Use of spironolactone for dermatological conditions may not increase risk of breast or uterine tumors: Study

Spironolactone is a blood pressure and congestive heart failure medication used off-label for treatment of dermatological conditions in women. As per a Food and Drug Administration warning included in the package insert, rat studies showed tumorigenicity with high oral spironolactone doses.1 Due to antiandrogen properties and structural similarity to estrogen, it has been hypothesized that spironolactone may increase breast/gynecologic cancer risk.2 Therefore, we examined whether spironolactone exposure for acne, hair loss, and/or hirsutism indications is associated with increased breast and/or gynecologic tumor risk.

Demographics and history of breast/gynecologic benign and malignant tumor diagnoses were collected for women with spironolactone exposure for acne, hair loss, and hirsutism indications and an unexposed group without spironolactone exposure prior to 4/30/2018 who presented for gynecology visits at our institution. Charts were queried through 8/1/2023 to allow for 5-year follow up after first spironolactone exposure, allowing adequate time to detect tumor development. Women with breast/gynecologic cancer diagnosis prior to spironolactone exposure were excluded. R version 4.2.2, with Pearson χ2, Wilcoxon/Kruskal-Wallis rank sum, and Fisher's exact tests were used for statistical significance (P < .05). Logistic regression determined effect of age, race, and spironolactone exposure on tumor occurrence. A total of 420 and 3272 women with and without spironolactone exposure were included (Table I). Median dose was 100 mg (range: 25-225 mg). Adjusting for age and race, risk of tumor development was similar between exposed and unexposed cohorts (P > .05). Among patients with a benign tumor, malignant tumor, or breast or uterine cancers, spironolactone exposure was not a risk factor (all P > .05) (Table II). Daily dose of spironolactone did not impact tumor development risk (P > .05).Interpretation: Patients in the exposed cohort were not more likely to develop a malignant tumor than a benign tumor when compared to the unexposed cohort (P > .05).

Open table in a new tab

We found no increased risk of benign or malignant breast or uterine tumors with spironolactone treatment for dermatologic indications, similar to a systematic review and meta-analysis that reported no increased risk of breast (n = 3 studies, very low certainty of evidence) or ovarian (n = 2 studies, very low certainty of evidence) cancers with spironolactone use (risk ratio = 1.04; 95% CI, 0.86-1.22, risk ratio = 1.52; 95% CI 0.84-2.20, respectively).3 In addition, spironolactone use was not associated with increased risk for other cancer types, including prostate, bladder, kidney, gastric, or esophageal.3 We also found no increased risk of tumor development with changes in spironolactone doses, similar to a retrospective study of 28,032 women >55 years old with exposure to spironolactone for any indication and 55,961 controls matched by socioeconomic score and age, which showed no evidence of a dose response risk among exposed patients.4

Limitations include retrospective design, lack of detailed information about spironolactone courses, lack of control for family malignancy history, and lack of quantitation of follow-up.

In sum, we found no association between spironolactone exposure for dermatological conditions and risk of breast or uterine tumors compared to unexposed women. Therefore, women taking spironolactone for acne, hair loss, and hirsutism and who are at low risk of breast or gynecologic cancers may be counseled to have regular gynecology follow up, but no more frequently than the general population. Future studies are needed to assess risk over longer time periods.

Reference:

Hill RC, Wang Y, Shaikh B, Lipner SR. No increased risk of breast or gynecologic malignancies in women exposed to spironolactone for dermatologic conditions: A retrospective cohort study. J Am Acad Dermatol. 2024 Jun;90(6):1302-1304. doi: 10.1016/j.jaad.2024.02.030. Epub 2024 Feb 27. PMID: 38423468; PMCID: PMC11095997.