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  • Title: Endocrine approaches to male fertility control.
    Author: Knuth UA, Nieschlag E.
    Journal: Baillieres Clin Endocrinol Metab; 1987 Feb; 1(1):113-31. PubMed ID: 3297020.
    Abstract:
    As in the female, gametogenesis in the male is under the control of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Their suppression should inhibit spermatogenesis. If a non-androgenic substance is used to suppress gonadotrophins, androgens must be supplemented to maintain virility, potency and metabolic processes. To avoid administration of several substances, testosterone and its esters were used to develop a male antifertility agent. Although azoospermia can be induced in a high proportion of men with administration of testosterone esters alone, this effect is not uniform. Even frequent injections with testosterone enanthate at weekly intervals fail to inhibit spermatogenesis in all participants. Combinations of gestagenic compounds with testosterone esters show a somewhat better effect, but again azoospermia is only achieved in around 50% of participants. LHRH analogues, although considered by many to offer a realistic potential for male fertility regulation, have not been proven to be successful for this purpose so far. Animal studies in monkeys and preliminary clinical trials demonstrate that agonistic analogues of LHRH have to be given continuously by pump or implant to achieve a pronounced effect on spermatogenesis. But even under these provisions, results in clinical trials have been worse than effects achieved with testosterone/gestagen combinations. Whether new antagonistic compounds offer a better potential awaits clinical trials. Studies in non-human primates demonstrate that testosterone by itself can maintain and initiate spermatogenesis. Based on these findings one could postulate an attenuating effect of high serum androgen levels after supplementation with available testosterone esters. Trials of alternative androgenic substances with slow-release characteristics and without high serum levels after single injections, like 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP), tend to support this theory. With slow-release testosterone preparations under development by the WHO and more advanced delivery systems for LHRH analogues it is not unreasonable to speculate that an effective endocrine antifertility agent for the male will become available. Interference with spermatogenesis via endocrinological mechanisms has potential for male fertility control. The general concept of endocrine male fertility regulation involves combination of an antigonadotrophic substance with an androgen. At first, testosterone and its esters were thought to be ideal agents for steroidal inhibition of spermatogenesis. The failure of testosterone esters alone injected at reasonable intervals to induce consistent azoospermia or severe oligozoospermia led of treatment schedules with a combination of different hormones. Combinations of gestogenic compounds with testosterone esters were somewhat more effective, but azoospermia was achieved in only about 50% of volunteers. Luteinizing hormone-releasing hormone (LHRH) analogues, although considered by many to offer realistic potential for male fertility control, have not been successful so far, even when LHRH agonistic analogues are given by pump or implant. Trials of alternative androgenic substances with slow-release characteristics and without high serum levels after single injections, such as 19-nortestosterone, suggest an attenuating effect of high serum androgen levels after supplementation with available testosterone esters. Slow-release testosterone preparations under development and more advanced delivery systems for LHRH analogues appear to offer the greatest potential for advances in male fertility regulation. Requiring discussion is the question of whether 100% infertility is essential or whether severely reduced fertility would be acceptable to some sectors of the world population.
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