Estrogen Therapy and Increased Porphyria Cutanea Tarda Risk

ESTROGEN therapy and porphyria cutanea tarda (PCT) have been linked in a nationwide Danish study, with oral estrogen-containing treatments associated with increased odds of developing the condition. The findings suggest that both the type of estrogen therapy and route of administration should be considered when evaluating PCT risk.

What Is the Association Between Estrogen Therapy and Porphyria Cutanea Tarda?

The matched case-control study used Danish nationwide registry data collected between January 1995 and November 2024. Researchers investigated whether estrogen-containing therapy was associated with incident PCT among female individuals, addressing an evidence gap previously informed primarily by clinical case series and case reports.

The study included 438 female patients with a first-time hospital diagnosis of PCT and 43,800 age-matched female controls. Exposure was defined as at least one redeemed prescription for estrogen-containing therapy during the 12 months preceding the index date.

Overall, 154 patients with PCT (35.16%) had received estrogen-containing therapy, compared with 9,433 controls (21.54%). After adjustment for PCT-related comorbidities, estrogen exposure was associated with approximately twice the odds of incident PCT (adjusted odds ratio [OR]: 2.03; 95% CI: 1.66–2.49).

Which Estrogen Treatments Were Associated with Increased PCT Risk?

Associations were identified across all three categories of estrogen-containing therapy investigated. Estrogen-containing contraceptives demonstrated the strongest association (adjusted OR: 2.52; 95% CI: 1.67–3.82).

Estrogen-only therapy was also associated with incident PCT (adjusted OR: 1.58; 95% CI: 1.23–2.03), as was combined estrogen and progestogen therapy (adjusted OR: 2.18; 95% CI: 1.53–3.11).

The researchers also examined whether the route of administration influenced the association. Oral estrogen-containing therapy was associated with increased odds of PCT (adjusted OR: 2.44; 95% CI: 1.66–3.59). However, non-oral administration routes were not associated with incident PCT.

What Do the Findings Mean for Estrogen Prescribing?

The findings provide further evidence supporting estrogen-containing therapy as a potential risk factor for PCT, a condition associated with chronic blistering and skin fragility.

Importantly, the association observed with oral administration, but not non-oral routes, highlights the potential relevance of administration route when assessing estrogen exposure. The results also demonstrate that the association extended across contraceptive preparations, estrogen-only treatments, and combined estrogen and progestogen therapies.

The researchers concluded that estrogen-containing therapy was associated with incident PCT in this nationwide population-based study. Consideration of administration route may therefore be important when evaluating potential PCT risk in individuals receiving estrogen-containing treatments.

Reference

Erichsen PA et al. Estrogen use and porphyria cutanea tarda. JAMA Dermatol. 2026;DOI: 10.1001/jamadermatol.2026.4329.