This hormone may be the missing ingredient for

Samar El Khoudary, Ph.D., MPH

image: Samar El Khoudary, Ph.D., MPH, professor of epidemiology, University of Pittsburgh School of Public Health
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Credit: University of Pittsburgh

Stay away from estrogen. Scientists at University of Pittsburgh discovered a predictor of blood lipid – or cholesterol – status for middle-aged women that may be key to understanding how hormone replacement therapy contributes to heart health.

In a study published today in the Journal of Clinical Lipidology, Samar R. El Khoudary, Ph.D., MPH, identified a link between a lesser-known hormone called anti-Mullerian hormone (AMH) and lower lipid or cholesterol levels in middle-aged women. With this information and what is known about estrogen, clinicians can get a better picture of cardiovascular risk for people entering menopause.

“Estrogen isn’t the only story,” said Dr. El Khoudary, professor of epidemiology in Pitt School of Public Health. “We are now getting more information about other markers that could play an important role in telling women more accurately and consistently where they are in relation to their transition to menopause.”

Throughout the period before, during and after menopause, also known as the menopausal transition, middle-aged women are at increased risk of cardiovascular disease with changes in their lipid levels, such as high increase in LDL-C or “bad” cholesterol.

Scientists have previously determined that this increased risk of cardiovascular disease may be partly due to decreased estrogen levels. However, estrogen replacement therapy did not have cardioprotective effects doctors hoped. So, scientists have been looking for other factors that might affect cholesterol levels.

AMH is a hormone that is most studied as an important factor in determining the sex of a fetus in utero. Recently, however, AMH has been shown to have a strong and reliable link with the timing of the menopausal transition and new technologies are making it increasingly easy and cost effective to monitor.

“AMH can be used to measure how long your ovaries can continue to produce eggs,” Dr. El Khoudary said. “The more eggs, the higher the AMH; the fewer the eggs, the lower the AMH level. When the levels get very low, we can use this to predict menopause.

With such a strong link between AMH and menopause, Dr. El Khourdary wondered if, like estrogen, the loss of AMH could have an impact on cholesterol.

“We wanted to understand the mechanism behind lipid changes during the menopausal transition and understand how this new biomarker, AMH, interacts with estrogen and impacts lipids,” explained Dr. El Khoudary.

Dr El Khoudary’s team analyzed blood samples from Nationwide Women’s Health Study (SWAN), which followed a diverse group of 1,440 middle-aged women through the transition to menopause. These blood samples were tested for estrogen and AMH levels as well as good and bad cholesterol.

Through this study, Dr. El Khoudary found that while high estrogen is important for lowering LDL-C or bad cholesterol, high AMH was responsible for lowering HDL. -C or “good” cholesterol. This means that as women go through the menopausal transition, they lose estrogen and AMH, increasing both their bad and good cholesterol levels.

This may seem contradictory but, for Dr El Khoudary, it supports his suspicions that good cholesterol is not always good for menopausal women. Previous studies by Dr. El Khoudary’s group have determined that good cholesterol levels in these women may mask other cardiovascular problems and may even be a sign of HDL dysfunction, preventing the good cholesterol from performing its cardioprotective functions.

In the future, Dr. El Khoudary hopes to examine blood samples from middle-aged women who are currently on hormone replacement therapy to determine the effects of estrogen on AMH and lipid levels and to conclude whether these treatments actually help or harm postmenopausal women. She hopes her studies will better inform patients and doctors when making decisions about their cardiovascular health.

The other authors of this research are Xirun Chen, MPH, Meiyuzhen Qi, MPH, Maria M. Brooks, Ph.D., Rebecca C. Thurston, Ph.D., and Karen A. Matthews, Ph.D., all of Pitt; Carol A. Derby, Ph.D., of the Albert Einstein College of Medicine; Imke Janssen, Ph.D., of Rush University; Sybil Crawford, Ph.D., of the University of Massachusetts; Jennifer S. Lee, MD, of Stanford University and Palo Alto Veterans Health Care System; Elizabeth A. Jackson, MD, of the University of Alabama; Claudia U. Chae, MD, of Massachusetts General Hospital; and Daniel McConnell, Ph.D., of the University of Michigan.


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