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The article discusses the importance of achieving optimal uterine growth during pubertal induction in hypogonadal females through the use of unopposed estrogen treatment. The study compared uterine development in hypogonadal females with a standard pubertal induction protocol to a reference group and found differences in uterine volume. The study highlights the significance of using natural estrogen preparations over synthetic ones and emphasizes the need for monitoring uterine maturation and endometrial thickness during treatment. The findings suggest that incremental doses of unopposed estrogen before introducing progestogen can lead to comparable uterine development in hypogonadal females. [Extracted from the article]

Background: Oestradiol has been implicated as a factor in substrate utilisation in male and mouse studies but the effect of acute changes during the menstrual cycle is yet to be fully understood. Objective: To determine the role of oestradiol in respiratory exchange ratio (RER) during exercise at various intensities. Methods: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. From inception to November 2023, four online databases (Cochrane, SPORTDiscus, MEDline and Web of Science) were searched for relevant articles. Studies that reported a resting oestradiol measurement in naturally menstruating women with exercise at a percentage of maximal aerobic capacity (%V˙O2max) were included. Mean and standard deviation for oestradiol, RER and exercise intensity were extracted and study quality assessed using a modified Downs and Black checklist. Risk of bias was assessed using I2 measure of heterogeneity and Egger's regression test, assessment of bias from methodological quality was identified by sensitivity analysis. Eligible datasets were extracted for pairwise comparisons within a meta-analysis and correlation between change in oestradiol and change in RER. Data were also pooled to produce a mean and standard deviation for RER for menstrual stage and for low and high oestradiol groups. Results: Twenty-four articles were identified, over 50% were identified as high quality. Sixteen articles included datasets eligible for meta-analysis. Eleven articles utilised a submaximal constant-load exercise intensity, finding a standardised mean difference of − 0.09 ([CI: −0.35–0.17], p = 0.5) suggesting no effect of menstrual phase on constant-load exercise RER. In six articles using incremental exercise tests to exhaustion, a standardised mean difference of 0.60 ([CI 0.00–1.19], p = 0.05) was identified towards a higher maximal RER attained in follicular compared to luteal phase. There was no correlation (R = −0.26, p = 0.2) between change in oestradiol and change in RER between phases. All 24 articles, totalling 650 participants, were included in pooled analysis. When grouped by menstrual cycle phase or when grouped by oestradiol levels, RER was higher in the follicular phase than the luteal phase at low and high constant load exercise intensities. Discussion: Findings from the pooled-analysis and meta-analysis suggest that there may be menstrual cycle phase differences in RER that are intensity dependent. These differences may be related to sex hormone levels, but this was not supported by evidence of correlation between differences in RER and differences in oestradiol. At present, it remains best practice to assess performance in the same menstrual cycle phase if seeking to assess change from baseline. [ABSTRACT FROM AUTHOR]

Objective: Reproductive hormones might impact disease course in cognitive decline. We examined the association between male and female endogenous reproductive hormones and subjective cognitive decline (SCD) score. Design, Patients and Measurements: A cross‐sectional study design was used with baseline data from the Pingyin cohort study, involving 1943 participants aged 45–70 years. Oestrogen (E2), testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured in females and E2 and testosterone were measured in males. We categorised hormones into three levels of low, intermediate and high level. The 9‐item subjective cognitive decline questionnaire (SCD‐Q9) scores were collected to assess the symptoms of SCD. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) between categorised hormone levels and SCD status. Multivariable linear regression models were also used. Results: Overall, 1943 participants were involved and 1285 (66.1%) were female. The mean age at baseline was 59.1 (standard deviation 7.1) years. Women with high testosterone levels had a higher probability of having SCD compared with those with low testosterone levels (OR 1.43, 95% CI 1.01–2.05). Men with a high level of testosterone (0.59, 0.35–0.98) and high testosterone/E2 ratio (0.55, 0.33–0.90) were related to decreased chances of having SCD. Each one‐unit increase of testosterone was linked to reduced SCD score in males [(β: −.029, 95% CI (−0.052, −0.007)]. Conclusion: There was sex‐specific relationship between hormone levels and SCD abnormal. Those with higher testosterone levels in females may increase likelihood of experiencing SCD. Males with higher testosterone levels and higher testosterone/E2 ratio may be associated with reduced likelihood of SCD. The roles of endogenous reproductive hormone levels and their dynamic changes in cognitive function need further investigation. [ABSTRACT FROM AUTHOR]

Opioids are the most prescribed drugs for the alleviation of pain. Both clinical and preclinical studies have reported strong evidence for sex-related divergence regarding opioid analgesia. There is an increasing amount of evidence indicating that gonadal hormones regulate the analgesic efficacy of opioids. This review presents an overview of the importance of gonadal steroids in modulating opioid analgesic responsiveness and focuses on elaborating what is currently known regarding the underlying mechanism. We sought to identify the link between gonadal hormones and the effect of oipiod antinociception. [ABSTRACT FROM AUTHOR]

Menopause marks a major milestone in female reproductive ageing. It is characterized by the cessation of ovarian function and a concomitant decline in hormones such as oestradiol. Subsequently, females undergoing menopausal transition experience a progressive increase in cardiovascular and cerebrovascular disease risk. During menopause, reductions in nitric oxide (NO) bioavailability, endothelial dysfunction, increases in systemic inflammation, oxidative stress, and impaired vascular remodelling may contribute towards an accelerated decline in the function of cerebral and peripheral vascular systems. Historically, hormone therapy (HT) has been used as a means of managing vascular disease risk and reducing menopause‐associated vasomotor symptoms such as hot flushes, though some studies suggest regular exercise has the potential to be a promising alternative. Regular aerobic exercise during early postmenopause may slow vascular decline by improving NO and oestradiol bioavailability, promoting positive vascular remodelling and lowering systemic inflammation. However, exercise‐mediated improvements in markers of vascular function are not consistently observed in oestradiol‐deficient postmenopausal women. Emerging evidence suggests that due to the greater oestradiol bioavailability during early postmenopause, vascular adaptations to exercise may be enhanced during this stage, as opposed to late postmenopause. Subsequently it may be important to begin regular exercise in the years preceding and immediately following the final menstrual period to slow the progression of vascular disease risk during perimenopause and beyond. The present review will provide a summary of our current understanding of how vascular function is affected during menopause and the role of regular aerobic and resistance exercise training in managing vascular disease risk. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) arise from the diffuse endocrine system and have been considered to be rare. However, the incidence and prevalence of these tumours have increased in recent years, and they are being seen in younger patients including women in the reproductive age group. Due to the paucity of data, diagnostic and therapeutic strategies in managing such tumours during pregnancy can be challenging to both treating physicians and patients. This article describes the experience and outcomes of managing pregnant women with NEN at a European Neuroendocrine Tumour Society (ENETS) Centre of Excellence. In this retrospective analysis, we evaluated a total of 22 pregnancies in 18 pregnant women with concurrent diagnoses of NENs who were managed at Royal Free Hospital ENETS Centre of Excellence throughout their pregnancy. These were identified from our tumour registry of 3500 NEN patients between 2015 and 2023. Cross‐sectional imaging (computed tomography (CT)/magnetic resonance imaging (MRI)), pre‐ and post‐pregnancy, for each patient was reviewed by an experienced radiologist. Tumour growth rate (TGR) was calculated using the formula: TGR = 100 × [exp (TG) − 1]; TG. [3 × log (D2/D1)]/time (months), where D1 is the tumour size at date 1; D2 is the tumour size at date 2; and time (months) = (Date 2 − Date 1 + 1)/30.44. Tumour growth rate pre‐conception (TGRpc) and tumour growth rate post‐partum (TGRpp) were calculated for each patient. In a sub‐group of patients, positivity for oestrogen and progesterone receptors were analysed on the tumour tissue to evaluate whether the presence of these receptors affected tumour progression during the pregnancy. We also reviewed the pregnancy outcome in patients treated with somatostatin analogues during pregnancy. We analysed the data of a total 22 pregnancy encounters in 18 women: 15 pregnancies (68%) preceded the diagnosis of the NEN, whereas the diagnosis of NEN was made during pregnancy or in the post‐partum period in 5 (23%) and 2 (9%) pregnancies respectively. Eight patients (44%) had a diagnosis of a pancreatic NEN, whereas 5 (28%) were diagnosed with mid‐gut NENs, and a further 5 at other sites. The majority of the patients (n = 12, 67%) had evidence of metastatic disease at the time of diagnosis. Most pregnancies had a successful outcome (n = 19, 86%), whereas 3 patients (14%) had miscarriages in the 1st trimester. Five patients in total of 6 pregnancies were treated with somatostatin analogues as monotherapy during the pregnancy, and all of them had stable disease after pregnancy. All of them delivered healthy babies without any side effects or complications due to therapy. The average TGRpc was −0.8% (n = 5) and the average TGRpp was +0.96% (n = 6); 2 patients who did not have suitable targets for calculation of TGRpc developed new lesions suggesting disease progression. Moreover, 2 of the 4 patients who have had both pre‐conception and post‐pregnancy scans showed an increase in TGRpp compared to TGRpc. The management of NENs during pregnancy should be multidisciplinary with an individualised approach to each patient. Somatostatin analogues appear to be safe during pregnancy, though further robust studies are needed. Pregnancy per se may accelerate tumour progression, and patients should be counselled regarding this possibility. [ABSTRACT FROM AUTHOR]

