7778 Factors Predicting Recovery of Hypogonadism in Men with Prolactinoma Treated with Dopamine Agonists
Authors: Constantinescu Stefan Matei , Alexopoulou Orsalia , Maiter Dominique M 
Published: October 2024

Disclosure: S. Constantinescu: None. O. Alexopoulou: None. D.M. Maiter: None.

Introduction: Recovery of hypogonadism is an important objective of dopamine agonist (DA) treatment in men with prolactinoma. However, the extent, timeline, and predictive factors of gonadotrope axis recovery are still unclear. Methods: We report data from a large cohort of 89 men with prolactinoma, looking at the evolution of testosterone levels after 6 and 12 months of treatment with DA. We excluded patients with peripheral hypogonadism, surgical treatment performed less than 12 months after onset of DA treatment, and patients with small tumors (≤ 5 mm and prolactin ≤ 50 µg/l) who did not achieve tumor shrinkage during treatment. We defined low testosterone as a morning value &lt; 10 nmol/l. Patients who had started testosterone supplementation were considered as having persistent hypogonadism. Results: Among the 89 men (mean age ± SD: 44 ± 14 years; 65/89 with a macroprolactinoma), 14 (16%) had normal initial testosterone levels (NT) and 75 (84%) had low testosterone at diagnosis (LT). Compared to LT, NT patients had significantly lower PRL (median 53 µg/l versus 490 µg/l, p=0.009) and smaller tumors (median 6.5 mm versus 21.2 mm, p=0.013). In the NT group, after 6 (n=11) and 12 months (n=10), testosterone rose from a median of 13.4 to 16.6 (p=0.266) and 17.9 nmol/l (p=0.012), respectively. In LT patients, after 6 (n=56) and 12 months (n=42), testosterone rose significantly from a median of 5.8 to 10.7 (p&lt;0.001) and 12.5 nmol/l (p&lt;0.001).In the LT group, 45% (32/71) had recovered eugonadism at 6 months and 57% (40/70) at 12 months. These proportions rose to 61% (22/36) and 67% (n=26/39) at 6 and 12 months when prolactin concentrations were normalized. Factors associated with persistent hypogonadism after one year were chiasmal compression at diagnosis (p=0.05), cavernous sinus invasion (p=0.042), cystic tumoral component (p=0.038), a greater tumoral diameter (mean 25 mm vs 15 mm, p&lt;0.01), lower testosterone concentrations at diagnosis (mean 3.6 nmol/l vs 6.8 nmol/l, p&lt;0.001) and at 6 months (mean 6.0 nmol/l vs 13.0 nmol/l, p&lt;0.03), and higher prolactin levels at one year (median 17.15 µg/l vs 8.4 µg/l, p=0.064). Testosterone &lt; 6.7 nmol/l at 6 months predicted the long-term persistence of hypogonadism with 72% sensitivity and 92% specificity. Conclusion: The sensitivity of the gonadotrope axis to high prolactin levels is highly variable in men with prolactinoma and 16% of them retain normal testosterone concentrations. However, this finding does not exclude partial inhibition of the gonadotrope axis that will improve with DA treatment. In patients with low testosterone levels, the recovery rate of hypogonadism is 45% at 6 months and 57% at 12 months, increasing to 67% if prolactin is normalized. Testosterone supplementation could be started early in patients with large, invasive, cystic and/or compressive tumors, with a testosterone concentration lower than 6.7 nmol/L after 6 months of treatment.

Presentation: 6/3/2024