MON-200 An Unfavorable Cardiovascular Profile Associates With The Development Of Vasomotor Symptoms In Premenopausal Women Undergoing Experimentally Induced Menopause

Abstract Disclosure: C.O. Sailer: None. A.Y. Cohn: None. A. Wiley: None. U.B. Kaiser: None. K.K. Miller: ; NIH - Grant. ; Amgen - Grant. ; Bristol-Myers Squibb (BMS) - Equity. ; General Electric - Equity. ; Boston Scientific - Equity. ; Becton Dickinson - Equity. S.A. Rahman: ; NIH - Grant. ; Merck & Co., Inc. - Grant. H. Joffe: ; NIH - Grant (R01AG053838, U54AG062322). ; ARPA-H – Grant. ; PCORI – Grant. ; Wellcome Trust – Grant. ; Merck – Grant. ; Bayer – Consultant. ; Novo Nordisk – Consultant. Background: Menopause is associated with increased cardiovascular risk factors such as central adiposity, dyslipidemia, and type 2 diabetes mellitus. The core menopause manifestation, vasomotor symptoms (VMS), has been associated with an unfavorable cardiovascular profile in postmenopausal women. The extent to which this is independent of age is unknown. We leveraged an experimental menopause model in young, premenopausal women to determine if an unfavorable cardiovascular profile (increased central adiposity, dyslipidemia, and higher blood glucose levels) predisposes to development of VMS, independent of age. Methods: We conducted a study in 27 healthy premenopausal women (mean [SD] age: 28.4 ± 5.6 years, BMI: 24.4 ± 3.6 kg/m2) who underwent gonadotropin-releasing hormone (GnRH) agonist-induced estradiol suppression, an experimental model mimicking menopause. Dual-energy X-ray absorptiometry (DXA) to assess body composition, fasting lipid panel, and HbA1c were measured before estradiol suppression. Women were categorized based on whether they developed objectively measured VMS (skin conductance). Pre-estradiol suppression differences in total body fat, trunk/limb fat mass ratio (a marker for visceral adiposity), lipid profile, and HbA1c (a marker for average blood glucose), were compared between VMS groups using t-test or Wilcoxon rank sum test based on data distribution. Results: As expected, following pharmacologic estradiol suppression, 18 (66.6%) women developed VMS, while 9 (33.3%) did not. There were no between-group differences in mean age (28.1±5.7 years vs. 29.1±5.8 years, p = 0.7), BMI (25.3±3.3 kg/m2 vs. 23.8±4.0 kg/m2, p = 0.3) or total body fat (25.9±7.7 kg vs.22.3±7.3kg, p = 0.3). Women who developed VMS, compared to women who did not, had significantly higher median pre-estradiol suppression trunk/limb fat mass ratios (0.8 [0.7, 0.9] vs. 0.7 [0.6, 0.7], p = 0.01), significantly lower median HDL (53 mg/dl [47, 59] vs. 70 mg/dl [62, 73], p = 0.001), higher median VLDL (14 mg/dl [12, 22] vs. 11 mg/dl [10, 12], p = 0.03), higher median triglyceride (73 mg/dl [61, 123] vs. 55 mg/dl [52, 61], p = 0.04), and higher median HbA1c (5.3% [5.1, 5.4] vs. 5.0% [5.0, 5.2], p=0.048). Conclusion: In healthy premenopausal women undergoing pharmacologic estradiol suppression mimicking menopause, the subset developing VMS exhibit an adverse pre-induction cardiometabolic profile relative to those who did not develop VMS. These findings suggest that cardiometabolic health impacts susceptibility to developing VMS and warrant further investigation of cardiometabolic health as a possible therapeutic target for lowering the risk of developing VMS during the menopausal transition. Presentation: Monday, July 14, 2025