Eucaloric High-fat Diet Effects on Reproductive Hormone Profiles: Mimicking Reprometabolic Syndrome in Normal Weight Women

Abstract Context Reprometabolic syndrome is associated with relative hypogonadotropic hypogonadism, reduced fecundability, and increased pregnancy loss in women with obesity. Objective Does a eucaloric, high-fat diet (HFD) decrease gonadotropins, urinary estrogen, and progesterone metabolites, characteristic of reprometabolic syndrome, in healthy women of normal body mass index (BMI)? Design Interventional study. Setting University medical center. Participants Eighteen healthy, eumenorrheic women with normal BMI (18-24.9 kg/m²), age 29.1 ± 6.3. Interventions A 4-month study including a prescribed 30-day, eucaloric HFD (48% calories from fat). Women collected daily first-voided morning urine for 4 menstrual cycles: pre-diet, on-diet, and 2 post-diet. Main Outcome Measures Urinary LH, FSH, estrone conjugate (E1c), and pregnanediol-3-glucuronide (Pdg) levels were measured daily before, during, and after HFD. Cycles were aligned by LH peak and standardized to a 28-day cycle. Peak and integrated hormone levels were compared across cycles using generalized estimating equations. Results Participants were weight-stable with no change in BMI. Peak E1c, Pdg, FSH, and LH were significantly lower during and after the HFD compared to pre-diet levels (P < .05). Post-diet luteal phase urinary FSH and LH (area under the curve) were also significantly lower than pre-diet (P < .01). No significant changes in menstrual cycle length were observed. Conclusion Consumption of a 1-month HFD was sufficient to induce a significant and sustained reduction in LH and FSH and lower E1c and Pdg characteristic of reprometabolic syndrome of obesity in normal-weight, eumenorrheic women. This indicates that dietary intervention may be an effective strategy to mitigate reproductive hormone deficiencies in women with obesity-related subfertility.