ORF38-05 - Distinct Patterns in Daily Hormone Profiles Underlie the Relationship between Elevated-BMI/Obesity and Pre/Perimenopausal Vasomotor Symptoms: The Study of Women'S Health Across the Nation (SWAN)

Background: While existing work indicates that higher BMI associates with more vasomotor symptoms (VMS) in pre/perimenopausal women, recent work has shown that measures of hormonal regularity (eg entropy) reveal unique patterns of dysregulation associated with VMS; alluding to potential heterogeneity within the BMI/VMS relationship.

Objective: To investigate for heterogeneous relationships underlying the broader positive trend between BMI and pre/perimenopausal VMS.

Methods: Entropy metrics were derived from daily urine-based measures of follicle-stimulating hormone (FSH), estrogen conjugates, pregnanediol glucuronide (PDG), and luteinizing hormone (LH) collected over a full menstrual cycle from 694 midlife women. Elevated/lowered entropy was defined as +/- 1 SD from the mean. Analyses applied to the whole sample (n=694) and a subset of overweight/obese women (n=420). Two entropy metrics were used to build a 3-tier classifier to capture variations in the positive BMI/VMS trend. Groups were: 1) elevated dispersion entropy of FSH (FSH-DispEn, n=58 and 41), 2) lowered cross-fuzzy entropy between LH and PDG (LH-PDG-XFuzzEn, n=73 and 62), and 3) everyone else (‘level group’, n=563 and 317). Relative to the ‘level group’, elevated FSH-DispEn and lowered LH-PDG-XFuzzEn were assessed for differences in BMI, daily VMS reports and hormone profiles (both concurrent to urine collection), and long-term VMS reporting over the menopause transition (MT); encompassing 2 years before/after menopause.

Results: Relative to healthy-weight, obese women had a higher likelihood of VMS for the daily reporting concurrent to urine collection (OR=1.29[1.16,1.44]) and long-term reporting over the MT (OR≈1.97[1.22,3.19]). Among both total and overweight/obese-only samples, women with higher FSH-DispEn and lower LH-PDG-XFuzzEn had significantly greater average BMI’s, ranging 2-5 kg/m2 above the ‘level group’ BMI of 26.2 and 29.9 kg/m2. For both populations, analysis of daily VMS showed elevated FSH-DispEn had an increased likelihood of VMS (OR=1.28[1.12,1.46] and 1.42[1.22,1.65]) while lowered LH-PDG-XFuzzEn had a lower likelihood (OR=0.67[0.58,0.78] and 0.69[0.58,0.81]). The trend for elevated FSH-DispEn does not persist long-term; showing common signs of perimenopausal dysregulation linked to orientation near the ‘peak’ of the MT. The trend for lowered LH-PDG-XFuzzEn persists long-term, but only for the overweight/obese subset (OR≈0.35[0.16,0.77]); where underlying hormone profiles associate with obesity-related hypogonadism.

Conclusion: A subgroup of overweight/obese women with lowered LH-PDG-XFuzzEn do not exhibit the positive BMI/VMS relationship, experiencing fewer VMS while showing evidence of obesity-related hypogonadism. The increased likelihood of VMS found with elevated FSH-DispEn is transient, likely reflecting peak perimenopausal cycle dysregulation.