The relationship between hypoprolactinemia and cardiometabolic health in women.

Background: An evidence-based definition for the lower reference limit of serum prolactin (PRL) is lacking. We recently examined the European Male Ageing Study (EMAS) data and derive a threshold set at 3.0ng/ml for hypoprolactinemia in men. Here, we identified the lower reference limit for PRL in women.

Methods: We used data from the Study of Health of Pomerania (SHIP-START, Germany, discovery cohort), and the Women's Health Study (WENDY, Finland, validation cohort). The two-sigma empirical rule was applied to obtain a threshold at 2.5% of the log10 PRL distribution. Logistic and Cox regressions were used to examine the association between PRL and cardiometabolic outcomes at baseline and follow-up, respectively.

Results: There were 2,048 women aged 20-81yr from SHIP-START and 1,730 women aged 33-37yr from WENDY. The low serum PRL threshold was derived at 2.60 ng/ml for premenopausal women and 2.29 ng/ml in women of all ages from SHIP-START, and 4.84ng/ml in WENDY. These thresholds were not far off from that previously identified in men (3ng/ml). In SHIP-START we further found that compared to PRL levels of 5.0-34.9ng/ml, lower PRL level were more commonly associated with type-2 diabetes and metabolic syndrome at baseline. Moreover, after a median of 12yr of follow-up (IQR=6.9-15.8yr), the risk of developing myocardial infarction was greater in women with PRL<2.30ng/ml (SHIP-START criteria): adjusted hazard ratio=4.19(95%CI:1.74-10.12), and in women with PRL<3ng/ml (EMAS criteria): hazard ratio=2.74(95%CI:1.44-5.21).

Conclusions: Our data suggests that a serum PRL level lower than 3ng/ml could be adopted for identifying PRL-associated cardiometabolic disease in both sexes.