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One in eight adults have taken a glucagon-like peptide 1 (GLP-1) agonist to lose weight or to treat a comorbidity like type 2 diabetes or cardiovascular disease. And by some accounts, more women than men are taking advantage of these medications, which are shown to help patients lose 10%-15% of their body weight.

For women struggling with the scale, the medications can be particularly impactful, especially during periods of life like pre- and postmenopause, which may be marked by precipitous weight gain and health issues like anxiety, depression, cancer, and cardiovascular events that may accompany obesity.

Although physicians prescribing these medications need to be cautious about the muscle and bone density loss that can happen as a result of rapid weight loss, when they’re taken alongside positive health changes like diet and exercise, they can be life-changing to women who have struggled long with their weight.

Weight Gain During the Transition to Menopause

It’s important to fully understand the issues that women face regarding weight gain in middle age before prescribing these medications, said Maria Daniela Hurtado Andrade, MD, PhD, an endocrinologist whose research is focused on the brain’s regulation of food intake at the Mayo Clinic, Jacksonville, Florida.

No research has been done specifically to show the impact that GLP-1s have on menopausal women and weight loss, but there are some things that we know may have an impact on treatment. Women have been shown to gain about 1.5 pounds per year from ages 40 to 65 years, which amounts to over 20 pounds of weight gain in middle age, according to the Mayo Clinic.

It’s also true that while women may attribute their weight gain to the transition from perimenopause through postmenopause, research has shown that it’s aging, not menopause, that causes weight gain in women — shown in the fact that men also experience around the same amount of weight gain during middle age.

“When women are in midlife, certain physiological processes happen simultaneously, including a decrease in lean muscle mass, which causes a reduction in metabolism,” said Hurtado Andrade. In addition, changes in diet and physical activity, especially in those with a more sedentary lifestyle, can also promote weight gain for women as they age.

However, the steep reduction in sexual hormones like estrogen during menopause does influence fat distribution in the body.

“The weight gain that occurs in women at midlife changes the body composition and deposits fat around the central part of the body, which is more noticeable in women,” said Hurtado Andrade.

GLP-1 medications are very effective for the treatment of overweight and obese women who have trouble losing weight during this period of life, especially those who experience cardiometabolic complications that can go along with the accumulation of visceral fat around the abdomen.

This type of fat is often referred to by physicians as “toxic” because it increases the risk for a host of conditions, including heart disease, type 2 diabetes, certain cancers, stroke, and dementia, by creating a constant state of inflammation in the body.

Impact of GLP-1s on Obesity-Related Conditions in Women

The transition of menopause is marked by fluctuating levels of estrogen and progesterone, which can increase a woman’s risk for anxiety and depression. Obesity and the neuroinflammation that it can cause are another risk factor for mental health illness. Simply losing weight will have an impact on reducing it, said Courtney Younglove, MD, an obstetrician-gynecologist and obesity medicine physician at Heartland Weight Loss in Lawrence and Overland Park, Kansas.

“We don’t know whether it’s the GLP-1 effect or the weight loss that’s having the impact on mental health,” said Younglove.

Lifestyle changes like eating whole foods and physical fitness on their own or those that go along with GLP-1 medications also reduce chronic inflammation, which can affect mental health as well, she added. You wouldn’t use a GLP-1 on a patient to treat a mental health condition, but in patients where weight or another comorbidity is an issue, this is another positive health outcome.

What’s more, one big risk factor for breast cancer, breast cancer recurrence, uterine, and ovarian cancer is fat accumulation because adipose tissue converts other hormones in the body to estrogen, which is a risk factor for certain types of cancer. Reducing excess fat in the body, whether it’s through GLP-1s or other lifestyle changes, reduces the risks for these cancers, said Younglove.

Cardiovascular events are also more likely to occur around menopause because of decreased estrogen levels, leading to changes in blood vessels, cholesterol levels, and blood pressure. Reduced estrogen stiffens the arteries, which can increase the risk for heart attack or stroke with age, said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. Al-Aly’s recent study in Nature showed that many of these cardiovascular symptoms could be reduced with GLP-1 medications. 

Importance of Lifestyle Changes for Women on GLP-1s

While these medications can help with visceral fat loss, which is especially important for staving off the cardiometabolic changes that can occur in menopause, it’s important to note that women also need to take into account lifestyle changes.

Patients taking these medications should be monitored frequently because a large amount of weight loss can also cause muscle as well as bone loss. It’s particularly important that women are instructed by their primary care physicians to include ample lean protein and fiber in their diet as well as resistance training, said Supriya Rao, gastroenterologist, director of Medical Weight Loss, Lowell General Hospital, Lowell, Massachusetts, and clinical assistant professor at Tufts University School of Medicine in Boston. If there’s a high percentage of muscle loss, physicians should consider maintaining or reducing the medication dosage.

Sarcopenia, or the dramatic loss of muscle mass and strength with age, has also been tied to early death because of the risk of falls, frailty, and the resulting decreased mobility. Muscle gain has also been shown to decrease metabolic issues with age, said Rao.

“If you’re losing more than 2 pounds per week, you’re going to also be losing muscle,” said Rao. “We want to be able to redefine the body composition, so as we get older, we need to be doing heavy lifting or some sort of resistance training.”

While lifestyle changes are important to staving off chronic diseases, for women who have already worked with diet and exercise and haven’t seen meaningful results, these medications can be an extra tool in their toolbox. “Weight gain is just what we see on the surface, but these medications can help mitigate a shift in the body’s metabolic machinery and its impact on women’s health as they age,” said Al-Aly.