For decades, women have been told that menopause is a slow, gradual slide into midlife. But groundbreaking research from Rehovot’s Weizmann Institute of Science reveals a dramatically different picture: Menopause isn’t a gentle taper, but an abrupt, body-wide biological overhaul.
Researchers used a novel computational technique inspired by deep-space astronomy to analyze over 300 million lab test results from more than a million women across Israel and the US. The sources were medical records collected over 20 years by Clalit Health Services (Israel’s largest health fund, covering half the population) and the US National Health and Nutrition Examination Survey.
Most women believe that menopause – the end of their fertility – creeps up on them gradually in their late 40s and early 50s, with the average age being 51 to 52. It’s a natural process that occurs when one’s ovaries stop producing reproductive hormones.
Gynecologists define it as the point in time when a woman has gone 12 consecutive months without a menstrual period.
The researchers discovered that the transition triggers sudden shifts across dozens of bodily systems – from liver and kidney function to bone health and cholesterol. The study also showed that the sudden shifts were preceded by escalating changes in the levels of the women’s sex hormone that began more than a decade before menopause – several years earlier than previously thought.
The discovery opens a critical new window for early preventive healthcare.
Prof. Uri Alon and his team identified abrupt changes in dozens of measures of bodily health and function, far beyond the familiar shifts in sex hormone levels and the loss of fertility.
“Menopause reshapes female physiology, yet current understanding has been limited by small longitudinal cohorts that characterize it as a gradual transition,” he asserted.
The changes appeared in 52 of the 90 types of lab tests they studied and included nearly all body systems, including those of liver and kidney function, bone health, and cholesterol levels. Interestingly, no such abrupt changes were observed in men of similar ages, and the changes were less pronounced in women receiving hormone replacement therapy.
The research team included Dr. Glen Pridham and Yoav Hayut from Alon’s lab in Weizmann’s molecular cell biology department; Dr. Noa Lavi-Shoseyov and Prof. Michal Neeman of Weizmann’s immunology and regenerative biology department; Dr. Noa Hovav of Clalit’s Menopause Community Center; and Dr. Yoel Toledano of the Rabin Medical Center in Petah Tikva.
Such large datasets are rarely used in menopause research because they usually lack information about the age at which women had their last period. To overcome this, the researchers developed a computational method inspired by the stars viewed through a telescope. Just as stargazers can sharpen an image by mathematically correcting distortions caused by a telescope, the new method removed the “blur” in medical data caused by differences in the age at which women reach menopause.
The team said that because most of the abrupt changes identified in the study are associated with increased disease risk, the findings could help women take preventive steps, such as exercising and improving their diet, years before menopause.
“Our study extends the window for potential preventive care to almost a decade before menopause,” Alon said. “More broadly, the method we developed may help study other major changes in life, such as puberty, pregnancy, or the onset of disease.”
They published their findings in the prestigious Nature Medicine journal under the title “Population-scale reconstruction of menopause dynamics reveals a physiological cliff at the final menstrual period.”
Asked to comment, Prof. Amnon Brzezinski – a leading expert on menopause at the Women’s Health Center in the obstetrics and gynecology department at Hadassah-University Medical School and former academic faculty chairman of obstetrics & gynecology at the Hebrew University Medical School – sent his congratulations to the Weizmann team.
“The study ratifies (in a very unique technique) that there is a sharp decline in reproductive hormones during the menopause transition and even before. It gives further support to the importance of menopausal hormonal therapy,” he told The Jerusalem Post.
Alon earned his first two degrees from the Hebrew University of Jerusalem and his doctoral degree in theoretical physics from Weizmann, going on to Princeton University for his postdoctoral work in experimental biology. He returned to the Weizmann Institute as a professor and in 2021 was named a visiting professor in the bioengineering department of Stanford University.
Asked what the most important physiological finding that would have been missed if they had treated menopause as a gradual process, Alon said: “We were not expecting this result. The Study of Women’s Health Across the Nation (SWAN) study – an ongoing, long-term study that began in 1994 and was funded by the US National Institutes of Health to address a critical lack of diverse, high-quality data regarding how women experience the menopause transition – which followed women every two years and is the gold standard in the field- suggested a gradual transition over about three years. When we saw the data, the hair on the back of our necks stood up. We never saw a cliff like that.”
As menopause is defined as a year after the final menstrual period, many women start hormone replacement therapy (HRT) only then.
Asked what the most striking changes were and which were clinically meaningful rather than merely statistically significant, the Weizmann expert said: “The changes in the body systems are affected by estrogen. Most important is bone mineral density, which drops by about half a standard deviation on average in the population. There is also a jump in liver tests, including markers of liver damage, and in risk factors for heart disease such as lipids and triglycerides.
“The silver lining is an improvement in iron and hemoglobin and less anaemia, because menstrual bleeding stops. However, the most dangerous of these, over decades, are fractures and heart disease. At age 70, about a quarter of women have osteoporosis. A trivial fall that you brush off at 50 can cause a hip fracture at 70, with about 20% mortality within a year and 50% disability.”
When the team members applied the same approach to men, they found that they don’t have a jump.
“They show the gradual changes of aging over decades. Women also have these gradual changes, plus the jump. On average we see gradual changes starting about a decade before menopause, accelerating in the years before the final menstrual period, and then a jump at the final period, which looks like it’s within that year,” Alon explained.
It was an observational study, “so we need randomized clinical trials to be sure. The biology fits, though. Menopause brings a large drop in important hormones, first and foremost estrogen, which has receptors in virtually every cell in the body – muscle, bone, brain, and liver. The hormone generally has protective effects for the vascular system and reduces inflammation. So a large and sudden drop has effects across the body, generally in the direction of increased risk.”
Clinical trials planned
Asked about the benefits of HRT, Alon said: “Our data on this are observational and based on a small minority of women who take it, so they should be taken with a grain of salt. We are planning a clinical trial of hormone therapy before the final menstrual period to test its effect on bone and brain health.”
He stressed that he hoped the new findings don’t cause stress or fear of menopause. The changes don’t mean an immediate health collapse, just increased risk. They emphasize taking care of exercise, nutrition, and other healthy habits before the final menstrual period, and consulting a physician, especially if you have risk factors for bone, heart, or liver disease.
“For some women, physicians may advise bone density tests earlier than usual. HRT is now given for symptoms; future clinical trials will show whether it can be given before menopause for prevention. Of course, we don’t want to overtreat, so this has to be done on the advice of a physician.”