Aims Oestrogen exerts beneficial cardiovascular effects by binding to specific receptors on various cells to activate nuclear and non-nuclear actions. Oestrogen receptor α (ERα) non-nuclear signalling confers protection against heart failure remodelling, involving myocardial cyclic guanosine monophosphate (cGMP)–cGMP-dependent protein kinase G (PKG) activation; however, its tissue-specific role remains elusive. Herein, we examine the cell type–specific role of ERα non-nuclear signalling in oestrogen-conferred protection against heart failure. Methods and results We first assessed the tissue-specific impacts of ERα on the cardiac benefits derived from oestrogen, utilizing endothelial ERα deletion (ERαf/f/Tie2Cre+) and myocyte ERα deletion (ERαf/f/αMHCCre+) female mice. Female mice were ovariectomized and the effect of estradiol (E2) was assessed in hearts exposed to 3 weeks of pressure overload [transverse aortic constriction (TAC)]. E2 failed to improve cardiac function in ERαf/f/Tie2Cre+ TAC hearts but provided benefits in ERαf/f/αMHCCre+ TAC hearts, indicating that endothelial ERα is essential. We next assessed the role of non-nuclear signalling in endothelial cells (ECs), employing animals with endothelial-specific inactivation of ERα non-nuclear signalling (ERαKI/KI/Tie2Cre+). Female ovariectomized mice were supplemented with E2 and subjected to 3-week TAC. ERαKI/KI/Tie2Cre+TAC hearts revealed exacerbated cardiac dysfunction and reduced myocardial PKG activity as compared to littermate TAC hearts, which were associated with attenuated myocardial induction of vascular endothelial growth factor (VEGF) and angiogenesis as assessed by CD31-stained capillary density. This phenotype of ERαKI/KI/Tie2Cre+was rescued by myocardial PKG activation from chronic treatment with a soluble guanylate cyclase (sGC) stimulator. We performed co-culture experiments to determine endothelial–cardiomyocyte interactions. VEGF induction by E2 in cardiac myocytes required a co-existence of intact endothelial ERα signalling in a nitric oxide synthase-dependent manner. On the other hand, VEGF was induced in myocytes directly with an sGC stimulator in the absence of ECs. Conclusion An endothelial oestrogen–myocardial cGMP axis stimulates angiogenic response and improves cardiac performance during pressure overload. [ABSTRACT FROM AUTHOR]

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Background: Oestradiol has been implicated as a factor in substrate utilisation in male and mouse studies but the effect of acute changes during the menstrual cycle is yet to be fully understood. Objective: To determine the role of oestradiol in respiratory exchange ratio (RER) during exercise at various intensities. Methods: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. From inception to November 2023, four online databases (Cochrane, SPORTDiscus, MEDline and Web of Science) were searched for relevant articles. Studies that reported a resting oestradiol measurement in naturally menstruating women with exercise at a percentage of maximal aerobic capacity (%V˙O2max) were included. Mean and standard deviation for oestradiol, RER and exercise intensity were extracted and study quality assessed using a modified Downs and Black checklist. Risk of bias was assessed using I2 measure of heterogeneity and Egger’s regression test, assessment of bias from methodological quality was identified by sensitivity analysis. Eligible datasets were extracted for pairwise comparisons within a meta-analysis and correlation between change in oestradiol and change in RER. Data were also pooled to produce a mean and standard deviation for RER for menstrual stage and for low and high oestradiol groups. Results: Twenty-four articles were identified, over 50% were identified as high quality. Sixteen articles included datasets eligible for meta-analysis. Eleven articles utilised a submaximal constant-load exercise intensity, finding a standardised mean difference of − 0.09 ([CI: −0.35–0.17], p = 0.5) suggesting no effect of menstrual phase on constant-load exercise RER. In six articles using incremental exercise tests to exhaustion, a standardised mean difference of 0.60 ([CI 0.00–1.19], p = 0.05) was identified towards a higher maximal RER attained in follicular compared to luteal phase. There was no correlation (R = −0.26, p = 0.2) between change in oestradiol and change in RER between phases. All 24 articles, totalling 650 participants, were included in pooled analysis. When grouped by menstrual cycle phase or when grouped by oestradiol levels, RER was higher in the follicular phase than the luteal phase at low and high constant load exercise intensities. Discussion: Findings from the pooled-analysis and meta-analysis suggest that there may be menstrual cycle phase differences in RER that are intensity dependent. These differences may be related to sex hormone levels, but this was not supported by evidence of correlation between differences in RER and differences in oestradiol. At present, it remains best practice to assess performance in the same menstrual cycle phase if seeking to assess change from baseline.

Background & Aims: Laportea aestuans is a medicinal plant used in ethnomedicine as an abortifacient, anthelminthic, anti-fibroid, antipyretic, and anti-microbial agent. Uterine leiomyoma, a menace of reproductive age in women, is characterized by the proliferation of smooth muscle cells (hyperplasia) in the uterus. This study aims to investigate the preventive and curative anti-leiomyoma activity of Laportea aestuans using monosodium glutamate-induced uterine hyperplasia models in female Sprague-Dawley rats. Materials & Methods: The methanol whole plant extract of Laportea aestuans (MELA) was prepared by extracting the pulverized, air-dried whole plant with 2.5 L of methanol in a Soxhlet apparatus, followed by filtration and oven-drying. The acute toxicity of MELA was then assessed using Lorke’s method. Subsequently, three doses of MELA were selected for this study. Uterine hyperplasia was induced with 200 mg/kg p.o. monosodium glutamate (MSG) for 30 days. MELA was either co-administered with the inducing agent (preventive study) or administered post-induction for another 30 days (curative study). The anti-leiomyoma activity of MELA was then assessed through haematological, biochemical, and histopathological findings. Results: Increased serum oestrogen, progesterone, and total cholesterol levels were observed in the untreated fibroid animal groups, but these were significantly attenuated (p < 0.05) in animals treated with different doses of MELA. This correlated with the histopathological findings, as MELA reversed uterine hyperplasia with its therapeutic potential noted from 500 mg/kg. Conclusion: These findings suggest that MELA contains bioactive agents that can reverse MSG-induced uterine hyperplasia. It may therefore be useful in reducing the proliferation of fibroblast cells and managing other symptoms associated with uterine leiomyoma upon successful clinical trials.

