roles during sex differentiation are largely unknown. In this study, we investigated the effects of long-term and short-term FSH injection on sex differentiation in the protogynous orange-spotted grouper (Epinephelus coioides). Long-term FSH treatment initially promoted the formation of ovaries but subsequently induced a male fate. The expression of female pathway genes was initially increased but then decreased, whereas the expression of male pathway genes was up-regulated only during long-term FSH treatment. The genes related to the synthesis of sex steroid hormones, as well as serum 11-ketotestosterone and estradiol, were also up-regulated during long-term FSH treatment. Short-term FSH treatment activated genes in the female pathway (especially cyp19a1a) at low doses but caused inhibition at high doses. Genes in the male pathway were up-regulated by high concentrations of FSH over the short term. Finally, we found that low, but not high, concentrations of FSH treatment activated cyp19a1a promoter activities in human embryonic kidney (HEK) 293 cells. Overall, our data suggested that FSH may induce ovarian differentiation or a change to a male sex fate in the protogynous orange-spotted grouper, and that these processes occurred in an FSH concentration-dependent manner.

SUN-239 A Case with Elevated Serum Follicle-Stimulating-Hormone (FSH) Concentrations Due to Macro-FSH

[Case report] A 64-year-old woman visited our hospital with the complaint of general malaise and anxiety lasting for two years. She had been diagnosed with idiopathic hypoparathyroidism because of hypocalcemia, hyperphosphatemia, low levels of intact PTH and calcification in the basal ganglia and was taking vitamin D and calcium phosphate. Endocrine workup disclosed high serum FSH [713mIU/mL (Elecsys), reference range for postmenopausal women: 10.5 - 142.8mIU/mL]. Other FSH assay platforms also showed high serum FSH levels: 523mIU/mL for Centaur and 457mIU/mL for Architect. Serum LH and E2 concentrations were 24.8mIU/mL and <11.8 pg/mL, respectively. Human anti-mouse antibody (HAMA) was not detected in the serum. [Methods] Large molecular weight FSH was precipitated using 12.5% polyethylene glycol (PEG) and the precipitation ratio (serum FSH - free FSH) / serum FSH was determined. The molecular size of FSH and IgG-bound FSH were examined using gel filtration chromatography (GFC) and protein G column (PG), respectively. Binding study was performed by incubating 125I-FSH (24000 cpm) with the serum and the specificity was examined by adding unlabeled FSH, LH, α-subunit of hCG, β-subunit of hCG and TSH. FSH was measured by enzyme immunoassay (EIA). We also examined these parameters in sera from 10 females with serum FSH>70 mIU/mL as controls. [Results] The dilution curve of the patient’s serum FSH was in parallel with that of reference one. The precipitation ratio by PEG was significantly elevated (95.4% vs. 20.3 ± 8.0% in controls). On GFC, a large proportion of serum FSH (89.4%) was eluted in the position of molecular weight > 150kDa, whereas FSH was mostly eluted at 36kDa in controls. Incubation of reference FSH (300mIU and 600mIU) with the serum (100µL) increased the peak levels of the large molecular weight FSH to be 84.0mIU/mL and 180.0 mIU/mL, respectively, from 21.6mIU/mL without exogenous FSH. Serum FSH bound to PG at a significantly higher ratio (87.3%) than that in controls (1.2 ± 1.4%). A significantly higher amount of 125I-FSH bound to the serum (5691 cpm) than that in controls (704 ± 170 cpm). The binding was displaced with an excess amount (600IU/mL) of unlabeled FSH to be 821 cpm (14.4%) and Scatchard analysis revealed the presence of anti-FSH autoantibodies (Ka 3.0 x 107 M-1, Bmax 0.92 x 10-8 M). The binding was slightly displaced by other hormones that shared α-subunit; 87.6% by LH, 90.4% by hCGα, 81.1% by hCGβ and 71.8% by TSH. [Conclusion] We report a woman with high serum FSH concentrations due to macro-FSH caused by anti-FSH autoantibodies. The possibility of macro-FSH should be considered in a case with unexpectedly high serum FSH concentrations.

