Menopause has long been described as a slow slide into midlife. A large new study from Israel’s Weizmann Institute of Science paints a different picture: a sudden, body-wide shift that hits bones, the liver and blood fats around the time of a woman’s last period1. The researchers call it a “physiological cliff”2. The study was published in the journal Nature Medicine on October 123, and the lead researchers spoke about it with Israeli press on October 241.
What the study found
The team looked at more than 300 million lab test results from over 1 million women in the United States and Israel, collected between 1999 and 20244. The records came from Clalit Health Services, Israel’s largest health fund, and from the US National Health and Nutrition Examination Survey, a long-running government health survey1.
In the US data, 52 of the 90 types of lab tests showed a statistically significant, sudden change around menopause4. These included tests of sex hormones, bone health, liver and kidney function, blood chemistry and blood fats4. The biggest shifts were in bone metabolism, liver tests and the way the body handles fats2.
Menopause itself is defined as the point when a woman has gone 12 months in a row without a period1. In the US it usually happens around age 52, though it can range from about 45 to 55 or later3.
Uri Alon, the senior author and a professor of molecular cell biology at the Weizmann Institute, described the pattern to Newsweek as “gradual changes starting about a decade before menopause on average and accelerating in the years before the final menstrual period and then a jump at the final period”3. On timing, he said: “We can’t say for sure how rapid it is but it looks like it’s within the year of the final menstrual period”3.
How the researchers did it
Big health databases are rarely used for menopause research because they usually do not record when a woman had her last period1. Long-term studies that do follow women closely have been relatively small4. The best known, the US-funded SWAN study that began in 1994 and checked in with women every two years, suggested a gradual transition over about three years1.
To get around the missing dates, the team built a computer method inspired by astronomy. Just as astronomers can mathematically sharpen a blurry telescope image, the method removed the “blur” in the data caused by women reaching menopause at different ages1. It is designed to separate a woman’s age in years from where she is in her reproductive timeline2.
Alon said the team “were not expecting this result,” given what SWAN had shown1.
Hormone shifts more than a decade earlier
The study also reports that three sex hormones began changing long before the last period. Anti-Müllerian hormone (a marker of the remaining egg supply) and estradiol (the main form of estrogen) started dropping quickly about 15 and 12 years beforehand. Follicle-stimulating hormone, which drives egg development, began rising faster about 14 years beforehand4.
Mia Schaumberg, a physiologist at the University of the Sunshine Coast in Australia who was not involved, said this “shows that systemic changes experienced during menopause could be predicted by hormone changes much sooner than originally thought”2. She also pointed out that the systems with the biggest changes, such as bone and liver, are very sensitive to estrogen, while systems with no detectable change have a weaker known link to it4.
Alon linked some of the shifts to later health risks. He said bone mineral density drops by about half a standard deviation on average, which can start bone loss or osteoporosis, and that by age 70 a quarter of women have osteoporosis3. He also described a jump in liver damage tests and in heart risk factors such as blood fats and triglycerides3. One change pointed the other way: iron and hemoglobin markers improved and anemia fell, which he attributed to the end of menstrual bleeding3.
Men, and women on hormone therapy
To check whether the jump was just aging, the team ran the same analysis on men of similar ages. “When we apply the same approach to data from men they don’t have a jump,” Alon said. “They show changes of gradual aging over decades. Women also have these gradual changes plus the jump”3. The authors wrote that this suggests “the cliff is a consequence of the menopausal transition rather than general aging”2.
Women taking menopausal hormone therapy, once called hormone replacement therapy, had smaller changes in many measures, especially those related to bone, liver and kidney function4. The researchers cautioned that this finding is observational and needs further study3.
Amnon Brzezinski, a menopause expert at Hadassah-Hebrew University Medical Center who was not part of the team, told The Jerusalem Post the study “gives further support to the importance of menopausal hormonal therapy”1. JoAnn Manson, a professor of medicine at Harvard Medical School, told Newsweek it “confirms the profound physiological changes that women experience at the time of their final menstrual period”3.
What it does not show yet
This is not a trial. The study used past records and self-reported menopause information, and the hormone therapy effects still need to be confirmed4.
Rebecca Thurston, who directs the Center for Women’s Biobehavioral Health Research at the University of Pittsburgh, told Newsweek: “It is a cross sectional analysis, and therefore they cannot rigorously distinguish menopause (e.g., reproductive aging) from chronological aging.” She added: “They have very large amounts of missing data on key variables”3. She said the findings should be treated with caution but show the need for more rigorous research on this transition3.
Martha Hickey, an obstetrics and gynecology professor at the University of Melbourne, objected to the word “cliff,” calling it “potentially alarming for women” and saying it “implies a dramatic physical and mental decline, which this study does not demonstrate”2. Andrew Shelling, a health scientist at the University of Auckland, said the results are interesting but not conclusive2.
The study also measured lab values, not illnesses. A shift in a blood test is a risk signal, not proof that a woman will develop a given disease.
Who is behind it
The study was led by Glen Pridham, a molecular cell biologist in Alon’s lab2. The team also included Yoav Hayut, Noa Lavi-Shoseyov and Michal Neeman of the Weizmann Institute, Noa Hovav of Clalit’s Menopause Community Center, and Yoel Toledano of the Rabin Medical Center in Petah Tikva1. The paper is titled “Population-scale reconstruction of menopause dynamics reveals a physiological cliff at the final menstrual period”4.
The sources reviewed for this article do not say who funded the study, and none reports a company tie or conflict of interest for the authors.
What to watch next
Because most of the sudden changes are linked to higher disease risk, the team said the findings could help women take preventive steps, such as exercise and diet changes, years before menopause1. “Our study extends the window for potential preventive care to almost a decade before menopause,” Alon said1.
Key open questions are whether studies that follow the same women over time confirm such a sharp jump, and whether trials back up the smaller changes seen in women on hormone therapy4. Alon also said the method may help study other big life changes, such as puberty, pregnancy or the start of disease1. Shelling called it “a new framework for future research”2.