Objective: To investigate the potential of N-acetylcysteine (NAC) and zinc sulphate (ZnSO4) in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate (DEHP) in rats and to understand the underlying mechanisms, specifically oxidative stress and sex hormone receptor activity. Methods: Thirty-five male Wistar rats were randomly divided into five equal groups (n=7 per group). Group 1 was administered 0.5 mL of distilled water and served as the control group. Group 2 was given only DEHP (750 mg/kg/day), while group 3, 4 and 5 were given DEHP (750 mg/kg/day) plus NAC (100 mg/kg/day), DEHP (750 mg/kg/day) plus ZnSO4 (0.5 mg/kg/day), and DEHP (750 mg/kg/day) plus NAC (100 mg/kg/day) as well as ZnSO4 (0.5 mg/kg/day), respectively. All treatments lasted for 21 days. Samples were obtained after the rats were sacrificed, and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay. The amount of androgen receptors in the testicles was determined by immunohistochemistry, and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies. Results: DEHP decreased reproductive hormones, testicular antioxidant enzymes, increased malondialdehyde levels, and negatively impacted histology of the pituitary and testes. NAC or ZnSO4 treatment showed a marked improvement in testicular antioxidant status and hormone levels, as well as a positive effect on the histology of the pituitary and testes. The combination of both treatments appeared to be more effective. The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling, which can further result in dysfunction of hormones related to androgen. However, NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors, as well as gonadotropin-releasing hormone receptors, when compared to DEHP. Conclusions: The possibility that NAC and ZnSO4 could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.

Hypopituitarism is a heterogenous disorder characterised by a deficiency in one or more anterior pituitary hormones. There are marked sex disparities in the morbidity and mortality experienced by patients with hypopituitarism. In women with hypopituitarism, the prevalence of many cardiovascular risk factors, myocardial infarction, stroke and mortality are significantly elevated compared to the general population, however in men, they approach that of the general population. The hypothalamic-pituitary-gonadal axis (HPG) is the most sexually dimorphic pituitary hormone axis. Gonadotropin deficiency is caused by a deficiency of either hypothalamic gonadotropin-releasing hormone (GnRH) or pituitary gonadotropins, namely follicle-stimulating hormone (FSH) and luteinising hormone (LH). HPG axis dysfunction results in oestrogen and testosterone deficiency in women and men, respectively. Replacement of deficient sex hormones is the mainstay of treatment in individuals not seeking fertility. Oestrogen and testosterone replacement in women and men, respectively, have numerous beneficial health impacts. These benefits include improved body composition, enhanced insulin sensitivity, improved atherogenic lipid profiles and increased bone mineral density. Oestrogen replacement in women also reduces the risk of developing type 2 diabetes mellitus. When women and men are considered together, untreated gonadotropin deficiency is independently associated with an increased mortality risk. However, treatment with sex hormone replacement reduces the mortality risk comparable to those with an intact gonadal axis. The reasons for the sex disparities in mortality remain poorly understood. Potential explanations include the reversal of women's natural survival advantage over men, premature loss of oestrogen's cardioprotective effect, less aggressive cardiovascular risk factor modification and inadequate oestrogen replacement in women with gonadotropin deficiency. Regrettably, historical inertia and unfounded concerns about the safety of oestrogen replacement in women of reproductive age have impeded the treatment of gonadotropin deficiency. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effect of a supraphysiological dose of testosterone on the levels of sex steroid hormones and the expression and distribution of sex steroid receptors in the uterus during the endometrial receptivity development period. In this study, adult female Sprague–Dawley rats (n = 24) were subcutaneously administered 1 mg/kg/day of testosterone alone or in combination with the inhibitors (finasteride or anastrozole or both) from day 1 to day 3 post-coitus, while a group of six untreated rats served as a control group. The rats were sacrificed on the evening of post-coital day 4 of to measure sex steroid hormone levels by ELISA. Meanwhile, gene expression and protein distribution of sex steroid receptors were analysed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), respectively. In this study, treatment with a supraphysiological dose of testosterone led to a significant reduction in oestrogen and progesterone levels compared to the control. The mRNA expression of the androgen receptor increased significantly in all treatment groups, while the mRNA expression of both the progesterone receptor and the oestrogen receptor-α decreased significantly in all treatment groups. The IHC findings of all sex steroid receptors were coherent with all mRNAs involved. This study shows that a supraphysiological dose of testosterone was able to interrupt the short period of the implantation window. This finding could serve as a basis for understanding the role of testosterone in endometrial receptivity in order to develop further therapeutic approaches targeting androgen-mediated disorders of endometrial receptivity. [ABSTRACT FROM AUTHOR]

Neuroactive steroids are a type of steroid hormones produced within the nervous system or in peripheral glands and then transported to the brain to exert their neuromodulatory effects. Neuroactive steroids have pleiotropic effects, that include promoting myelination, neuroplasticity, and brain development. They also regulate important physiological functions, such as metabolism, feeding, reproduction, and stress response. The homoeostatic processes of metabolism and reproduction are closely linked and mutually dependent. Reproductive events, such as pregnancy, bring about significant changes in metabolism, and metabolic status may affect reproductive function in mammals. In females, the regulation of reproduction and energy balance is controlled by the fluctuations of oestradiol and progesterone throughout the menstrual cycle. Neurosteroids play a key role in the neuroendocrine control of reproduction. The synthesis of neuroestradiol and neuroprogesterone within the brain is a crucial process that facilitates the release of GnRH and LH, which in turn, regulate the transition from oestrogen-negative to oestrogen-positive feedback. In addition to their function in the reproductive system, oestrogen has a key role in the regulation of energy homoeostasis by acting at central and peripheral levels. The oestrogenic effects on body weight homoeostasis are primarily mediated by oestrogen receptors-α (ERα), which are abundantly expressed in multiple brain regions that are implicated in the regulation of food intake, basal metabolism, thermogenesis, and brown tissue distribution. The tight interplay between energy balance and reproductive physiology is facilitated by shared regulatory pathways, namely POMC, NPY and kisspeptin neurons, which are targets of oestrogen regulation and likely participate in different aspects of the joint control of energy balance and reproductive function. The aim of this review is to present a summary of the progress made in uncovering shared regulatory pathways that facilitate the tight coupling between energy balance and reproductive physiology, as well as their reciprocal interactions and the modulation induced by neurosteroids. [ABSTRACT FROM AUTHOR]

Kidney cancer is a common malignancy that constitutes around 5% of all cancer cases. Males are twice as likely to acquire renal cell carcinoma (RCC) compared to females and experience a higher rate of mortality. These disparities indicate that sex hormone (SH)-dependent pathways may have an impact on the aetiology and pathophysiology of RCC. Examination of SH involvement in conventional signalling pathways, as well as genetics and genomics, especially the involvement of ribonucleic acid, reveal further insights into sex-related differences. An understanding of SHs and their influence on kidney cancer is essential to offer patients individualized medicine that would better meet their needs in terms of prevention, diagnosis and treatment. This review presents the understanding of sex-related differences in the clinical manifestation of kidney cancer patients and the underlying biological processes. [ABSTRACT FROM AUTHOR]

