Cigarette smoking and circulating androgens in women from the Epic Florence cohort

The harmful effects of smoking on health include respiratory and cardiovascular diseases, adverse reproductive outcomes, and an increased risk of several cancers, including breast cancer. While the effect of circulating estrogens on breast cancer development is well established, recent studies suggest androgen involvement, but little is known about lifestyle factors influencing their levels. We investigated the relationship between smoking habits and circulating androgen levels in pre- and postmenopausal women.

We conducted a cross-sectional study on 867 women randomly selected from participants enrolled in the EPIC Florence study between 1993 and 1998. At enrollment, participants provided data on diet, lifestyle, reproductive history, and anthropometry. Blood samples were collected, aliquoted, and stored in liquid nitrogen. To assess the association between active smoking and circulating androgens, we used linear regression models adjusted for age, body mass index, waist circumference, education level, physical activity level, alcohol consumption, caloric intake, and reproductive history, separately for pre- and postmenopausal women.

In pre- and postmenopausal women, current smokers had higher testosterone (premenopause: exp(β) 1.13; 95% CI 1.01-1.26 and postmenopause: exp(β) 1.13; 95% CI 1.00-0.26) and androstenedione levels (premenopause: exp(β) 1.14; 95% CI 1.04-1.26 and postmenopause: exp(β) 1.14; 95% CI 1.02-1.28) compared to never smokers. A significant trend toward increasing androstenedione with increasing pack-years of smoking was observed in postmenopausal women.

Our analysis revealed a direct association between circulating levels of testosterone and androstenedione and smoking habit, and a dose-response effect for androstenedione in postmenopausal women. This association could provide insights into the mechanisms linking smoking to breast cancer risk.