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.
Keywords: Cardiovascular risk; Dopamine agonists; Insulin sensitivity; Metformin; Prolactin deficiency; Women.
© 2025. The Author(s).