Plasma Steroid Profiles in Individuals With Class II/III Obesity

Mari Ibusuki, Kohta Nakatani, Yayoi Matsuda, Hironobu Umakoshi, Maki Yokomoto-Umakoshi, Hiroki Takayanagi, Ryuichi Sakamoto, Tetsuro Kawazoe, Eiji Oki, Tomoharu Yoshizumi, Yoshihiro Izumi, Takeshi Bamba, Yoshihiro Ogawa
Journal of the Endocrine Society, Volume 9, Issue 11, November 2025, bvaf151
https://doi.org/10.1210/jendso/bvaf151

Abstract

Context

Although steroid metabolism is altered in individuals with obesity, comprehensive profiles of steroid metabolites remain unexplored, some of which may be related to weight loss after metabolic surgery.

Objective

We aimed to characterize comprehensive steroid profiles in individuals with class II/III obesity (body mass index ≥35 kg/m²) and identify metabolite(s) related to weight loss outcomes after laparoscopic sleeve gastrectomy (LSG).

Methods

Using liquid chromatography–tandem mass spectrometry, we measured 27 plasma steroid metabolites in individuals with class II/III obesity (n = 93), healthy controls (n = 15), and those after LSG (n = 20).

Results

Discriminant analysis revealed distinct steroid profiles between individuals with class II/III obesity and healthy controls, with statistical significance for 9 metabolites in men (n = 53) and 11 in premenopausal women (n = 44). One year after LSG, the insufficient and sufficient weight loss groups (percent total weight loss (%TWL) < 20%; n = 10 and %TWL ≥ 20%; n = 26) showed distinct preoperative steroid profiles. Preoperative 17α-hydroxypregnenolone (17α-OHPreg) levels, which were lower in individuals with class II/III obesity, were the most significant factor contributing to this distinction, and remained significantly lower in the insufficient weight loss group even after adjusting for confounders (P = .012). The 17α-OHPreg levels significantly increased postoperatively in men (n = 9, P = .024).

Conclusion

This study is the first detailed analysis of comprehensive steroid profiles in individuals with class II/III obesity and suggests that lower preoperative 17α-OHPreg levels are associated with insufficient weight loss after LSG.

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