Assessment of parenteral estradiol and dihydroxyprogesterone use among other feminizing regimens for transgender women: insights on satisfaction with breast development from community-based healthcare services.

The practice of hormone therapy is crucial in aligning secondary sex characteristics with the gender identity of transgender adults. This study examines the effects of a commonly used injectable hormone combination, specifically estradiol enanthate with dihydroxyprogesterone acetophenide (EEn/DHPA), on serum hormonal levels and self-reported satisfaction with breast development in transwomen. Our research focused on a retrospective longitudinal study involving a large cohort of transwomen evaluated between 2020 and 2022, comprising 101 participants. We assessed serum levels of estradiol (E2), testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), comparing the EEn/DHPA hormonal regimen with other combined estrogen-progestogen (CEP) therapies. Additionally, a subset of 43 transwomen completed a 5-question survey to evaluate self-reported satisfaction with breast development using Tanner scales. Our findings indicated that participants using the EEn/DHPA regimen exhibited significantly higher serum E2 levels (mean: 186 pg/mL ± 32 pg/mL) than those using other therapies (62 ± 7 pg/mL), along with lower FSH levels, but no significant differences in T and LH levels. Concerning satisfaction with breast development, 76% reported increased fulfillment with breast augmentation while using EEn/DHPA. These results suggest that an injectable, low-cost EEn/DHPA administered every three weeks could serve as an alternative feminizing regimen, particularly considering the extensive long-term experience of the local transgender community. Further longitudinal studies on the efficacy of feminizing-body effects and endovascular risks of various parenteral CEP types are warranted to improve primary healthcare provision for transgender persons.

Is polycystic ovary syndrome a risk factor for depression and anxiety?: a cross-sectional study.

OBJECTIVE: The objective of this study was to learn more about the prevalence and pathophysiology of depression and anxiety that may be caused by polycystic ovary syndrome and to make plans for taking necessary precautions for this vulnerable group. METHODS: This case-control study was conducted between January 2022 and October 2022. A total of 120 women with polycystic ovary syndrome and 143 controls were included in the study. All healthy volunteers and women with polycystic ovary syndrome were evaluated using self-administered questionnaires and physical examination. Anthropometric data such as weight and height and laboratory value were documented. RESULTS: There was no significant difference between the groups in terms of demographic characteristics. When the Hospital Anxiety and Depression Scale scores of both groups were compared, both depression and anxiety scores were found to be significantly higher in women with polycystic ovary syndrome compared with the control group (OR: 3.319, 95%CI, 1.563-7.047, p<0.001 and OR: 3.238, 95%CI, 1.659-6.315, p<0.001). In the Hospital Anxiety and Depression Scale questionnaire, the rate of irregular menstruation and Ferriman-Gallwey score were statistically significant in women with polycystic ovary syndrome with high depression and anxiety scores. While serum LH levels and LH/FSH ratios were significantly different in women with polycystic ovary syndrome with high depression scores, serum LH, LH:FSH ratios, and serum total testosterone levels were found significant in women with polycystic ovary syndrome with high anxiety scores. CONCLUSION: It is clear that depression and anxiety are more common in patients with polycystic ovary syndrome than in healthy women. Our findings support previous recommendations regarding routine screening for depression and anxiety in this population.

Systemic Sirtuin 1 as a Potential Target to Mediate Interactions Between Body Fat and Testosterone Concentration in Master Athletes.

Evidence indicates that master athletes have higher concentration of Sirtuin 1 (Sirt1), lower body fat (BF), and greater activity of the hypothalamic-pituitary-gonadal axis in comparison to untrained peers. However, no published data have demonstrated possible mediation effect of Sirt1 in the interaction of BF and testosterone in this population. Therefore, this study compared and verified possible associations between Sirt1, BF, fat mass index (FMI), testosterone, luteinizing hormone (LH), and testosterone/luteinizing hormone (T/LH) ratio in middle-aged master athletes (n = 54; 51.22 ± 7.76 years) and control middle-aged peers (n = 21; 47.76 ± 8.47 years). Venous blood was collected for testosterone, LH, and Sirt1. BF was assessed through skinfold protocol. Although LH concentration did not differ between groups, master athletes presented higher concentration of Sirt1, testosterone, and T/LH ratio, and lower BF and FMI in relation to age-matched nonathletes. Moreover, Sirt1 correlated positively with testosterone and T/LH ratio, negatively with BF, and was not significantly correlated with LH (mediation analysis revealed the effect of BF on testosterone is mediated by Sirt1 and vice versa; R2 = .1776; p = .032). In conclusion, master athletes have higher testosterone, T/LH ratio, and Sirt1, and lower BF and FMI in relation to untrained peers. Furthermore, Sirt1 was negatively associated with BF and positively associated with testosterone and T/LH ratio. These findings suggest that increased circulating Sirt1, possibly due to the master athlete's training regimens and lifestyle, exhibits a potential mediation effect on the interaction between endocrine function and body composition.

