Use of progestins in male contraception

Hormonal male contraception aims at suppression of spermatogenesis to azoospermia or at least to severe oligoasthenozoospermia, incompatible with the ability to induce a pregnancy. The general principle of this approach is based on interference with the endocrine regulation of spermatogenesis, i.e. the suppression of gonadotropins. Since both FSH (through the Sertoli cell) and LH (through the Leydig cell and testosterone (T)) are required for normal spermatogenesis, both gonadotropins need to be suppressed as strongly as possible. In East Asian men this can be achieved with T alone (preferably in depot preparations such as T undecanoate) but only two-thirds of Caucasian men respond with adequate sperm suppression. Therefore, in Caucasian men additional substances such as GnRH antagonists or progestins are required to suppress the pituitary. Over the past 30 years many combinations of various T preparations with different progestins have been tested in clinical trials. Since self-applicable steroid combinations (e.g. oral levonorgestrel or desogestrel with transdermal T) showed low effectiveness, currently injections and implants are under clinical development. Long-acting intramuscular T esters (e.g. T undecanoate), T pellets or implants (e.g. MENT) are combined with injections of DMPA or noresthisterone enanthate or with implants containing levonorgestrel or etonogestrel. Acute side-effects of these combinations appear to be minimal and tolerable, long-term effects need to be investigated.     

A new non-steroidal drug for long-acting contraception.

A new contraceptive compound had been prepared with the common ingredients and it was applied in female rats. The efficacy and toxicity tests of this compound showed that this drug has along-acting contraceptive value not causing any side-effects.     

BET proteins: Investigating BRDT as a potential target for male contraception

While many contraception options are available for women, birth control methods for men are limited to condoms and vasectomy. Past research into male contraceptives has focused on hormonal options but the associated side effects have thus far precluded this method from reaching the market. Non-hormonal male contraceptives and vas occlusion have also been explored, but to date no method has progressed past clinical testing. Recent interest in epigenetic research has unveiled a new potential non-hormonal male contraceptive target: the testis-specific bromodomain BRDT. Potent inhibitors for bromodomain-containing proteins are described in the literature, but a BRDT-specific compound has yet to be designed, prepared and tested. The high similarity between bromodomain proteins of the BET family makes development of selective and specific inhibitors both difficult and necessary. Selective inhibition of BRDT by a small molecule is an exciting new target in the search for a new non-hormonal male contraceptive.     

Apoptosis in the epididymal epithelium of adult male golden hamster exposed to diethylstilbestrol.

Apoptosis in the testis and prostate exposed to disrupters of endocrine function, including diethylstilbestrol (DES), during neonatal or postnatal periods has repeatedly been demonstrated, but not in the mature epididymis. We investigated the effects of DES, a potent and synthetic estrogen, on apoptosis in the adult. Adult male golden hamsters received an SC injection of DES and were then sacrificed to collect epididymides after 1, 4, or 7 days of treatment. A significant decrease in epididymal weight and an increase in apoptotic cells were shown on the first day after DES injection. Flow cytometry showed that DES treatment (1 mg/kg) for 1, 4, or 7 days induced significant apoptosis both in the caput and the cauda epididymides. Greater numbers of apoptotic cells were detected in the caput than in the cauda at a fixed time after DES treatment. Serum levels of testosterone decreased markedly within 24 hr after DES administration, reaching undetectable levels of 0.1 ng/ml at 4 days and thereafter. These results indicate that DES administration can increase epididymal apoptosis with a decrease in serum testosterone levels. Because DES used to be injected into domestic animals, adult males also have a chance to take this substance through food. Our study indicates that exposure to DES in adults is as toxic as that in the perinatal period.