Let’s Talk About Cholesterol and Menopause

Midlife women need to calculate their lifetime heart disease risks.

By Selene Yeager

We can’t let American Heart Month pass without a discussion on one of the most vexing cardiovascular factors menopausal women face—the changes that happen to their lipid levels during this transition.

Cardiovascular disease, such as heart disease and stroke, is the number one cause of death for women (and men). Though we’ve made progress in bringing those deaths down with medical intervention like lipid-lowering therapy, there has been a recent rise in cardiovascular mortality for midlife women. So now is really the time to pay attention to our heart health.

Women develop heart disease later than men, largely because our ovarian hormones, especially estrogen (though research on other hormones like FSH and other factors is ongoing), helps to protect us during our reproductive years. When we hit menopause, as estrogen levels decrease, our risk rises, and women often see an increase in blood pressure, glucose, inflammation, weight, as well as dyslipidemia, which usually shows up as increases in total cholesterol, LDL cholesterol (LDL-C), triglycerides, lipoprotein(a) or Lp(a), and a decrease in high density lipoprotein cholesterol (HDL-C).

To understand what’s behind this dyslipidemia, how it might look different for active women, what it means for our cardiovascular disease risk, and what to do about it, we sat down with Samia Mora, MD, MHS, who is a cardiologist at the Brigham and Women’s Hospital, where she is the Director of the Center for Lipid Metabolomics, and Professor of Medicine at Harvard Medical School, for episode 167 of Hit Play Not Pause. Here’s what we covered, along with some recent related research.

What is Cholesterol Anyway?

Cholesterol is a waxy, fat-like substance that our bodies produce, primarily in the liver. Our bodies use it for building cell membranes, producing hormones like estrogen and testosterone and vitamin D, and creating bile acids. Contrary to what many people imagine, cholesterol does not float freely through the bloodstream, but rather is transported on little biological “boats” called lipoproteins, which are made of fat (lipid) on the inside and fat and proteins on the outside.

What’s “Good” and “Bad” About Lipids?

It’s important to recognize that though researchers have been investigating lipids for decades, the science behind them is complex, ever evolving, and there’s still much about lipid metabolism we don’t know. With that in mind, here’s our current understanding.

LDL: When we’re concerned about cholesterol, we’re most concerned about low-density lipoprotein (LDL), which is often referred to as “bad” cholesterol. LDL is the boat that carries cholesterol from the liver to cells throughout the body. Problems arise when there are too many boats carrying an excess of LDL cholesterol in your bloodstream. That’s when LDL starts damaging the endothelium (lining of your blood vessels), especially if you have other risk factors that also damage the endothelium (such as hypertension and/or diabetes), and kick start an immune and inflammatory response as well as penetrate the arterial wall. Once inside the arterial wall, LDL cholesterol becomes oxidized and continues to promote an immune and inflammatory response, triggering a process that forms fatty streaks and eventually plaques, which can narrow the arteries and also can rupture or ulcerate, which leads to heart attacks, strokes, and other cardiovascular events. There are also very low density lipoprotein (VLDL) particles, which are similar to LDL cholesterol, but mainly carry triglycerides (another type of fat, more on those in a bit).

“We have extensive data back from the 70s that LDL cholesterol is a causative factor for cardiovascular disease and stroke,” Mora says.

HDL: High-density lipoprotein (HDL) cholesterol is generally known as the “good” cholesterol because one of its key functions is to transport excess cholesterol back to the liver for processing and elimination. This is a process known as reverse cholesterol transport and it helps prevent the buildup of cholesterol in the arteries, reducing the risk of atherosclerosis and cardiovascular disease. HDL also has anti-inflammatory properties, but is not always “protective” especially if you have other risk factors.

“Cholesterol is more complex than ‘bad’ and ‘good’, but we do know that having a higher HDL cholesterol generally tracks with lower risk of heart disease events over time,” Mora says. 

Triglycerides: Though not cholesterol, triglycerides are another form of lipid (fat) that you get from your diet, which gets stored in your fat tissue and circulates in your blood to be used for energy. Your body also makes triglycerides. When you consume more food than your body needs, the excess gets converted into triglycerides, which are stored in fat cells like surplus food in your pantry. When you need energy between meals or for your workouts, your body releases triglycerides from fat cells to be broken down into fatty acids to be used as energy. Elevated triglycerides can contribute to the development of atherosclerosis and increase the risk of heart disease and stroke.

ApoB: ApoB is a protein found on certain lipoproteins (the “boats” that also carry cholesterol and triglycerides), and it’s getting a lot of attention for being perhaps a better indicator of your cardiovascular disease risk than LDL alone. The reason why is because LDL isn’t a precise measurement. When you get a blood panel, LDL is often calculated based on your other lipid measurements. (There are tests that measure it directly, but they also have limitations.) That’s where apoB comes in. Every LDL particle carries exactly one molecule of apoB.