Polycystic ovary rat model exposure to 150 kHz intermediate frequency: hypothalamic-pituitary-ovarian axis at the receptor, cellular, tissue, and hormone levels.

INTRODUCTION: The hypothalamic-pituitary-ovarian (HPO) axis is the principal regulator of the reproductive system. The neurons in the arcuate nucleus of the hypothalamus signal the basophilic cells of the anterior pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH), which bind to the granulosa and theca cells of a follicle in the ovary to promote healthy follicular development. Disruption of this process at any time can lead to polycystic ovaries and, if left untreated, can lead to Polycystic Ovarian Syndrome (PCOS), one of the leading causes of infertility. A novel treatment option using 150 kHz Intermediate Frequency (IF) Electromagnetic Radiation (EMR) has been proposed to monitor the effect of this frequency during cystic development. METHODS: To prove this, an experiment was conducted to study the effect of whole-body exposure to 150 kHz EMR for 8 weeks at receptor, cellular, tissue and hormonal levels on the HPO axis of 25 young cyclic female rats. RESULTS: The results showed that 150 kHz EMR did not affect the histoarchitecture of neurons of arcuate nucleus of the hypothalamus of PCO-induced rats. It was also found that the number of basophilic cells of the pituitary gland was increased and the immunoreactivity of LH and FSH secretion increased. This EMR field also decreased the development of follicular cysts in the ovary and possibly increased the immunoreactivity of the LH and FSH receptors as well on the theca and granulosa cells of follicles in the ovary. CONCLUSION: There are still many limitations to this study. If properly evaluated, the results of this experiment could help develop a new non-invasive treatment option for women with PCOS in the near future.

Prediction of ovarian response in IVF/ICSI cycles.

OBJECTIVE: Our study aims to evaluate the various correlations between demographic, biochemical, ultrasound, and ovarian stimulation parameters with the percentage of mature oocytes in conventional stimulation for IVF/ICSI cycles in order to develop a predictive model to improve our understanding of the oocyte maturation process. METHODS: This is a retrospective cohort study; patients underwent conventional antagonist ovarian stimulation protocols for fresh IVF/ICSI cycles. A total of 256 IVF/ICSI cycles were included. Age, antral follicle count (AFC), baseline serum follicle-stimulating hormone (FSH) levels, baseline serum luteinizing hormone (LH) levels, baseline serum estradiol (E2) levels, peak estradiol, P4 on hCG day, the body mass index (BMI), and stimulation length were measured. The variables were tested for correlations with the number of retrieved oocytes (#RO) and the number of mature oocytes (#MO). A backward stepwise regression was performed to identify the variables that correlated more strongly with percentage of mature oocytes (%MO). RESULTS: A predictive equation was obtained with the variables that were not excluded in the model. % MO = 72.700 - 0.910 (Age) + 0.979 (BMI) + 1.209 (Baseline serum LH) - 0.647 (Progesterone on human Chorionic Gonadotropin day). CONCLUSIONS: We concluded that age, the BMI, baseline serum LH, and progesterone level on hCG day may predict %MO. Prospective studies are required to validate this predictive equation.

Functions of the GABAergic system on serum LH concentrations in pre-pubertal Nellore heifers.

This study was conducted to evaluate the luteinizing hormone (LH) secretion pattern after gamma-aminobutyric acid (GABAA) antagonist to determine the effects of the GABAergic system on LH secretion during reproductive maturation in pre-pubertal Nellore heifers. Nellore heifers (n = 10) were administered a picrotoxin injection of 0.18 mg/kg, i.v. Blood samples were collected every 15 min for 3 h at different developmental stages (8, 10, 14 and 17 mo of age). Plasma concentrations of LH were quantified using an RIA (sensitivity of 0.04 ng/mL and CV of 15 %). There was an interaction between treatment and age (P = 0.034). Picrotoxin-treated heifers had lesser (P ≤  0.05) LH mean concentrations during a 3 h period at 10 and 17 mo of age compared to control heifers (P ≤  0.05). Comparing the period before and after Picrotoxin injection in the same animals, there was a 33 % decrease in LH concentration at 8 mo of age (P = 0.0165). These results indicate the GABAergic system has a stimulatory function in inducing LH secretion in pre-pubertal Nellore heifers. These findings corroborate previous results that GABA increases GnRH/LH secretion in other species during the pre-pubertal period.

