Abstract PS3-05-24: Sex Hormone Responses to Alternate-Day Fasting-Low-Carbohydrate in Premenopausal and Postmenopausal Women

Abstract Background: Intermittent fasting is increasingly used to manage weight and metabolic disease. Alternate-day fasting (ADF) combined with low carbohydrate (ADF-LC) lowers body weight and insulin. Because insulin suppresses hepatic sex hormone-binding globulin (SHBG), ADF-LC is expected to increase SHBG without increasing free testosterone (free T); the adrenal androgen dehydroepiandrosterone (DHEA) may also shift with metabolic changes. We tested the impact of an ADF-LC intervention on insulin and androgen-related hormones and evaluated whether changes in these markers (SHBG, free T, DHEA) tracked with body weight change, and whether hormone levels and menopausal status were associated with body weight over 24 weeks. Methods: Women with obesity completed a single-arm, 24-week ADF-LC intervention (12-week loss; 12-week maintenance). Fasting morning body weight and SHBG, free T, DHEA, and insulin were assessed at weeks 0, 12, and 24. Analyses included women (n=28; premenopausal n=13; postmenopausal n=15). We ran change-on-change regressions of Δweight on ΔSHBG, ΔDHEA, Δfree T, and Δinsulin (univariable; multivariable with age and height; plus models adding menopausal status and the interactions ΔSHBG×menopause and Δinsulin×menopause). We also fit a random-intercept mixed model for weight over time including time, SHBG, DHEA, free T, insulin, menopausal status, age, height, and time×hormone interactions. Estimates are reported as β (95% CI, p). Results: Participants lost weight over 24 weeks intervention (p<0.01). In the mixed-effects model, body weight decreased over time (β=−4.7; 95% CI -6.3, -3.0). Higher SHBG was associated with lower body weight (β=-5.8; -11.0, -0.99), and higher insulin with higher body weight (β=7.8; 3.7, 12.0). DHEA, age, and menopausal status were not significant (e.g., DHEA β=0.02; −2.6, 2.7). A time×free T interaction was significant (β=-4.7; -9.1, -0.30), indicating greater weight loss over time at higher testosterone. In change-on-change analyses, insulin change was positively associated with weight change (univariable β=0.76; 0.13, 1.4; p=0.019; multivariable β=0.80; 0.15, 1.5; p=0.018; model including menopause β=0.97; 0.09, 1.9; p=0.033), whereas changes in SHBG, DHEA, and free T were not significant; ΔSHBG×menopause and Δinsulin×menopause were non-significant. Conclusions: Over 24 weeks, ADF-LC was associated with weight loss. In the models, higher SHBG related to lower body weight, higher insulin to higher body weight, and larger insulin reductions tracked with greater weight loss; DHEA, age, and menopausal status were not determinants. A time×testosterone interaction indicated greater weight loss at higher testosterone. Overall, no adverse androgenic signal was observed. These findings support testing ADF-LC in larger, controlled trials and mechanistic mediation along insulin-SHBG pathways relevant to breast-cancer prevention. Citation Format: F. Kalam, R. Akasheh, F. Tounkara, M. Hafez, K. Varady, T.-Y. Cheng. Sex Hormone Responses to Alternate-Day Fasting-Low-Carbohydrate in Premenopausal and Postmenopausal Women [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-05-24.