Analgesic use and circulating estrogens, androgens, and their metabolites in the Women's Health Initiative Observational Study.

Though studies have observed inverse associations between use of analgesics (aspirin, non-aspirin nonsteroidal anti-inflammatory drugs [NSAIDs], and acetaminophen) and the risk of several cancers, the potential biological mechanisms underlying these associations are unclear. We investigated the relationship between analgesic use and serum concentrations of estrogens, androgens, and their metabolites among postmenopausal women to provide insights on whether analgesic use might influence endogenous hormone levels, which could in turn influence hormone-related cancer risk. The study included 1,860 postmenopausal women from two case-control studies nested within the Women's Health Initiative Observational Study. Analgesic use was reported at study baseline. Fifteen estrogens and estrogen metabolites and twelve androgens and androgen metabolites were quantified in baseline serum by liquid chromatography-tandem mass spectrometry. Linear regression with inverse probability weighting, stratified by menopausal hormone therapy (MHT) use, was used to estimate adjusted geometric mean concentrations of each hormone by analgesic use. Among women not currently using MHT (n=951), low-dose aspirin (<100 mg) use was associated with a higher serum concentration of estrone, estradiol, and 2,4, and 16 hydroxylated metabolites. Use of regular-dose aspirin ( {greater than or equal to} 100 mg), non-aspirin NSAIDs, and acetaminophen were not associated with serum concentrations of estrogens, androgens, or their metabolites. This study highlights the importance of examining aspirin use by dose and suggests that low-dose aspirin may influence endogenous estrogen concentrations.