Oestrogen plays a crucial physiological role in both women and men. It regulates reproductive functions and maintains various non-reproductive tissues through its receptors, such as oestrogen receptor 1/oestrogen receptor α (ESR1/Erα), oestrogen receptor 2/oestrogen receptor β (ESR2/Erβ), and G protein-coupled oestrogen receptor 1 (GPER). This hormone is essential for the proper functioning of women's ovaries and uterus. Oestrogen supports testicular function and spermatogenesis in men and contributes to bone density, cardiovascular health, and metabolic processes in both sexes. Nuclear receptors Er-α and Er-β belong to the group of transcription activators that stimulate cell proliferation. In the environment, compounds similar in structure to the oestrogens compete with endogenous hormones for binding sites to receptors and to disrupt homeostasis. The lack of balance in oestrogen levels can lead to infertility, cancer, immunological disorders, and other conditions. Exogenous endocrine-active compounds, such as bisphenol A (BPA), phthalates, and organic phosphoric acid esters, can disrupt signalling pathways responsible for cell division and apoptosis processes. The metabolism of oestrogen and its structurally similar compounds can produce carcinogenic substances. It can also stimulate the growth of cancer cells by regulating genes crucial for cell proliferation and cell cycle progression, with long-term elevated levels linked to hormone-dependent cancers such as breast cancer. Oestrogens can also affect markers of immunological activation and contribute to the development of autoimmune diseases. Hormone replacement therapy, oral contraception, in vitro fertilisation stimulation, and hormonal stimulation of transgender people can increase the risk of breast cancer. Cortisol, similar in structure to oestrogen, can serve as a biomarker associated with the risk of developing breast cancer. The aim of this review is to analyse the sources of oestrogens and their effects on the endogenous and exogenous process of homeostasis. [ABSTRACT FROM AUTHOR]

The Vandenbergh effect, or male-mediated maturation, occurs when females reach sexual maturation upon exposure to a novel male. Male-mediated maturation is found across mammals, including in geladas, Theropithecus gelada , where it may be an adaptive counterstrategy to infanticide that follows the immigration of a new male; maturing after male immigration maximizes a female's chances of weaning her first offspring before the next infanticidal male immigrates (the 'optimal timing hypothesis'). Alternatively, the nonadaptive 'Bruce effect by-product hypothesis' posits that male-mediated maturation in geladas (and possibly other mammals) is triggered by the same physiological changes that, in pregnant females, produce spontaneous abortion (the Bruce effect). We test both hypotheses using theory and observational data. We show that neither male-mediated maturation nor its associated hormonal changes occur in baboons (Papio cynocephalus × Papio anubis), a primate without the Bruce effect. An individual-based model suggests that male-mediated maturation should not evolve via adaptive evolution in either geladas or baboons. Finally, we derive the selection coefficient for male-mediated maturation and show it is likely to be very small because male-mediated maturation yields only marginal potential benefits unless the system is extremely fine-tuned. We conclude that male-mediated maturation in geladas is a by-product of the Bruce effect and more broadly that the Vandenbergh effect may be nonadaptive. • Male-mediated maturation does not occur in Amboseli baboons (Papio cynocephalus × Papio anubis). • Female Amboseli baboons do not show an endocrinological response to male immigration. • Male-mediated maturation does not evolve in simulations of two primate populations. • Selection for male-mediated maturation is very weak without extreme fine-tuning. • The Vandenbergh effect may be a by-product of the Bruce effect. [ABSTRACT FROM AUTHOR]

Background: Gender-affirming hormone therapy (GAHT) is used in individuals with gender identity dysphoria to align their secondary sexual characteristics with their affirmed gender. We conducted a systematic review of the literature to explore the mechanisms regarding the effects of GAHT on the vasculature. Methods: A literature search using PubMed, Embase, Scopus and LILACS was performed using search terms for GAHT, cardiovascular disease (CVD) risk and transgender. Studies were screened by two independent reviewers. Comparison to a cohort of transgender individuals naive or prior to GAHT or a cisgender population was required. Quality assessment was done using the relevant Critical Appraisal Skills Programme checklists. Results: Out of 2,564 potentially eligible studies, 69 studies met the inclusion criteria. Studies provided evidence of beneficial changes in CVD risk profile, including reduced haemoglobin and pro-inflammatory markers, and atheroprotective changes in lipids in transgender women. In transgender men, there was evidence of negative changes in CVD risk profile, including atherogenic changes in lipids and increased haemoglobin, arterial stiffness and pro-inflammatory markers. Conclusions: There is a paucity of research across non-traditional measures of CVD risk, which in combination with heterogeneous study design, loss of follow-up, low sample sizes and lack of diversity in age and ethnicity requires the results to be interpreted with caution. More evidence is required to elucidate the mechanisms behind the increased risk of CVD in the transgender population and determine whether GAHT is a contributing factor.

The urogenital tract is sensitive to the effect of oestrogen and progesterone throughout adult life. Epidemiological studies have implicated oestrogen deficiency in the aetiology of lower urinary tract symptoms and Genitourinary Symptoms of the Menopause (GSM) occurring following the menopause. The role of systemic and local oestrogen replacement therapy in the management of postmenopausal lower urinary tract symptoms remains controversial although the use of vaginal oestrogens in the management of women complaining of lower urinary tract symptoms and GSM is now well established.This aim of this paper is to review the history of post-menopausal hormonal therapy in the management of postmenopausal urinary incontinence, recurrent lower urinary tract infections and GSM with a special focus on the lifelong research in the field by Professor Linda Cardozo.

Oestradiol withdrawal at menopause predisposes women to metabolic syndrome, a cluster of interrelated conditions including obesity, insulin resistance, dyslipidaemia and hypertension that together confer an increased risk of developing type 2 diabetes mellitus and cardiovascular disease. Hormone replacement therapies are commonly used to treat acute symptoms of the perimenopausal period, and whilst they have been associated with metabolic improvements in many studies, long-term use is considered unviable. Novel approaches are required to mitigate the risk of postmenopausal metabolic syndrome. In 2012, the exercise-inducible myokine irisin was isolated from the skeletal muscle of mice and identified to have anti-obesity and antidiabetic effects in vivo. Irisin is now recognised to exert pleiotropic action on cognitive, bone and metabolic health. There is accumulating evidence from in vitro and in vivo rodent studies that irisin can mitigate each component condition of metabolic syndrome. In postmenopausal women, independent associations have been observed between (a) exercise and plasma irisin concentration and (b) plasma irisin concentration and reduced incidence of metabolic syndrome. To date, however, no study has considered the mechanistic basis by which irisin, whether exercise-induced or exogenously administered, could reduce the incidence or severity of metabolic syndrome in postmenopausal women. This review aims to analyse the literature concerning the metabolic actions of irisin, with a focus on its therapeutic potential for metabolic syndrome driven by a state of oestradiol depletion. It evaluates the practicality of exercise as a therapy and discusses other irisin-based therapeutic strategies that may alleviate postmenopausal metabolic syndrome. Finally, it highlights areas where future research is required to advance knowledge of irisin’s biological action such that it could be considered a viable candidate for clinical application. [ABSTRACT FROM AUTHOR]

Purpose: The menopausal transition brings with it many physical, cognitive, and affective changes in a woman's life, impacting quality of life. Whereas prior work has examined impact on general mental health and cognitive function, research on basic affective processing during menopause remains scarce. Methods: Using a median-split procedure, this pre-registered study examined the impact of stronger (N = 46 women) vs. milder (N = 47 women) menopausal symptoms using a behavioural task of subjective emotion perception (embody) and a passive eye tracking viewing task of emotional faces in addition to self-report questionnaires. After 3 months, participants completed the questionnaires again to examine whether objective measures of emotion perception (eye tracking) might predict mental health at follow-up. Results: As anticipated, women with stronger vs. milder menopausal symptoms reported increased symptoms of anxiety, depression, stress, emotion regulation difficulties, and lower quality of life during both time points. While no evidence was found in the behavioural task, eye tracking data indicated blunted emotion perception in women with high menopausal symptoms, while women with low symptoms spent more time looking at happy faces relative to fearful or surprised faces. Although eye tracking or hormonal data did not predict mental health at follow-up, a higher estradiol/FSH ratio indicated a higher quality of life. Conclusions: This study documented an impact of the menopausal transition and strength of menopausal symptoms in particular on objective emotion perception as well as mental health and quality of life in women suffering from stronger vs. milder menopausal symptoms. Clinical implications are discussed. [ABSTRACT FROM AUTHOR]

