Prolactin, a pituitary peptide hormone with multiple effects, stimulates prostate growth in experimental models. In humans, prolactin receptors are present in the prostate and are particularly abundant in pre-cancerous lesions. This suggests that prolactin could also be involved in the development of prostate cancer. In this study, we tested the hypothesis that elevated levels of circulating prolactin are associated with an increase in prostate cancer risk. We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort using plasma samples collected from 29,560 men at a health survey. We measured prolactin in plasma from 144 men who had a diagnosis of prostate cancer after a median follow-up time of 4 years after health survey and from 289 controls matched for age and date of recruitment. Risk was not associated with plasma prolactin levels in univariate regression analysis. Odds ratios of prostate cancer for increasing quartiles of prolactin were 1.0, 0.92 (95% CI 0.51-1.65), 0.82 (0.45-1.51) and 0.85 (0.49 -1.47). Relative risk estimates remained unchanged after adjustments for height and weight or for plasma levels of testosterone, sex hormone-binding globulin, Prolactin, a pituitary peptide hormone, stimulates prostate growth in experimental studies. In vitro, prolactin induces proliferation and antagonises apoptosis in prostate organ culture 1 and in some tumour cell lines 2,3 but not in others. 3,4 In vivo studies have consistently shown that hyperprolactinaemia induces prostate proliferation 5-7 and differentiation 8 in the rat prostate, and prolactin stimulated growth of the Dunning R3327 PAP tumour. 5 Wennbo et al. 9 showed in a transgenic mouse model that mice over-expressing prolactin had a 20-fold increase in prostate weight compared with control animals. Furthermore, the development of inflammation 10 and dysplasia 11 of the prostate in rats chronically treated with androgen and oestrogen combinations is mediated by increased plasma prolactin.In humans, receptors for prolactin are expressed in the prostate, 1 and the expression is particularly elevated in high-grade prostate intra-epithelial cell neoplasia (PIN), a precursor of prostate cancer. 12 Local production of prolactin has also been demonstrated in the prostate. 1 Plasma prolactin rises sharply at puberty and continues to increase in parallel with the age-related increase seen in the incidence of benign prostatic hyperplasia and prostate cancer. 13 Collectively, these experimental and chronobiological results suggest that increased levels of circulating prolactin induce prostate growth and possibly prostate tumour growth. However, epidemiological data concerning prolactin and prostate cancer are sparse and inconclusive: several small case-control studies 14 -17 and 2 prospective cohort studies 18,19 have not shown a consistent association between circulating prolactin concentrations and prostate cancer risk. To further investigate the relationship between circulating prolactin levels and prostate cancer dev...