Prolactin determinants in healthy women: A large cross-sectional study within the EPIC cohort

Background: Experimental and epidemiologic data suggest that higher circulating prolactin is associated with breast cancer risk; however, how various risk factors for breast cancer influence prolactin levels in healthy women is not clear. Methods: We analyzed cross-sectional associations between several suggested reproductive and lifestyle risk factors for breast cancer and circulating prolactin among pre- and postmenopausal women, taking into account the use of current postmenopausal hormone therapy, among 2,560 controls from a breast cancer nested case-control study within the EPIC cohort. Results: Adjusted geometric mean prolactin levels were significantly higher among premenopausal women, and among postmenopausal women using hormone therapy compared with nonusers (8.2, 7.0, and 6.3 ng/mL, respectively; Pcat = <0.0001). Furthermore, prolactin levels were significantly higher among users of combined estrogen-progestin hormone therapy compared with users of estrogen-alone hormone therapy (6.66 vs. 5.90 ng/mL; Pcat = 0.001). Prolactin levels were lower among parous women compared with nulliparous women (8.61 vs. 10.95 ng/mL; Pcat = 0.0002, premenopausal women); the magnitude of this difference depended on the number of full-term pregnancies (22.1% lower, ≥3 vs. 1 pregnancy, Ptrend = 0.01). Results for parity were similar but lower in magnitude among postmenopausal women. Prolactin did not vary by other studied factors, with the exception of lower levels among postmenopausal smokers compared with never smokers. Conclusions: Our study shows that current hormone therapy use, especially the use of combined hormone therapy, is associated with higher circulating prolactin levels in postmenopausal women, and confirms prior findings of lower circulating prolactin in parous women. Impact: Our study extends the knowledge linking various breast cancer risk factors with circulating prolactin.