Professor Uri Alon, who heads the Sagol Center for Longevity Research at Israel's Weizmann Institute, led an analysis of more than 300 million routine laboratory test results from over a million women in the United States and Israel, collected between 1999 and 2024.
The researchers traced changes in 90 common blood and laboratory markers around menopause. Long before the final menstrual period, several reproductive hormones were already moving: anti-Müllerian hormone, a marker of egg reserve, began falling about 15 years before menopause; oestradiol, the main form of oestrogen, about 12 years before; and follicle-stimulating hormone began rising about 14 years before.
Those hormonal changes developed gradually over years. The study found a sharper turn around the final menstrual period, when more than half the tests tended to shift suddenly for women.
Of the 90 markers, 52 showed an abrupt change around menopause instead of a slow, steady drift. The clearest changes involved bone density, liver and kidney function, and cholesterol levels.
The findings challenge the established view of menopause as a gradual age-related decline across body systems. The final menstrual period appeared to mark the point at which changes across several systems became measurable in clinical tests.
Men of the same age showed gradual changes and no equivalent abrupt shift in laboratory markers, a pattern the researchers said suggested the changes were tied to the menopausal transition rather than ageing alone.
Women using menopausal hormone therapy showed smaller changes in many markers. Only about 9 per cent of the women in the study were using the treatment.
Perimenopause can begin as early as the mid-to-late 30s, and about 40 per cent of women reach menopause in their 40s.
The peer-reviewed observational study was published in Nature Medicine. Its use of existing data and self-reported information about women’s last periods limits the certainty of its conclusions, since those reports can be inaccurate.
Martha Hickey, head of menopause services at The Women's Hospital Victoria and an obstetrics and gynecology professor at the University of Melbourne, called the description of “cliff-like” changes “unnecessarily alarming”. “Physiological cliff is not a scientific or medical term,” she said.
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