SAT-114 Use of an Eucaloric Low-Fat Diet to Explore Reversal of Reprometabolic Syndrome in Women with Obesity

Abstract Disclosure: K. Kuhn: None. I. Flores-Garcia: None. K. Duffy: None. A.P. Bradford: None. C. Moore: None. D. Mitchell-Leef: None. N.F. Santoro: Astellas Pharma, Ansh Labs, Novo Nordisk. Introduction: Women with obesity women suffer from a wide variety of metabolic and reproductive endocrine disorders including low conception rates, adverse pregnancy outcomes, increased serum fats and relative hypogonadotrophic hypogonadism; a phenotype we term Reprometabolic Syndrome (RMS). We have previously shown that a month long eucaloric high-fat diet in normal weight women decreases reproductive hormones and impairs GnRH responsiveness, mimicking RMS, in the absence of changes in weight. Since this high-fat diet was able to induce the reproductive endocrine dysfunction characteristic of RMS in women of normal BMI, we hypothesized that an analogous low-fat diet may ameliorate RMS in women with obesity. We have initiated a test-of-concept pilot study to investigate whether a month long, eucaloric low-fat diet (LFD) can affect rescue of gonadotropin secretion and follicular and luteal function. Materials and Methods: Two healthy, eumenorrheic, reproductive women with obesity aged 36.5±2.1 years were enrolled into the study lasting 3 menstrual cycles (one cycle prior to LFD, one cycle on LFD, and one cycle post LFD). Inclusion criteria are normal TSH, prolactin, AMH, HbA1c, not taking reproductive hormones and no use of medication that affects reproductive hormones. Participants consumed a custom, eucaloric low-fat diet (22% calories from fat, replacing the fat calories with protein and complex carbohydrates) during the second menstrual cycle of the study. Compliance was monitored by interviews and recording of any unconsumed food. Both serum (weekly) and urine (daily) were collected from participants throughout the 3 cycles. Urine was analyzed for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and normalized to creatinine. Ongoing assays are currently being conducted for urinary estrone-3-glucuronide and pregnanediol glucuronide. Serum and plasma lipids and metabolite analyses are planned. Results: Both participants were weight stable throughout the study with no change in BMI (pre-LFD BMI 31.84±0.79 and post-LFD BMI 31.59±0.86). The LFD was well-tolerated with both participants indicating that by the end of the diet they preferred low-fat foods to previously eaten high-fat foods. Analysis of participant’s urinary reproductive hormones showed a change in urinary gonadotropin levels. LH and FSH were lower pre-diet compared to on-diet. Post diet levels remained increased but were lower than on-diet. Conclusion: This ongoing pilot study supports the feasibility and proof of concept that a low-fat eating plan, a simple, palatable and scalable intervention, absent the need for weight loss, may be beneficial for reproductive hormone secretion in women with the RMS of obesity. Thus the ‘food as medicine ‘paradigm may be applicable to address the impact of obesity on fertility and potentially mitigate the adverse health impacts on women and their offspring. Presentation: Saturday, July 12, 2025