Effect of 150 kHz electromagnetic radiation on the development of polycystic ovaries induced by estradiol Valerate in Sprague Dawley rats.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common complex endocrine disorder affecting approximately 2-20% of reproductive aged females. Tumour Treating Fields (100-300 kHz) is a recent innovative, non-invasive therapeutic approach to cancer therapy. This frequency as an alternative therapy for the management of polycystic ovaries has not yet been explored. OBJECTIVES: To explore the effect of full-body exposure of 150 kHz Electromagnetic Radiation (EMR), on the development of polycystic ovaries in an estradiol valerate-induced PCO rat model. METHOD: Twenty-one female adult rats were divided into three groups (n = 7 each): control, Estradiol Valerate (EV) and EV + EMR groups. The EV + EMR group was subjected to full body exposure at 150 kHz EMR continuously for eight consecutive weeks. Estradiol valerate was administered orally to induce polycystic ovaries in EV and EV + EMR groups. Body and ovarian weights were recorded and analysed. The regularity of the estrous cycle was assessed in all three groups. The histological study of ovarian tissue was carried out by haematoxylin and eosin staining. The serum concentration levels of Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH) and testosterone were measured using the ELISA method. RESULTS: The body and ovary weights did not differ significantly between the EV and EV + EMR groups. The estrous cycle was found to be irregular in both the EV and EV + EMR groups. Ovarian histology revealed near normal morphology with little or no degenerative and morphological changes in developing follicles in the exposed group. Histometrical analysis showed an increased number of developing follicles and a significant reduction in the number and size of follicular cysts (p < 0.05) in the EV + EMR group. Hormonal analysis revealed no significant difference in the testosterone and FSH levels between the EV + EMR and EV groups. However, the LH, LH/FSH ratio decreased significantly in the EV + EMR group compares to the EV group. CONCLUSION: The 150 kHz EMR appear to have little or no degenerative and morphological changes in the developing follicles, an increased number of typical developing follicles and a significant reduction in the number and size of the follicular cysts (p < 0.05).

Effect of high-intensity interval training on metabolic parameters in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Our aim was to assess the effect of high-intensity interval training (HIIT) on metabolic parameters and body composition in women with polycystic ovary syndrome (PCOS). METHODS AND ANALYSIS: A systematic review and meta-analysis of randomized controlled trials was conducted using Embase, MEDLINE (via Ovid), PubMed, Sport Discus, Scopus, Web of Science, Cochrane Library and Google Scholar (advanced feature) up to September 2020. Two authors independently screened citations and determined the risk of bias and quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were conducted using random effects model. RESULTS: Seven trials (n = 423) were included in the systematic review. The studies included HIIT interventions vs. moderate exercise or control groups. Most studies were small (average 32, range 24-110 participants) and of relatively short duration (10-16 weeks). The training intensity was performed between 90% and 95% of the maximum heart rate, three times a week, for at least 10 weeks. Insulin resistance, measured using homeostatic model assessment for insulin resistance (HOMA-IR), and body mass index (BMI) showed a significant decrease (MD -0.57; 95% CI, -0.98 to -0.16, p = 0.01), (MD -1.90, 95% CI -3.37, -0.42, p = 0.01) with moderate and high certainty of evidence, respectively. CONCLUSION: Results support that HIIT alone is effective for reducing HOMA-IR and BMI in women with PCOS. However, evidence is limited to discern the effect of HIIT on other outcomes. Future studies with a longer duration (> 16 weeks), larger sample sizes and other outcomes are needed.

Serum vitamin D content is associated with semen parameters and serum testosterone levels in men.

