The importance of estradiol for body weight regulation in women

Abstract

Obesity in women of reproductive age has a number of adverse metabolic effects, including Type II Diabetes (T2D), dyslipidemia, and cardiovascular disease. It is associated with increased menstrual irregularity, ovulatory dysfunction, development of insulin resistance and infertility. In women, estradiol is not only critical for reproductive function, but they also control food intake and energy expenditure. Food intake is known to change during the menstrual cycle in humans. This change in food intake is largely mediated by estradiol, which acts directly upon anorexigenic and orexigenic neurons, largely in the hypothalamus. Estradiol also acts indirectly with peripheral mediators such as glucagon like peptide-1 (GLP-1). Like estradiol, GLP-1 acts on receptors at the hypothalamus. This review describes the physiological and pathophysiological mechanisms governing the actions of estradiol during the menstrual cycle on food intake and energy expenditure and how estradiol acts with other weight-controlling molecules such as GLP-1. GLP-1 analogs have proven to be effective both to manage obesity and T2D in women. This review also highlights the relationship between steroid hormones and women's mental health. It explains how a decline or imbalance in estradiol levels affects insulin sensitivity in the brain. This can cause cerebral insulin resistance, which contributes to the development of conditions such as Parkinson’s or Alzheimer’s disease. The proper use of both estradiol and GLP-1 analogs can help to manage obesity and preserve an optimal mental health in women by reducing the mechanisms that trigger neurodegenerative disorders.

Still searching for the female norm: a GLUT of knowledge remains to be revealed

“…At first glance, this may not seem particularly startling, but it allows more appropriate interpretation of existing research findings about glucose control to be considered in females. These alterations in measured induced d ‐glucose uptake contribute some mechanistic support towards developing biological explanations for the long‐held observations in some female mammals of lower food intake (including humans: Virgil et al., 2022 ) and increased energy expenditure just prior to the behavioural expression of oestrus and the physical event of ovulation. Moreover, this adds more impetus to the new drive to fund, perform and publish research with equal representation of male and female subjects and/or physiology (e.g., US National Institute of Health, NIH; UK Medical Research Council, MRC) to address the imbalance in the underlying knowledge base.…”

“…However it is timely to consider the implications of these combined preliminary findings and important to clearly establish the norms of equivalent control mechanisms operating within the human ovarian cycle. This is because the incretin properties of analogues of GLP‐1, one signal within this complex regulatory system, are already being used clinically to treat type II diabetes, and similar pharmaceutical products are now being approved more widely for use to achieve body mass reductions (Vigil et al., 2022 ), increasingly in females of reproductive age. What cannot be gained from Overduin et al.’s small study is why a reduction in glucose uptake from the small intestine might be characteristic of or biologically important in the short pre‐ovulatory period, or even whether the same occurs in humans.…”

Genetic variants in genes involved in creatine biosynthesis in patients with severe obesity or anorexia nervosa

“…Obesity and body weight regulation are influenced by sex hormones (e.g., Brettle et al, 2022 ; Vigil et al, 2022 ). As the mean age of our study groups was around 50 years (non-obese: 55.8 years old; participants with obesity: 46.9 years old) and most women experience their menopause by the age of 49 years (e.g., Davis et al, 2015 ), we subsequently excluded all participants above the age of 50 years (n = 465) to circumvent a putative menopause-based bias.…”

Brain insulin responsiveness is linked to age and peripheral insulin sensitivity

“…70 In women, oestrogen is not only crucial for reproductive functions, but it also influences cognitive function, food intake, energy expenditure and, in general, weight control. 71,72 In particular, during and post-menopause, oestrogen levels decline, which was identified as a further risk factor for neurodegenerative disorders. 72 Thus far, however, an influence of oestrogen on brain insulin action could not be confirmed in humans.…”

“…In animal studies, oestrogen seems to modify brain insulin action 70 . In women, oestrogen is not only crucial for reproductive functions, but it also influences cognitive function, food intake, energy expenditure and, in general, weight control 71,72 . In particular, during and post‐menopause, oestrogen levels decline, which was identified as a further risk factor for neurodegenerative disorders 72 .…”