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 3.0 ng/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 2048 women aged 20-81 year from SHIP-START and 1730 women aged 33-37 year 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 4.84 ng/mL in WENDY. These thresholds were not far off from that previously identified in men (3 ng/mL). In SHIP-START, we further found that compared to PRL levels of 5.0-34.9 ng/mL, lower PRL level were more commonly associated with type-2 diabetes and metabolic syndrome at baseline. Moreover, after a median of 12 year of follow-up (IQR = 6.9-15.8 year), the risk of developing myocardial infarction was greater in women with PRL < 2.30 ng/mL (SHIP-START criteria): adjusted hazard ratio = 4.19 (95% CI: 1.74-10.12), and in women with PRL < 3 ng/mL (EMAS criteria): hazard ratio = 2.74 (95% CI: 1.44-5.21).

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