With menopause, many physical processes in women change fundamentally and abruptly - and not just with regard to fertility. This is the central result of a study presented in the journal “Nature Medicine”.
The research team led by Uri Alon from the Weizmann Institute of Science in Israel describes the changes in various areas of the body as a “physiological cliff” that sometimes occurs more than a decade before the actual menopause.
The term is sometimes used differently in everyday language. In fact, the term menopause refers to the time of the last menstrual period and is determined retrospectively when no period has occurred for twelve months. Research into what happens around menopause is made more difficult by the fact that the timing is rarely reliably documented and the data is therefore incomplete. Long-term studies are relatively rare.
The research team used a mathematical procedure to retrospectively determine the time of menopause of the women included in the analysis and to compensate for the bias that would arise if only the average age at menopause - around 51 years - was used.
The scientists evaluated more than 300 million laboratory data from more than a million women in the USA and Israel. This is routinely collected health data from 1999 to 2022 in the case of the USA and 2004 to 2024 in the case of Israel.
The US data showed statistically significant, abrupt changes around menopause in 52 of 90 parameters - such as liver and kidney function, blood lipids, bone metabolism and sex hormones.
In the latter, the changes could be observed a long time before the last bleeding: a greater decline in anti-Müllerian hormone - a marker for egg cell reserve - was observed around 15 years before menopause, and in estradiol - central to the menstrual cycle, among other things - around twelve years before that. However, there was a greater increase in follicle-stimulating hormone (FSH), which causes eggs to mature, around 14 years before menopause.
Bone density decreases at an accelerated rate around menopause, which increases the risk of osteoporosis, the study continues. There was also an accelerated increase in the incidence of other diseases among postmenopausal women, including joint and metabolic diseases such as arthritis and gout, as well as cardiovascular disease.
A comparison with data from men of comparable age showed no such abrupt physical changes, which the researchers see as further evidence of the connection to menopause. For them, changes were more gradual.
The expert Petra Stute, who is not involved in the study and heads a menopause center at a hospital in Bern, is critical of the term “physiological cliff” and describes it as an exaggeration. “The study shows statistically reconstructed average courses and no directly observed decline in health in individual women,” says Stute.
"The jump sizes are described, among other things, over a window of several years before and after the last menstrual period. Menopause is a relevant physiological change, but not a sudden onset of the disease."
In women who underwent hormone therapy, the changes were milder and less abrupt in many aspects, according to the study. The team emphasizes that this needs to be examined more deeply in further studies. Based on the results, independent experts also see no reason for new recommendations for hormone therapy.
Hormone therapy is used, among other things, to alleviate menopausal symptoms such as severe sleep disorders.
Peyman Hadji, who heads the Hormone and Osteoporosis Center in Frankfurt am Main and was not involved in the study himself, explained: "The results support a systemic understanding of menopause: it affects much more than reproduction and marks a measurable, much longer period or transition than previously thought, with potentially long-term health consequences."
The significance of the study is strengthened by the large, independent data sets. There are limitations, among other things, due to retrospective cross-sectional data and possible biases in the assessment of hormone therapy. These results should be confirmed in larger studies, says Hadji.
