Adiposity and sex steroid hormones: evidence on direct measures and changes over time -- a systematic review and meta-analysis.

Introduction: The evidence synthesis on literature characterizing changes in body fatness and adiposity distribution with sex steroid measurements in different matrices (blood, tissue, urine and other excreted matrices) is lacking. Methods: PubMed and Web of Science were used to identify eligible studies published until June 2026. Random-effects meta-analyses were conducted, and the strength of evidence was determined based on the Continuous Update Project criteria. Results: Of 16,875 screened references, 140 studies deemed relevant: 96 on circulating blood biomarkers from 39 weight loss intervention (surgical and lifestyle) and 60 observational studies reporting direct measure of adiposity distribution (e.g., DEXA, MRI), 20 studies on biomarkers measured in urine or other excreted matrices (i.e., saliva, urine, breast ductal lavage), and 25 tissue-based studies (e.g., adipose, breast, endometrial, skin). Weight loss was associated with a reduction of total and free testosterone, and an increase in sex hormone binding globulin (SHBG). While no significant associations were found between weight loss and premenopausal estradiol, dehydroepiandrosterone sulfate, and androstenedione. Decrease in total and free estradiol and estrone were observed in postmenopausal women. Findings in observational studies generally supported those results, as well as tissue-based studies on estrogen-related markers despite the heterogeneous tissue types. Studies on biomarker measured in excreted matrices were largely inconclusive. Conclusion: Strong evidence of a probable association was found between body fatness and SHBG, androgens, and postmenopausal estrogens. Limited evidence remained for other sex steroids.