Menopause Marked by Abrupt Physiological Shifts at Final Menstrual Period

Menopause was marked by abrupt, step-like changes across most physiological systems at the final menstrual period (FMP), according to a study in Nature Medicine that analyzed more than 300 million laboratory tests from cohorts in the US and Israel.

The investigators noted that understanding of menopause has been limited by small longitudinal cohorts that characterize it as a gradual transition and that FMP age is rarely recorded in large datasets. They developed a computational deconvolution framework, inspired by astronomy, that reconstructs FMP-anchored trajectories from cross-sectional data. The method estimates population-mean trajectories and does not predict FMP timing for individuals.

The researchers applied the method to 90 laboratory tests from the National Health and Nutrition Examination Survey (NHANES; 1999-2022) and from Israeli health insurer Clalit, which included 1.3 million women aged 30 to 70 years. Compared with men, women showed a significant jump at the FMP in 52 of 90 tests, with jump sizes ranging from 0.1 to 1.4 SD. Jumps spanned sex hormones, liver tests, blood counts, kidney function, bone tests, lipids, and osmolality, and jump sizes were strongly correlated between the 2 datasets (r = 0.89). Men showed no jumps. Most shifts were in the direction of increased disease risk; iron, hemoglobin, and red blood cell measures were the main exceptions.

Accelerated changes in anti-Müllerian hormone, follicle-stimulating hormone, and estradiol began about 12 to 15 years before the FMP. In NHANES, most jumps were smaller among women reporting current menopausal hormone therapy (MHT), and 39 of 80 tests differed between MHT users and nonusers; MHT was associated with elevated C-reactive protein. Osteoporosis prevalence and cardiovascular outcomes, including heart attack and stroke, rose more steeply after menopause.

The authors noted that the study relied on retrospective cross-sectional data and self-reported menopause status and that healthy user bias among MHT users could not be fully eliminated. They stated that the effects of MHT need to be tested in prospective randomized trials.

Source: Pridham G, Hayut Y, Lavi-Shoseyov N, et al. Population-scale reconstruction of menopause dynamics reveals a physiological cliff at the final menstrual period. Nat Med. Published online October 12, 2026. doi:10.1038/s41591-026-04614-0