Women and cholesterol: Study sees link with menopausal changes



When she was 52, Nancy A. Smith routinely ran 3 to 6 miles a day and ate a healthy diet. Her cholesterol levels were firmly in the good range and she had excellent blood-pressure readings in the range of 110/68 mm Hg. 

Seven years later, the Collier resident still runs the same daily distances and follows the same healthy diet. So why has her blood pressure climbed to 160/110, requiring hypertension medication, with her total cholesterol soaring to 250 -- well outside the recommended range and at a level that typically brings a prescription for statin drugs?

The common villain for women in their 40s or 50s is that anxiety-ridden change of life known as menopause. Women -- and the men in their lives -- are well aware of the discomforts and challenges it poses, including hot flashes, mood changes and sleep disruptions.

“I‘‍m an avid runner and have been running for 35 years and had some weight gain around the middle, but my main issue was the hot flashes,” Ms. Smith said. “They were horrible -- so bad that they would make me nauseous.”

But worsening cholesterol and blood pressure posed the major puzzle for her, especially after her doctor told her it was not related to menopause. “The only thing that changed in my life was that I entered menopause,” Ms. Smith said.

As it turns out, menopause may have been an important factor after all with the jump in her cholesterol and blood pressure. 

A study led by Samar El Khoudary, who holds a Ph.D. in epidemiology at the University of Pittsburgh Graduate School of Public Health, details an association between lower levels of the sex hormone estradiol and higher concentrations of small cholesterol-carrying lipoproteins that are known to cause the buildup of plaque in the arteries.

The study found an association between the lower levels of estradiol and higher concentrations of small and medium-small low-density lipoproteins and small high-density lipoproteins. These proteins carry or coat the cholesterol and other lipids so the fatty substances can be transported through the water-based blood. But those specific types of lipoproteins can enter the lining of arteries and remain there and contribute to plaque formation, which narrows and hardens arteries, reduces blood flow and induces inflammation that can lead to a heart attack.

Published online last month in the Journal of Lipid Research, the study results “suggest that sex-hormone oscillation at midlife may increase women‘‍s risk of cardiovascular disease.”

The association between lower sex hormones and unhealthful changes in cholesterol may help explain why women with excellent vital signs can quickly show signs of decline during menopause and eventually develop cardiovascular disease. More than 400,000 women per year die of heart disease in the United States, with women now representing 50.8 percent of all heart-disease deaths, according to the American Heart Association. The study advises women to exercise and eat a healthy diet, as Ms. Smith continues to do, to counteract the effects of worsening cholesterol levels. Previous studies already had documented increases in low-density lipoproteins (LDL), typically described as bad cholesterol, as women proceed through menopause. 

“We know that cardiovascular disease is the leading cause of death in the United States and worldwide, and cardiovascular disease increases as women transition through menopause,” the study said. “The change in sex hormones could be one path to cardiovascular disease.” 

The Pitt research team drew data from the Study of Women‘‍s Health Across the Nation (SWAN) on the cholesterol-carrying lipoproteins of 120 women, each at different stages of menopause. SWAN, underway at seven sites including Pitt, has been collecting data since 1994 on the health of women, with a broad-based focus on physical, biological, psychological and social changes they undergo during their middle years. The study website is www.swanstudy.org.

While the estradiol study did not track each woman through menopause, it focused on point-in-time data to show cholesterol and hormone levels at different stages of menopause.

“We know that the lipid profile is adversely changed in post-menopausal women, with higher cholesterol levels and triglycerides -- higher lipid levels that are bad and lower or unchanged ones that are good,” Ms. El Khoudary said. “What we have done is to link it to the carriers of cholesterol and not the cholesterol itself.

”Carriers (lipoproteins) have specific characteristics. Good cholesterol involves high-density lipoproteins that carry away cholesterol from the arteries to prevent buildup in the arteries. The low-density lipoproteins are the main source of cholesterol and blockage in the arteries. What matters are the characteristics of the lipoproteins, which affect what they carry.“

Such changes in lipoproteins in women during and after menopause have been a hidden factor in health, in part because conventional cholesterol testing does not measure lipoprotein particle concentration or size. For that reason, conventional characterizations of LDL and high-density lipoproteins (HDL) as good vs. bad cholesterol do not tell the full story about a woman’‍s likelihood of developing cardiovascular disease. 

“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, ” Ms. El Khoudary said. “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 to mitigate these risks.”

The National Institutes of Health funded the research. Ms. El Khoudary said her team hopes next to follow a larger group of women through menopause to better understand how declining hormone levels negatively affect or serve as a biomarker of changing lipoprotein characteristics, among other factors that can lead to cardiovascular disease.  

“We want to highlight this because at a future time an independent study is needed to evaluate the change in the level of hormones’‍ association with the change in the quality of cholesterol carriers,“ Ms. El Khoudary said.

”The main message here is that we really care about knowledge and action. We want to say goodbye to the No. 1 cause of death for women,“ she said. ”Eating a healthy diet and including exercise into the routine can give an edge in the fight against heart disease, and being aware of risk and prevention will help women prepare for a long, healthy life.“ 

Nanette Santoro, a professor of obstetrics and gynecology at the University of Colorado School of Medicine, said she reviewed the study and it sheds ”new light on the conundrum of lipid and lipoprotein changes across menopause.”

Ms. Smith, a psychotherapist with a private practice in Bridgeville, also developed the autoimmune disorder Sjogren‘‍s syndrome during her years of menopause. It causes dry mouth and eyes.

Menopause has been such an ordeal that it might seem that a psychotherapist is necessary to help a woman withstand its effects. But as bad as menopause can be, she said, high cholesterol and blood pressure now pose the latest health challenges she must face, especially now that she has gone a full year without significant menopausal symptoms.  

“I don’‍t want to develop heart disease,” Ms. Smith said. “If I can‘‍t manage it myself, what kind of role model am I? I must practice what I preach.” 

For an online publication about menopause from the National Institute on Aging, see http://www.nia.nih.gov/health/publication/menopause-time-change/introduction.


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