Is estrogen use associated with the development of porphyria cutanea tarda?

Porphyria cutanea tarda (PCT) is a rare skin disorder characterized by blistering, erosions and vesicles in sun-exposed areas, particularly the dorsal hands, forearms and face. Estrogen-containing therapy is considered to be a risk factor for PCT, but the evidence is limited to clinical series and case reports. To investigate this issue on a larger scale, Danish researchers studied whether estrogen-containing therapy is associated with incident PCT, and whether the risk varies according to estrogen-containing therapy type and route of administration.The matched case-control study used data from Danish nationwide registries and was conducted from 1995–2024. Female individuals with a first-time hospital diagnosis of PCT were matched 1:100 with population control patients on age, sex and index date.Individuals in the study had redeemed at least one prescription of estrogen-containing therapy within the one-year period before the index date.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.Key results:The study included 438 female case patients with incident PCT (median age, 61.16 years) and 43,800 age-matched female control patients;In total, 154 cases (35.16%) and 9,433 control patients (21.54%) had been exposed to any estrogen-containing therapy within one 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 (vaginal, transdermal, parenteral) were not;In premenopausal settings, 40 case patients (9.13%) had used estrogen-containing contraceptives within one year before the index date compared with 2,248 control patients (5.13%), corresponding to an OR of 2.47 (95% CI, 1.64–3.74); In postmenopausal settings, 38 case patients (8.68%) had used combined estrogen-progestogen therapy within one year before the index date compared with 1,865 control patients (4.26%), corresponding to an OR of 2.27 (95% CI, 1.60–3.24).The authors concluded that in this nationwide matched case-control study spanning almost 30 years, estrogen-containing therapy was associated with incident PCT in both premenopausal and postmenopausal patients. 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. The authors stressed that at a population level, the risk of PCT associated with estrogen-containing therapies is negligible. However, their study supports the recommendation to avoid estrogen in patients with PCT, when possible. In addition, avoidance of oral estrogen-containing therapy in patients with PCT may be more clinically relevant than nonoral routes and patients should be counselled accordingly. ReferenceErichsen PA, Heerfordt IM, Mogensen M, et al. Estrogen use and porphyria cutanea tarda. JAMA Dermatol 2026. Published Online: October 28, 2026 (accessed October 29, 2026).

Is estrogen use associated with the development of porphyria cutanea tarda?

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