Biology: Menopause marks a physiological ‘cliff’ (Nature Medicine)
13 October 2026
The final menstrual period is preceded by abrupt ‘cliff-like’ biological changes across multiple body systems, some of which show early signs more than a decade beforehand, according to research published in Nature Medicine. The findings suggest that menopause-related physiological changes may occur over a shorter time frame than previously thought and advance our understanding of how early these changes can be detected.
Menopause is the permanent end of menstruation and occurs when ovarian follicles are exhausted, which leads to changes in the levels of several sex hormones. Menopause has been linked to changes across multiple biological systems beyond fertility. However, the timing of these changes has been difficult to establish because the final menstrual period is rarely recorded and long-term studies are relatively small.
Uri Alon and colleagues developed a computational method to reconstruct physiological changes around the final menstrual period using more than 300 million laboratory tests from over one million women in the United States and Israel 1999–2024. Across both datasets, abrupt changes were observed in multiple body systems at menopause. In the US dataset, 52 of 90 laboratory tests showed a statistically significant, abrupt change, including measurements related to sex hormones, bone health, liver and kidney function, blood chemistry, and blood fats.
The levels of three sex hormones also changed more than a decade before the final menstrual period: anti-Müllerian hormone and oestradiol declined rapidly around 15 and 12 years beforehand, respectively, while follicle-stimulating hormone increased more rapidly around 14 years beforehand. Menopausal hormone therapy was associated with smaller changes in many measures, particularly those related to bone, liver and kidney function.
The findings suggest that menopause is an abrupt, body-wide physiological transition inherent to female individuals, rather than a gradual part of ageing, as comparable changes were not observed in male individuals. The authors describe the changes as a step-like physiological ‘cliff’. However, the research used retrospective data and self-reported menopause information, and the effects of hormone therapy will need to be confirmed in future studies.
- Article
- Open access
- Published: 12 October 2026
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 (2026). https://doi.org/10.1038/s41591-026-04614-0
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