Estrogen Use and Porphyria Cutanea Tarda

Importance: Estrogen-containing therapy is considered a risk factor for porphyria cutanea tarda (PCT), but the evidence is limited to clinical series and case reports. Objective: To investigate whether estrogen-containing therapy is associated with incident PCT, overall and according to estrogen-containing therapy type and route of administration. Design, Setting, and Participants: In this matched case-control study using data from Danish nationwide registries conducted from January 1, 1995, through November 1, 2024, female individuals with a first-time hospital diagnosis of PCT were matched 1:100 with population control patients on age, sex, and index date. Exposure: At least 1 redeemed prescription of estrogen-containing therapy within 1 year before the index date. Main Outcomes and Measures: Odds ratios (ORs) with 95% CIs for incident PCT were calculated from conditional logistic regression. Analyses were stratified by estrogen-containing therapy type and route of administration. Analyses were adjusted for PCT-related comorbidities: HIV infection; liver disease, viral hepatitis, or iron overload; smoking-related diagnosis or treatment; and alcohol or drug misuse diagnosis or treatment. Results: The study included 438 female case patients with incident PCT (median age, 61.16 years [IQR, 51.08-69.17 years]) and 43 800 age-matched female control patients. In total, 154 cases (35.16%) and 9433 control patients (21.54%) had been exposed to any estrogen-containing therapy within 1 year before the index date (adjusted OR, 2.03; 95% CI, 1.66-2.49). Estrogen-containing contraceptives were associated with incident PCT (adjusted OR, 2.52; 95% CI, 1.67-3.82) as were estrogen-only therapy (adjusted OR, 1.58; 95% CI, 1.23-2.03), and combined estrogen and progestogen therapy (adjusted OR, 2.18; 95% CI, 1.53-3.11). When stratified by route of administration, oral therapy was associated with PCT (adjusted OR, 2.44; 95% CI, 1.66-3.59), whereas nonoral routes were not. Conclusions and Relevance: This nationwide matched case-control study found that estrogen-containing therapy was associated with incident PCT. In route-specific analyses, only oral therapy was associated with PCT, suggesting that route of administration should be considered when evaluating estrogen exposure as a potential risk factor for PCT.