The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels. This is a cross-sectional study conducted at Androscience, Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo, Brazil, with 508 male patients, aged 18-60 years, from 2007 to 2017. Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria. Patients were divided into normozoospermic group (NZG, n = 124) and a group with seminal abnormalities (SAG, n = 136). Evaluation included complete physical examination, past medical history, habits and lifestyle factors, two complete seminal analysis with sperm functional tests, serum levels of 25-hydroxy-vitamin D3(25(OH)VD3), total and free testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR) index, and karyotype. The mean concentration of 25(OH)VD3was significantly lower in the SAG (P < 0.001) and positively correlated with all baseline seminal parameters and total testosterone levels. In addition, serum vitamin D3concentration was found to be positively correlated with sperm concentration (ß= 2.103; P < 0.001), total number of spermatozoa with progressive motility (ß = 2.069; P = 0.003), total number of motile spermatozoa (ß = 2.571; P = 0.015), and strict morphology (ß = 0.056; P = 0.006), regardless of other variables. This is the first comparative study to address the issue of serum vitamin D3content between normozoospermic patients and those with sperm abnormalities. It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality, male reproductive potential, and testosterone levels.

Complex Y chromosome anomalies in an infertile male.

Y chromosome anomalies are closely associated with non-obstructive azoospermia (NOA), a major etiology in male infertility. Klinefelter syndrome (KS) and Y chromosome microdeletions are some of the well-identified genetic defects in this regard, while Y chromosome aneuploidies have been reported to be susceptive. We report the rare case of a patient presenting with three complex genetic defects: mosaic Y chromosome aneuploidy; loss of the heterochromatin region in the q arm of the Y chromosome (Yqh-); and azoospermia factor C subregion (AZFc) microdeletion. The patient reported he had been subfertile for five years. Semen analysis confirmed total azoospermia along with an unaffected hormonal profile for serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels. Since the microdeletion analysis of azoospermia factor (AZF) region revealed the presence of three microdeletions in the AZFc region, the patient was offered intracytoplasmic sperm injection (ICSI) upon the retrieval of sperm by testicular sperm extraction (TESE) as the best possible assisted reproductive treatment (ART) option. It was further suggested to carry out pre-implantation genetic screening (PGS) in order to facilitate the transfer of only female embryos, thus preventing the dissemination of Y chromosomal anomalies.

Testosterone Levels Are Decreased and Associated with Disease Duration in Male Spinocerebellar Ataxia Type 2 Patients.

Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder due to an unstable expansion of a CAG repeat in the ATXN2 gene. Despite clinical and experimental evidence indicating the relevance of the gonadotropic axis to the prognosis and therapeutics for several late-onset neurodegenerative disorders, its functioning and association with disease severity have not been previously explored in SCA2. To assess serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and their clinical relevance in SCA2 patients. A case-control study involving 94 Cuban SCA2 patients and 101 gender- and age-matched healthy controls was conducted. Testosterone, LH, and FSH serum levels were determined by radioimmunoassay or immunoradiometric assay systems. Clinical outcomes included age at onset, disease duration, Scale for the Assessment and Rating of Ataxia (SARA) score, and progression rate. Univariate general linear models were generated. Testosterone, LH, and FSH serum levels were significantly reduced in male SCA2 patients relative to control individuals. On average, there was a 35% reduction in testosterone levels in male patients versus male control individuals. Testosterone levels were associated with disease duration (r = 0.383; p = 0.025) and age at onset (r = 0.414; p = 0.011) in male SCA2 patients, but no association was observed between testosterone and CAG expansion size, SARA score, or progression rate. Testosterone levels might be a biomarker of disease progression in male SCA2 patients. Further studies are needed to explore the effects of low testosterone levels on non-motor symptoms, and to assess the potential of testosterone replacement therapy in male SCA2 patients.

Interactions of circulating estradiol and progesterone on changes in endometrial area and pituitary responsiveness to GnRH†.

Changes in circulating progesterone (P4) and estradiol (E2) during proestrus produce dynamic changes in endometrial function and pituitary release of gonadotropins. Independent and combined effects of P4 and E2 on endometrium and pituitary were evaluated. In a preliminary study, an exogenous hormone model of proestrus was created by removal of corpus luteum and follicles ≥5 mm followed by gradual removal of intravaginal P4 implants during 18 h and treatment with increasing doses of estradiol benzoate during 48 h to mimic proestrus using high E2 (n = 9) or low E2 (n = 9). Decreased P4, increased E2, and increased endometrial area (EA) simulated proestrus in high-E2 cows and this was used subsequently. The main experiment used a 2 × 2 factorial design with: high E2 and low P4 (n = 11); high E2 and high P4 (n = 11); low E2 and high P4 (n = 11); low E2 and low P4 (n = 10). At 48 h, gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) and follicle stimulating hormone (FSH) release was determined. Variables were analyzed using PROCMIXED of Statistical Analysis System. The EA increased dramatically during 48 h only in high-E2 and low-P4 cows. For FSH, high-E2 cows had greater area under the curve (AUC) and FSH peak after GnRH than low E2, with mild negative effects of high P4. For LH, concentration at peak and AUC were 2-fold greater in high E2 compared to low-E2 groups, with low P4 also 2-fold greater than high-P4 groups. Thus, maximal changes in uterus and pituitary during proestrus depend on both low P4 and high E2, but different physiologic responses are regulated differently by E2 and P4. Changes in endometrium depend on low P4 and high E2, whereas GnRH-induced FSH secretion primarily depends on high E2, and GnRH-induced LH secretion is independently increased by high E2 or reduced by high P4.