“Each one of the bad particles carries one and only one apoB,” says Mora. “So apoB is the number of these particles, and that’s why it seems to be a better measure of risk than just cholesterol itself.”

Lp(a): Finally, there is lipoprotein(a) or Lp(a), which is a specific type of lipoprotein that is similar to LDL in structure, but has an additional protein called apolipoprotein(a) attached to it. Lp(a) is also associated with an increased risk in cardiovascular disease regardless of the LDL level. Levels of Lp(a) are almost entirely genetically determined and relatively stable over a lifetime, but do increase modestly around menopause. This isn’t part of the standard blood panel; your doctor will generally measure it if you have a personal history or first degree relative with premature cardiovascular disease or if you have very high LDL.

“It’s generally sufficient to have that checked just once to know if you have a genetic predisposition to having high Lp(a),” Mora says.

What the Heck Happens to Our Lipids During Menopause?

If you’ve been cruising through life with normal, healthy lipid levels only to see them increase or even skyrocket when you hit menopause, you’re not alone. Members in our community report dramatic increases in LDL around the time of the menopause transition. That’s because estrogen plays a crucial role in lipid metabolism and maintaining lipid levels. When it declines during menopause and as we age, we can experience dyslipidemia and an increased risk for cardiovascular disease.

“In general, LDL cholesterol goes up, HDL cholesterol, which is inversely related to cardiovascular disease risk, goes down, and triglycerides also go up,” Mora says.

Regular exercise can raise HDL, lower LDL and triglycerides, and generally improve your lipid profile, and also reduces inflammation, so as an active woman, you may have better lipid profiles than your sedentary peers, even post menopause. That said, exercise alone will not necessarily protect you from broadly negative changes, elevated LDL, and increased risk for cardiovascular disease.

How Does Diet Influence Lipids?

What you eat impacts your cholesterol levels. To be clear, dietary cholesterol in and of itself is not correlated with blood cholesterol. The issue is that foods high in dietary cholesterol like processed meats also tend to be high in saturated fats that can lead to high LDL cholesterol levels. So, it’s still wise to keep your saturated fat in check. For reference, the American Heart Association recommends keeping saturated fat to about 5 to 6% of your daily calories. So, if you eat 2,000 calories a day, that’s about 120 calories or 13 grams of saturated fat per day.

Ultraprocessed foods and high levels of simple carbs also elevate lipids like triglycerides. Trans fats, which still exist in small amounts in packaged baked goods and fried foods, have no redeeming value, and raise LDL cholesterol, and carry very high risk for cardiovascular disease; so they should be completely cut out of the diet.

The best diet for lipids is one that is rich in monounsaturated fats like olive oil, fish, and avocado, as well as high in fiber (menopausal women should aim for 25 to 30 grams of fiber per day). That’s why the Mediterranean style diet has gotten so much attention—it’s rich in unsaturated fats, high in fiber-rich whole grains and fruits and vegetables and is associated with a 39% lower coronary mortality risk and a 29% lower cardiovascular mortality risk, which is about the same benefit as statins, and is additive to the benefit of statins, Mora says. While Mediterranean style diets do not generally lower total or LDL cholesterol, they have many benefits including a healthier endothelium lining, reducing inflammation, improving insulin resistance, and improving HDL function. 

Can We Cut Through the Confusion on Hormone Therapy?

It might be a while. Hormone therapy isn’t used as a lipid lowering therapy. But there’s long been interest in how it impacts cardiovascular health, and some research suggests favorable effects for younger menopausal women. The bottom line at this time (and honestly, for the foreseeable future) is that the risks/benefits of menopausal hormone therapy for cardiovascular health is individual and largely depends on how healthy your arteries are when you start. (To cut to the chase, If you already have or are at high risk of cardiovascular disease, hormone therapy is not recommended.)

For reference, hormone therapy, primarily in the form of estrogen therapy, was introduced in the 1940s to alleviate vasomotor symptoms and vaginal dryness. At the time, doctors believed that estrogen therapy could also benefit cardiovascular health, based on observational studies suggesting lower rates of heart disease among women who had undergone surgical menopause and were receiving estrogen therapy.

Hormone therapy (which by the 80s included progestin to protect the uterus) rose in popularity over the following decades. In the 90s, the NIH launched the Women’s Health Initiative hormone trials to clearly define the effects of estrogen as a primary prevention measure of coronary heart disease. In 2002, the estrogen plus progestin arm of the WHI trial was halted prematurely due to an increased risk of cardiovascular events, including heart attacks, strokes, and blood clots, among women receiving HT compared to those receiving a placebo

Those findings led to subsequent analysis and a better understanding of how hormone therapy impacts cardiovascular health. In short, when given to women who are well past menopause (as many women in the WHI study were), you can see an increased risk, because estrogen can have an adverse effect on established arterial plaques. That’s why the current hormone recommendations state that it’s best initiated within 10 years of menopause or before age 60, and you are free from other risk factors.

