Current Opinion in Endocrine and Metabolic Research最新文献

The pulsatile release of gonadotropin-releasing hormone (GnRH) and its frequency are crucial for healthy reproductive function. To understand what drives GnRH pulses, a combination of experimental and mathematical modelling approaches has been used. Early work focussed on the possibility that GnRH pulse generation is an intrinsic feature of GnRH neurons, with autocrine feedback generating pulsatility. However, there is now ample evidence suggesting that a network of upstream neurons secreting kisspeptin, neurokinin-B and dynorphin are the source of this GnRH pulse generator. The interplay of slow positive and negative feedback via neurokinin-B and dynorphin, respectively, allows the network to act as a relaxation oscillator, driving pulsatile secretion of kisspeptin, and consequently, of GnRH and LH. Here, we review the mathematical modelling approaches exploring both scenarios and suggest that with pulsatile GnRH secretion driven by the KNDy pulse generator, autocrine feedback still has the potential to modulate GnRH output.

Overweight and obesity patterns demonstrate a sexual dimorphism, with women being more prone to weight gain and overweight/obesity compared to men. As a result, weight gain is an important concern in women, particularly during midlife, when reproductive and physiological aging coincide, altering body composition. During this time, multiple factors contribute to the accumulation of body weight and adipose tissue, inducing a decrease in lean mass. These factors include hormonal changes -mainly hypoestrogenism-, genetic and exogenous factors, poor nutritional intake and physical inactivity, all of which might act synergistically to promote weight gain. Basal metabolic rate is also reduced due to aging, muscle mass loss, and the reduction in brown tissue activity. Impairments of the circadian system are associated with reduced endogenous melatonin secretion, altered sleep–wake cycles and metabolic inflexibility. Inflammaging, gut dysbiosis and physical inactivity further promote weight gain and the loss of lean skeletal muscle, leading to sarcopenic obesity.

It is known that the menopause transition (MT) is a complex period during a woman's life, but there has been an ongoing debate on whether the increase in cardiovascular disease (CVD) during midlife is due to chronological aging or ovarian aging. The purpose of this review is to summarize the recent findings on the role of ovarian aging versus chronological aging on CVD outcomes and its risk factors in women.

Recent data from longitudinal studies have shown that menopause-related factors, such as earlier age at menopause and surgical menopause are associated with higher CVD outcomes. The MT is also associated with detrimental changes in vascular health as well as cardiometabolic risk factors including body composition, visceral fat accumulation, lipids/lipoproteins, blood pressure, and the metabolic syndrome.

The robust evidence from recent research indicating increases in CVD risk over the MT beyond aging call for immediate efforts to raise awareness among women and their health care providers of CVD risk acceleration accompanying the MT. Efforts should also be directed toward developing and testing novel preventive approaches that target women during this time period to counteract the expected increase in CVD risk.

Evidence suggests that menopausal transition can have a profound experience on women's work. However, there is a lack of contextually rich research identifying the range and diversity of factors that further details the multiplicity of women's experiences of menopausal transition at work. The review draws together four factors that provide a more detailed insight into factors that may impact working through menopausal transition. In light of this, more knowledge is needed to understand how low paid, precarious and insecure work impacts menopausal transition, as well as recognising the workplace experience of menopause transition for those identifying as LGBTQI+.

Understanding the human hypothalamic-pituitary-gonadal (HPG) axis presents a major challenge for medical science. Dysregulation of the HPG axis is linked to infertility and a thorough understanding of its dynamic behaviour is necessary to both aid diagnosis and to identify the most appropriate hormonal interventions. Here, we review how quantitative models are being used in the context of clinical reproductive endocrinology to: 1. analyse the secretory patterns of reproductive hormones; 2. evaluate the effect of drugs in fertility treatment; 3. aid in the personalization of assisted reproductive technology (ART). In this review, we demonstrate that quantitative models are indispensable tools enabling us to describe the complex dynamic behaviour of the reproductive axis, refine the treatment of fertility disorders, and predict clinical intervention outcomes.

The paraventricular hypothalamic nucleus (PVH) organizes neuroendocrine and autonomic responses to rapidly and slowly developing metabolic stressors that limit their impact on energy balance. The PVH together with the lateral hypothalamic area, and the arcuate and dorsomedial nuclei form a network that is defined by its inputs from medullary catecholamine neurons. These medullary neurons convey important glycemia and glucocorticoid feedback information that is integrated by the PVH and the rest of this network to control a variety of responses to metabolic stressors that have rapid (hypoglycemia) or slow onsets (eating a high calorie diet). This review focuses on how the responses to these two challenges are enabled by these catecholamine neurons, and the integrative nature of the network into which they project.

The activity of the hypothalamic-pituitary-adrenal (HPA) axis is characterised by complex dynamics spanning several timescales. This ranges from slow circadian rhythms in blood hormone concentration to faster ultradian pulses of hormone secretion and even more rapid oscillations in electrical and calcium activity in neuroendocrine cells of the hypothalamus and pituitary gland. Here, we focus on the system's oscillations on the short timescale. We highlight some of the mathematical modelling and experimental work that has been carried out to characterise the mechanisms regulating this highly dynamic mode of neuroendocrine signalling and discuss some future directions that may be explored to enhance understanding of HPA function.

Vasomotor symptoms (VMS) result from menopausal hypoestrogenism with subsequent instability of central thermoregulation. VMS cause stress and decreased QOL. Menopausal hormone therapy (MHT) significantly alleviates VMS when compared to placebo or other available non-hormonal options. MHT protects the urogenital system, bone, and cardiovascular system, has beneficial effects on sleep and mood disorders, and may offer protection against colorectal cancer. Negative effects include a risk of thromboembolic disease and the promotion of breast cancer. Adverse effects can be mitigated by initiating MHT within the window of opportunity, using the transdermal route, using estrogen alone or combined with natural progesterone or dydrogesterone, and using the minimum effective dose. Initial findings from the WHI have been widely (and persistently) misinterpreted. Subsequent age-stratified analysis of WHI data indicates that MHT is safe when initiated by women younger than age 60 or within 10 years of menopause onset.

MHT remains the first choice for the treatment of VMS.