Pairing Hormone Replacement Therapy and Weight Loss Drugs

Gaining weight despite following a healthy lifestyle? The root of the problem may be your declining hormone levels. (Photo: SpeedKingz/Shutterstock)
By Sarah Hicks
Medical review by Anna Carlisle, MSN, APRN, FNP-C
Unexplained weight gain is one of the most unwelcome side effects of perimenopause and menopause. If you’re a women in your 40s and 50s who has gained weight despite exercising and eating well, this can be a confusing, deflating and downright annoying experience.
The good news is that a healthy, personalized weight loss solution is possible. Hormone replacement therapy (HRT) and semaglutide or tirzepatide, weight loss medications, are helping women manage their weight and related symptoms. And new research shows that combining these tools may be more effective than using either treatment alone.
How Do Hormones Affect Weight?
To understand why these treatments are effective, it helps to know how declining hormones during perimenopause and menopause affect body weight.
Hormonal changes lead to decreased metabolism, weight gain and changes in body composition, which explains why up to 70% of women experience weight gain during this transition.
The extra pounds often show up around the waist and are stubbornly immune to exercise and diet — even approaches that have worked in the past.
The biggest drivers of “menopause belly” and other body changes are declining estrogen, progesterone and testosterone, which together cause an increase in abdominal fat and fat mass overall plus a decrease in muscle mass.
In general, your metabolism slows as you age, and decreasing hormones slow it down even more. Decreased muscle mass means you burn fewer calories, which can lead to more fat accumulation. Add a lack of exercise and less quality sleep, and it’s clear why maintaining a healthy weight can be difficult.
“When my patients say, ‘I went to sleep and I woke up and I felt like I was 20 pounds heavier,’ I believe them because it can be a fairly rapid change if they’re not doing something about it,” said University of Chicago Medicine gynecologist Dr. Monica Christmas, director of the health system’s menopause program and the Center for Women’s Integrated Health.
And the changes aren’t purely aesthetic. Weight gain can increase a woman’s risk of type 2 diabetes, unhealthy lipid levels in the blood and cardiovascular disease.
The Role of HRT in Weight Loss
Many women turn to hormone replacement therapy (HRT) to treat other perimenopause and menopausal symptoms and reduce their risk of serious disease, but HRT also plays a role in how the body loses weight.
Replacing the estrogen that your body has stopped making can help mitigate some of the body composition changes associated with perimenopause and menopause. It can slow the increase in visceral abdominal fat, which is the fat that accumulates around the organs in the abdominal cavity, and it may also increase lean muscle mass.
It also provides benefits to overall health that can lead to an increase in activity, including:
- Improved sleep
- Reduction of hot flashes
- Improved glucose levels, which reduces risk of diabetes.
- Improved lipid profile
By improving sleep and other quality-of-life measures, HRT may make it easier for women to stay on track with their health goals.
“Hormones allow us to treat the underlying issue of perimenopause or menopause rather than treating the symptom — weight gain. We can address the cause as well as facilitate weight loss,” says Anna Carlisle, SHINE’s board-certified nurse practitioner who specializes in medical weight loss and hormone replacement therapy.
Carlisle has been using bioidentical hormones for more than six years and has treated more than 1,500 patients. She and the SHINE team focus on a personalized approach that includes customized bioidentical hormone pellets, which are plant-based, processed hormones that mimic the hormones made by the endocrine glands.
The Role of Semaglutide in Weight Loss
At the same time, semaglutide and tirzepatide have emerged as extremely effective weight loss treatments. Semaglutide and tirzepatide, which were first introduced as type 2 diabetes treatments, are glucagon-like peptide 1 (GLP-1) receptor agonists that help the pancreas release the right amount of insulin when blood sugar levels are high.
They work through two mechanisms:
- It slows gastric emptying, meaning you feeling full longer.
- It improves blood sugar control and insulin sensitivity. Insulin helps move sugar from the blood into other body tissues where it’s used for energy.
Semaglutide and HRT: Better Together?
Each of these treatments is effective alone, but a study published in the journal Menopause suggests combining semaglutide and HRT may offer even greater weight loss benefits.
In the study, overweight or obese postmenopausal women who used both HRT and semaglutide for a year experienced 30% more successful weight loss than women who took semaglutide alone. In addition, a greater percentage of women on hormone therapy achieved at least 5% total body weight loss or at least 10% total body weight loss.
“The data clearly suggest that there is something about postmenopausal women taking hormone therapy that allows for better weight loss response to semaglutide,” study author Dr. Maria D. Hurtado Andrade of the Division of Endocrinology, Diabetes and Metabolism at the Mayo Clinic in Jacksonville, Florida, told Medscape Medical News.
The study authors say more research is needed, but they theorize that HRT may enhance the body’s response to semaglutide by improving overall quality of life.
Create Your Healthy Weight Loss Plan
Each woman is different and needs to create an individualized healthy weight loss plan. One variable that won’t change is the importance of a healthy lifestyle, including a balanced diet and regular weight-bearing exercise.
But no one has to take on this challenge alone. It’s important to consult with a hormone specialist to determine your treatment options. A specialist will know if you are a good candidate for either or both of these treatments, help monitor your progress, test your hormones regularly and adjust treatment plans as needed.
Consult with the team at SHINE to create your personalized treatment plan.
Sarah Hicks is an editor and writer with expertise in health, wellness and science.