Hormone Replacement Therapy Does Not Cause Weight Gain in Postmenopausal Women
The evidence clearly demonstrates that hormone replacement therapy (HRT) does not cause weight gain in postmenopausal women; in fact, it may prevent the weight gain and unfavorable body composition changes that naturally occur after menopause. 1, 2
Key Evidence on HRT and Weight
Meta-Analysis Findings
A systematic review of 22 randomized controlled trials found no statistically significant difference in weight gain between women using unopposed estrogen and non-HRT users (0.66 kg difference, 95% CI -0.62 to 1.93) 1
Similarly, no significant difference in weight gain was found between women using combined estrogen/progestogen therapy and non-HRT users (-0.47 kg, 95% CI -1.63 to 0.69) 1
The largest longitudinal study, the Women's Health Initiative with 8,506 postmenopausal women, found only an average 1 mm Hg increase in systolic blood pressure over 5.6 years—not clinically meaningful weight gain 3
HRT Actually Prevents Unfavorable Body Composition Changes
HRT reverses menopause-related obesity and sarcopenia without overall weight change: 4
- Lean body mass increased by 347 g during HRT versus a loss of 996 g with placebo (p < 0.01) 4
- Total fat mass decreased by 400 g during HRT versus an increase of 836 g with placebo (p = 0.06) 4
- Abdominal fat decreased by 185 g during HRT versus an increase of 253 g with placebo (p = 0.04) 4
- Relative fat mass was significantly reduced (-0.5% vs. +1.24%, p < 0.01) 4
HRT Prevents Central Fat Redistribution
Untreated postmenopausal women show a shift to central android fat distribution with increased trunk fat (from 10.2 to 11.3 kg over 12 months) 5
Women on HRT showed no increase in trunk or arm fat, but a beneficial increase in leg fat (from 7.1 to 8.3 kg), maintaining a healthier gynoid fat distribution pattern 5
HRT counteracts the postmenopausal increase in body weight and body fat and prevents central body fat distribution 5
Specific Context: Your Patient on Testosterone, Estrogen, and Semaglutide
Testosterone Effects in Women
Testosterone therapy in women with HIV wasting showed minimal impact on overall weight in meta-analysis, with only minimal difference between testosterone and placebo groups 6
Testosterone is not associated with significant weight gain in women, though it may have modest effects on muscle mass 6
Synergistic Effect with GLP-1 Receptor Agonists
HRT use enhances weight loss response to semaglutide: 7
Women on HRT achieved significantly greater total body weight loss at all time points: 7% vs 5% at 3 months (p = 0.01), 13% vs 9% at 6 months (p = 0.01), 15% vs 10% at 9 months (p = 0.02), and 16% vs 12% at 12 months (p = 0.04) 7
This association remained significant after adjusting for confounders including age, BMI, race, and comorbidities 7
A greater percentage of women on HRT achieved ≥5% and ≥10% total body weight loss at 12 months 7
Both groups experienced improvement in cardiometabolic risk markers (glucose, blood pressure, lipids) 7
Clinical Algorithm for Your Patient
Assessment of Weight Changes
Attribute weight gain to factors other than HRT:
- Natural menopause-related metabolic rate decrease 2
- Dietary factors
- Activity level changes
- Other medications
Recognize HRT's protective effects:
Monitoring Recommendations
Blood pressure monitoring every 6 months for women on HRT, as modest BP increases (1 mm Hg) may occur 3
Body composition assessment rather than weight alone, as HRT increases lean mass while decreasing fat mass 4
Continue current regimen as the combination of estrogen, testosterone, and semaglutide is optimal for weight management 7
Common Pitfalls to Avoid
Do not discontinue HRT due to weight concerns, as this will likely result in increased fat mass and central fat redistribution 4, 5
Do not attribute normal menopausal weight gain to HRT, as menopause itself causes metabolic changes independent of hormone therapy 2
Do not focus solely on scale weight, as HRT improves body composition by increasing muscle and bone mass while decreasing fat mass 4
Bottom Line
Your patient's HRT regimen (estrogen and testosterone) is not causing weight gain and is actually enhancing the weight loss effects of semaglutide. 7 The evidence consistently shows HRT prevents the unfavorable body composition changes of menopause, including central fat accumulation and muscle loss. 1, 4, 5 Any weight concerns should be addressed through optimization of the GLP-1 therapy, dietary modifications, and exercise rather than modification of the hormone replacement regimen.