Estrogen therapy may increase the risk of Porphyria Cutanea Tarda (PCT) in some people, particularly those who already have underlying risk factors. PCT is a rare liver-related disorder that affects the body’s ability to process porphyrins, substances involved in producing heme, a component of hemoglobin.
The condition can cause skin to become unusually sensitive to sunlight. People with PCT may develop fragile skin, blisters, and slow-healing sores, especially on areas exposed to the sun, such as the hands and face.
The link between estrogen and PCT is important because estrogen-containing treatments, including some forms of hormone replacement therapy and oral contraceptives, have been associated with the condition. However, this does not mean everyone using estrogen will develop PCT.
What Is Porphyria Cutanea Tarda?
Porphyria Cutanea Tarda (PCT) is the most common type of porphyria. It develops when the liver enzyme uroporphyrinogen decarboxylase (UROD) becomes less active.
This causes porphyrins to build up in the liver and body. When these substances reach the skin, exposure to sunlight can trigger skin damage.
Common symptoms include:
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Blisters on sun-exposed skin, especially the hands.
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Fragile skin that tears easily.
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Slow-healing wounds and scars.
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Darkened skin in affected areas.
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Increased hair growth on the face or hands.
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Small white bumps known as milia.
PCT mainly affects the skin and is different from acute porphyria, which can cause serious internal symptoms.
What Does the New Study Reveal About Estrogen Therapy?
A study published in JAMA Dermatology on October 28, 2026, examined the relationship between estrogen-containing treatments and the development of PCT.
Researchers from Denmark conducted a nationwide matched case-control study using health registry data collected between 1995 and 2024.
The study included:
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438 women with a first-time diagnosis of PCT.
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43,800 women in a matched control group.
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Estrogen exposure recorded during the year before the diagnosis or corresponding index date.
Researchers found that 35.16% of women with PCT had used estrogen-containing therapy, compared with 21.54% of women in the control group.
After adjusting for several known PCT-related risk factors, estrogen exposure was associated with approximately twice the odds of developing PCT.
Which Types of Estrogen Therapy Were Associated With PCT?
The researchers examined different types of estrogen-containing treatments. Each showed an association with PCT.
| Type of estrogen therapy | Adjusted odds ratio |
|---|---|
| Estrogen-containing contraceptives | 2.52 |
| Estrogen-only therapy | 1.58 |
| Combined estrogen and progestogen therapy | 2.18 |
These figures represent adjusted odds ratios, not the percentage of users who will develop PCT.
The findings suggest that the association is not limited to one type of estrogen treatment. Both contraceptive use and hormone replacement therapy were included in the analysis.
Oral Estrogen May Carry a Different Risk Than Nonoral Treatment
One of the most important findings concerned how estrogen was administered.
The study found an association between oral estrogen therapy and PCT. The adjusted odds ratio was 2.44.
However, researchers did not find a statistically significant association for nonoral estrogen routes in their analysis.
This distinction matters because estrogen can affect the liver differently depending on how it enters the body. Oral estrogen passes through the liver after absorption from the digestive system, while treatments such as patches deliver hormones through the skin.
However, the study does not prove that nonoral estrogen is completely risk-free. More research is needed to understand the differences between treatment routes.
Why Can Estrogen Increase the Risk of PCT?
The exact biological mechanism is not fully understood. However, estrogen exposure is already recognized as one of several factors associated with PCT.
PCT develops when UROD activity in the liver decreases. This leads to the accumulation of porphyrins.
Several factors can contribute to this process, including:
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Excess iron in the liver.
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Long-term alcohol consumption.
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Hepatitis C infection.
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HIV infection.
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Smoking.
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Estrogen-containing medications.
These factors may increase susceptibility, especially when more than one is present. Estrogen should therefore be considered alongside other health and lifestyle factors rather than as the only possible cause.
Who Should Be Aware of This Risk?
The findings may be relevant to people using estrogen-containing medications, including:
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Women taking combined oral contraceptives.
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Women receiving estrogen-only hormone replacement therapy.
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Women using combined estrogen and progesterone treatments.
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People receiving other prescribed estrogen-containing treatments.
People with existing liver disease, iron overload, hepatitis C, or other PCT risk factors may need additional medical consideration.
Anyone who develops unexplained skin fragility, blisters, or wounds on sun-exposed areas should seek medical evaluation. Doctors can investigate PCT through porphyrin testing and other blood tests.
Should People Stop Estrogen Therapy?
The study does not recommend that everyone stop estrogen therapy.
Estrogen treatments may be prescribed for important reasons, including contraception and relief from menopause symptoms. Stopping a prescribed treatment without medical advice can create other health concerns.
People with active PCT should discuss their hormone treatment with their healthcare provider. Depending on their medical history, a clinician may consider changing the dose, treatment type, or route of administration.
The British Porphyria Association advises people with active PCT to avoid estrogen where possible. If hormone replacement therapy is necessary, the lowest effective dose and an appropriate alternative route may be considered under medical supervision.
Limitations of the Study
Although the research provides important evidence, some limitations should be considered.
First, the study was observational. It identified an association between estrogen therapy and PCT but cannot establish that estrogen directly caused the condition.
Second, the research used Danish health registry records. Its findings may not apply equally to every population or healthcare system.
Third, the study focused on women with recorded hospital diagnoses of PCT. It may not capture every person with undiagnosed or less severe disease.
Further research could help explain why oral estrogen showed an association while nonoral treatment did not.
Conclusion
The new study published in JAMA Dermatology adds important evidence to the relationship between estrogen therapy and Porphyria Cutanea Tarda.
Researchers found that estrogen-containing treatments were associated with higher odds of a first PCT diagnosis. The association was observed with contraceptives, estrogen-only therapy, and combined hormone treatment. Oral estrogen showed an association, while nonoral routes did not show a statistically significant one.
These findings highlight the importance of considering estrogen exposure when assessing PCT risk. However, treatment decisions should always be made with a healthcare professional, taking individual health needs and risk factors into account.