Over the last 70 years, oestrogen therapy for the management of menopausal symptoms has undergone a metamorphosis from perceived cardiovascular protection to perceived cardiovascular risk. The former perception is based on the convincing evidence from the Nurses' Health Study cohorts and the epidemiological data surrounding early menopause. The latter, and later, perception is based on the disquieting results from two randomised controlled studies, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative study (WHI). The reality is probably more nuanced than the conclusions presented by any of these studies. When face to face with a patient, the clinician must negotiate the appropriate decision pathway around the interaction between cardiovascular risk, cardiovascular disease, menopause, and oestrogen +/− progestogen–containing hormone therapy. The metamorphosis from perceived cardiovascular protection to perceived cardiovascular risk, a perception largely led by the Women's Health Initiative study, has shifted the clinician's risk/benefit decision-making away from prescribing menopausal hormone therapy (MHT) for menopausal symptoms. A more nuanced view of the literature and the greater availability of different modes of delivery and formulations of MHT should give the clinician the knowledge and confidence to prescribe appropriate MHT for the greater benefit of midlife health and cardiovascular safety. Image by Bronwyn G. A. Stuckey. [ABSTRACT FROM AUTHOR]

Increasing incidence of prolonged oestrus reported in cross-bred dairy cows bred through artificial insemination (AI), is attributed to various causative factors and underlying mechanisms. The present study was to assess the pattern of follicular growth, oestrogen secretion, and conception on the first and second day of oestrus and to understand the influence of thermal stress as a causative factor for oestrus prolongation. The year-round study involved 52 crossbred cows intensively managed under a hot humid climate, during their second and third months postpartum. Animals were examined for the status of ovarian follicles, oestrogen level, and conception to AI on Day 0 and Day 1 of oestrus confirmation and the findings were compared across seasons. While oestrus detection rate (ODR) and conception of AI were lowest during the summer season attributable to maximum TS, better ODR (P<0.05) and more prolonged oestrus (P<0.01) occurred during the seasons of favourable climate having least TS and better green fodder availability. Besides, the occurrence of larger follicles and almost similar oestradiol levels on Day 0 and Day 1 of oestrus, better conception rate for double AI (63.16 %) than total AI (48.48 %) indicated prolonged oestrus and involvement of delayed ovulation among the causation. Comparison of the seasonal pattern of follicular growth, oestrogen level, and conception to AI between Day 0 and Day 1 further clarifies the influence of TS and increased milk production as the potential contributors to the occurrence of prolonged oestrus in cross-bred cows under the hot humid tropical climate. [ABSTRACT FROM AUTHOR]

Highlights We investigated the effects of resistance exercise (RE), hydrolysed collagen (HC) ingestion and circulating oestrogen concentration on collagen synthesis in a naturally menstruating female CrossFit athlete. In a double‐blind, randomised cross‐over design, the participant (36 years; height 1.61 m; mass 82.6 kg) consumed 0 or 30 g HC prior to performing back‐squat RE when endogenous circulating oestrogen concentration was low (onset of menses, OM) and high (late follicular phase, LF) during two consecutive menstrual cycles. Ten 5‐mL blood samples were collected during each of the four interventions to analyse concentrations of serum 17β‐oestradiol, and biomarkers of type I collagen turnover, that is serum procollagen type I N‐terminal propeptide (PINP, a biomarker of collagen synthesis) and plasma β‐isomerised C‐terminal telopeptide of type I collagen (β‐CTX, a biomarker of collagen breakdown), as well as the serum concentration of 18 collagen amino acids. 17β‐Oestradiol concentration was 5‐fold higher at LF (891 ± 116 pmol L−1) than OM (180 ± 13 pmol L−1). The PINP concentration × time area under the curve (AUC) was higher in the 30 g HC OM intervention (201 μg L−1 h) than the 30 g HC LF (144 μg L−1 h), 0 g HC OM (151 μg L−1 h) and 0 g HC LF (122 μg L−1 h) interventions. β‐CTX concentration decreased 1.4‐fold from pre‐RE to 6 h post‐RE in all interventions. Thus, high circulating oestrogen concentration was associated with lower collagen synthesis following RE in this female athlete. Ingesting 30 g HC, however, augmented the collagen synthesis response at LF and particularly at OM. What is the central question of this study? Does resistance exercise‐induced collagen synthesis vary according to circulating oestrogen concentration in a naturally menstruating female athlete, and if so, does hydrolysed collagen ingestion have any impact? What is the main finding and its importance? Exercise‐induced collagen synthesis was low when circulating oestrogen concentration was high and vice versa. However, ingesting 30 g hydrolysed collagen prior to exercise reduced the negative effect of oestrogen on collagen synthesis. As high circulating oestrogen has been associated with greater injury risk in females, supplementing exercise with hydrolysed collagen may help protect these tissues from injury. What is the central question of this study?Does resistance exercise‐induced collagen synthesis vary according to circulating oestrogen concentration in a naturally menstruating female athlete, and if so, does hydrolysed collagen ingestion have any impact?What is the main finding and its importance?Exercise‐induced collagen synthesis was low when circulating oestrogen concentration was high and vice versa. However, ingesting 30 g hydrolysed collagen prior to exercise reduced the negative effect of oestrogen on collagen synthesis. As high circulating oestrogen has been associated with greater injury risk in females, supplementing exercise with hydrolysed collagen may help protect these tissues from injury. [ABSTRACT FROM AUTHOR]

Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki‐67 expression, along with the Apoptotic Index (AI) determined through Caspase‐3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti‐Ki‐67 and Caspase‐3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki‐67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase‐3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland. [ABSTRACT FROM AUTHOR]

Attention Deficit/Hyperactivity Disorder (ADHD) between the sexes is generally considered to be more similar than different, however, it appears that males tend more towards hyperactivity, impulsivity and externalising symptoms and females more towards inattention and internalising symptoms. This variance in ADHD symptom presentation between the sexes* may be influenced by sex hormones and hormonal fluctuations across the menstrual cycle. This scoping review describes the impact of sex hormones on adult ADHD neurobiology and symptomatology. As this field of investigation is emerging, a limited number of observational papers including pre-clinical and case studies were selected for review. Based on the reviewed studies, it appears that oestrogen concentration and balance relative to progesterone plays a role in the symptomatology, and possibly the neurobiology, of ADHD. Further research is needed to address this relationship, an understanding of which is essential for targeted and personalised naturopathic treatment approaches for women with ADHD. [ABSTRACT FROM AUTHOR]

