Although androgens may play an etiologic role in breast, ovarian and endometrial cancers, little is known about factors that influence circulating androgen levels. We conducted a cross-sectional analysis among 646 postmenopausal women in the Nurses' Health Study to examine associations between adult risk factors for cancer, including the Rosner/Colditz breast cancer risk score, and plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). All analyses were adjusted for age, laboratory batch and other cancer risk factors. Free testosterone levels were 79% higher among women with a body mass index of > or =30 vs. <22 kg/m(2) (p-trend <0.01) and 25% higher among women with a waist circumference of >89 vs. < or =74 cm (p-trend = 0.02). Consuming >30 g of alcohol a day vs. none was associated with a 31% increase in DHEA and 59% increase in DHEAS levels (p-trend = 0.01 and <0.01, respectively). Smokers of > or =25 cigarettes per day had 35% higher androstenedione and 44% higher testosterone levels than never smokers (p-value, F-test = 0.03 and 0.01, respectively). No significant associations were observed for height or time since menopause with any androgen. Testosterone and free testosterone levels were approximately 30% lower among women with a hysterectomy vs. without (both p-values < 0.01). Overall breast cancer risk was not associated with any of the androgens. Thus, several risk factors, including body size, alcohol intake, smoking and hysterectomy, were related to androgen levels among postmenopausal women, while others, including height and time since menopause, were not. Future studies are needed to clarify further which lifestyle factors modulate androgen levels.