Menopause as a 'cliff': 300 million lab tests show sharp changes at the final period

What it is

The team used two large data sets: the US National Health and Nutrition Examination Survey (NHANES, 1999 to 2022) and records from Clalit, an Israeli health insurer that covers about half the country (2004 to 2024). Together they held more than 300 million lab tests from more than 1 million women.¹

Most big data sets record age, not the date of a woman's final period, and women reach that point at different ages. In NHANES the middle age was 50, and half of women fell between 45 and 53.¹ Averaging by age blurs any sudden change. So the researchers borrowed an idea from astronomy, where a blurry telescope image is sharpened by correcting for the known blur. They used the known spread of menopause ages to rebuild what an average lab result looks like year by year before and after the final period.¹ The method doesn't tell any one woman when her final period happened. It estimates the average path.¹

What it found

• A step at the final period. In NHANES, 52 of 90 lab tests showed a significant jump in women at the final period. Men, analyzed the same way around age 50, changed gradually with no jump.¹ Ferritin, an iron test, is one example: it jumped by 0.6 of a standard deviation.¹
• Across the body. The biggest shifts were in bone tests, liver tests, lipid handling and the blood's salt and water balance.¹ A few tests showed no jump, including free thyroid hormones, folate and fibrinogen.¹
• Mostly in the wrong direction. The authors say most jumps moved toward higher disease risk. Iron, hemoglobin and red blood cell tests were the exception: they improved, probably because monthly bleeding stopped.¹
• The same pattern in two countries. The jump sizes in the US and Israeli data lined up closely, with a correlation of 0.89.¹
• Hormone changes start early. Three sex hormones changed course long before the final period. On average, AMH began dropping faster about 15 years before the final period. FSH began rising faster about 14 years before, and estradiol began falling faster about 12 years before. The FSH and estradiol timings are about 7 years earlier than previous studies had found.¹
• Health conditions followed. In NHANES, the team also tracked health problems such as diabetes, osteoporosis, liver disease and heart disease. Most became more common after menopause. Osteoporosis climbed faster than in men of the same age, and heart attack and stroke also rose faster after menopause.¹

What about hormone therapy?

Women in NHANES who said they were currently using hormone therapy had smaller jumps in most body systems, especially bone, liver and kidney tests. Their results after menopause looked more like a smooth continuation of their results before it.¹ One marker went the other way: hormone therapy users had higher CRP, a sign of inflammation.¹ A separate before-and-after look at Clalit members prescribed hormone therapy broadly agreed with the US findings.¹

This is not proof that hormone therapy protects these systems. Only 9% of the NHANES women were using it, and they may differ from non-users in symptoms, access to care and other ways.¹ The authors adjusted for income, smoking, insurance and other factors, but write that this "cannot entirely eliminate healthy user bias" and that "the effects of MHT need to be tested by prospective randomized trials".¹ (MHT is menopausal hormone therapy.)

Hormone therapy also carries real risks, including blood clots and breast cancer. The Menopause Society says women who have breast cancer, uterine cancer, unexplained uterine bleeding, liver disease, a history of blood clots or cardiovascular disease generally should not use it.²

The limitation

The study relies on cross-sectional data: the timeline is rebuilt by a model from many women at different points, rather than by following the same women through menopause. Menopause status was self-reported, and the results depend on the assumed spread of menopause ages, though the authors' checks found shifting that spread made little difference.¹ The averages also can't tell any one woman what her own results will do. The study was funded mainly by the European Research Council and institutes at the Weizmann Institute of Science, and the authors declare no competing interests.¹

It measured blood tests, not how many calories you burn. Our brief on whether metabolism crashes at 40 covers that question.

One thing to try, one thing to ask

The study lined up lab results by time since the final period, not by age. Once you've gone 12 months without a period, write down the month and year of your last one, and keep copies of your routine lab results together. Our printable tracker has room for period dates. Then ask: "My last period was around [month and year]. Which of my routine results, like cholesterol, liver, kidney or bone tests, are worth watching over the next few years?"

Our weight and metabolism guide covers what else changes in midlife.

Talk to a menopause-trained provider