Aspirin and serum estrogens in postmenopausal women: a randomized controlled clinical trial

Epidemiologic studies suggest a reduced risk of breast cancer among women who use aspirin. A plausible mechanism is through aspirin's effect on estrogens, possibly mediated through interference with estrogen synthesis via reduction in inflammation, which is increased in adipose tissues, including breast. In a randomized placebo-controlled trial, we evaluated the effects of six-month administration of 325 mg/day aspirin on serum estrogens (estradiol, estrone, free estradiol, and bioavailable estradiol) and sex hormone-binding globulin (SHBG) in 144 healthy postmenopausal women. Eligible participants, recruited 2005-2007, were not taking nonsteroidal anti-inflammatory medication, including aspirin >2 times/week or menopausal hormone therapy, and had a Breast Imaging-Reporting and Data System (BI-RADS) mammographic density classification of 2, 3, or 4. The intervention effects (intent-to-treat) were evaluated by differences in the geometric mean outcome changes at six months between aspirin and placebo groups using generalized estimating equations (GEE). Participants were a mean 59.4 (SD, 5.4) years of age, with a mean body mass index (BMI) of 26.4 (SD, 5.4) kg/m(2). Between baseline and six months, none of the serum estrogens or SHBG changed substantially and there were no differences between groups. Stratifying by BMI did not change results. In conclusion, a single daily administration of 325 mg of aspirin for six months had no effect on serum estrogens or SHBG in postmenopausal women. Larger doses or longer duration of aspirin administration may be needed to affect circulating estrogens. Alternately, if aspirin influences breast cancer risk in postmenopausal women, it may do so through direct breast tissue effects, or through pathways other than estrogens.