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To observe developmental changes in the ovarian tissue structure and distribution characteristics of oestrogen receptors (ERs) in the ovaries of Huanghuai goats at different ages, we selected healthy Huanghuai goats ewes and divided them into five groups (i.e. 3‐, 30‐, 60‐, 90‐ and 120‐day‐old groups), with 10 animals in each group. The serum was separated after blood collection through the jugular vein, and the contents of oestrogen (E) and progesterone (P) in the serum of Huanghuai goats at each age were determined. Three goats were randomly selected from each group and sacrificed after anaesthesia, and the ovarian tissue was quickly obtained and placed in 4% paraformaldehyde fixative to prepare the tissue sections. Using HE, oestrogen receptors were immunohistochemically stained and observed. These results showed many primordial follicles and occasional secondary follicles in the ovaries of 3‐day‐old Huanghuai goats. Ovarian reticular structures were observed in 30‐day‐old ovarian medulla, with occasional near‐mature growing follicles. Mature follicles and corpus luteum were occasionally detected in 60‐day‐old ovarian cortex. The 90–120‐day‐old ovarian cortices contained growing and mature follicles, and the number of mature follicles and corpora lutea increased, implying a significant luteal involution period. The E and P contents in the 120‐day‐old group were significantly higher than those in the 3‐, 30‐, 60‐ and 90‐day‐old groups. The levels of ERα and ERβ in the 3‐ and 30‐day‐old groups were mainly distributed in the granulosa cells of ovarian reproductive epithelial cells, primordial follicles, atretic follicles, and primary and secondary follicles. The ERα and ERβ levels of the 60‐, 90‐ and 120‐day‐old groups were also distributed in the granulosa cells and luteal cells of mature follicles, especially in the 120‐day‐old endometrial cells of mature follicles, where ERβ was distributed significantly. The overall expression of ERβ in the ovary was higher than that of ERα. The results of this study provide basic data on the ovarian development and the specific expression of ERs and PRs in the ovaries of Huanghuai white goats, which play an important role in ovarian development and precocity. [ABSTRACT FROM AUTHOR]

The current study aimed to explore the molecular mechanism by which the cholecystokinin (CCK)‐mediated CCKAR and CCKBR, as well as the molecular mechanisms of CCK‐mediated insulin signalling pathway, regulate oestrogen in the granulosa cells. Also, the expression of CCK in ovaries, uterus, hypothalamus and pituitary gland was investigated in Camelus bactrianus. Ovaries, uterus, hypothalamus and pituitary gland were collected from six, three before ovulation (control) and three after ovulation, slaughtered Camelus bactrianus. Ovulation was induced by IM injection of seminal plasma before slaughtering in the ovulated group. The results showed that there were differences in the transcription and protein levels of CCK in various tissues before and after ovulation (p <.05, p <.01). After transfection with p‐IRES2‐EGFP‐CCK, the mRNA and protein levels of CCK, CCKAR, CCKBR and ER in follicular granulosa cells were significantly upregulated (p <.05, p <.01), and the content of E2 was significantly upregulated (p <.01); On the contrary, after transfection with si‐CCK, the mRNA and protein levels of CCK, CCKAR, CCKBR and ER in follicular granulosa cells were significantly downregulated (p <.05, p <.01), and the content of E2 was significantly downregulated (p <.01). Regulating CCK can affect the mRNA levels of INS, INSR, IGF and IGF‐R. In summary, regulating the expression level of CCK can activate insulin‐related signalling pathways by CCKR, thereby regulating the steroidogenic activity of granulosa cells. [ABSTRACT FROM AUTHOR]

Gallstone disease (GSD) is a worldwide disease ranging from 10% to 20% of the global population and four times higher in women than in men. Several studies have proclaimed that risk of developing cholesterol gallstones is increased by pregnancy, contraceptive steroids and conjugated oestrogens suggesting that oestrogen could be an important risk factor in forming cholesterol gallstones by increasing the cholesterol saturation index, altering bile salt and promoting nucleation of cholesterol into crystals. To evaluate gonadotropin (FSH and LH) level and their ratio including their correlation with study variables among gallstones patients in Kolkata. 46 subjects were enrolled during a period of April to June, 2022 in West Bengal. Serum level of FSH and LH and its ratio were measured using sandwich ELISA. The data was analysed using statistical package of social science (SPSS) and results was expressed as percentage (%) and mean ± SD, and significance difference was considered as P<0.05. Analyses of frequency showed that GSD is more common in premenopause (76.1%) than post-menopause (23.9%). Independent t-test revealed that, FSH/LH ratio is significantly increased in gallstone patients in comparison with control group (P<0.048). In addition, Pearson's correlation results noted positive correlation between both FSH and FSH/LH ratio with BMI while significant negative correlation in between LH and BMI. The data suggests that obese premenopausal women are much more susceptible to gallstones and FSH/LH ratio specifically is for all intents and purposes higher in gallstone patients, which specifically is fairly significant. [ABSTRACT FROM AUTHOR]

Oestrogen is known to be strongly associated with ovarian cancer. There was much work to show the importance of lncRNA SNHG17 in ovarian cancer. However, no study has revealed the molecular regulatory mechanism and functional effects between oestrogen and SNHG17 in the development and metastasis of ovarian cancer. In this study, we found that SNHG17 expression was significantly increased in ovarian cancer and positively correlated with oestrogen treatment. Oestrogen could promote M2 macrophage polarization as well as ovarian cancer cells SKOV3 and ES2 cell exosomal SNHG17 expression. When exposure to oestrogen, exosomal SNHG17 promoted ovarian cancer cell proliferation, migration, invasion and epithelial‐mesenchymal transition (EMT) in vitro, and tumour growth and lung metastasis in vivo by accelerating M2‐like phenotype of macrophages. Mechanically, exosomal SNHG17 could facilitate the release of CCL13 from M2 macrophage via the PI3K‐Akt signalling pathway. Moreover, CCL13‐CCR2 axis was identified to be involved in ovarian cancer tumour behaviours driven by oestrogen. There results demonstrate a novel mechanism that exosomal SNHG17 exerts an oncogenic effect on ovarian cancer via the CCL13–CCR2–M2 macrophage axis upon oestrogen treatment, of which SNHG17 may be a potential biomarker and therapeutic target for ovarian cancer responded to oestrogen. [ABSTRACT FROM AUTHOR]

Abstract Keratoderma climactericum is characterized by palmoplantar hyperkeratosis developing after the onset of menopause. Although rare, keratoderma climactericum can profoundly impact quality of life and may be refractory to prescription‐strength topical steroids and keratolytics. We report a 52‐year‐old female with a 1‐year history of palmoplantar keratoderma. She had a medical history of generalized anxiety disorder and had reached menopause 2 years before presentation. Previously failed treatments included clotrimazole 1% cream twice daily, triamcinolone 0.1% cream twice daily, and betamethasone 0.05% cream mixed with tazarotene 0.1% cream twice daily. She was diagnosed with keratoderma climactericum, and conjugated oestrogen 0.625 mg/g cream twice daily was initiated. After 4 weeks, she had dramatically reduced erythema and hyperkeratosis of her bilateral palms and soles. No adverse effects to treatment were reported. Although the utility of topical oestrogen for keratoderma climactericum has been debated, our case provides further evidence for its efficacy and safety.

Aims: To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. Methods: In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed. Results: The CM and exosomes collected from senescent MLO-Y4 cells inhibited osteogenic differentiation of MC3T3-E1 cells. RNA sequencing detected significantly lower expression of miR-494-3p in senescent MLO-Y4 cell-derived exosomes compared with normal exosomes. The upregulation of exosomal miR-494-3p by miRNA mimics attenuated the effects of senescent MLO-Y4 cell-derived exosomes on osteogenic differentiation. Luciferase reporter assay demonstrated that miR-494-3p targeted phosphatase and tensin homolog (PTEN), which is a negative regulator of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overexpression of PTEN or inhibition of the PI3K/AKT pathway blocked the functions of exosomal miR-494-3p. In SAMP6 mice, senescent MLO-Y4 cell-derived exosomes accelerated bone loss, which was rescued by upregulation of exosomal miR-494-3p. Conclusion: Reduced expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenic differentiation and accelerates age-related bone loss via PTEN/PI3K/AKT pathway. Cite this article: Bone Joint Res 2024;13(2):52–65.

