Sex Hormone Levels at Midlife Linked to Bad Cholesterol Carriers that Increase Heart Disease Risk in Women

As hormone levels change during the transition to menopause, the quality of a woman’s cholesterol carriers degrades, leaving her at greater risk for heart disease, researchers at the University of Pittsburgh Graduate School of Public Health discovered.
The first-of-its-kind evaluation, supported by the National Institutes of Health (NIH), was done using an advanced method to characterize cholesterol carriers in the blood and is published in the July issue of the Journal of Lipid Research.
The results call for further research to evaluate the menopause-related dynamic changes in sex hormones on the quality of cholesterol carriers over time, as well as increased emphasis on the importance of healthy diet and exercise for women undergoing menopause.
“Higher levels of HDL, or what we know as ‘good cholesterol,’ may not always be protective, as we have thought before,” said lead investigator Samar R. El Khoudary, Ph.D., M.P.H., assistant professor in Pitt Public Health’s Department of Epidemiology. 

Dr. El Khoudary explains that normal levels of LDL, or “bad cholesterol,” do not imply normal cholesterol levels in all individuals. Rather, quality of cholesterol carriers may provide more accurate information about risk related to levels of cholesterol.
“We found that lower levels of estradiol, one of the main hormonal changes that mark menopause, are associated with low-quality cholesterol carriers, which have been found to predict risk for heart disease,” she said. “Our results suggest that there may be value in using advanced testing methods to evaluate changes in cholesterol carriers’ quality in women early in menopause so that doctors can recommend appropriate diet and lifestyle changes.”

Estrogen levels drop during menopause

Estrogen helps arteries be more flexible and strengthens their interior walls. Menopause leads to a decline in estrogen; this may be a reason in an increase of heart disease in post-menopausal women.

Note: The American Heart Association does not recommend using postmenopausal hormone therapies. Studies have shown that these treatments do not reduce the risk of heart disease.

According to Dr. Goldberg, scientists and doctors say a decrease of estrogen isn’t the only reason for an increase in heart disease, and that researchers are actively searching for more comprehensive answers.

Blood pressure, bad cholesterol increase during menopause
In addition to a drop in estrogen, a woman’s body goes through other changes when in menopause. For starters, blood pressure levels start to go up. In addition, bad cholesterol, or LDL cholesterol, levels may increase and good cholesterol, or HDL, may decline or stay the same.

Triglycerides, or groups of fatty cells contained within blood vessels, also go up during and after menopause.

How to fight postmenopausal heart disease
There are several ways to stay healthy during and after menopause. The American Heart Association recommends eating healthy, whole foods (4.5 cups of fruits and veggies and 6 to 8 servings in whole grains per day) and exercising at least 150 minutes per week to stay heart healthy.


Sex Hormone Levels at Midlife Linked to Bad Cholesterol Carriers that Increase Heart Disease Risk in Women Cholesterol travels through the bloodstream in small particles called lipoproteins, or cholesterol carriers. Conventional blood tests show the amount of cholesterol carried by these lipoproteins, rather than the characteristics of the lipoproteins themselves. There are two major types of lipoproteins: high-density lipoprotein (HDL), which helps keep cholesterol from building up in the arteries, and low density lipoprotein (LDL), the main source of cholesterol buildup and blockage in the arteries. Research studies have shown that the characteristics of LDL and HDL particles, including the number and size of these particles, significantly predict risk of heart disease.
Previous studies evaluating the associations between sex hormones and cardiovascular disease as women went through menopause looked only at cholesterol measured through conventional blood tests. Dr. El Khoudary and her colleagues used nuclear magnetic resonance spectroscopy to measure the size, distribution and concentration of lipoproteins that carry cholesterol in the blood.
The Pitt Public Health team found that as estrogen levels fall, women have higher concentrations of low-quality, smaller, denser LDL and HDL particles, which are associated with greater risk of heart disease. The conventional blood tests often don’t pick up on such a nuance in particle size.

Many women think that heart disease is a man’s disease. It isn’t. Heart disease is the number one killer of women. In fact, after age 50, nearly half of all deaths in women are due to some form of cardiovascular disease.

Once a woman reaches the age of 50, about the age of natural menopause, her risk for heart disease increases dramatically. In young women who have undergone early or surgical menopause, who do not take estrogen, their risk for heart disease is also higher. Women who have gone through menopause and also have other heart disease risk factors, such as the following, are at even greater risk:

  Diabetes
  Smoking
  High blood pressure
  High LDL (low density lipoproteins) or “bad” cholesterol
  Low HDL (high density lipoproteins) or “good” cholesterol
  Obesity
  Inactive lifestyle
  Family history of heart disease

How Is Heart Disease Linked to Menopause?

Heart disease becomes more of a risk for women after menopause.
How Can Menopausal Women Reduce Their Risk of Heart Disease?

A healthy lifestyle goes a long way in preventing heart disease in women. Incorporating the following tips into your everyday life may help you reduce your risk of heart disease during and after menopause:

  Avoid or quit smoking. Smokers have twice (or higher) the risk of heart attack than nonsmokers. In addition to eliminating cigarettes, stay away from secondhand smoke, as it also increases the risk of heart disease.
  Maintain a healthy body weight. The more you are over your ideal weight, the harder your heart has to work to give your body nutrients. Research has shown that being overweight contributes to the onset of heart disease.
  Exercise throughout the week. The heart is like any other muscle - it needs to be worked to keep it strong and healthy. Being active or exercising regularly (ideally, at least 150 minutes total each week) helps improve how well the heart pumps blood through your body. Activity and exercise also help reduce many other risk factors. It helps lower high blood pressure and cholesterol, reduces stress, helps keep weight off, and improves blood sugar levels.  Check with your doctor if you have been inactive before increasing your activity level.
  Eat well. Follow a diet low in saturated fat; low in trans fat (partially hydrogenated fats); and high in fiber, whole grains, legumes (such as beans and peas), fruits, vegetables, fish, folate-rich foods, and soy.
  Treat and control medical conditions. Diabetes, High cholesterol, and high blood pressure are known risk factors for heart disease.


The study evaluated 120 women from Pittsburgh who were enrolled in the Study of Women’s Health Across the Nation (SWAN). The women were an average of 50 ½ years old and not on hormone replacement therapy.
Sex Hormone Levels at Midlife Linked to Bad Cholesterol Carriers that Increase Heart Disease Risk in Women SWAN is an ongoing study of the biological, physical, psychological and social changes in more than 3,000 middle aged women who were recruited at seven sites across the U.S. The goal is to help scientists, health care providers and women learn how mid-life experiences affect health and quality of life during aging.
“As a woman transitions to menopause, many biological changes take place that can put her at greater risk of many conditions, including osteoporosis and heart disease,” said Dr. El Khoudary. “Our most recent study underscores the importance of having clinicians aware of these risk factors and prepared to work with their patient to help her best mitigate these risks.”
Dr. El Khoudary is collaborating with other scientists to identify funding to study a larger sample of women over time to definitively tie changes in hormone levels and the quality of cholesterol carriers with heart disease.
Additional authors on this study are Maria M. Brooks, Ph.D., Rebecca C. Thurston, Ph.D., and Karen A. Matthews, Ph.D., all of Pitt.
This research is supported by NIH grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, HL065581 and HL065591.

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