Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study

Abstract

BackgroundProlactin is an anterior pituitary hormone that may modulate the adverse effects of obesity. Prolactin has been associated with cardiovascular disease mortality, but less is known about whether prolactin predicts incidence of cardiovascular disease risk factors.Methods and ResultsOur sample (n=3232, mean age 40.4 years, 52.1% women) was drawn from Framingham Heart Study participants who attended 2 examinations an average of 6.1 years apart. After excluding those with elevated prolactin (>30 mg/dL for women, >20 mg/dL for men), multivariable‐adjusted regressions modeled the associations between baseline prolactin and changes in cardiovascular disease risk factors. Models were adjusted for age, sex, baseline value of the risk factor, smoking status, hormone replacement therapy, and menopausal status and additionally for body mass index. Mean prolactin levels were 11.9 mg/dL (SD 5.2) in women and 8.0 mg/dL (SD 2.9) in men. No associations were observed for change in weight, body composition, total cholesterol, triglycerides, or fasting glucose. In women, for example, for each 5‐mg/dL increment in prolactin, odds of incident hypercholesterolemia were 1.06, which was not significant (95% CI 0.91–1.23, P=0.46). Some exceptions were of note. In women, for each 5‐mg/dL increment in prolactin, we observed increased odds of low high‐density lipoprotein cholesterol at follow‐up (odds ratio 1.50, 95% CI 1.18–1.91, P=0.001) that persisted after adjustment for body mass index (P=0.001). In men, a 5‐mg/dL increment in prolactin was associated with increased odds of incident hypertension (odds ratio 1.61, 95% CI 1.18–2.20 P=0.002) and incident diabetes (odds ratio 1.70, 95% CI 1.04–2.78, P=0.03).ConclusionsProlactin is not associated with a comprehensive panel of incident cardiovascular disease risk factors. Measurement of circulating prolactin levels in the community likely does not provide substantial insight into cardiometabolic risk.

Circulating prolactin concentrations and risk of type 2 diabetes in US women

“…Furthermore, our study demonstrated that the inverse association between prolactin and type 2 diabetes risk in women remained significant after adjustment for a variety of lifestyle and reproductive factors as well as other sex and growth hormones, suggesting that prolactin may be linked to type 2 diabetes through independent pathways. Two prospective studies of men and women combined reported null associations between prolactin and type 2 diabetes risk after multivariable adjustment [18, 21]. This lack of association might be due to the limited number of incident cases ( n =163 and 78), especially among women ( n =84 and 27), and a potentially different association by sex.…”

“…This lack of association might be due to the limited number of incident cases ( n =163 and 78), especially among women ( n =84 and 27), and a potentially different association by sex. In fact, several recent prospective studies suggested that the associations between prolactin and risk of type 2 diabetes and the metabolic syndrome were more likely to be beneficial in women but tended to be null or even detrimental in men [17–21]. The reason underlying this sex difference is unclear, as both beneficial and detrimental effects of prolactin on IR have been reported in men [12, 44].…”

“…However, long-term prospective data evaluating the relationship between prolactin and future type 2 diabetes risk remain limited, and existing evidence has been inconsistent [18–20]. Some studies reported an inverse association between prolactin and type 2 diabetes risk, particularly among women, while a few others reported null or positive associations in men and women combined [18– 21]. These studies had a limited number of participants (N<200) and a short follow-up (a median of <6 years).…”

Different Effects of Atorvastatin on Cardiometabolic Risk Factors in Young Women With and Without Hyperprolactinemia

“…17 In the Framingham Heart Study, however, after patients with elevated prolactin levels had been excluded, measurement of prolactin did not provide substantial insight into cardiometabolic risk. 18 In the light of our recent studies, it seems that pleiotropic effects of hypolipidemic agents may be attenuated by some endocrine and metabolic disturbances. A negative effect on extralipid effects of statins was exerted by untreated subclinical hypothyroidism and by low vitamin D status.…”

“…Finally, in the population‐based Study of Health in Pomerania, prolactin concentrations were correlated with all‐cause mortality and cardiovascular mortality . In the Framingham Heart Study, however, after patients with elevated prolactin levels had been excluded, measurement of prolactin did not provide substantial insight into cardiometabolic risk …”