The integral role of the hypothalamic-pituitary-gonadal axis in reproductive processes makes it a prime therapeutic target. By inhibiting sex steroid synthesis, gonadotropin-releasing hormone (GnRH) analogues are used in the management of cancers, benign neoplasms, infertility and gender dysphoria. However, the wide application of these therapeutics raises concerns regarding the unintended effects upon the cardiovascular system. In males with prostate cancer, GnRH analogues when used as an androgen deprivation therapy appear to increase the risk of cardiovascular disease, which is the leading cause of death in this population. Therefore, due to the utilisation of GnRH analogues across the lifespan and gender spectrum, this relationship merits discussion. Existing data suggest an association between GnRH analogues and major adverse cardiovascular events in males. Conversely, females receiving GnRH analogues for breast cancer treatment appear to be at an increased risk of developing hypertension. In this narrative review, we describe the uses of GnRH analogues in adults, adolescents and children. We discuss whether sex plays a role in the cardiovascular effects of GnRH analogues and explore the significance of sex hormone receptors in the vasculature. We also consider confounding factors such as malignancy, advanced age and infertility. [ABSTRACT FROM AUTHOR]

Context: New animal welfare legislation and ethical guidelines encourage alternative approaches for canine contraception, instead of surgical gonadectomy which is considered invasive and unjustified in healthy dogs. Aims: Reversible contraception might be achieved by inhibition of aromatase (CYP19), an enzyme catalysing the conversion of androgens to oestrogens. This study provides insights into the spatio-temporal expression and distribution of aromatase in canine ovarian tissue. Methods: Ovarian tissue was collected from 39 healthy and sexually mature bitches during different stages of the oestrous cycle: pro-oestrus (n = 8), oestrus (n = 12), dioestrus (n = 9) (luteal phase) and anoestrus (n = 10). Localisation of cytochrome P450 aromatase was determined by immunohistochemistry. Key results: Aromatase activity in the dog is high during pro-oestrus, ovulation and early dioestrus. Comparing types of follicles and corpora lutea, the highest aromatase abundance was found in antral follicles and luteinising follicles, whereas corpora lutea and early antral follicles showed an intermediate presence of the enzyme. Interesting was the high abundance of aromatase in luteinising theca interna cells, prevailing over granulosa cells. Conclusions and implications: Understanding of cells involved in oestradiol production is important for targeted inhibition of oestradiol synthesis, possibly offering an approach for contraception and suppression of oestrus. In clinical practice, contraception in female dogs is traditionally achieved by surgical gonadectomy. As this method is discouraged by new animal welfare legislation in some parts of the world and is also related to several side effects, alternative possibilities for contraception are needed. Here, we report the distribution of aromatase in the canine ovary during different stages of the oestrous cycle. In-depth knowledge of oestrogen synthesis in the female dog is mandatory for targeted inhibition of oestradiol, possibly by the use of aromatase inhibitors. Photograph by M. P. Kowalewski. [ABSTRACT FROM AUTHOR]

Context: Declining fertility is an issue in multiple mammalian species. As the site of fertilisation and early embryo development, the oviduct plays a critical role in embryo survival, yet there is a paucity of information on how the oviduct regulates this process. Aims: We hypothesised that differences in steroid hormone signalling and/or immune function would be observed in a model of poor embryo survival, the peripubertal ewe. Methods: We examined expression of steroid hormones in systemic circulation, oviductal expression of oestrogen receptor α and genes important in steroid hormone signalling, and immune function in pregnant and cyclic peripubertal and adult ewes on day 3 after oestrus. Key results: Concentrations of progesterone, but not oestradiol, were decreased in the peripubertal ewe compared to the adult ewe. Oestrogen receptor α protein expression was increased in the peripubertal ewe, but pathway analysis of gene expression revealed downregulation of the oestrogen signalling pathway compared to the adult ewe. Differential expression of several genes involved in immune function between the peripubertal and adult ewe was consistent with an unfavourable oviductal environment in the peripubertal ewe lamb. Oestradiol concentration was positively correlated with the expression of multiple genes involved in the regulation of immune function. Conclusions: Differences in the immune environment of the oviduct, potentially linked to differential modulation by steroid hormones, may partially underly the poor fertilisation and early embryo survival observed in the peripubertal ewe. Implications: A unfavourable oviductal environment may play an important role in limiting reproductive success. Declining fertility is an issue in multiple mammalian species, with around 15% of couples experiencing infertility. Differential expression of genes involved in inflammation, linked with altered steroid signalling in the oviduct, was observed in peripubertal ewes, a model of poor fertility. Ensuring that the oviductal environment does not become hostile to fertilisation and early embryo development may provide a novel approach to improve fertility, particularly in conditions associated with chronic low-grade inflammation. Photograph by Jenny Juengel. [ABSTRACT FROM AUTHOR]

Primary mucinous carcinoma of the skin (PMCS) is a rare cancer. It is indolent and progresses slowly but can recur locally, damaging the structure. The majority of mucinous carcinoma that occurs in the skin are metastatic lesions originating from various sites. In terms of morphology, PMCS is almost indistinguishable from secondary metastatic deposits. We reported a case of a 44-year-old male with left axillary skin PMCS that had spread to axillary lymph nodes. The pathologic diagnosis was challenging but was facilitated by expert pathologists from different centers. A multidisciplinary meeting concluded that the best management approach was to include a wide local excision and axillary clearance followed by adjuvant tamoxifen. The role of adjuvant radiotherapy was discussed but was declined by the patient. The patient is well now with no recurrence, 22 months since the diagnosis. [ABSTRACT FROM AUTHOR]

The importance of menopause and the short and long term effects of this have been underestimated and under discussed. With the media currently highlighting issues that affect women, it is important to understand menopause, the effects of this and how to mitigate these effects. When prescribing any drug or treatment, the risks must be properly discussed and women given as much information as possible to make an informed choice about their health. This is likely to look different for every woman who comes for a consultation as menopause and subsequent reactions to HRT are individual. [ABSTRACT FROM AUTHOR]

Aim: This study aims to study the awareness of musculoskeletal changes in postmenopausal women in rural areas. Postmenopausal women experience many changes due to menopause and musculoskeletal changes are highly prevalent which adversely affects the health of women. Objectives: The objective was to determine the awareness of musculoskeletal changes among the postmenopausal women in rural areas, and to determine the awareness about adverse effects of these musculoskeletal changes. Methods: This was an observational study with 94 participants aged above 50 years. This study was done by using a standardized validated questionnaire. Results: Out of 94 participants in this study 8.51% of women were completely aware of menopause effects on the musculoskeletal system, 27.66% of women had good knowledge whereas 63.83% were unaware. Conclusion: According to the study awareness of musculoskeletal changes due to menopause in women in rural areas is poor. Few women were completely aware of musculoskeletal changes due to menopause whereas most women were unaware. [ABSTRACT FROM AUTHOR]

Endocrine therapy is widely used to treat cancers whose growth is dependent on hormonal stimulation, most commonly breast, prostate and endometrial cancers. The principles behind its use, indications, different medications available and some of the evidence to support its use are described. Endocrine therapies avoid the toxicities associated with chemotherapy, but do have recognized side effects that can impact on quality of life. [ABSTRACT FROM AUTHOR]

