Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Nov 7:13:951186.
doi: 10.3389/fendo.2022.951186. eCollection 2022.

The importance of estradiol for body weight regulation in women

Pilar Vigil  1 , Jaime Meléndez  1 , Grace Petkovic  2 , Juan Pablo Del Río  3   4
Affiliations
Review

The importance of estradiol for body weight regulation in women

Pilar Vigil et al. Front Endocrinol (Lausanne). .

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.

Keywords: GLP-1; body weight; estrogens; menstrual cycle; mental health.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Potential interaction between meal-related gastrointestinal signals and estradiol on control of the body weight in women. Meal-related gastrointestinal signals (CCK, GLP-1, others) act through a paracrine-neuronal pathway (shown in purple and red). These meal-related gastrointestinal signals act paracrinally upon vagal afferent neurons (VAN). The VANs activate secondary neurons located in the NTS, in the brainstem. The NTS integrates a variety of peripheral signals, and in turn activates tertiary neurons located in different nuclei in the hypothalamus. These hypothalamic nuclei control feeding behavior. Circulating estradiol (shown in green) modulates the responsiveness to these gastrointestinal satiety signals by acting on all levels of this paracrine-neuronal pathway: The VAN, NTS and the hypothalamic nuclei. Gastrointestinal satiety signals also act directly upon the hypothalamic nuclei through a hormonal pathway (shown in purple). Additionally, estradiol (green) has a direct anorexigenic effect at the level of the hypothalamic nuclei (PVH, LH and ARC), thereby reducing food intake. Metabolic signals such as insulin and leptin also influence centers in the hypothalamus to regulate body weight. Brown adipose tissue (BAT) thermogenesis contributes to regulation of body weight by increasing energy expenditure. Estradiol acts all three points of the VMH-SNS-BAT pathway to increase thermogenesis. Within the VMH hypothalamic nucleus, estradiol acts by inhibiting AMPK. Thus, estradiol increases energy expenditure by increasing BAT thermogenesis, and WAT browning. This, in combination with estradiol’s effects to decrease food intake, can result in weight loss. NST, nucleus of the solitary tract; DMH, dorsomedial hypothalamus; LH, lateral hypothalamus; PVH, paraventricular hypothalamus; ARC, arcuate nucleus; VMH, ventromedial hypothalamus; BAT, brown adipose tissue; WAT, white adipose tissue.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity and severe obesity among adults: United states, 2017-2018. NCHS Data Brief (2020) 360):1–8. Available at: https://www.cdc.gov/nchs/products/index.htm. - PubMed
    1. Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D, et al. . European Guidelines for obesity management in adults. Obes Facts (2015) 8(6):402–24. doi: 10.1159/000442721 - DOI - PMC - PubMed
    1. Gambineri A, Laudisio D, Marocco C, Radellini S, Colao A, Savastano S. Female infertility: which role for obesity? Int J Obes Suppl (2019) 9(1):65–72. doi: 10.1038/s41367-019-0009-1 - DOI - PMC - PubMed
    1. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity among adults and youth: United states, 2015–2016. In: NCHS data brief, no 288, vol. 288). Hyattsville, MD: National Center for Health Statistics. NCHS Data Brief; (2017). p. 1–8. Available at: https://www.cdc.gov/nchs/data/databriefs/db288.pdf. - PubMed
    1. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis. Hum Reprod (2016) 31(12):2841–55. doi: 10.1093/humrep/dew218 - DOI - PubMed