Hormone Therapy and Increased Risk of Psoriasis in Reproductive-age and Postmenopausal Women: A Nationwide Cohort Study and Target Trial Emulation

Abstract Background Hormonal therapy (HT) is widely administered for contraception and menopausal symptom management. However, its impact on psoriasis risk remains unclear, requiring an evaluation across diverse age groups to inform clinical practice and optimize treatment strategies. Objective To investigate the association between HT and the risk of psoriasis in reproductive-age and postmenopausal women. Methods This study utilized both nationwide cohort design and target trial emulation, analyzing data from Taiwan's National Health Insurance Database (2001–2021). Women over 20 years old without a prior history of psoriasis, ovarian cancer, or breast cancer were included, segmented into reproductive-age (≤50 years) and postmenopausal (>50 years) groups. Women who initiated HT were assigned as the exposed group, while women without HT formed the comparison group. The primary outcome was the incidence of psoriasis over a five-year period. The study applied inverse probability of treatment weighting (IPTW) and Cox proportional hazards models to estimate hazard ratios (HRs). Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to enhance the robustness of the findings. Results In the postmenopausal cohort, comprising 1,482,302 HT users and 1,313,799 nonusers, the IPTW-adjusted HR for psoriasis in the ITT analysis was 1.48 (95% CI 1.44–1.52). The PP analysis indicated a more pronounced risk, with an HR of 5.93 (95% CI 5.66–6.22). Among the reproductive-age cohort, which included 3,849,721 HT users and 1,585,461 nonusers, the IPTW-adjusted HR in the ITT analysis was 1.93 (95% CI 1.90–1.99). In the PP analysis, the risk increased, showing an HR of 7.85 (95% CI 7.56–8.15). These findings highlight the significantly elevated psoriasis risk associated with HT, especially in younger women. Conclusion This study establishes an association between HT and an increased risk of psoriasis in both reproductive-age and postmenopausal women using a nationwide cohort design and target trial emulation. These findings further highlight the potential influence of hormonal factors on psoriasis development. Clinicians should remain attentive to early signs of psoriasis in women receiving HT to ensure timely recognition and management.