Vigil, P., Meléndez, J., Petkovic, G., & Del Río, J. P. (2022). The importance of estradiol for body weight regulation in women. Frontiers in Endocrinology, 13, 951186. https://doi.org/10.3389/fendo.2022.951186
Vigil P, Meléndez J, Petkovic G, Del Río JP. The importance of estradiol for body weight regulation in women. Front Endocrinol (Lausanne). 2022;13:951186. doi:10.3389/fendo.2022.951186
Vigil, Pilar, et al. "The importance of estradiol for body weight regulation in women." Frontiers in Endocrinology, vol. 13, 2022, pp. 951186.
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Estradiol lowers appetite in women and raises energy use in animals
Estradiol lowers appetite in women and raises energy expenditure in animal models, according to a 2022 review of laboratory and human studies. The authors describe how estradiol acts on appetite centers in the brain and on signals such as GLP-1. They suggest that a drug joining estradiol and GLP-1 could someday help with weight control and brain protection.
Key Findings
Clinical studies cited by the review find lower food intake around ovulation, when estradiol surges, and higher intake in the early follicular and luteal phases. The drop reflects smaller meals.
In laboratory and animal studies cited by the review, estradiol increased activity of appetite-suppressing neurons, inhibited appetite-stimulating neurons and raised heat production in brown fat, which increases energy expenditure.
In rats whose ovaries were removed, estradiol replacement strengthened the appetite-suppressing effect of GLP-1 and cholecystokinin. The review also describes a rodent estradiol-leptin interaction that appears to limit food intake.
The authors report that the usual cyclical change in food intake appears to be absent in cycles without ovulation, which can involve low or constantly elevated estradiol.
In obese male mice, a stable GLP-1-estradiol conjugate produced greater weight loss than GLP-1 controls or a labile conjugate. It did not increase uterine weight in ovariectomized female mice.
Interpretation
This review examined lab, animal and human studies on estradiol and appetite. The authors note mixed lab findings on whether estradiol and GLP-1 work together. The findings support more study of a combined estradiol-GLP-1 approach in women, including timing and safety.
RRM Context
Restorative reproductive medicine treats the ovulatory cycle as a vital sign of overall health. The review adds appetite and energy balance to the body systems that follow the estradiol rise around ovulation. It associates ovulatory dysfunction with weight gain and insulin resistance. The cycle therefore bears on metabolic health as well as fertility.
Our editorial summary of this paper, not the article's abstract.
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.
