Daijiworld Media Network – New Delhi

New Delhi, Oct 15: Menopause may trigger sudden physiological changes across multiple organs rather than being merely a gradual process of ageing, according to a new study published in Nature Medicine on October 12.

Researchers at Israel's Weizmann Institute of Science analysed more than 300 million laboratory test results from over one million women in the United States and Israel, identifying abrupt changes in several measures of bodily health and function around the final menstrual period. The findings suggest that menopause involves a significant physiological transition affecting multiple systems, including bone health, liver and kidney function, blood chemistry and cholesterol levels.

The researchers described the phenomenon as a “physiological cliff”, challenging the conventional understanding of menopause as an exclusively gradual transition. While hormonal changes begin years before menstruation permanently stops, several other biological changes appear to occur more abruptly around the final menstrual period.

The study, led by Glen Pridham, Yoav Hayut and their collaborators under the guidance of Professor Uri Alon, drew on two major datasets covering the period from 1999 to 2024. These included data from the United States' National Health and Nutrition Examination Survey (NHANES) and medical records maintained by Israel's Clalit health service.

In the US dataset, 52 of the 90 types of laboratory tests examined showed statistically significant abrupt changes around menopause. These covered a wide range of biological functions, including hormone levels, bone metabolism, liver and kidney function, blood chemistry and lipid regulation. Similar patterns were observed in the Israeli dataset, strengthening the findings across the two populations.

Hormonal changes begin years before menopause

Although several physiological changes occurred abruptly around the final menstrual period, the researchers found that changes in reproductive hormones began much earlier.

Anti-Müllerian hormone (AMH), a marker associated with ovarian reserve, began declining more rapidly approximately 15 years before the final menstrual period. Follicle-stimulating hormone (FSH), which regulates reproductive function, also began increasing more rapidly around 14 to 15 years beforehand.

Levels of oestradiol, a major form of oestrogen, began declining more rapidly approximately 12 years before the final menstrual period. These findings indicate that the biological processes associated with menopause may begin well over a decade before menstruation permanently stops.

To identify these changes, the researchers developed a mathematical modelling method that reconstructs biological patterns relative to the timing of menopause. The approach helps distinguish changes associated with the final menstrual period from those linked to chronological ageing.

“Our study extends the window for potential preventive care to almost a decade before menopause,” Professor Uri Alon said in a statement released by the Weizmann Institute of Science.

Bone, liver and kidney functions affected

The study found that the physiological changes associated with menopause extend beyond the reproductive system.

Bone health is particularly sensitive to declining oestrogen levels. The hormone plays an important role in maintaining bone density, and its decline is associated with increased bone loss and a higher risk of osteoporosis.

The liver, which helps regulate cholesterol and other fats in the bloodstream, also showed changes around menopause. Researchers identified shifts in several liver-related laboratory measurements, alongside changes in kidney function and blood chemistry.

The study also found changes in blood osmolality, which measures the concentration of dissolved substances in the blood. This balance is regulated partly by antidiuretic hormone, also known as vasopressin, whose activity can be influenced by oestrogen.

Researchers additionally observed changes in levels of certain substances, including lead, around menopause. They suggested that these changes could be associated with the release of lead stored in bones as bone metabolism changes. However, further research would be required to establish the mechanisms behind such observations.

Men did not show similar changes

To determine whether the observed changes were associated specifically with menopause rather than ageing alone, the researchers compared the laboratory results with those of men of similar ages.

The analysis found that men did not experience the same pattern of abrupt physiological changes around comparable ages. The findings support the interpretation that the changes observed in women are associated with the menopausal transition rather than being solely a consequence of ageing.

The researchers also examined women receiving menopausal hormone therapy (MHT) and compared their results with those of women who were not receiving the treatment.

Measurements from 39 laboratory tests differed between the groups, and many of the abrupt changes appeared less pronounced among women receiving hormone therapy. The effect was particularly evident in measurements associated with bone, liver and kidney function.

However, the findings do not establish that hormone therapy prevents all menopause-related physiological changes or that it is suitable for every woman. Treatment decisions depend on individual symptoms, medical history and potential risks.

Further research needed

The researchers said the findings could help scientists better understand when different organs begin responding to the menopausal transition and identify opportunities for preventive healthcare before the final menstrual period.

However, the study does not establish that every observed laboratory change leads to illness or requires medical intervention. Further research will be needed to determine whether earlier monitoring and interventions based on these findings can improve long-term health outcomes.

The study also has limitations because it relies on large-scale medical records and population-level modelling rather than directly tracking every participant's biological changes over time. Its findings therefore reveal broader patterns but cannot predict precisely when or how menopause will affect an individual woman.

The researchers believe the mathematical approach developed for the study could also be used to investigate other major biological transitions, including puberty, pregnancy and the onset of disease.

The findings offer a broader understanding of menopause as a transition affecting multiple body systems and highlight the importance of studying its health implications well before the final menstrual period.