Luteinizing Hormone Suppression Profiles in Men Treated with Exogenous Testosterone

Abstract

ABSTRACT Background Due to the negative feedback mechanism involved in the hypothalamic-pituitary-gonadal axis, testosterone therapy (TTh) may result in suppression of luteinizing hormone (LH) secretion, but clinical experience demonstrates the level of LH suppression is variable. Aim We sought to define the relationship between TTh and LH levels, specifically predictors of LH suppression in men on TTh. Methods We performed a retrospective analysis of a prospectively maintained database of patients with testosterone deficiency (TD) treated with TTh. Patient demographic and clinical data including vascular risk factor (VRF) status were collected. Serum total T and LH levels before TTh and after ≥3 months (m) were recorded. LH suppression was defined as serum LH level <1.0 IU/ml. Main Outcome Measures Predictors of LH suppression were searched though a series of logistic regression models assessing suppression status at the final observation, and then a series of Cox proportional hazards models assessing time to first suppression were performed. Results A total of 227 patients with mean age of 58±14 years at time of TTh initiation were included in our analysis. Just under half of subjects received transdermal T as the only modality (n = 101, 44%), while one third (n = 77, 34%) received intramuscular only, and the remainder (n = 49, 22%) received both modalities during follow-up. The mean baseline LH level was 10 ± 12 IU/ml. The percent of men who had baseline LH level above 1 IU/ml and at any given point of TTh was 84% and 78%, respectively, thus 22% of men had suppressed LH levels on TTh considering the definition of LH <1 IU/ml. Most men (73%) had a suppressed LH level of <1 IU/ml at least once during follow-up. In the final adjusted model for LH suppression, intramuscular route (OR = 2.44), baseline LH (OR = 0.94), estradiol (OR = 1.05) remained significant. Clinical Implications LH suppression profiles may be relevant for dose titration during TTh and perhaps to minimize testicular atrophy. Strengths & Limitations A strict definition for TD was applied using LCMS for T measurements and patients had long-term follow-up. Conclusion While 73% of patients had at least one LH <1 IU/ml during TTh, only 22% maintained suppressed throughout the treatment.