Findings are inconsistent with regards to whether menstrual cycle phase-associated changes in physical functioning exist. It is possible that such discrepancies are due to varying rigour in experimental approaches. The current study aimed to systematically evaluate any effect of carefully tracked menstrual cycle phase on precisely measured muscle structure and function in a physically active group (contemporary dancers). Eleven women aged (M [SD]) 23.5 [2.94] years, undergoing 10.5 [1.73] hours of contemporary dance practice and 6.12 [2.36] hours of other physical activity per week, were recruited. Sex hormone level (enzyme-linked immunosorbent assays (ELISA), skin temperature and ovulation kits), physical pain assessments (Ice Water Test, Visual Analogue Scale, The Physical Activity Readiness Questionnaire, Self-Estimated Functional Inability Because of Pain Questionnaire, and Pain Anxiety Symptoms Scale), muscle architecture measurement (B-mode ultrasonography), and physical functioning (dynamometry, force-platform and electromyography) on both lower limbs were measured at three time points during one cycle, following three months of menstrual cycle monitoring. There was no difference in musculoskeletal flexibility variables between follicular, ovulatory, or luteal phases. Nonetheless, oestrogen change was associated with variability in 11 musculoskeletal variables, progesterone change was associated with variability in 7, and relaxin change was associated with variability in 15. Negative correlations existed between progesterone and flexibility and between oestrogen and jump variables. Moreover, oestrogen and relaxin were associated with increased musculoskeletal compliance, whilst progesterone was associated with increased muscle stiffness. In short, in absolute sex hormone levels, 'inter-individual' variances appear more impactful than 'intra-individual' variances. Not only are oestrogen and progesterone associated with differing musculoskeletal outcomes, but relaxin is also associated with musculoskeletal compliance changes. These effects are anticipated to impact jump height and flexibility, and hence, they could be expected to affect overall physical performance, including dance. [ABSTRACT FROM AUTHOR]

Müllerian ducts are paired embryonic tubes that give rise to the female reproductive tract. In humans, the Müllerian ducts differentiate into the Fallopian tubes, uterus and upper portion of the vagina. In birds and reptiles, the Müllerian ducts develop into homologous structures, the oviducts. The genetic and hormonal regulation of duct development is a model for understanding sexual differentiation. In males, the ducts typically undergo regression during embryonic life, under the influence of testis-derived Anti-Müllerian Hormone, AMH. In females, a lack of AMH during embryogenesis allows the ducts to differentiate into the female reproductive tract. In the chicken embryo, a long-standing model for development and sexual differentiation, Müllerian duct development in females in asymmetric. Only the left duct forms an oviduct, coincident with ovary formation only on the left side of the body. The right duct, together with the right gonad, becomes vestigial. The mechanism of this avian asymmetry has never been fully resolved, but is thought to involve local interplay between AMH and sex steroid hormones. This mini-review re-visits the topic, highlighting questions in the field and proposing a testable model for asymmetric duct development. We argue that current molecular and imaging techniques will shed new light on this curious asymmetry. Information on asymmetric duct development in the chicken model will inform our understanding of sexual differentiation in vertebrates more broadly. [ABSTRACT FROM AUTHOR]

Senile deafness and hearing loss in adults over 50 are major public health issues as a result of the population's ageing demographic. Menopausal women tend to develop hearing loss, while no clear link has been found between the two. The purpose of this study was to determine how menopause and diabetes mellitus affects hearing loss. We assessed 158 menopausal women in total. Pure Tone Audiometry and HbA1c levels was measured, along with appropriate clinical history and examination. The association between those levels and hearing was researched by chi-square test. There were 158 study participants. Mean age of the study population was 50.5 (± 2.49) years. Onset and duration of hard of hearing was assessed in 41 patients (25.9%). 33% (N = 53) of the patients had history of Diabetes mellitus, of which 52.8% offered history of the disease for more than or equal to five years. On audiological assessment, 74.1% had no hearing loss (N = 117), 4.4% had unilateral sensorineural hearing loss (N = 7) and 21.5% had bilateral sensorineural hearing loss (N = 34). Statistics show that hearing loss is statistically connected with ageing and poor glycemic management. With chi square values of 9.629 and P value 0.002 found a significant correlation between ageing and hearing loss. Poor glycemic control is significantly associated with hearing loss with a chi-square value of 4.304 and P value 0.038. Poor glycemic control and menopause is found to be strongly associated with sensorineural hearing loss. Further prospective, hormonal studies including larger population is recommended. [ABSTRACT FROM AUTHOR]

1. The bioflavonoid quercetin is a biologically active component, but its functional regulation of granulosa cells (GCs) during chicken follicular development is little studied. To investigate the effect of quercetin on follicular development in laying hens, an in vitro study was conducted on granulosa cells from hierarchical follicles treated with quercetin. 2. The effect of quercetin on cell activity, proliferation and apoptosis of granulosa cells was detected by CCK-8, EdU and apoptosis assays. The effect on progesterone secretion from granulosa cells was investigated by enzyme-linked immunosorbent assay (ELISA). Expression of proliferating cell nuclear antigen (PCNA) mRNA and oestrogen receptors (ERs), as well as the expression of steroid acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA during progesterone synthesis, were measured by real-time quantitative polymerase chain reaction (RT-qPCR). PCNA, StAR and CYP11A1 protein expression levels were detected using Western blotting (WB). 3. The results showed that treatment with quercetin in granulosa cells significantly enhanced cell vitality and proliferation, reduced apoptosis and promoted the expression of gene and protein levels of PCNA. The levels of progesterone secretion increased significantly following quercetin treatment, as did the expression levels of StAR and CYP11A1 using the Western Blot (WB) method. 4. The mRNA expression levels of ERα were significantly upregulated in the 100 ng/ml and 1000 ng/ml quercetin-treated groups, while there was no significant difference in expression levels of ERβ mRNA. [ABSTRACT FROM AUTHOR]

Vaginal changes during the menopause may cause women to present to their practice nurse. Pearl Clark Brown explains diagnosis and management. Vaginal symptoms which appear around the time of the menopause often occur as a result of declining levels of oestrogen within the epithelial tissues. Vaginal dryness, painful sex, itching, inflammation, burning and soreness are common symptoms around this time. It is thought that up to 80% of women will develop vaginal symptoms in varying degrees once menopausal. The effect that this can have on theindividual can be far reaching, impacting on normal day to day tasks such as sitting, the ability to have sex and being able to take part in exercise. Treatment options include vaginal oestrogen, non hormonal vaginal moisturisers, use of personal lubricants and emollients for washing with. Optimal relief can involve a combined treatment approach used regularly alongside a sliding scale of product use according to the severity of symptoms in response to stressors such as sex, stress or situations known to exacerbate symptoms. [ABSTRACT FROM AUTHOR]

Oestradiol withdrawal at menopause predisposes women to metabolic syndrome, a cluster of interrelated conditions including obesity, insulin resistance, dyslipidaemia and hypertension that together confer an increased risk of developing type 2 diabetes mellitus and cardiovascular disease. Hormone replacement therapies are commonly used to treat acute symptoms of the perimenopausal period, and whilst they have been associated with metabolic improvements in many studies, long-term use is considered unviable. Novel approaches are required to mitigate the risk of postmenopausal metabolic syndrome. In 2012, the exercise-inducible myokine irisin was isolated from the skeletal muscle of mice and identified to have anti-obesity and antidiabetic effects in vivo. Irisin is now recognised to exert pleiotropic action on cognitive, bone and metabolic health. There is accumulating evidence from in vitro and in vivo rodent studies that irisin can mitigate each component condition of metabolic syndrome. In postmenopausal women, independent associations have been observed between (a) exercise and plasma irisin concentration and (b) plasma irisin concentration and reduced incidence of metabolic syndrome. To date, however, no study has considered the mechanistic basis by which irisin, whether exercise-induced or exogenously administered, could reduce the incidence or severity of metabolic syndrome in postmenopausal women. This review aims to analyse the literature concerning the metabolic actions of irisin, with a focus on its therapeutic potential for metabolic syndrome driven by a state of oestradiol depletion. It evaluates the practicality of exercise as a therapy and discusses other irisin-based therapeutic strategies that may alleviate postmenopausal metabolic syndrome. Finally, it highlights areas where future research is required to advance knowledge of irisin's biological action such that it could be considered a viable candidate for clinical application.