Proportion and predictors of Hypogonadism Recovery in Men with Macroprolactinomas treated with dopamine agonists

Abstract

Introduction: Hypogonadism is the most common form of hypopituitarism in men with macroprolactinoma. However, evidence on factors related to hypogonadism recovery is limited.

Objectives: We estimated the proportion of hypogonadism in men with macroprolactinoma exclusively treated with dopamine agonists, and we assessed the factors predicting hypogonadism recovery.

Patients and methods: This was a multicenter retrospective study of men with macroprolactinoma identified using ICD 9 and 10 codes and treated between 2009 and 2019 in five centers in the United Arab Emirates and Saudi Arabia. We evaluated hypogonadism, defined as low total testosterone (TT) level with normal or low gonadotropins on presentation and during the last clinic visit.

Results: A total of 79 patients (median age 32 years) were included in the study. The most common symptoms at presentation were headache (73.7%), erectile dysfunction (55.4%), and low libido (54.3%). The median tumor size was 2.9 cm (1.0-9.7) at diagnosis. Sixty-three patients (79.7%) had hypogonadism at baseline. Growth hormone deficiency (GHD) and hypothyroidism were present in 34.4% and 32.9% of patients, respectively. The median serum prolactin (PRL) level was 20,175 (min-max 2254 - 500,000) mIU/l with a median serum TT of 4.5 (min-max 0.4-28.2) nmol/l. Most patients were treated with cabergoline (n = 77, 97.5%) with a median of 6 (min-max 0.6-22) years. At follow-up, 65% of patients recovered their pituitary-testicular axis. Patients with recovered hypogonadism had smaller median tumor size (2.4 [1-5.4] vs. 4.3 [1.6-9.7], p = 0.003), lower PRL level (18, 277 [2254 - 274, 250] vs. 63,703 [ 3,365-500,000], p = 0.008 ), higher TT level (4.6 [0.6-9.2] vs. 2.3 [0.5-7.3], p = 0.008), lower PRL normalization time on medical therapy (8 months (0.7-72) vs. 24 (3-120), p = 0.009) as well as lower frequency of GHD (17.1% vs. 60%, p = 0.006) and secondary hypothyroidism (17.9% vs. 57.1%, p = 0.003) compared with those with persistent hypogonadism respectively. Age at diagnosis, presenting symptoms and duration of medical therapy did not predict hypogonadism recovery.

Conclusions: About two-thirds of men with macroprolactinoma recover from hypogonadism, mostly with 24 months of therapy. Smaller adenoma size, lower prolactin level, earlier prolactin normalization, and higher testosterone patients were related to testosterone normalization.

Keywords: Dopamine agonist; Hypogonadism; Hypopituitarism; Prolactinoma.