Suppression of spermatogenesis by means of continuous delivery of danazol in combination with dihydrotestosterone from ALCAP drug delivery devices.

The objectives of this investigation were to evaluate the release of Danazol (D) and dihydrotestosterone (DHT) from nonimpregnated and polylactic acid (PLA) impregnated ALCAP ceramic reservoirs implanted in male rats, and to study the effects of delivered androgens on the reproductive system of male rats. A total of 120 Sprague-Dawley male albino rats were distributed equally into three groups. Two ALCAP capsules, one nonimpregnated and the other impregnated with polylactic acid (PLA) were implanted into each rat in group I and II. Capsules implanted into group I rats were loaded with a mixture of 20 mg D and 20 mg DHT. Group II rats were implanted with two empty capsules (sham group), and group III animals served as unimplanted controls. Eight rats from each group were euthanized at the end of one, three, six, nine, and twelve months following the implantation of the ceramics. No significant change in the weights of vital organs of rats were observed among any of the three groups. Vas deferens and epididymal fluid were devoid of normal spermatozoa within three months of implanting the steroid containing ceramics. Testicular and epididymal weights decreased significantly in the rats implanted with ALCAP containing steroid and the seminiferous tubules became oligospermic after one month and azoospermic after three months. The levels of circulating testosterone, luteinizing hormone, and follicle stimulating hormone were suppressed in rats implanted with steroid containing ceramics. Data collected in this study suggest that: (1) ALCAP ceramic capsules are capable of delivering D and DHT continuously for 12 months, (2) the amount of D and DHT released by ALCAP capsules was sufficient to suppress spermatogenesis and induce azoospermia in rats.