How Does the Body Change Around Menopause? Million-Woman Study Finds Abrupt Changes Across Multiple Systems

As menstruation approaches its end, do changes in the body accumulate gradually, or do they accelerate noticeably during a particular period? A large study published in *Nature Medicine* reconstructed physiological trajectories around menopause using laboratory test data from more than one million women, finding abrupt shifts across multiple systems near the final menstrual period. This broadens the scope of menopause research from reproductive function to the whole body, but the researchers’ “physiological cliff” metaphor has also drawn criticism from independent experts.

The study integrated more than 300 million laboratory test records. The Israeli Clalit healthcare database covered approximately 1.3 million women aged 30 to 70 between 2004 and 2024, while the US data came from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2022. Because women reach menopause at different ages, arranging the data solely by age may flatten more concentrated changes into a gradual slope. The team’s YoGlen computational method uses the population distribution of menopause ages to reconstruct average trajectories relative to the final menstrual period; it cannot predict when an individual woman will reach menopause.

In the US data, 52 of 90 laboratory markers showed statistically significant abrupt changes, involving sex hormones, bone health, liver and kidney function, blood biochemistry, and blood lipids. According to *EL PAÍS*, the magnitudes of change observed in the two countries’ data were highly consistent, with a correlation coefficient of 0.89. However, shifts in laboratory values cannot be directly equated with everyone’s organ function deteriorating at the same moment, nor do they mean that all changes have the same clinical impact.

Another clue emerged further back in time. The analysis showed that anti-Müllerian hormone (AMH), which reflects ovarian reserve, began declining at an accelerated rate approximately 15 years before the final menstrual period; follicle-stimulating hormone (FSH) began rising at an accelerated rate approximately 14 years beforehand, while estradiol began declining at an accelerated rate approximately 12 years beforehand. These findings describe the timing of changes at the population level and cannot yet turn a single hormone test into an individual countdown to menopause.

The study also found that women using menopausal hormone therapy had smaller changes in multiple markers, particularly measurements related to bones, the liver, and the kidneys. This offers clues about which physiological processes treatment might affect, but the data show an association: the study did not randomly assign treatment and therefore cannot establish that starting medication earlier can prevent changes throughout the body.

How the data were obtained lies at the heart of the debate. The study used a retrospective analysis, with some menopause information relying on women’s self-reports; the large volume of data cannot eliminate recall errors or differences between populations. Australia’s ABC reported that menopause expert Martha Hickey, who was not involved in the study, believes the “cliff” wording could cause women excessive concern. She also cautioned that the hormone therapy comparison may involve “healthy user bias”: women using treatment may have been healthier to begin with, so the smaller changes may not be entirely attributable to treatment.

Uri Alon of the research team told ABC that clinical trials are being planned to assess the outcomes of starting hormone therapy before the final menstrual period. This large analysis proposes testable hypotheses about how menopause affects multiple physiological systems; prospective follow-up and intervention studies are now needed to clarify when these shifts occur, their actual effects on disease risk, and which changes can be modified by treatment.