Increased Sympathetic Cardiac Autonomic Modulation after Two Consecutive Tilt Tests in Women with Polycystic Ovary Syndrome.

OBJECTIVE: The present study aimed to analyze cardiac autonomic modulation via spectral and symbolic analysis of heart rate variability (HRV) in women with polycystic ovary syndrome (PCOS) who were subjected to two consecutive tilt tests. METHODS: A total of 64 women were selected and divided into 2 groups: control (without PCOS), and PCOS. Concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, homocysteine, sex hormone-binding globulin, thyroid stimulating hormone, fasting insulin, testosterone, androstenedione, and 17-hydroxyprogesterone levels, triglycerides, free androgen index (FAI), and homeostasis assessment model (HOMA-IR) were assessed. Cardiac autonomic modulation was evaluated by spectral and symbolic analyses during two consecutive tilt tests (two moments) and supine moments before, between and after (three moments) the tilt tests. RESULTS: Women with PCOS had higher fasting insulin, HOMA-IR indexes, testosterone and FAI. Additionally, we observed that the PCOS group had greater sympathetic autonomic cardiac modulation in supine 2, tilt 1, and supine 3 moments compared with controls. CONCLUSION: Women with PCOS had higher autonomic sympathetic cardiac modulation even after a second tilt test. No adaptation to this provocative test was observed. Spectral analysis was more sensitive for identifying differences between groups than the symbolic analysis.

OBJETIVO: O presente estudo teve como objetivo analisar a modulação autonômica cardíaca por análise espectral e simbólica da variabilidade da frequência cardíaca (VFC) em mulheres com síndrome dos ovários policísticos (SOP) que foram submetidas a dois testes consecutivos de inclinação. MéTODOS: Um total de 64 mulheres foram selecionadas e divididas em 2 grupos: controle (sem SOP) e SOP. Concentrações de hormônio folículo-estimulante, hormônio luteinizante, prolactina, estradiol, homocisteína, globulina de ligação a hormônios sexuais, hormônio estimulante da tireóide, insulina em jejum, testosterona e androstenediona e níveis de 17-hidroxiprogesterona, triglicerídeos, índice de andrógeno livre (FAI) e homeostase modelo de avaliação (HOMA-IR) foram avaliados. A modulação autonômica cardíaca foi avaliada por análises espectrais e simbólicas durante dois testes de inclinação consecutivos (dois momentos) e momentos supinos antes, entre e após (três momentos) os testes de inclinação. RESULTADOS: Mulheres com SOP apresentaram insulina em jejuM, índices HOMA-IR, testosterona e FAI mais altos. Além disso, observamos que o grupo PCOS apresentou maior modulação cardíaca autonômica simpática nos momentos supino 2, inclinado 1 e supino 3 em comparação aos controles. CONCLUSãO: Mulheres com SOP apresentaram modulação cardíaca simpática autonômica mais alta mesmo após um segundo teste de inclinação. Nenhuma adaptação a esse teste provocativo foi observada. A análise espectral foi mais sensível para identificar diferenças entre os grupos do que a análise simbólica.

Polycystic ovary syndrome associated with increased adiposity interferes with serum levels of TNF-alpha and IL-6 differently from leptin and adiponectin.

