Statin Medications and the Risk of Gynecomastia

Sean C. Skeldon; Bruce Carleton; James M. Brophy; Mohit Sodhi; Mahyar Etminan


Clin Endocrinol. 2018;89(4):470-473. 

In This Article

Material and Methods

Data Sources and Study Design

The data for this study have been previously published.[14] In brief, we used a random sample of PharMetrics Plus (QUINTILES IMS, Parsippany, NJ, USA), a large health claims database in the US which captures health records for over 150 million US residents. The database captures physician visits through international classification of diseases, ninth and tenth editions (ICD-9 and 10). All outpatient prescription drugs are captured, which includes information on drug name, dose quantity dispensed and days supply. The database has shown to have a good representation of all geographic areas of the United States.[15] Our study used a case-control design including a random sample of 9 053 240 subjects from 2006 to 2016. Ethics approval was obtained from the University of British Columbia Clinical Research Ethics Board.

Case and Control Definition

Cases were defined as those newly diagnosed with gynecomastia, defined as the first diagnosis of gynecomastia (ICD-9 611.1). Each case had to have received a subsequent code for gynecomastia within 1 year of the first code with the first code deemed as the index date. For each case, ten male controls were identified from the database and matched to the case by follow-up time and age. Each control was allowed to become a future case and could have been selected more than once. As such, a control was allowed to be at risk of developing gynecomastia until that subject became a case, at which time they could no longer be a control. This method of control selection, also referred to as density-based sampling, has shown to generate an odds ratio which closely approximates a rate ratio (RR) derived from a Cox regression model in a cohort study.[16]

Exposure Definition and Statistical Analysis

We identified all statin prescriptions in the year prior to the index date including atorvastatin, rosuvastatin, pitavastatin, pravastatin, lovastatin, simvastatin and fluvastatin. We stratified statin use prior to the index date as current, recent or past use. Current use of a statin was defined as those who received at least one prescription from day 1 to 30 preceding the index date. Similarly, we categorized recent and past use as those who received a statin prescription between days 31–60 and days 61–365 prior to the index date, respectively. As a quality measure, we also studied finasteride, a drug widely recognized as increasing the risk of gynecomastia.[4] A conditional logistic regression model was constructed to compute adjusted rate ratios. In the model, we included the following covariates: alcoholic cirrhosis, hyperthyroidism, testicular cancer, Klinefelter syndrome, obesity, hypogonadism, hyperprolactinemia and use of spironolactone, ketoconazole, H2 receptor antagonists (H2 blockers), risperidone, testosterone and androgen deprivation therapy. The reference group for this analysis were those not taking any statins.