Prolactin Determinants in Healthy Women: A Large Cross-Sectional Study within the EPIC Cohort

Abstract

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; P cat ¼ <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; P cat ¼ 0.001). Prolactin levels were lower among parous women compared with nulliparous women (8.61 vs. 10.95 ng/mL; P cat ¼ 0.0002, premenopausal women); the magnitude of this difference depended on the number of full-term pregnancies (22.1% lower, !3 vs. 1 pregnancy, P trend ¼ 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. Cancer Epidemiol Biomarkers Prev; 23(11); 2532-42. Ó2014 AACR.

Determinants of prolactin in postmenopausal Chinese women in Singapore

“…It was unexpected that we did not observe a relationship between parity and prolactin, given that lower prolactin levels have been consistently reported among postmenopausal women who had at least one birth, compared with no births [9–11]. There exists the possibility that with only 25 nulliparous women, or 5.7% of our study population, the study lacked the statistical power to observe statistically significant differences in mean prolactin levels by parity.…”

“…There exists the possibility that with only 25 nulliparous women, or 5.7% of our study population, the study lacked the statistical power to observe statistically significant differences in mean prolactin levels by parity. Two other studies using a cross-sectional design included 131 nulliparous women (12% of their study population) in Nurses Health Study and 136 (13% of their study population) nulliparous women in the European Prospective into Cancer [9, 11]. One case–control study in an Australian cohort used a similar number of nulliparous women but specifically collected biospecimens during the 21 or 22 day of the menstrual cycle which may have been critical to observe a difference in their population [10].…”

“…One case–control study in an Australian cohort used a similar number of nulliparous women but specifically collected biospecimens during the 21 or 22 day of the menstrual cycle which may have been critical to observe a difference in their population [10]. For the other pregnancy characteristics, such as number of births and age at first birth, results from larger studies among postmenopausal women also report no relationship with prolactin [9, 11, 13]. Our findings are consistent with these previous studies for no association with number of births, age at first birth, or years since first birth (data not shown).…”

“…Our findings are consistent with these previous studies for no association with number of births, age at first birth, or years since first birth (data not shown). Lactation information was not available in our dataset, but duration of breastfeeding does not appear to influence prolactin levels [11]. In Singapore, breastfeeding is prevalent with 99% of women enrolled in the National Breastfeeding Survey ( n = 1,962) attempting nursing in the hospital and 42% still breastfeeding to some degree 6 months postpartum [56].…”

Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

“…Linear trends for OR estimates were calculated over a continuous log 2 scale of prolactin. Circulating prolactin levels vary by menopausal status [ 10 ], and therefore the tertile cutpoints were defined separately for pre- and postmenopausal women, based on distributions in the control population. We decided a priori to adjust all models for parity (nulliparous, parous, or missing data), smoking status (current, never, previous, missing data) and body mass index (BMI) in kg/m 2 (continuous scale), due to modest variation in prolactin levels over these factors in healthy women [ 10 ].…”