Objective The aim of this study was to investigate polycystic ovary syndrome (PCOS) and to explore the relationship between body fat percentage and metabolic markers. Subjects and methods Sedentary women were assigned to PCOS (N = 60) and CONTROL (N = 60) groups. Each group was subdivided into three subgroups according to body fat percentage (22-27%, 27-32% and 32-37%). The protocol consisted of assessments of glucose, insulin, androgens, follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-hydroxyprogesterone (17-OHP), leptin, adiponectin, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Results The PCOS subgroups showed higher concentrations of androgens, LH and 17-OHP. Leptin showed direct relationship with increased body fat percentage, whereas adiponectin showed the inverse effect. However, both were unaffected by PCOS. TNF-α and IL-6 were higher in PCOS women and showed a direct relationship with increased body fat percentage. Glucose showed direct relationship with body fat percentage, whereas insulin presented higher values in PCOS women and direct relationship with increased body fat percentage. Conclusions Our findings indicate that PCOS and body fat percentage directly influence concentrations of insulin, TNF-α and IL-6, whereas leptin and adiponectin are influenced only by the increase in body fat percentage in these women. Arch Endocrinol Metab. 2020;64(1):4-10.

Estradiol Potentiates But Is Not Essential for Prolactin-Induced Suppression of Luteinizing Hormone Pulses in Female Rats.

Hyperprolactinemia causes infertility by suppressing gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion. Because effects of prolactin (PRL) on the hypothalamus usually require estradiol (E2), we investigated the role of E2 in PRL-induced suppression of LH pulses. Ovariectomized (OVX) rats treated with oil or E2 (OVX + E2) received a subcutaneous injection of ovine PRL (oPRL) 30 minutes before serial measurement of LH in the tail blood by enzyme-linked immunosorbent assay. E2 reduced pulsatile LH secretion. oPRL at 1.5 mg/kg further reduced LH pulse frequency in OVX + E2 but had no effect in OVX rats. The higher dose of 6-mg/kg oPRL decreased LH pulse frequency in both OVX and OVX + E2 rats, whereas pulse amplitude and mean LH levels were lowered only in OVX + E2 rats. Kisspeptin immunoreactivity and Kiss1 messenger ribonucleic acid (mRNA) levels were decreased in the arcuate nucleus (ARC) of OVX + E2 rats. oPRL decreased both kisspeptin peptide and gene expression in the ARC of OVX rats but did not alter the already low levels in OVX + E2 rats. In the anteroventral periventricular nucleus, oPRL did not change kisspeptin immunoreactivity and, paradoxically, increased Kiss1 mRNA only in OVX + E2 rats. Moreover, oPRL effectively reduced Gnrh expression regardless of E2 treatment. In this study we used tail-tip blood sampling to determine the acute effect of PRL on LH pulsatility in female rats. Our findings characterize the role of E2 in the PRL modulation of hypothalamic components of the gonadal axis and LH release, demonstrating that E2 potentiates but is not essential for the suppression of pulsatile LH secretion caused by hyperprolactinemia.

Polycystic ovary syndrome associated with increased adiposity interferes with serum levels of TNF-alpha and IL-6 differently from leptin and adiponectin

ABSTRACT Objective The aim of this study was to investigate polycystic ovary syndrome (PCOS) and to explore the relationship between body fat percentage and metabolic markers. Subjects and methods Sedentary women were assigned to PCOS (N = 60) and CONTROL (N = 60) groups. Each group was subdivided into three subgroups according to body fat percentage (22-27%, 27-32% and 32-37%). The protocol consisted of assessments of glucose, insulin, androgens, follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-hydroxyprogesterone (17-OHP), leptin, adiponectin, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Results The PCOS subgroups showed higher concentrations of androgens, LH and 17-OHP. Leptin showed direct relationship with increased body fat percentage, whereas adiponectin showed the inverse effect. However, both were unaffected by PCOS. TNF-α and IL-6 were higher in PCOS women and showed a direct relationship with increased body fat percentage. Glucose showed direct relationship with body fat percentage, whereas insulin presented higher values in PCOS women and direct relationship with increased body fat percentage. Conclusions Our findings indicate that PCOS and body fat percentage directly influence concentrations of insulin, TNF-α and IL-6, whereas leptin and adiponectin are influenced only by the increase in body fat percentage in these women. Arch Endocrinol Metab. 2020;64(1):4-10

Increased sympathetic cardiac autonomic modulation after two consecutive tilt tests in women with polycystic ovary syndrome / Aumento da modulação autonômica cardíaca simpática após dois testes de inclinação consecutivos em mulheres com síndrome dos ovários policísticos