FSH inhibits AMH to support ovarian estradiol synthesis in infantile mice

Anti-Müllerian hormone (AMH) regulates ovarian function in cyclic females, notably by preventing premature follicle-stimulating hormone (FSH)-mediated follicular growth and steroidogenesis. Its expression in growing follicles is controlled by FSH and by estradiol (E2). In infantile females, there is a transient increase in the activity of the gonadotrope axis, as reflected by elevated levels of both gonadotropins and E2. We previously demonstrated in mice that elevated FSH concentrations are necessary to induce E2 production by preantral/early antral follicles through the stimulation of aromatase expression without supporting their growth. However, whether this action of FSH could involve AMH is unknown. Here, we show that Amh mRNA and protein abundance and serum AMH levels are elevated in infantile mouse females, compared with those in adults. By experimentally manipulating FSH and E2 levels in infantile mice, we demonstrate that high FSH concentrations lower Amh expression specifically in preantral/early antral follicles, whereas E2 has no effect. Importantly, treatment of infantile ovaries in organotypic cultures with AMH decreases FSH-mediated expression of Cyp19a1 aromatase, but it does not alter the expression of cyclin D2-mediating granulosa cell proliferation. Overall, our data indicate that the infantile elevation in FSH levels suppresses Amh expression in preantral/early antral follicles, thereby favoring Cyp19a1 aromatase expression and E2 production. Together with recent discoveries that AMH can act on both the hypothalamus and the pituitary to increase gonadotropin levels, this work suggests that AMH is a critical regulator of the gonadotrope axis during the infantile period, thereby contributing to adult reproductive function programming.

Anti-Müllerian hormone, follicle stimulating hormone, antral follicle count, and risk of menopause within 5 years

To evaluate the ability of concentration of anti-Müllerian hormone (AMH), antral follicle count (AFC), and concentration of follicle stimulating hormone (FSH) to predict the onset of menopause. The Coronary Artery Risk Development in Young Adults Study (CARDIA) Women's Study was an ancillary study to CARDIA, a population-based study of adults aged 18-30 years followed for 3 decades. For this report, participants were women (n=426) who had attended the CARDIA year 15-16 (2000-2001) examination, had at least one ovary, were not pregnant, and underwent serum AMH and FSH measurement and transvaginal ultrasonography in 2002-2003. The probability of menopause in 5 years based upon AMH, FSH, and AFC. The mean age of the women at the time of AMH, FSH, and AFC assessment was 43 years. The cumulative incidence of menopause at 25 years (or follow-up) was 27% (n=426), and the incidence within 5 years was 13% (n=55). Among women aged 45-49 years, undetectable AMH concentrations were associated with a greater than 60% probability of menopause within 5 years, whereas approximately 1/3 of women with no or just one antral follicle experienced menopause within 5 years. Both low and high concentrations of FSH were associated with greater odds of menopause than intermediate concentrations. Models with multiple markers did not improve the prediction of menopause over that afforded by models with single markers. The ability to predict onset of menopause was improved with any of the three menopausal markers in addition to age. AMH concentrations were more closely associated with menopause than AFC or FSH.

ЗАВИСИМОСТЬ РЕЗУЛЬТАТА ЛАЗЕРНОГО ЛЕЧЕНИЯ ГИПЕРТРОФИЧЕСКИХ РУБЦОВ ОТ ИСХОДНОЙ РЕАКТИВНОСТИ ОРГАНИЗМА

The purpose of the study was to identify the relationship between the initial state of the organism and the result of the treatment of hypertrophic scars. 38women of 16–35years of age were examined on the 5–7th days of the menstrual cycle, 16 of them had normotrophic scars and 22 – hypertrophic scars. The quality of scars, lipid profile, the concen-tration of thyrotropin, free fraction of thyroxine, growth hormone (GH), luteinizing and follicle stimulating hormone (FSH), cortisol, prolactin, estradiol, testosterone, progesterone , the concentration of TNF-α, IL-4, IL-6, IL-10, and the level of autoantibodies to DNA, IFN-α , IFN-γ, b2-glycoprotein, Fc-fragments, collagen-2 were determined. Further on the laser treatment was performed: the scar surface was treated by multiple perforations under local anesthesia. Treatment outcome was assessed in 3months by the clinical characteristics of the scar. It was found that in 10women hypertrophic scars reformed in normotrophic scars after the treatment, and 12women still had hypertrophic scars. Patients with a positive result of treatment had a low concentration of GH (0.5±0.1) and high concentrations of proges-terone (6.0±0.4) and FSH (6.7±0.5 in the follicular phase of the cycle). The negative result of the treatment obtained in patients with significant shifts reactivity indicators: high atherogenic index (2.6±0.2) and the level of GH (2.1±0.5), low levels of cortisol (346.8±39), testosterone (1.5±0.2), IL-10 (3.89±1.6) and antibodies to IFN-γ (0.206±0.05), IFN-α (0.385±0.02), Fc-fragments (0.317±0.04).

Pubertal Development

Pubertal Development

High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway.

The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.

