Effect of Chronic Cabergoline Treatment and Testosterone Replacement on Metabolism in Male Patients with Prolactinomas

Abstract

Introduction: Hyperprolactinemia and hypogonadism are reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of testosterone replacement and cabergoline (CAB) treatment on the metabolic profile in male hyperprolactinemic patients. Patients and Methods: Thirty-two men with prolactinomas, including 22 with total testosterone (TT) <8 nmol/l (HG, 69%) and 10 with TT >8 nmol/l (non-HG, 31%), were entered in the study. In all patients, metabolic parameters were assessed at diagnosis and after 12- and 24-month treatment. Results: Compared to non-HG patients, at baseline the HG patients had higher waist circumference (WC). TT significantly correlated with body mass index (BMI). Twelve-month CAB induced PRL normalization in 84%. HG prevalence significantly decreased (28%) and non-HG prevalence significantly increased (72%). Anthropometric and lipid parameters, fasting insulin (FI), insulin sensitivity index (ISI₀), homeostatic model assessment of insulin secretion (HOMA-β) and homeostatic model assessment of insulin resistance (HOMA-IR) significantly improved compared to baseline. TT was the best predictor for FI. Percent change (Δ) of TT significantly correlated with ΔCholesterol, ΔWeight and ΔBMI. Compared to non-HG patients, the HG patients had a higher weight, BMI, WC and HOMA-β. In HG, testosterone replacement was started. After 24 months, PRL normalized in 97%. HG prevalence significantly decreased (6%) and non-HG prevalence significantly increased (94%). Anthropometric and lipid parameters, FI, ISI₀, HOMA-β and HOMA-IR significantly improved compared to baseline, with FI, ISI₀, HOMA-β and HOMA-IR further ameliorating compared to the 12-month evaluation. Compared to non-HG patients, the HG patients still had a higher weight, BMI and WC. Conclusions: In hyperprolactinemic hypogonal men, proper testosterone replacement induces a significant improvement in the metabolic profile, even though the amelioration in the lipid profile might reflect the direct action of CAB.

Hyperprolactinaemia

“…However, it is difficult to discern whether these favourable metabolic effects are directly related to resolution of hyperprolactinaemia or are due to restoration of gonadal function or a combination of both. Notably, a study of 32 men with prolactinoma demonstrated significant decreases in the prevalence of metabolic syndrome after 12 months of treatment with cabergoline only amongst those with hypogonadism at baseline [131]. Nonetheless, significant improvements in weight, BMI, waist circumference, lipid profile, and insulin resistance were seen in both hypogonadal and eugonadal patients, suggesting that PRL may play a direct role in mediating these adverse metabolic effects [131].…”

Glucose Abnormalities Associated to Prolactin Secreting Pituitary Adenomas

“…Several studies (2–7, 22, 47–70) have investigated the link between PRL levels and gluco-insulinemic metabolism. In rodents, PRL is responsible for peculiar changes in pancreatic β-cell mass and function during pregnancy (2–7).…”

“…Such metabolic gain appears to be independent on the degree of reduction in PRL levels, and may be directly attributable to cabergoline dose instead (42, 43). In men with prolactinomas and persistent hypogonadism, accounting for up to 50% of cases (44–46), proper testosterone treatment may enhance the effects of cabergoline by further reducing insulin resistance and metabolic syndrome (47).…”

DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview

“…When the signs of hypogonadism related to the drug-induced hyperprolactinaemia are evident (i.e. amenorrhea in women or androgen deficiency symptoms in men) or there is an increased risk of bone loss, it is recommended to add estrogen or testosterone replacement therapy (51). Asymptomatic, drug-induced hyperprolactinaemia usually does not require treatment.…”