TMS 2026: Menopause hormone therapy was associated with greater weight loss on semaglutide, but not sustained additional benefits with tirzepatide, in a new study.
Women receiving
In the analysis of more than 3800 women aged 45 years and older, concomitant HT use was associated with greater total body weight loss (TBWL) among semaglutide users beginning at 9 months, with the difference persisting through 15 months and the last follow-up. Among tirzepatide users, HT was associated with modestly greater weight loss at 3 months, but no statistically significant differences were observed at later time points.¹
The findings add to emerging evidence suggesting that ovarian hormones may influence weight loss responses to glucagon-like peptide-1 (GLP-1)–based obesity medications, although the observational design does not establish a causal relationship.
Investigators led by Regina Castaneda, MD, of Mayo Clinic Florida, examined electronic health record data collected between February 2017 and December 2025 through the nSights federated platform. The study included women aged 45 years and older with a body mass index (BMI) of at least 27 kg/m² who had received semaglutide or tirzepatide for at least 12 months, with or without concomitant HT.¹
HT included oral or transdermal estrogen, with or without progesterone. Women with prior bariatric surgery, active malignancy, or concurrent use of other obesity medications were excluded.
To account for potential confounding, investigators used 1:2 propensity score matching based on age, baseline BMI, previous obesity medication use, and type 2 diabetes status. The primary outcome was percentage TBWL at 3, 6, 9, 12, and 15 months and at the last follow-up. Secondary outcomes included the proportion of participants achieving weight loss thresholds ranging from 5% to 30%.¹
The semaglutide cohort included 2379 women, of whom 793 were receiving HT and 1586 were not. Mean age was 57 years, and mean BMI was 36 kg/m². Baseline demographic characteristics and adiposity-related comorbidities were well balanced between groups.
At 9 months, women receiving HT experienced a mean TBWL of 9.8%, compared with 8.2% among women not receiving HT (P<.001). The association persisted at subsequent assessments:
Median follow-up was 26 months in both groups.¹
Women receiving concomitant HT were also significantly more likely to achieve higher weight loss thresholds. At the last follow-up, 55% of HT users achieved at least 10% TBWL, compared with 51% of nonusers (P=.045). Similarly, 22% versus 18% achieved at least 20% TBWL (P=.037), and 13% versus 10% achieved at least 25% TBWL (P=.008).
The proportion achieving at least 30% TBWL was also higher among HT users (6% vs 4%; P=.015).¹
The tirzepatide cohort included 1476 women, including 492 receiving HT and 984 not receiving HT. Mean age was 57 years, and mean BMI was 36 kg/m².
At 3 months, women receiving concomitant HT experienced greater mean TBWL than nonusers (6.6% vs 5.9%; P=.031). However, the difference was not statistically significant at subsequent assessments through 15 months or the last follow-up.
At the last follow-up, 88% of HT users achieved at least 5% TBWL, compared with 84% of nonusers (P=.041). No significant between-group differences were observed for higher weight loss thresholds, including 10%, 15%, 20%, 25%, and 30% TBWL.¹
Median follow-up was 17 months for HT users and 16 months for nonusers.
The findings suggest that concomitant menopause HT may be associated with a modest but sustained additional weight loss response to semaglutide in midlife women, although a comparable long-term association was not demonstrated with tirzepatide.
The investigators noted that previous smaller observational studies had suggested greater weight loss among postmenopausal women receiving HT alongside semaglutide or tirzepatide. The current analysis expands on those findings in a larger population spanning the menopausal transition and beyond.
However, residual confounding remains possible despite propensity score matching. The abstract did not report analyses by menopausal stage, HT formulation, obesity medication dose, or treatment adherence, limiting conclusions about which patients might experience greater benefits.
For primary care physicians managing obesity in midlife women, the findings highlight the potential importance of reproductive and hormonal factors when evaluating responses to GLP-1–based therapies. They do not, however, establish that initiating HT improves obesity treatment outcomes or support prescribing HT specifically to enhance weight loss.
The authors concluded that larger prospective studies are needed to confirm the observed associations and determine whether menopause HT status should inform individualized obesity treatment strategies.
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