Role of Adipose Tissue in Sex Steroid Dynamics in Postmenopausal Women on Hormone Therapy

Overview

In postmenopausal women, adipose tissue acts as a key site for sex steroid metabolism, with menopausal hormone therapy (MHT) significantly altering estrogen and androgen concentrations within adipose depots. MHT users exhibit higher estrogen levels and estrogen-to-androgen ratios in both subcutaneous and visceral adipose tissue compared to nonusers, suggesting local metabolic changes induced by therapy.

Background

After menopause, circulating estrogens primarily derive from androgen precursors converted in peripheral tissues, notably adipose tissue, which contains higher concentrations of sex steroids than serum. Adipose tissue distribution shifts during menopause, favoring central (visceral) fat accumulation associated with increased cardiometabolic risk. Menopausal hormone therapy may mitigate these changes by influencing local sex steroid metabolism within adipose tissue, impacting body fat distribution and metabolic health.

Data Highlights

Key Findings

• Postmenopausal women on oral MHT have significantly elevated estrogen concentrations and estrogen-to-androgen ratios in both subcutaneous and visceral adipose tissue compared to nonusers.
• Visceral adipose tissue in MHT users shows a dose-dependent increase in estrogen-to-androgen ratio and lower testosterone levels.
• Messenger RNA expression of sex steroid–metabolizing enzymes and receptors in adipose tissue does not differ significantly between MHT users and nonusers, though sample size limits conclusions.
• Higher estrone sulfate levels in MHT users may reflect conversion of exogenous estrogens and possibly increased steroid sulfatase activity, although enzyme activity was not confirmed to differ.
• Adipose tissue serves as an important intracrine site for conversion of adrenal androgen precursors into estrogens, especially relevant postmenopause.
• Changes in local sex steroid metabolism in adipose tissue may contribute to more favorable fat distribution patterns and potentially mitigate menopause-associated metabolic risks.

Clinical Implications

These findings highlight the importance of considering adipose tissue as an active site of sex steroid metabolism when managing postmenopausal women on hormone therapy. MHT may beneficially modulate local estrogen and androgen balance in adipose depots, potentially influencing body fat distribution and reducing cardiometabolic risk. Clinicians should be aware of these local tissue effects when evaluating the benefits and risks of MHT.

Conclusion

Menopausal hormone therapy significantly alters sex steroid concentrations within adipose tissue, enhancing estrogen presence and shifting the estrogen-to-androgen ratio, which may favor healthier fat distribution and metabolic profiles in postmenopausal women. Further longitudinal studies are needed to clarify these relationships and their clinical impact.

References

1. Hetemäki et al. 2023 -- Effects of Menopausal Hormone Therapy on Sex Steroid Concentrations in Adipose Tissue
2. General knowledge on adipose tissue and sex steroid metabolism in menopause