Spironolactone use and the risk of breast and gynecologic cancers
Section snippets
Methods
Since 1995, prescription drug use records have been maintained by the Danish Register of Medicinal Products Statistics [19], using individual identifiers that permit linkage to other registries. In the current study we examined use of spironolactone (aldactone) and furosemide (lasix) by using the ATC code C03DA01 and C03CA01, respectively (World Health Organization Collaborating Centre for Drug Statistics Methodology, Norwegian Institute of Public Health, P.O. BOX 4404, Nydalen NO-0304, Oslo,
Results
Overall, the study evaluated cancer incidence in 2.3 million women followed for 28.8 million person-years (p-y). From 1995 through 2010, there were 1.3 million prescriptions for spironolactone (follow-up: current and former use: 214,112 and 152,746 p-y, respectively) and 7.4 million prescriptions for furosemide (1,132,983 and 987,053 p-y). Patient characteristics and drug exposures are provided in Table 1. Breast cancers (58,000 cases) were most common, followed by uterus (9386), ovary (7899)
Discussion
In this cohort evaluation of women in Denmark, positive associations between exposure to spironolactone and these cancers were often found. With the exception of ovary cancer, discussed below, increases in risk were generally weak, although often statistically significant. However, there was no difference in patterns of risk for cancers that are relatively estrogen-sensitive and -insensitive. Furthermore, the patterns of associations were generally similar in women using furosemide, a drug
Funding
Work was supported by a grant from the Danish Medical Research Council (271-06-0352). The agency had no role in the design, access to data, conduct of the analysis or decision to publish the results. Ethical approved by the Danish Data Protection Agency was obtained before initiation of the study.
Conflict of interest statement
The authors report no conflict of interests.
Acknowledgements
Dr. Biggar conceived the study, designed the analysis, and primarily wrote the manuscript; Dr. Andersen prepared the data set and undertook the statistical analyses with the help of Dr. Wohlfahrt; Dr. Melbye provided direction and insight on study methods and data resources. All authors reviewed and provided input into the final manuscript preparation.
References (29)
- et al.
Efficacy and tolerance of spironolactone in essential hypertension
Am J Cardiol
(1987) - et al.
Spironolactone-related inhibitors of type II 17β-hydroxysteroid dehydrogenase: chemical synthesis, receptor binding affinities, and proliferative/antiproliferative activities
Bioorg Med Chem
(1999) - et al.
On the inhibitory action of 29 drugs having side effect gynecomastia on estrogen production
J Steroid Biochem Mol Biol
(2002) - et al.
Letter: breast cancer and spironolactone
Lancet
(1975) - et al.
Letter: breast cancer associated with administration of spironolactone
Lancet.
(1975) - et al.
The hirsute woman: challenges in evaluation and management
Endocr Pract
(2011) - et al.
Potassium-sparing diuretics
Ren Physiol
(1987) - et al.
Interaction of digitalis and spironolactone with human sex steroid receptors
J Clin Endocrinol Metab
(1978) - et al.
Drugs that affect the breast and lactation
Clin Obstet Gynecol
(1975) Gynecomastia
N Engl J Med
(1993)
Male Gynecomastia
Mayo Clin Proc
Molecular pathways: digoxin use and estrogen-sensitive cancers—risks and possible therapeutic implications
Clin Cancer Res
Digoxin treatment is associated with an increased incidence of breast cancer: a population-based case control study
Breast Cancer Res
Digoxin use and the risk of breast cancer in women
J Clin Oncol
Cited by (40)
No increased risk of breast or gynecologic malignancies in women exposed to spironolactone for dermatologic conditions: A retrospective cohort study
2024, Journal of the American Academy of DermatologyThe challenging role of antiandrogens in the management of polycystic ovary syndrome
2022, Polycystic Ovary Syndrome: Challenging Issues in the Modern Era of Individualized MedicineManagement of female acne
2021, FMC Formacion Medica Continuada en Atencion PrimariaSpironolactone use does not increase the risk of female breast cancer recurrence: A retrospective analysis
2020, Journal of the American Academy of Dermatology