Predictors of Chronic LH-Testosterone Axis Suppression in Male Macroprolactinomas With Normoprolactinemia on Cabergoline

Context: Data are limited regarding prevalence, predictors, and mechanisms of persistent hypogonadotropic hypogonadism (HH) in males with a macroprolactinoma who achieve normoprolactinemia on dopamine-agonist therapy. None of the previous studies provide cutoffs to predict the achievement of eugonadism. Objective: The objective of this work is to evaluate the prevalence of persistent HH and its determinants in men with a macroprolactinoma who achieve normoprolactinemia on cabergoline monotherapy. Design and Setting: This retrospective study with prospective cross-sectional evaluation took place at a tertiary health care center. Patients: Study participants included men with a macroprolactinoma and baseline HH who achieved normoprolactinemia on cabergoline monotherapy. Main Outcome Measures: Outcome measures of this study included the prevalence of persistent HH and its predictors. Results: Thirty participants (age, 38.3 +/- 10.1 years) with baseline tumor size of 4.08 +/- 1.48 cm and median (interquartile range) prolactin of 2871 ng/ml (range, 1665-8425 ng/mL) were included. Eight of 30 participants achieved eugonadism after a median follow-up of 3 years. Patients with persistent HH had suppression of the luteinizing hormone (LH)-testosterone axis with sparing of other anterior pituitary hormonal axes, including follicle-stimulating hormone-inhibin B. Baseline prolactin (1674 vs 4120 ng/ml; P= .008) and maximal tumor diameter (2.55 +/- 0.36 vs 4.64 +/- 1.32 cm; P= .003) were lower in patients who achieved eugonadism. Baseline maximal tumor diameter less than or equal to 3.2 cm sensitivity: 75%, specificity: 63.6%) and serum prolactin less than or equal to 2098 ng/mL (sensitivity: 87.5%, specificity: 77.3%) best predicted reversal of HH. Conclusion: Recovery of the LH-testosterone axis occurred in 26.7% of men with a macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy. Higher baseline tumor size and serum prolactin predict persistent HH. Our data favor chronic functional modification of the hypothalamicpituitary-gonadal axis over gonadotroph damage as the cause of persistent