As everyone who spends any time on menopause social media knows, there’s been a resurgence of interest in using hormone therapy to protect cardiovascular health and prevent heart disease. And it’s causing a lot of confusion.

Even reading recent reports from the American Heart Association can give you whiplash. A 2020 release reports, “Taking an estrogen pill early in menopause could slow the progress of fatty buildups in the neck arteries.” Another in 2023 reports, “Women who take estrogen hormone pills to relieve menopausal symptoms may be more likely to develop high blood pressure than women using other forms of the medication.”

And then you have the latest results of the Kronos Early Estrogen Prevention Study (KEEPS) published in Menopause that reports that hormone Therapy (oral or transdermal) use around the menopause transition shows no cardiovascular and/or metabolic benefits or adverse effects. That study was a randomized, double-blind placebo-controlled trial of HT designed to test the hypothesis that HT given to recently postmenopausal women (within 3 years of menopause) in good cardiovascular health would slow the progression of atherosclerosis. During the 4 years of HT with either oral conjugated equine estrogens (oCEE) or transdermal 17β-estradiol (tE2), the effect of HT on the progression of atherosclerosis (measured by coronary artery calcification and carotid intimal medial thickness) was neutral in comparison to placebo. It’s worth noting that during the 4 years of the KEEPS trial, HDL-C and LDL-C cholesterol levels improved with oCEE and insulin resistance decreased with tE2. The researchers concluded that the data suggest that the effects of HT on HDL-C, LDL-C cholesterol levels, and insulin resistance were limited to the time when HT was in use. The study also didn’t examine effects on heart attack and stroke.

We also tend to speak about hormone therapy as though it’s one thing, when in reality it’s many different doses, forms, and formulations that all can have varying effects on different women. In short, it’s complicated. Right now, hormone therapy is not recommended for the primary or secondary prevention of cardiovascular disease, which is not to say that it can’t be beneficial for some women. “For women in early menopause, it's really an individualized risk assessment,” Mora says. “It should be avoided in women with or at high risk for cardiovascular disease or breast cancer.”

An in-depth 2023 review published in Circulation, echoes that recommendation with investigators suggesting that providers take a risk-stratified approach to HT, with women with healthy arteries being low risk and those with existing coronary/peripheral artery disease and other cardiovascular conditions being high risk. You can also check out the 2022 Hormone Therapy Position Statement from The Menopause Society, which devotes an entire section to cardiovascular health.

Source: https://medlineplus.gov/cholesterollevelswhatyouneedtoknow.html

Triglycerides, which are not on this chart, should be below 150 mg/dL. Lp(a) should be less than 50 mg/dL or less than 125 nmol/L, and ApoB should be less than 100 mg/dL.

You can calculate your atherosclerotic cardiovascular disease (ASCVD) risk using an online calculator like this one from the American College of Cardiology, which provides a 10-year risk of heart disease for adults ages 40 to 79 and a lifetime risk for those ages 40 to 59.

The problem is that these calculators don’t work as well for women (shocking, we know). “Standard risk calculators may underestimate risk because women have their cardiovascular events 10 or 15 years down the road compared to a man of the same profile,” Mora says. “Most women in this audience [that’s you] will end up being low risk, less than 5%, but we need to consider other risk factors for a full picture.”

“You want to consider your lifetime risk,” Mora says. “Rather than look short term, the next 10 years, you need to look long term, because women live longer than men, and you don’t want a stroke when you’re 75.” 

This is where working with your doctor is key. Women have specific risk factors such as gestational diabetes, preeclampsia, other pregnancy-related risk factors, and premature (<40 years of age), early, or medical menopause that are important to consider. 

What Women Should Know About Statins

Recent research shows women are less likely to be offered statin therapy and are 20% more likely to refuse it than men. “Statins can reduce your risk for heart attack or stroke by about 20 to 30%” Mora says. “Among the highest risk people, it also reduces deaths from cardiovascular disease.”

Recent research shows statin use can also reduce the risk of blood clots in women taking hormone therapy.

The main concern with women in our audience is statin-related muscle pain. The good news is there are options if you experience muscle-related side effects. According to the Cleveland Clinic, lipophilic statins (meaning they passively diffuse into the muscle) like atorvastatin (Lipitor®), simvastatin (Zocor®) and fluvastatin (Lescol®), may be more likely to cause muscle aches. Hydrophilic statins like rosuvastatin (Crestor®) and pravastatin (Pravachol®) may cause fewer muscle aches. However, each woman is different and no one statin works for all women.

You can also lower the dose, Mora says. “You can cut down [the statin dose] to very low levels and even take it just a few times a week.” For women at risk for heart disease, having some statin on board is beneficial to having no statin on board. For women who cannot tolerate a statin or whose lipids remain elevated even on a statin, there are now also newer medications that lower LDL cholesterol and cardiovascular risk that you can discuss with your doctor.