It seems demand is growing amongst women in perimenopause, menopause and postmenopause looking for multifaceted weight loss treatment. While telehealth companies offering compounded versions of GLP-1 medications remain a bit controversial, they've taken note of the added weight loss benefit of hormone replacement therapy (HRT) -- also known as hormone therapy (HT).
And existing research proves there's good reason for women going through midlife hormonal fluctuations to seek out both GLP-1 drugs and HRT: the combination results in more significant weight loss.
Study proves GLP-1 and HRT leads to more weight loss
A Mayo Clinic study published in the journal Menopause set out to compare weight loss response as well as changes in cardiovascular and metabolic risk markers in postmenopausal women using semaglutide with and without menopause HRT use.
Study authors note that during the menopause transition, up to 70 percent of women experience weight gain of around 2.1 kg. (about 4.6 pounds). This is due to multiple factors including aging, estrogen decline, decrease in total 24-hour energy expenditure by 9 percent and spontaneous physical activity energy expenditure by 30 percent.
"Aside from weight gain, the menopause transition is associated with changes in body composition including an increase in fat mass, a decrease in lean mass, and an increase in abdominal adiposity," say researchers.
"These changes in weight and body composition increase the risk for cardiometabolic diseases, as evidenced by the increased prevalence of type 2 diabetes, dyslipidemia, metabolic dysfunction-associated steatotic liver disease (MASLD-previously referred to as nonalcoholic fatty liver disease) and cardiovascular disease (CVD) after menopause."
How was the study set up?
The study is a retrospective review of the electronic medical records (EMRs) of patients in the Mayo Clinic Health System using semaglutide for the treatment of people diagnosed overweight or obese (BMI greater than 27 kg/m2) between January 1, 2021, and March 31, 2023.
Researchers compared weight loss outcomes and changes in cardiometabolic risk markers in response to semaglutide between 106 postmenopausal women with and without the use of HRT. Menopause status was defined as women 40 years and older who went 12 or more months without menstruating not related to other causes like use of contraceptives or history of ovary removal.
Women in the no-HRT group had to have never received systemic HRT, and those included in the HRT group were required to have started HRT prior to and continued through semaglutide treatment.
Data were collected from the EMRs at baseline (beginning semaglutide) and at three, six, nine and 12 months after semaglutide initiation. In addition to socioeconomic and demographic information, data collected included weight, height and body mass index (BMI); blood pressure; medical history pertaining to diseases including abnormal blood lipids, high blood pressure, type 2 diabetes, gastroesophageal reflux disease (GERD), MASLD and obstructive sleep apnea.
Mental health history including depression and anxiety; and laboratory data including HbA1c (average blood sugar over two to three months), fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were also noted.
Medication data included semaglutide dosing categorized as low dose (0.25 to 1 mg weekly) and high dose (1.7 to 2.4 mg weekly), and dose and type of systemic HRT (transdermal or oral estrogen and progestogen use). Information on the use of medications that may promote weight gain during the time of semaglutide treatment was collected as well.
Finally, age at menopause onset as well as whether patients met with a dietitian or a behavior modification therapist for weight loss were also included.
Study results show substantial weight loss
The main endpoint of the study was the percentage of total body weight loss (TBWL percentage) at 12 months after semaglutide initiation by HRT use. The secondary endpoints included: TBWL percent at three, six and nine months after semaglutide initiation and the percentage of women achieving 5 percent or more, 10 percent or more, 15 percent or more and 20 percent or more of TBWL 12 months after semaglutide initiation by HRT use.
Changes in cardiometabolic risk markers from baseline to 12 months were evaluated including blood pressure, fasting glucose, HbA1c, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides.
When compared to the no-HRT use cohort, women on both semaglutide and HRT achieved greater TBWL percent at three, six, nine and 12 months: two percent, four percent, five percent and four percent more, respectively. Compared to participants in the no-HRT group, a higher proportion of women using HRT achieved TBWL of five percent or more and 10 percent or more at 12 months, respectively.
Additionally, both groups saw improvement in cardiometabolic risk markers regardless of HRT use.
"In this study, the weight loss response to semaglutide differed between postmenopausal women with and without HT use," note study authors. "Three, six, nine and 12 months after semaglutide initiation, HT use was associated with approximately 30 percent more weight loss. After adjusting for potential confounding variables this association remained significant across time. Similarly, at 12 months, HT use was associated with a greater probability of achieving 5 percent or more and 10 percent or more TBWL."