In 1990, NASA discovered that the mirror of the Hubble Space Telescope had a very small polishing defect that caused blurred images. While waiting for a repair, astronomers turned to mathematics. Because they knew exactly how that faulty mirror was distorting light, they could undo the blurring with a technique known as “deconvolution.”
Three decades later, a team at Israel’s Weizmann Institute of Science has used that tool to bring into focus something much closer to home: what happens to a woman’s body when she reaches menopause. The resulting image, published on Monday in Nature Medicine, does not show the gentle slope described in textbooks. It shows a cliff.
“A telescope blurs each point of light in a way that astronomers understand precisely, and they can correct for it to obtain a sharper image,” explains Ari Alon, a systems biologist at Weizmann and the paper’s lead author. “For us, the blurred image represented the value of a test result — for example, cholesterol levels — as a function of age. When we corrected for that effect, we saw a cliff.”
The problem they set out to solve is easy to state and devilishly difficult to tackle. Almost no medical record includes the date of a woman’s last period, so analyses of thousands of women are arranged by age. But some reach menopause at 45 and others at 53.
It is like a crowd in which each person steps down a stair at a different moment: viewed from a distance, it appears as though everyone is descending a gentle ramp. “It seemed gradual, but it was almost an optical effect,” says Silvia P. González, president of the Spanish Association for the Study of Menopause (AEEM), who was not involved in the research. “When you mix them together by age, the change becomes blurred.”
To bring the image into focus, it is not necessary to know when each woman went through menopause. It is enough to know how menopause is distributed across the population: how many women experience it at 45, how many at 50, how many at 55. That is a well-known figure.
Using that information, the algorithm works backwards and looks for what kind of step change, distributed in that way across all women, would produce exactly the blurred ramp that is observed. It is the same thing astronomers did with the Hubble telescope: because they knew the mirror’s defect, they could calculate the sharp image hidden behind it.
The method does not infer the menopause date of any individual woman. What it reconstructs is the average trajectory of the population, as if all women could have been aligned according to the day of their last menstrual period.
The researchers named their method YoGlen, after the first names of its two lead authors, Yoav Hayut and Glen Pridham, and applied it to two complementary databases.
The first was the U.S. health survey NHANES. It includes around 36,000 women assessed between 1999 and 2022. That is a relatively small sample by comparison, but all of the women underwent the same tests in a systematic way, and all reported the age at which they had their last menstrual period.
The second was the medical records of the Israeli insurer Clalit, which covers half of the country’s population: 1.3 million women aged between 30 and 70 followed from 2004 to 2024. It is a much larger dataset, but also a messier one, because each test was ordered for a different medical reason and the date of menopause is not recorded anywhere.
Together, the two datasets contain more than 300 million laboratory tests. The aim was not to pit them against each other, but to see whether two countries and two very different ways of collecting data would lead to the same result.
The results were unequivocal. In the U.S. cohort, 52 of the 90 parameters analyzed showed an abrupt shift right around the time of the last menstrual period. As expected, sex hormone levels declined, but so did bone density, liver enzyme levels, kidney function, cholesterol, red blood cell counts and blood osmolality, a measure of the concentration of salts in the blood.
There were also unexpected findings: blood lead levels increased as well, probably because bone, as it loses mass, releases lead that had been stored there for decades. The shifts measured in Israel and the United States matched almost point for point. The correlation between the two datasets was 0.89, with 1 representing a perfect match.
To rule out the possibility that the findings were merely an artifact of the algorithm itself, the authors applied exactly the same calculation to men, as if they too experienced a “menopause” at the same age. In that case, no abrupt step appeared, only gradual aging.
“We wanted to be sure we weren’t fooling ourselves,” Alon says. That is why the team also tested the method on simulated data and using different average ages of menopause. Hayut and Pridham, moreover, each wrote their own version of the algorithm independently and arrived at the same result.
“This confirms what we have been saying for years,” González says. “Menopause is not just stopping periods, nor is it just hot flashes. Estrogens act in almost every tissue of the body and their decline affects bone, metabolism, the heart.”
Almost all of the shifts point in the direction of a higher risk of disease. The exceptions are iron levels and red blood cell counts, which improve once menstrual bleeding stops and, with it, anemia declines. The clinical consequences follow the same pattern. After the last menstrual period, osteoporosis accelerates, with a much steeper trajectory than that seen in men of the same age. Rates of heart attacks and strokes also increase.
Depression and sleep problems show a temporary surge: in the year following menopause, 19% of the women in the U.S. sample experienced moderate or severe depression, compared with 11% in the years thereafter.
A signal 15 years earlier
The finding that most interests the Spanish gynecologist is a different one. Three key hormones begin to shift long before the last menstrual period. Anti-Müllerian hormone, an indicator of ovarian reserve, begins to decline more rapidly about 15 years earlier. Follicle-stimulating hormone (FSH) starts rising more quickly around 14 years earlier, and estradiol begins to fall roughly 12 years before menopause. That is about seven years earlier than had been described in major longitudinal studies such as the U.S. SWAN study. “It moves the window for prevention forward to the 40s,” González says.
Alon, however, cautions that these measurements cannot yet be used as an individual clock. “FSH and estradiol are not good enough to detect the exact moment of menopause because of the large fluctuations of perimenopause. It’s still an unresolved problem,” he admits. His practical advice — which he stresses is a personal opinion rather than a finding of the study — is for women to get a bone density scan when they are in their late thirties or early forties in order to establish a baseline. From then on, he recommends monitoring cycles and symptoms. “Almost anything that changes after 40 can be a symptom of menopause.”
Both agree on the most important caveat. “That cliff is a population measure, not what happens to each woman on the last day of her period,” González stresses. “Each woman’s menopause is like a fingerprint — personal and nontransferable. But it does tell us that the transition is sharper and more systemic than we thought and that, as physicians, we need to start preventive measures earlier.”
The effect of hormone therapy
The study also compared women who were taking hormone therapy with those who were not. Among the former, the shifts were much smaller, especially in the bone, liver and kidneys: 39 of the 80 parameters differed between the two groups. The same pattern was observed in the Israeli medical records of more than 9,000 women who had been prescribed the treatment.
“It is consistent with what we know, but the study is observational, and observational studies always make us cautious,” González warns. The authors themselves acknowledge that women who receive hormone therapy may be healthier or have better access to medical care than the rest. “Nothing can replace a randomized clinical trial,” Alon admits. His laboratory is in fact preparing one, involving hormone therapy before the last menstrual period, to measure its effects on bone and brain health.
There is, however, one striking exception. Women using hormone therapy had higher levels of C-reactive protein, a marker of inflammation. “There is a known explanation for that,” says González. “The women in the study were taking estrogen mainly in oral form, which passes through the liver first and stimulates production of that protein. With the transdermal route, using gels or patches, this does not happen. It is not that the therapy causes inflammation; it is that the route of administration matters. And that is precisely what we take into account when tailoring treatment to each patient.” That transdermal therapy is, in fact, the very treatment currently in short supply in Spain.
Alon and his team are now turning their telescope toward the other end of reproductive life. “We are working on puberty,” he says. “I am fascinated by the differences between boys and girls: they seem to have very few differences until the hormonal upheaval of puberty, and then they become very different.”
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