Estrogen Therapy May Increase Risk of 3 Skin Cancers

Estrogen use was linked to increased risks of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous malignant melanoma (cM) among women in a recent population-based study.¹

The findings were published in Photodermatology, Photoimmunology & Photomedicine, and suggest physicians should counsel patients on this potential risk of photosensitizing medications.

“We do not recommend discontinuation of any of the medications studied in this paper,” the authors said. “Future well-designed prospective studies are warranted to further investigate the relationships between common photosensitizing drugs and the risk of skin cancer.”

Researchers noted it's important to weigh these risks with the benefits of estrogen-based therapies. | Image credit: Debalina - stock.adobe.com

Data from more than 29,000 Swedish women were analyzed. Compared with never-use of estrogen therapy, the study authors found that estrogen-driven hormone replacement therapy was associated with a:

• 24% increased risk of BCC (95% CI, 1.11-1.39)
• 23% increased risk of cSCC (95% CI, 1.03-1.47)
• 31% increased risk of cM (95% CI, 1.01-1.6)

The prospective study utilized national registries to track participants’ pharmaceutical use and skin cancer diagnoses while controlling for known risk factors. Researchers grouped photosensitizing medications into 9 categories according to the Anatomical Therapeutic Chemical system, including hormone replacement therapy, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs).

According to the authors, estrogen drove this increased risk, as higher doses of estrogen therapy correlated with a greater risk of BCC and cM.

“When separating the hormonal drugs in this study, it became evident that the effect was predominantly due to the estrogen component in hormone treatments,” the authors said. “Our results align with the research that implicates estrogen and estrogen/progesterone combination treatments in the risk of developing cM, BCC, and cSCC. However, studies are conflicting, and several of those describe no association.”

Of 21,062 women with complete trial data and no prior skin cancer before the start of the study, 1875 women developed skin cancer during the study. Of this group, 1668 women developed 1 of the 3 types, while 11 developed all 3, and the most common combination was BCC and SCC. The authors recorded:

• 1308 cases of primary BCC
• 528 cases of primary SCC
• 257 cases of primary cM

Loop diuretics were associated with a 60% increased risk of cSCC compared with never-use, with a positive dose-response relationship (95% CI, 1.3-2.0). Meanwhile, thiazide diuretics were linked to a 25% increased risk of BCC (95% CI, 1.09-1.44) and a 41% increased risk of cM (95% CI: 1.03-1.93), and NSAIDs showed a possible curvilinear relationship with BCC and cSCC.

BCC is the most common form of skin cancer, with the majority of cases thought to be caused by long-term ultraviolet (UV) exposure.² However, this is not always the case, and while limiting sun exposure is one of several steps that patients can take, there are several potential factors to account for, such as:

• Age
• Skin color
• Personal or family history
• Genetic predisposition
• Radiation therapy
• Taking immune-suppressing drugs
• Arsenic exposure

The authors emphasized that the increased risk associated with estrogen therapy is particularly concerning given its widespread use.¹ They pointed to prior research indicating that estrogen receptors are present in melanocytic lesions and that melanoma incidence is higher in women before menopause, suggesting a hormonal influence on skin cancer development.

“Our major finding highlights the plausible role of female hormones in skin carcinogenetic processes,” the authors wrote. “Estrogen is known to have photosensitizing properties, to increase skin thickness, and to improve wound healing in postmenopausal women.”

Limitations of the study include potential confounding factors such as the influence of other treatments or underlying conditions, with the authors adding that they “recognize that hazard ratios between examined drugs and skin cancer risk are modest and must be considered in relation to health benefits from the treatment of the prescribed drugs.”

References

1. Christensen GB, Kappelin J, Sandgren J, Nielsen K, Ingvar Å. Photosensitizing drugs and risk of skin cancer in women-a prospective population-based study. Photodermatol Photoimmunol Photomed. 2025;41(2):e70013. doi:10.1111/phpp.70013
2. Basal cell carcinoma. Mayo Clinic. Updated October 1, 2021. Accessed March 20, 2025. https://www.mayoclinic.org/diseases-conditions/basal-cell-carcinoma/symptoms-causes/syc-20354187