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REVIEW article

Front. Endocrinol.

Sec. Obesity

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1682231

This article is part of the Research TopicSex steroid metabolism and obesity: insights from animal studiesView all articles

Metabolic Impact of Endogenously Produced Estrogens by Adipose Tissue in Females and Males Across the Age SLifespan

Provisionally accepted
  • University of Washington, Seattle, United States

The final, formatted version of the article will be published soon.

The aged population, expected to double by 2050, makes up a large proportion of people living with metabolic disease. Obesity rates in the elderly are rapidly increasing, with estimates that nearly 40% of men and women over the age of 60 are classified as obese. White adipose tissue (WAT) is a highly metabolically active organ that undergoes significant changes during both obesity and aging, and metabolic dysfunction in WAT is a major cause for elevated diabetes risk. A marked difference in fat distribution is often reported between men and women. Many studies suggest that pre-menopausal women are protected from the accumulation of visceral adiposity due to gonadal estrogen, which exerts cardiometabolic benefits. Men with obesity harbor a disproportionately higher volume of intra-abdominal fat than premenopausal age-matched women with obesity, an effect that is negated by menopause as women begin to gain intra-abdominal fat. Post-menopausal women are at increased risk of developing diabetes, which can be mitigated by estrogen replacement therapy, suggesting an important role for sex steroids in diabetes risk. In addition to being highly responsive to gonadal estrogens, WAT has the capacity to convert androgens into estrogens, which may similarly impact WAT distribution and metabolism. Estrogens, comprised primarily of estrone (E1) and estradiol (E2) within WAT, are biosynthesized from circulating androgens androstenedione (A4) and testosterone (T) by aromatase (CYP19A1), which is highly expressed in human and mouse adipose tissue. In post-menopausal women, WAT becomes the predominant source of estrogen production, with age-associated increases in WAT aromatase expression that are mirrored by obesity. In contrast to ovarian estrogen production, in which E2 is the predominant estrogen type, E1 tends to be the predominant estrogen post-menopause. To date, little is known about WAT-derived estrogens and their impact on metabolic health, but emerging evidence suggests that increased E1 levels may contribute to metabolic dysfunction in aging. This review will introduce known sex differences in adipose metabolism associated with aging, obesity, and diabetes, and discuss the impact of WAT-derived sex hormones on local and systemic metabolism.

Keywords: sex steroids, sex hormones, Adipocyte, Aromatase, Estradiol, Estrone

Received: 08 Aug 2025; Accepted: 06 Oct 2025.

Copyright: © 2025 Lee and Den Hartigh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Laura J Den Hartigh, lauradh@uw.edu

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