The impact of hypoprolactinemia on cardiometabolic effects of metformin in young women: a pilot prospective cohort study.

BACKGROUND

Subnormal prolactin concentrations were found to be associated with increased risk of metabolic complications. Thus, many patients with prolactin deficiency may be candidates for treatment with insulin-sensitizing drugs. The aim of this pilot prospective cohort study was to investigate metformin action on cardiometabolic risk factors in women with iatrogenic hypoprolactinemia.

METHODS

The study included three groups of reproductive-age women (18-50 years old) with recently diagnosed prediabetes or type 2 diabetes: 18 women with cabergoline-induced hypoprolactinemia (prolactin below 5 ng/mL) [group A], 19 normoprolactinemic women receiving cabergoline treatment because of previous prolactin excess [group B] and 25 cabergoline-naïve women with prolactin levels within the reference range [group C]. The groups were matched for age, fasting glucose and insulin sensitivity. All participants were treated with metformin for the following six months. The outcomes of interest included: glucose homeostasis markers, prolactin, testosterone, plasma lipids, concentrations of uric acid, high-sensitivity C-reactive protein [hsCRP], homocysteine and fibrinogen, and the urinary albumin-to-creatinine ratio [UACR].

RESULTS

Fifty-eight patients (17 in group A, 18 in group B and 23 in group C) completed the study. There were no statistical differences between groups A and B in cabergoline dose (1.19 ± 0.52 mg vs. 1.05 ± 0.46 mg weekly), cabergoline treatment duration (43 ± 12 vs. 47 ± 14 weeks), and long-term glycemic control (HbA1c in the range between 6.4 ± 0.5% and 6.6 ± 0.5%). At baseline, uric acid, hsCRP, fibrinogen and UACR were higher in group A than in the remaining two groups, while the opposite relationships were found for prolactin and testosterone. Metformin decreased glycated hemoglobin, fasting glucose, HOMA1-IR and hsCRP in all study groups, but this effect was less pronounced in group A than in groups B and C -6 ± 8% vs. -12 ± 8% and - 11 ± 7% [HbA1c], -13 ± 10% vs. -25 ± 14% and - 23 ± 15% [glucose], -26 ± 20% vs. -52 ± 25% and - 53 ± 30% [HOMA1-IR], -45 ± 30% vs. -47 ± 35% and - 53 ± 30% [HOMA1-IR]). The decrease in triglycerides, uric acid, homocysteine and UACR was observed only in normoprolactinemic women, not differing between groups B (-13 ± 19% -49 ± 31%), and C (-16 ± 23% -58 ± 26%). In neither group did the drug affect levels of prolactin and total testosterone.

CONCLUSION

Coexisting hypoprolactinemia may attenuate cardiometabolic effects of metformin in women.