Serum prolactin level is an independent predictor of mortality among adults without prolactinoma, according to study results published in the Journal of Clinical Endocrinology & Metabolism.

Researchers conducted a systematic review and meta-analysis to evaluate and quantitatively synthesize the association between serum prolactin levels and mortality risk among adults without prolactinoma. Inclusion criteria were prospective and retrospective cohort studies reporting on the prognostic effects of serum prolactin levels.

The primary outcome was long-term all-cause mortality, whereas secondary outcomes were long-term cardiovascular mortality and in-hospital or intensive care unit (ICU) mortality. The researchers used a random-effects model to quantify the adjusted hazard ratios (aHRs) for mortality during follow-up.

The systematic review included 28 studies, of which 14 were included in the meta-analysis. Among these 28 studies, 14 explored in-hospital or ICU mortality, with stays ranging from 3 to 64 days.

The pooled sample comprised 23,596 individuals. The mean serum prolactin levels among deceased participants and survivors spanned from 6.8 to 73 ng/ml and 6 to 28 ng/ml, respectively.

Among the 12 studies that reported the link between serum prolactin levels and all-cause or cardiovascular mortality, follow-up ranged from 8 months to 10 years. Most of these studies’ findings suggested that higher prolactin levels were associated with adverse long-term outcomes, whereas findings from 2 studies suggested specific prolactin thresholds (50 ng/ml and 13.8 ng/ml) for mortality prediction among patients with liver disease.

From 3 studies including 15,009 adults with and without chronic kidney disease or diabetes, increasing prolactin levels were associated with all-cause mortality (aHR, 1.17; 95% CI, 1.08-1.27) and cardiovascular mortality (aHR, 1.54; 95% CI, 1.14-2.09).

Additionally, 5 studies with 25,741 adults, including those with and without diabetes or heart failure, revealed an association between mortality risk and the highest vs lowest prolactin category (aHR, 1.81; 95% CI, 1.43-2.30).

Across 4 studies with 18,931 adults, including participants with and without diabetes or heart failure, “high prolactin” vs low prolactin was associated with cardiovascular mortality (aHR, 1.59; 95% CI, 1.04-2.42).

Among 7 studies involving 1447 patients, prolactin levels were not significantly associated with in-hospital or ICU mortality (mean difference (MD), 1.88; range, -0.91 to 4.67; P =.19). Similarly, the researchers identified no significant association between serum prolactin levels and ICU mortality alone (MD, -0.71; range, -1.53 to 0.10; P =.09).

Study limitations include potential confounding in the in-hospital and ICU mortality analyses, high degrees of heterogeneity, and inherent challenges associated with using prolactin as a biomarker.

The researchers concluded, “This meta-analysis suggests that prolactin measurements can help identify individuals — beyond patients with prolactinoma — with a higher risk for adverse outcomes and in need for a tighter follow-up and better management of comorbidities.”