7299 An Eucaloric High-Fat Diet Suppresses Urinary Estrogen and Progesterone Metabolites, Mimicking Reprometabolic Syndrome in Normal Weight Women

Abstract Disclosure: K. Kuhn: None. A.P. Bradford: Consulting Fee; Self; Amazon. N.F. Santoro: Advisory Board Member; Self; Menogenix, Astellas, Que Oncology, Amazon. Consulting Fee; Self; Ansh. Introduction: Reprometabolic syndrome is associated with relative hypogonadotropic hypogonadism, reduced fecundability, and increased pregnancy loss in women with obesity. We employed a eucaloric, high-fat diet (HFD) to attempt to reproduce the decreased urinary estrogen and progesterone metabolites, characteristic of this phenotype, in healthy women of normal BMI. Materials and Methods: 18 women with normal BMI (18-24.9kg/m²), mean age 29.1±6.3, were recruited for a four-month study including a prescribed 30-day, eucaloric, high-fat, dietary intervention (48% calories from fat). Women collected daily morning urine for 4 menstrual cycles. Daily urinary estrone conjugate (E1c) and pregnanediol-3-glucuronide (Pdg) levels were measured by immunoassay before, during and after the HFD. Paired t tests were used to compare average urinary E1c and Pdg levels and area under the curve (AUC) to determine the impact of the HFD. Cycles were aligned by LH peak (day 0). Results: Participants were weight stable throughout the 4 month study period with no change in BMI (pre-diet BMI 21.46±1.95 kg/m2 and post-diet BMI 21.35±1.81 kg/m2). Average mid cycle E1c peak was significantly lower during (32.4 ng/mg creatinine) and after the HFD (26.5 ng/mg creatinine), compared to pre-diet levels (43.2 ng/mg creatinine; p< 0.001). Post-diet urinary Pdg (AUC) was also significantly lower than pre-diet (p< 0.01). Follicular (days -14 to 0) and luteal phase (days 2-14) E1c AUC was significantly decreased post HFD (p< 0.05). Follicular and luteal phase Pdg levels were also significantly decreased post HFD (p<0.001, both). No significant changes in menstrual cycle length were observed throughout the study. Conclusion: Consumption of a high-fat diet for one month was sufficient to induce a significant reduction in E1c and Pdg, characteristic of Reprometabolic Syndrome of obesity, in normal weight, eumenorrheic women. This finding provides important insights regarding the mechanisms underlying reproductive dysfunction in obesity and indicates that a dietary intervention may be an effective strategy to mitigate sub-optimal reproductive hormone levels in women with obesity-related subfertility. Presentation: 6/1/2024