Abstract Objective The present study aimed to analyze cardiac autonomic modulation via spectral and symbolic analysis of heart rate variability (HRV) in women with polycystic ovary syndrome (PCOS) who were subjected to two consecutive tilt tests. Methods A total of 64 women were selected and divided into 2 groups: control (without PCOS), and PCOS. Concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, homocysteine, sex hormone-binding globulin, thyroid stimulating hormone, fasting insulin, testosterone, androstenedione, and 17-hydroxyprogesterone levels, triglycerides, free androgen index (FAI), and homeostasis assessment model (HOMA-IR) were assessed. Cardiac autonomic modulation was evaluated by spectral and symbolic analyses during two consecutive tilt tests (two moments) and supine moments before, between and after (three moments) the tilt tests. Results Women with PCOS had higher fasting insulin, HOMA-IR indexes, testosterone and FAI. Additionally, we observed that the PCOS group had greater sympathetic autonomic cardiac modulation in supine 2, tilt 1, and supine 3 moments compared with controls. Conclusion Women with PCOS had higher autonomic sympathetic cardiac modulation even after a second tilt test. No adaptation to this provocative test was observed. Spectral analysis was more sensitive for identifying differences between groups than the symbolic analysis.

Resumo Objetivo O presente estudo teve como objetivo analisar a modulação autonômica cardíaca por análise espectral e simbólica da variabilidade da frequência cardíaca (VFC) em mulheres com síndrome dos ovários policísticos (SOP) que foram submetidas a dois testes consecutivos de inclinação. Métodos Um total de 64 mulheres foram selecionadas e divididas em 2 grupos: controle (sem SOP) e SOP. Concentrações de hormônio folículo-estimulante, hormônio luteinizante, prolactina, estradiol, homocisteína, globulina de ligação a hormônios sexuais, hormônio estimulante da tireóide, insulina em jejum, testosterona e androstenediona e níveis de 17-hidroxiprogesterona, triglicerídeos, índice de andrógeno livre (FAI) e homeostase modelo de avaliação (HOMA-IR) foram avaliados. A modulação autonômica cardíaca foi avaliada por análises espectrais e simbólicas durante dois testes de inclinação consecutivos (dois momentos) e momentos supinos antes, entre e após (três momentos) os testes de inclinação. Resultados Mulheres com SOP apresentaram insulina em jejuM, índices HOMA-IR, testosterona e FAI mais altos. Além disso, observamos que o grupo PCOS apresentou maior modulação cardíaca autonômica simpática nos momentos supino 2, inclinado 1 e supino 3 em comparação aos controles. Conclusão Mulheres com SOP apresentaram modulação cardíaca simpática autonômica mais alta mesmo após um segundo teste de inclinação. Nenhuma adaptação a esse teste provocativo foi observada. A análise espectral foi mais sensível para identificar diferenças entre os grupos do que a análise simbólica.

Exploring the activity of the enzyme 11ß-hydroxylase in the polycystic ovary syndrome.

Background Hyperandrogenemic polycystic ovary syndrome (PCOS) may have occult corticosteroidogenic enzyme abnormalities. The current study compares the activities of 11ß-hydroxylase between normoandrogenemic PCOS (NA-PCOS) and hyperandrogenemic PCOS (HA-PCOS) phenotypes. Materials and methods Anthropometric, and biochemical variables were compared between normal cycling women [n = 272] and those with PCOS [n = 453]; either normoandrogenemic [n = 98] or hyperandrogenemic [n = 355]. Univariate and multivariate logistic regression analyses were performed using 11ß-hydroxylase enzyme activity as the criterion variable. Results 11ß-Hydroxylase enzyme activity tended to be slightly higher in both PCOS subgroups and did not change with ethnicity. Using univariate logistic regression, 11ß-hydroxylase activity in controls was associated with dehydroepiandrosterone, insulin, homeostatic model for insulin resistance (HOMA-IR), and high-density lipoprotein cholesterol (HDL-C). In NA-PCOS women the activity of 11ß-hydroxylase was associated with estradiol (E2), androstenedione (A4), and androstenedione/dehydroepiandrosterone ratio; in the hyperandrogenemic (HA-PCOS) group, 11ß-hydroxylase activity associated with sex-hormone binding globulin (SHBG), 17-hydroxypregnenolone (17-OHPE), fasting glucose, and ß-cell activity. After multivariate logistic regression, androstenedione/dehydroepiandrosterone ratio, and ß-cell activity were the best predictors of 11ß-hydroxylase activity in controls; in NA-PCOS group only androstenedione/dehydroepiandrosterone ratio was confirmed as a significant predictor of 11ß-hydroxylase activity, and in HA-PCOS patients, 17-OHPE and ß-cell activity demonstrated to be significant predictors. Conclusions 11ß-Hydroxylase activity was equal in different ethnicities. The prevalence of decreased 11ß-hydroxylase activity was higher in the HA-PCOS phenotype. 17-OHPE, and ß-cell function are significant predictors of 11ß-hydroxylase activity in HA-PCOS subjects. These findings may help to identify which PCOS patient would have benefit in measuring 11-deoxycortisol (compound S) and 11ß-hydroxylase enzyme activity.

