Menopause involves abrupt physiological changes across multiple body systems, rather than being an entirely gradual process, according to a new study published in Nature Medicine.
Researchers analysed more than 300 million laboratory tests from over one million women in the US and Israel between 1999 and 2024.
In the US dataset, 52 of 90 laboratory tests showed statistically significant abrupt changes around menopause, including measures of bone health, liver and kidney function, and blood chemistry.
Hormonal changes began much earlier, with anti-Müllerian hormone and follicle-stimulating hormone showing accelerated changes about 15 years before the final menstrual period.
Researchers found that menopausal hormone therapy was associated with differences in 39 laboratory measurements, suggesting it may moderate some changes, although further research is needed.
Analysis of more than 300 million laboratory tests suggests menopause involves sudden physiological changes across multiple organs, with early hormonal shifts beginning more than a decade before the final menstrual period.
Menopause is not simply a gradual process of ageing but involves abrupt biological changes across multiple systems in the body, according to a new study published in the journal Nature Medicine on 12 October 2026.
Researchers at Israel's Weizmann Institute of Science found that women experience what they describe as a “physiological cliff” around their final menstrual period, with sudden changes in measures of bone health, liver and kidney function, blood chemistry and cholesterol levels.
The findings challenge the understanding of menopause as an exclusively gradual transition, suggesting that some biological changes occur sharply around the final menstrual period, even though hormonal changes can begin more than a decade earlier.
Impacts beyond reproductive health
The study, led by Glen Pridham, Yoav Hayut and collaborators, analysed two large datasets comprising more than 300 million laboratory tests from over one million women in the United States and Israel between 1999 and 2024.
Researchers identified abrupt changes in dozens of measures of bodily health and function, extending beyond the familiar changes in reproductive hormones and fertility.
In the US dataset, 52 of 90 laboratory tests showed statistically significant abrupt changes around menopause.
These included measurements associated with sex hormones, bone health, liver and kidney function, blood chemistry and blood fats.
Earlier long-term research, including the Study of Women's Health Across the Nation (SWAN), had documented hormonal changes and bone loss during menopause.
The latest study builds on that evidence by examining a much wider range of biological measurements across a large population.
Hormonal changes begin over a decade before menopause
Although many physiological changes occurred abruptly around the final menstrual period, researchers found that changes in several reproductive hormones began much earlier.
Anti-Müllerian hormone (AMH), which is associated with ovarian reserve, began declining more rapidly approximately 15 years before the final menstrual period.
Follicle-stimulating hormone (FSH), which helps regulate reproductive function, began increasing more rapidly around the same time.
Levels of oestradiol, a major form of estrogen (also known as oestrogen), began declining more quickly about 12 years before menopause.
These findings suggest that some of the biological processes associated with menopause begin well before menstruation stops.
The researchers used mathematical modelling to reconstruct the timing of menopause from laboratory data and identify changes that might otherwise be difficult to distinguish from normal ageing.
“Our study extends the window for potential preventive care to almost a decade before menopause,” said Alon, one of the researchers, in a statement published by the Weizmann Institute. “More broadly, the method we developed may help study other major changes in life, such as puberty, pregnancy or the onset of disease.”
Why different organs respond to menopause
The researchers found that the size of the abrupt changes varied across biological systems, partly reflecting how sensitive different organs are to estrogen.
For example, FSH levels are highly sensitive to changes in estrogen because of the hormonal feedback system connecting the brain and ovaries.
Bones are also particularly sensitive to estrogen, which helps maintain bone density and protect against bone loss.
The liver, which plays an important role in regulating cholesterol and other fats in the blood, is another organ affected by changing estrogen levels.
The study also identified changes in blood osmolality, a measure of the concentration of dissolved substances in the blood. This is regulated partly by antidiuretic hormone, also known as vasopressin, whose activity is influenced by estrogen.
Researchers observed changes in levels of certain substances, including lead, around menopause.
They suggested that this could be related to the release of lead previously stored in bones as bone metabolism changes.
However, the study does not establish that every observed laboratory change causes illness or requires medical treatment.
Changes not seen in men of similar ages
To distinguish menopause-related changes from those associated with ageing more generally, researchers examined laboratory measurements in men.
They found that men did not experience the same pattern of abrupt physiological changes at comparable ages.
The researchers said this supported the interpretation that the changes observed in women were associated with menopause rather than ageing alone.
The study also examined differences between women receiving menopausal hormone therapy (MHT) and those who were not.
Results from 39 laboratory tests differed between the two groups, suggesting that hormone therapy might moderate some of the abrupt physiological changes associated with menopause.
However, these findings do not establish that hormone therapy prevents all menopause-related changes or that it is appropriate for every woman. Treatment decisions depend on individual symptoms, medical history and potential risks.
Implications for preventive healthcare
The findings suggest that menopause-related changes could potentially be identified earlier than previously recognised, creating opportunities to investigate preventive healthcare before the final menstrual period.
By detecting changes in reproductive hormones more than a decade in advance, researchers believe it may be possible to better understand when different organs begin responding to the menopausal transition.
However, further research is needed to determine whether earlier monitoring or interventions based on these findings would improve health outcomes.
The researchers also said their mathematical approach could help identify biological transitions in other stages of life, including puberty, pregnancy and the onset of disease.