Hormonal Contraception and Initiation of Semaglutide Therapy

Importance: Concerns regarding weight changes during hormonal contraceptive use may influence health care-seeking behavior and contraceptive use patterns. While semaglutide use for weight management has increased substantially among women of reproductive age, the association of hormonal contraception use with semaglutide initiation remains unexplored. Objective: To investigate the association between hormonal contraception use and subsequent initiation of semaglutide therapy among females of reproductive age. Design, Setting, and Participants: This nested case-control study used Danish health registers to identify all females aged 12 to 49 years from January 1, 1996, to December 31, 2023. Eligible participants included females who filled their first prescription for semaglutide with no prior fill of prescriptions for drugs to lower glucose levels (semaglutide users). The date of first semaglutide prescription fill was the index date. Semaglutide users were each matched by birth year to 10 nonusers (nonuser controls) with no prior use of drugs to lower glucose levels. Data were analyzed from November 25, 2025, to May 18, 2026. Exposure: Hormonal contraception use was summarized based on the chronological order of all hormonal contraceptives for which individuals had filled prescriptions from 12 years of age (or study entry) until the index date. Main Outcome and Measure: First filled prescription of semaglutide of any dose. Results: A total of 22 694 cases and 229 640 matched controls (249 634 participants; median age, 37 [IQR, 30-44] years) were included in the analysis. All hormonal contraception utilization patterns were associated with semaglutide initiation compared with nonuser controls. Among utilization patterns involving a single contraceptive type, adjusted hazard ratios ranged from 1.42 (95% CI, 1.34-1.51) for combined oral tablets to 1.63 (95% CI, 1.46-1.82) for progestin-only intrauterine devices. For utilization patterns involving 2 or more contraceptive types, adjusted hazard ratios ranged from 1.64 (95% CI, 1.47-1.82) for combined oral tablets followed by progestin-only oral tablets to 2.11 (95% CI, 1.97-2.25) for other utilization patterns. Adjustment for body mass index attenuated but did not eliminate associations. Subgroup analyses by age, educational attainment, income, parity, immigrant status, and semaglutide type showed consistent associations across most utilization patterns. Conclusions and Relevance: In this nationwide case-control study, use of hormonal contraception was associated with subsequent semaglutide initiation across all utilization patterns compared with controls, highlighting a need to examine factors associated with weight management in females.