Using a Composite Summary of Daily Sex Hormones to Gauge Time Until Menopause: A Focus on Pregnanediol Glucuronide (PDG).

Abstract

Context: The timing of a woman's final menstrual period (FMP) in relation to her age is considered a valuable indicator of overall health, being associated with cardiovascular, bone health, reproductive, and general mortality outcomes.

Objective: This work aimed to evaluate the relationship between hormones and the "time to FMP" when daily hormone trajectories are characterized by their 1) entropy, and 2) deviation from premenopausal/stable cycle patterns (representing a textbook "gold standard"; GS).

Methods: As part of the Study of Women's Health Across the Nation, urinary luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen conjugates (E1C), and pregnanediol glucuronide (PDG) were measured daily from a multiracial sample of 549 mid-life women for the duration of one menstrual cycle. Hormone trajectories were mapped onto a plane with axes representing Fuzzy entropy (FuzzEn) and the normalized dynamic time warping distance (DTW) from the GS.

Results: Viewing FSH, E1C, PDG, and LH through this lens reveals that, contrary to existing wisdom, PDG stands out as a powerful predictor/descriptor of "time to FMP." Using cluster analyses to discretize PDG on the DTW/FuzzEn plane yields statistically different survival curves, and Cox proportional hazards analyses confirm that this separation persists in the presence of known covariates of FSH, antimüllerian hormone, age, body mass index, financial hardship, smoking status, and cycle length.

Conclusion: Since PDG is generally not considered a predictor/descriptor of ovarian aging, this work validates the DTW/FuzzEn analytical framework and introduces another metric/hormone to be used in FMP-related preventive care.