Injectable semaglutide shows early promise to improve fertility in women with PMOS, suggests research

Researchers at the University of Colorado Anschutz have published a proof-of-concept study in Fertility and Sterility demonstrating that injectable semaglutide may offer meaningful reproductive benefits for women with polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS).

The report is the first to examine how injectable semaglutide may improve reproductive outcomes in women with PMOS while also addressing obesity and metabolic dysfunction. Researchers evaluated participants enrolled in the ongoing CU Anschutz-led RESTORE clinical trial, which is investigating the role of semaglutide in restoring ovulation and improving reproductive health in adolescents and adults with PMOS.

“Women with PMOS frequently face a frustrating choice between treatments that target reproductive symptoms and those that address metabolic health,” says Melanie Cree, MD, PhD, professor at CU Anschutz and first author of the report. “Our early findings suggest injectable semaglutide may have the potential to improve both, offering a more comprehensive approach to care. This medication is incredibly promising when someone responds with 10% weight loss.” Cree is also a pediatric endocrinologist at Children’s Hospital Colorado.

PMOS is a complex endocrine and metabolic disorder characterized by irregular menstrual cycles, elevated testosterone levels, infertility risk and increased rates of obesity and cardiometabolic disease. Existing therapies such as metformin and hormonal contraceptives often fail to adequately address both reproductive and metabolic complications simultaneously.

The proof-of-concept analysis focused on a subset of participants aged 12–35 years who achieved at least 10% body weight loss during treatment. According to investigators, reproductive improvements emerged earlier than expected during the trial, prompting the team to report preliminary findings while the larger study remains ongoing.

“What makes this work particularly important is that it focuses specifically on women with PMOS receiving injectable semaglutide,” says Cree. “Although GLP-1 medications have transformed obesity treatment, there remains a significant need for rigorous data examining how these therapies affect fertility and reproductive function in this population.”

The RESTORE study is currently evaluating semaglutide treatment in girls and women with PMOS and obesity, with the overarching goal of determining whether weight loss and metabolic improvements can restore ovulation and improve reproductive outcomes. The trial continues to enroll and follow participants.

The authors note that the current publication represents an early proof-of-concept analysis and that larger, longer-term studies will be needed to confirm the durability of the reproductive benefits observed. However, the findings provide encouraging evidence that injectable semaglutide may emerge as a promising therapeutic option for women with PMOS seeking improvements in both metabolic and reproductive health.

Reference:

Melanie G. Cree, Yesenia Garcia-Reyes, Allison Shapiro, Grayson Carey, Katherine Spencer, Gabriel I. Medrano, Carly Faulkner, Lauryn P. Roth, Patricia Huguelet, Ann E. Caldwell, Victoria A. Catenacci, Heidi Vanden Brink, Nanette Santoro, Weight Loss Associated with Semaglutide Use is Linked to Improved Reproductive Measures in PMOS: a Proof-Of-Concept Analysis, Fertility and Sterility, 2026, https://doi.org/10.1016/j.fertnstert.2026.06.002.