Abstracts

Rationale: Hyposexuality is commonly associated with low bioactive testosterone (BAT) and relative estradiol (E) elevation in men with epilepsy (MWE) (Herzog AG et al. Neurol 2005;65:1016-20). This prospective, double-blind trial compared the effects of depotestosterone + the aromatase inhibitor anastrozole (T-A) versus depotestosterone + placebo (T-P) on sexual function, hormone levels, mood and seizure frequency in MWE. Methods: Forty MWE, aged 18-50, with hyposexuality and hypogonadism, were randomized 1:1 to 2 groups (T-A or T-P) for a 3-month treatment trial. Efficacy outcomes included monthly measures of 1) sexual interest & function (S-score), 2) hormone levels of BAT, E, FSH, LH and PRL, 3) emotional state (BDI-II, POMS), and 4) seizure frequency. Safety measures included 1) BP, 2) CBC, 3) LFTs, 4) PSA, 5) lipid profile and 6) AED levels. Treatment was 300 mg. of depotestosterone q2wk and either anastrozole 1 mg. or matching placebo daily. Results: Normalization of S-score (≥16/20) occurred with notably greater frequency in the T-A group (13 of 18, 72.2%) than in the T-P group (9 of 19, 47.4%) but not significantly so (Χ2=1.45, p=0.228). T-A showed a trend for greater improvement in S-score than T-P (3.7±1.6 vs 2.5±2.2; t=1.830, p=0.076). T-A resulted in significantly lower E levels than T-P (t=3.80, p=0.001). S-scores correlated significantly and inversely with E levels at baseline (r =-0.458, p=0.004) and during treatment (r=-0.367, p=0.026). BDI-II scores improved in 16 of 18 (88.9%) men in the T-A group and in 16 of 19 (84.2%) in the T-P group (Χ2: p=NS). There was no significant correlation between the changes in BDI and changes in any hormone level. Changes in S-score correlated inversely with changes in BDI score (r=-0.460, p=0.004). Changes in seizure frequency correlated with changes in BDI score (r=0.540, p=0.031). Lower seizure frequency occurred in 7 of the 7 (100%) men with active seizures in the T-A group and in 9 of the 10 (90%) men in the T-P group (p=NS) without significant change in AED levels. Seizure frequency correlated significantly with E levels during treatment (r=0.480, p=0.015) but not baseline. Changes in generalized motor seizure (GMS)frequency correlated significantly with changes in E levels for the 7 subjects with GMS (Spearman’s rho=0.809, p=0.028). There was a trend for a correlation between changes in overall seizure frequency and changes in E levels for the T-A group (r=0.413, p=0.088). Triglyceride (TG) levels increased with T-P from 130.1±61.4 to 153.4±75.5 mg/dl (t=2.079, p=0.050). In contrast, TG decreased from 140.5±93.9 to 130.1±83.2 with T-A (t=1.045, p=NS). The difference in TG changes between the two treatments was significant (t=2.241, p=0.032). Changes in TG correlated significantly with changes in E levels (r=0.392, p=0.020). Conclusions: Significant correlations between E levels and S-score, mood and seizure outcomes, as well as TG levels, suggest further study regarding a potential role for anastrozole in the treatment of men with epilepsy who have hyposexuality and hypogonadism.