Hormonal mechanisms regulating follicular wave dynamics II: Progesterone decreases diameter at follicle selection regardless of whether circulating FSH or LH are decreased or elevated.

Selection of a single dominant follicle is morphologically manifested by diameter deviation between the future dominant follicle (F1) and the future largest subordinate follicle (F2). Conventional deviation is defined as F2≥7 mm when F1 reaches ∼8.5 mm whereas, undersized deviation is if F2<7 mm when F1 reaches ∼8.5 mm. Greater frequency of undersized deviation has been temporally associated with greater circulating progesterone (P4) and greater FSH but reduced LH in observational studies. Experiment 1 was conducted to directly test if elevating P4 increased the likelihood of undersized deviation and altered circulating concentrations of LH and FSH. Experiment 2 was conducted to test if increasing LH action by treatment with exogenous porcine LH or human chorionic gonadotropin (hCG) in the presence of elevated P4, would stimulate growth of F2 and increase the likelihood of conventional deviation. Ovaries were evaluated by ultrasound and blood samples collected every 12 h after development of a new wave following follicle ablation on D6 (D0 = ovulation). Data were normalized to F1≥7.5 mm and compared using SAS software. In experiment 1 (n = 20), the CL was regressed by prostaglandin F2α treatment and heifers were randomized on D6 into control (no P4 treatment) or P4 treatment (75 mg every 12 h for 5.5 d) beginning when F1 reached ∼3 mm (P4-3 mm group) or ∼6 mm (P4-6 mm group). The P4 treatment significantly increased the frequency of undersized deviation from 0% (controls) to 54%, decreased LH by 44%, and increased FSH by 32%. In experiment 2 (n = 27) heifers were randomized on D6 into control (saline) or treatment with the LH analogs - pLH (1.25 mg porcine LH/12 h) or hCG (160 IU initially and subsequently 96 IU/24 h). Treatment with LH analogs significantly increased P4 (control, 4.6 ±â€¯0.3 ng/mL; pLH, 6.6 ±â€¯0.4 ng/mL; and hCG, 8.9 ±â€¯0.4 ng/mL) and decreased FSH (control, 0.46 ±â€¯0.03 ng/mL; combined-pLH/hCG, 0.34 ±â€¯0.02 ng/mL). However, F1 and F2 diameter and frequency of conventional (37%) and undersized (48%) deviations were similar between the control and combined-pLH/hCG groups. In conclusion, elevated P4 was directly linked to undersized deviation but the P4 effect on decreasing F2 diameter occurred independently of the P4 effects on FSH and LH concentrations.

Daily luteal serum and urinary hormone profiles in the menopause transition: Study of Women's Health Across the Nation.

OBJECTIVE: To further characterize the endocrinology of the menopause transition, we sought to determine: whether relationships between urine and serum hormones are maintained as women enter their sixth decade; whether a single luteal phase serum progesterone (P) is reflective of integrated-luteal urinary pregnanediol glucuronide (uPdg); and whether serum P, like luteal uPdg, declines as women approach their final menses (FMP). METHODS: The Study of Women's Health Across the Nation (SWAN) Daily Hormone Study's (DHS) is a community-based observational study. A subset of participants underwent a timed, luteal blood draw planned for cycle days 16 to 24 during the same month of DHS collection. Serum-luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and P, and urine LH, FSH, estrone conjugates (E1c), and daily and integrated luteal uPdg were measured in 268 samples from 170 women. Serum/urine hormone associations were determined using Pearson's correlation and linear regression, adjusted for concurrent age, body mass index, smoking status, and race/ethnicity. RESULTS: Pearson's r ranged from 0.573 (for LH) to 0.843 (for FSH) for serum/urine correlations. Integrated luteal uPdg weakly correlated with serum P (Pearson's r = 0.26, P = 0.004) and explained 7% of the variability in serum P in adjusted linear regression (total R 0.09, P = 0.002). Serum P demonstrated a marginally significant decline with approaching FMP in adjusted analysis (P = 0.04). CONCLUSIONS: Urine and serum hormones maintain a close relationship in women into their sixth decade of life. Serum luteal P was weakly reflective of luteal Pdg excretion.