Gonadotropins Are Related to Lean Mass in Healthy Postmenopausal Women

Background. It has been suggested that the changes in hormone levels that occur with menopause and aging are related to loss of muscle mass. However, the role of gonadotropins in this process is unknown. Objectives. To analyze the relationship between follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and lean mass in a cohort of healthy women. Methods. This is a cross-sectional study including 91 postmenopausal women (48–65 years old). Serum FSH, LH, and estradiol (E2) were measured. Lean mass was estimated by bioelectrical impedance analysis and expressed as appendicular skeletal muscle mass (AMM) index. Results. AMM index was negatively correlated with FSH levels (r = −0.33, p = 0.001) and LH (r = −0.293, p = 0.005), while there was no association with E2. When muscle mass expressed as AMM index was stratified into tertiles, there were significant differences between the lowest and the highest tertile for both FSH (82.4 ± 30, vs. 67.9 ± 25.8 mIU/mL, p = 0.04) and LH (40.9 ± 15.2 vs. 36.1 ± 12.3 mIU/mL, p = 0.03). In logistic regression analysis adjusted for age and E2 levels, high concentrations of FSH (OR = 1.03, 95% CI = 1.01–1.05, p = 0.008) and LH (OR = 1.06, 95% CI = 1.01–1.1, p = 0.01) were risk factors for having lower lean mass expressed as AMM index. Conclusions. Menopausal women with high levels of gonadotropins have lower levels of lean mass than those with lower gonadotropins levels.

Further Evidence of the Clinical, Hormonal, and Genetic Heterogeneity of Klinefelter Syndrome: A Study of 216 Infertile Egyptian Patients

This study aims to provide further insight into the phenotypic heterogeneity of Klinefelter syndrome (KS) by presenting clinical, hormonal, and genetic data from a large series of Egyptian infertile patients with KS. A retrospective case series of KS patients was studied over a period from January 2003 to April 2010. All patients underwent a complete history and physical examination; color duplex examination; semen analysis; measurement of total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and prolactin (PRL); and chromosomal typing. Mosaic KS diagnosis was confirmed by fluorescence in situ hybridization. The series included 216 KS patients (198 nonmosaic, 16 mosaic, and 2 KS variants). Typical clinical signs of hypoandrogenism were observed in 86% of patients. Gynecomastia affected 20.8% of the patients. Eunuchoidal body proportions, with arm span exceeding height and lower segment length exceeding upper segment length, were detected in 43.9% and 64.4% of the patients, respectively. In all patients, a reduction in testicular size and azoospermia were detected. Normal levels of T, FSH, LH, E2, and PRL were detected in 44.5%, 3.7%, 3.3%, 93.5%, and 91.2% of patients, respectively. Differences were not significant between patients with classic KS and those with mosaic KS in terms of the frequency of clinical signs of hypoandrogenism, gynecomastia, low T concentrations, or high concentrations of FSH, LH, E2, and PRL (all P > .05). The results of the current study emphasize the heterogeneous clinical, hormonal, and genetic phenotype of infertile KS patients. Our findings support the usefulness of cytogenetic studies in infertile patients showing small testicular size and azoospermia, regardless of the presence of other clinical or endocrine findings.

Unpredictable endocrinology of the menopause transition: clinical, diagnostic and management implications

The approach to menopause can be divided into the early (E) and late (L) menopausal transitions (MT) on the basis of menstrual irregularity (EMT) and subsequent observation of at least one episode of 60 or more days amenorrhoea (LMT). In total, 40-60% of cycles in the LMT are anovulatory, often with low oestradiol (E2) and high follicle-stimulating hormone concentrations. The ovulatory cycles have variable endocrine characteristics, none of which is specific to EMT or LMT. Hormonal measurements of FSH and E2 are thus of little diagnostic value because of their unpredictable variability. Symptoms during the transitions may result from high or low E2 and can often be satisfactorily managed with low-dose oral contraceptives, which suppress pituitary-ovarian function.

Follicle-stimulating hormone is independently associated with lean mass but not BMD in younger postmenopausal women

Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated. We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT). FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β=-0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD. After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight.

Controlled ovarian hyperstimulation for low responders in in vitro fertilization/intracytoplasmic sperm injection: a low-dose flare protocol

In this retrospective study of 652 anticipated low response women, the overall clinical outcomes (live birth rate and clinical pregnancy rate [PR]) of low-dose flare (LDF) protocol appeared lower than those of conventional down-regulation (DR) (LDF: 15.1% vs. DR: 20.6% and LDF: 10.3% vs. DR: 17.4%, respectively). The findings that LDF protocol improved the clinical outcome in older women, or when LDF followed an unsuccessful IVF/intracytoplasmic sperm injection (ICSI) cycle with DR (LDF: 19.4% vs. DR: 9.76% and LDF: 13.9% vs. DR: 4.2% respectively), need further evaluation through randomized trials.