Recovery of Male Hypogonadism Following Successful Treatment of Prolactinoma: The Experience of an Integrated Health Network
Authors: Voica Mihail , Tetlay Maryam , Thompson Diane V , Hasan Farhad 
Published: May 2021

Abstract
Background: Hypogonadism is the most prevalent deficiency in male patients with prolactinomas (PrL). The recovery rates of hypogonadism (HGo) following treatment of PrL is variable and can be as high as 62%. In this study we aimed to identify predictors of HGo recovery in mean with PrL. We hypothesized that younger and leaner men and smaller tumor size predict HGo recovery after successful PrL treatment. We also hypothesized that higher baseline serum T predicts HGo recovery.
Methods: We conducted a retrospective review of the electronic medical records of adult males with a diagnosis of hyperprolactinemia or PrL who were treated at Allegheny Health Network (Pittsburgh, PA) between January 1, 2016 and December 31, 2019. Serum prolactin and testosterone (T) levels, and pituitary tumor size (microadenoma &lt;10mm, macroadenoma 10-39mm, or giant adenoma ≥ 40 mm) on MRI scan at diagnosis and up to 2 years follow up were analyzed. HGo was defined as serum T below reference range at diagnosis. HGo recovery was defined as total T in the reference range within 2 years from PrL treatment onset in the absence of T replacement.
Results: We screened 215 male patients who met initial search criteria. Of the 37 subjects who met eligibility criteria, 26 had HGo while 11 had normal serum T (Fig 1). Mean age of men with HGo was 44.6 ± 13.7 years (range 21 – 64). Median serum prolactin at diagnosis was 283.5 ng/mL (range 31-14,830), and mean serum T was 167.07 ± 61.12 ng/dL. Median tumor (max) diameter was 17.5 mm (range 4-81mm). Of the included 26 patients 20 (77%) achieved normal prolactin with therapy after a median of 5 months. Only 10 of the 26 men with HGo (38.5%) attained recovery of HGo following treatment of PrL, and the mean time to recovery was 8.8 ± 6.9 months. HGo recovery was predictably more common in persons with microadenoma (n=6) while none of patients with giant Prl achieved HGo recovery. Baseline serum prolactin and T levels and baseline tumor size predicted subsequent HGo recovery, while age did not. Baseline serum prolactin was lower in men whose HGo recovered (median = 105 ng/mL, IQR = 202) than in men who did not (median = 931 ng/mL, IQR = 3714); p = 0.014. Baseline serum T was higher in men who attained HGo recovery (173.2 ± 59.6) than in men who failed to do so (103.1 ± 85.9); p = 0.03. Mean tumor size was significantly smaller in men who attained HGo recovery (max diam: 9.8 ± 5.5 mm) than in men who did not (31.8 ± 20.3 mm); p = .003. There were no statistically significant differences between men categorized by remission status with respect to age (p = .367) nor weight at the time of diagnosis (p = .591).
Conclusion: In this retrospective study of 26 males with PrL and low T at presentation, 38.5% achieved HGo recovery. Lower baseline serum prolactin, smaller tumor size and higher baseline T predicted recovery of HGo, while presenting age and weight did not. This study was limited by its retrospective nature and small sample size.