Takeaways
- Women using hormone therapy during tirzepatide treatment achieved similar weight loss to premenopausal and perimenopausal women.
- Possible explanations include healthy user bias, improved symptom management, and potential estrogen–GLP-1 synergy.
- Hormone therapy should not be used for weight loss; findings highlight the need for individualized treatment and further study.
In a retrospective observational study presented at The Menopause Society 2025 Annual Meeting, Regina Castaneda, MD, of Mayo Clinic, Florida, reported that menopausal status and hormone therapy use may influence weight loss outcomes among women treated with tirzepatide.1,2
“We observed that the premenopausal and perimenopausal group achieved nearly 20% total body weight loss, compared to 15% among those in the postmenopausal group who had never been exposed to hormone therapy,” Castaneda said. “Interestingly, those using hormone therapy concurrently with tirzepatide lost nearly 20% total body weight, so their outcomes closely resembled what we observed in the pre- and perimenopausal group.”
Possible mechanisms behind the observed trend
Castaneda emphasized that while the results are intriguing, further prospective studies are needed to identify underlying mechanisms. She outlined several hypotheses for the observed association.
“First of all, we are potentially seeing the effect of healthy user bias, whereby hormone therapy users engage in healthier lifestyles overall,” she said. “The mitigation of vasomotor symptoms is probably helping these women to engage in healthier lifestyles, adhere to diet or overall lifestyle interventions.”
She also referenced preclinical evidence suggesting a biological interaction between estrogen and GLP-1 signaling. “We have some preclinical data from female rodents suggesting a potential synergistic interaction between estrogen and GLP-1 signaling, where estrogen amplifies the appetite-suppressing effect of GLP-1,” she added.
Caution urged in interpretation
Although a trend favoring hormone therapy users was also observed for cardiometabolic parameters, Castaneda underscored that these findings are preliminary.
“We need to emphasize that we're not promoting the use of hormone therapy for weight loss. This is not an indication,” she said. “However, our research is a reminder that we need to individualize therapy. If the patient is dealing with the burden of vasomotor symptoms and has a clinical indication for hormone therapy, then we can have a different conversation.”
Castaneda cautioned against drawing causal conclusions from the data. “It’s still too premature to conclude that hormone therapy comes along with superior weight loss outcomes. We are describing an association. However, association does not translate to causation,” she said.