Abstract
OBJECTIVE: To compare the effect of exogenous short-acting and long-acting testosterone on male reproductive potential in mice. DESIGN: In vivo mouse model. SETTING: University-based basic science research laboratory. ANIMALS: A total of 30 wild-type C57BL/6 male and female mice were used for this experimentation. The male mice were used for control group and testosterone supplementation, while both male and female mice were used for the breeding portion of the study. INTERVENTIONS: Exogenous testosterone was administered either in short-acting formulation (Monday-Wednesday-Friday dosing schedule, testosterone propionate 0.2 mg/kg), or long-acting formulation (3-month dosing schedule - testosterone pellets 150 mg) to male mice. MAIN OUTCOME MEASURES: Time to pregnancy, Luteinizing hormone (LH) levels, and testicular weight. RESULTS: Mice treated with long-acting testosterone appear to have longer time to pregnancy when compared to wild-type (33 ± 11 vs 23 ± 2.6 days, p ≤ 0.05) and mice that received short-acting testosterone propionate (26 ± 5.9 days). Mice treated with long-acting testosterone had smaller testes weight when compared to control (0.08 ± 0.01 vs 0.11 ± 0.01g; p ≤ 0.01), while the short-acting testosterone treated mice had similar testis weight when compared to control (0.09 ± 0.02 vs 0.11 ± 0.01g; ns). The serum testosterone level was elevated in mice that received testosterone pellets (285.78 ng/dL) and testosterone propionate (122.16 ng/dL) versus control (68.4 ng/dL). In mice that received long-acting testosterone pellets, LH levels at 3 months were almost undetectable while those that received short-acting testosterone remained similar to control (0.017 ± 0.058 vs 0.348 ± 0.232 IU/L; p ≤ 0.01). Female reproductive potential parameters including litter size and pup weight were collected and observed to have no difference between groups. CONCLUSION: Through a mouse breeding study, mice that received short-acting testosterone were shown to have fertility potential similar to wild-type male mice. Long-acting exogenous testosterone appeared to impair male reproductive capacity and LH levels when compared to short-acting testosterone. Short-acting testosterone appeared to cause less LH suppression. Identifying strategies to increase testosterone while simultaneously preserving male fertility is important for treating young men with hypogonadism.