October 28, 2026, 4:29 pm | Read time: 6 minutes
Menopause refers to a multi-year phase during which a woman’s hormonal supply gradually changes. But is there a misunderstanding in this? A new study shows that numerous bodily systems change abruptly at several points—from bone metabolism to various blood values to kidney markers. This knowledge could help identify health risks earlier. Additionally, it once again brings the topic of hormone replacement therapy into focus.
The endpoint of the so-called menopause (climacteric) is marked by menopause—the moment when the follicles in the ovaries are exhausted and the last menstruation has occurred. As FITBOOK explains in this article, the concentrations of important sex hormones change as a result of this process. These changes affect not only reproductive ability but also numerous other health areas.
Abrupt Changes in Menopause?
There have already been long-term studies describing changes in hormone levels and accelerated bone loss around menopause.1 However, most of these studies were relatively small or only captured a limited number of lab values or health parameters.
Another common issue is data collection. Typically, studies consider age but not the specific timing of the last menstruation. The timing of menopause can only be determined retrospectively. It occurs when the last menstrual period was twelve months ago, as explained by gynecologist Dr. Heidi Gößlinghoff.
The current study examines changes in various body systems more closely, taking into account the last menstruation.2 The authors aimed to make abrupt changes visible and determine whether hormone therapy during menopause can mitigate these changes.
Details of the Study
The study was a retrospective, predominantly cross-sectional data analysis, not a randomized clinical trial. The researchers analyzed two large medical datasets: the U.S. NHANES study (1999–2022) and anonymized health data from the Israeli insurer Clalit (2004–2024).3 The entire analysis included more than one million women, over 300 million lab tests, and men were used as a comparison group. Pregnant women were excluded. The researchers also removed measurements that could have been influenced by certain diseases or medications.
Ninety different lab values were examined—including hormones and various blood components, liver and kidney markers, and blood fats—as well as 31 clinical features. The researchers looked at how these changed in women depending on the time since the last menstruation. Were there abrupt changes around this time?
For their analysis, they used a specially developed statistical method, “YoGlen.” This can account for different age distributions at the last menstruation and correct temporal inaccuracies in the evaluation. This allowed the authors to reconstruct average changes in lab values depending on the distance to menopause.
The researchers compared the results between both datasets and then again with the male comparison group. Additionally, they looked at any potential connection between menopausal hormone therapy and changes in lab values. For this, they used statistically comparable control groups and regression analyses.
Last Menstruation Correlates with Numerous Changes
The analysis showed that numerous body functions change significantly around the last menstruation. In 52 of the 90 lab values examined, the changes in women (compared to the male comparison group) were statistically significantly more pronounced.
Changes in sex hormones were particularly noticeable. But other areas of the body were also affected—from bones to the liver and kidneys to fat metabolism. They also affected various blood components. An example of the observed changes is ferritin—a key lab value that provides information about how much iron the body has stored. This ferritin value changed significantly around the last menstruation.
Also interesting: The Impact of Iron Deficiency in Menopause
Many of these changes can be associated with a higher health risk, according to the authors. However, they also emphasize that not all changes were unfavorable. For example, certain values for iron and red blood cells developed in a more favorable direction. This is likely due to the fact that with the end of menstruation, regular blood loss also ceases.
The results of the analyzed datasets largely agreed. In men, no comparable abrupt changes were found around the corresponding age (about 50 years).
Menopause a “Physiological Cliff”
Since numerous lab values jump significantly around the last menstruation within a relatively short period, rather than slowly changing with age, researchers refer to menopause as a kind of “physiological cliff.”
A clear temporal sequence was also observed in hormone changes. The accelerated decline of the Anti-Müllerian Hormone (AMH)—this lab marker provides information about the egg reserve—began on average about 15 years before the last menstruation. The accelerated rise of the follicle-stimulating hormone (FSH) started about 14 years earlier. The estradiol level (E2), an important female sex hormone, began to decline rapidly about twelve years before the last menstruation.
After menopause, the frequency of various health problems increased. These included cases of osteoporosis, heart attack, and stroke. However, the frequency of anemia decreased. Moderate to severe depression scores were relatively common in the first year after the last menstruation, but became less frequent in the following 24 years.
Interestingly, in women who received menopausal hormone therapy, abrupt changes in many lab values were less common. Of the 80 values examined, 39 differed statistically significantly between the groups, particularly in markers for bones, liver, and kidneys. However, the connection was not confirmed for the inflammation marker CRP.
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Significance of the Results
The study suggests that menopause is associated with relatively abrupt changes in numerous body systems. Some hormonal changes begin more than ten years before the last menstruation and then accelerate. For healthcare, the results could mean that it might be sensible to focus more on the time before menopause.
Particularly noteworthy are the observations that the frequency of osteoporosis, heart attack, and stroke increased after menopause. And likewise, that in women who received menopausal hormone therapy, the changes in many lab values were less pronounced. However, one should not infer from this that hormone therapy can prevent diseases. Additionally, the treatment is not suitable for all women.
Limitations
It is important to emphasize that the study is primarily based on retrospectively evaluated cross-sectional data. The statistical method allowed average courses to be reconstructed. However, the observations cannot be equated with those of a long-term study that follows the same sample over several years. It should also be noted that menopause timings are partly based on self-reports or statistical estimates. Additional sensitivity analyses were conducted, yet uncertainties remain.
Finally, the results regarding hormone therapy should be interpreted with caution. Since the treatment was not randomly assigned, women with and without therapy may differ in other characteristics. Therefore, the observations cannot prove that the therapy is responsible for the lesser changes.
The authors themselves acknowledge the need for further research, ideally through prospective randomized studies.