Due to the increasing trends of gender equality as one of the most essential reforms, the concept of male contraception and development of novel methods has been emphasised. So far, mostly females have taken this additional burden of contraception and reproductive health till recently either due to the routine social stigma or non-availability of viable options for contraception in males. Till date, the most popular and commonly used methods of male contraception are usage of condoms and vasectomy.
The usage of condoms has gained more popularity for its multiple advantages – easy to use, easy availability, reversible and protection from sexually transmitted infections. However condoms are only 98% effective and do have few limiting factors like tearing. Different kinds of condoms are available in the market such as latex, polyurethane, lambskin, textured, lubricated, spermicidal and non-spermicial.
Any mode of contraception should meet a few criteria to be qualified as an effective contraception on a daily basis. The most important criteria would be ease of use and accessibility, speed of action, reversibility of the method, with minimal side effects (especially should not be detrimental to secondary sexual characters, sexual pleasure and performance) and maximum contraceptive benefits.
Vasectomy is almost 100% effective with no major side effects and is considered as a minor surgical procedure. The reader is referred to the articles on vasectomy and vasectomy reversal, for further details.
More diverse methods of male contraceptives are to be developed in view of the greater demand. So the quest for novel methods of male contraception has begun but being hindered by multiple factors such as lack of funding for development of male contraception, disinterest from the industry, slow research on newer testosterone preparations and most considerably the male reproductive physiology where we are dealing with a daily production of millions of sperms rather than one or two eggs in a month.
The development of novel methods of male contraception can be either hormonal or non hormonal. The non hormonal approach though have potential advantages with its emphasis on blocking spermatogenesis and sperm maturation in the epididymis or vas deferens, motility or during the transportation but unfortunately are still in the very early stages of research. These can be infiltrated physically in the form of soluble compounds into the vas to either block the vas or damage the spems in their transit through the vas.
The non hormonal methods can be classified based on their site of action into those acting on spermatogenesis or epididymis or vas deferens.
AGENTS ACTING ON THE VAS for male contraception
Adrenoceptor antagonists such as tamsulosin and silodosin are believed to inhibit the smooth muscle contractility which affects the transit of sperms from epididymis along the vas which reduces the sperm concentration in semen. Adequate doses to achieve anejaculation are associated with side effects and lower doses were insufficient.
This involves injection of a polymer which can affect the integrity of the cell membrane of the sperm into the vas and is also reversible by either mechanical massage or by injecting a dissolving agent. Further preclinical studies are being carried out to establish its safety and efficacy.
DRUGS TARGETING SPERMATOGENESIS
The novel male contraceptives based on a hormonal approach, act via gonadotrophin suppression involving the hypothalamic-pituitary-testicular (HPT) axis achieved by administration of exogenous testosterone in combination with progestogen.
Next option was the combination of progestogen along with testosterone which allows a much lower dose of testosterone to be used (comparable to physiological doses), since the progestogen does the gonadotrophin suppression. But the limiting factor was the non availability of long acting testosterone formulations in the 1990’s. Later came the long acting testosterone undecanoate, alone or in combination with norethisterone enanthate (both given at 8 week intervals) proving itself with a good contraception efficacy, but the trials were halted by the World Health Organization due to side effects. Both GnRH agonists and antagonists can act as contraceptives but do not result in adequate gonadotrophin suppression in men, the agonists being very less effective and the antagonists being comparably less effective to the testosterone-progestogen combinations. Also the GnRH antagonists being only available in parenteral preparations requiring either serial injections or infusions have compliance and cost issues.
The most recent development is a nestorone-testosterone gel (NES/T) which is under phase IIb clinical trial to establish efficacy and side effects. This is a newer and effective progestogen with minimal activity at the androgen receptor, and was shown to suppress FSH and LH to less than 1 IU/L, more consistently and effectively than testosterone gel alone. A significant decrease in sperm concentrations were noted even with a 4 weeks treatment with no significant side effects.
Synthetic androgen-progestogen compounds and selective androgen receptor modulators
Multiple chemical compounds have been developed that exhibit both androgenic and progestogenic effects and represent potential male contraceptives. Several studies are being run to develop these drugs, both as implantable and oral contraceptives. Recently, two oral preparations, 11-beta-methyl-19-nortestosterone dodecylcarbonate and dimethandrolone undecanoate, have been shown to achieve adequate gonadotrophin suppression and can be considered as potential male contraceptive pills in early stages. 7alpha-methyl-19-nortestosterone (MENT) is another promising androgen which does not undergo 5-alpha reduction but can be aromatised. This in combination can even have protective effects against prostate. It can be administered as an implant (because of rapid clearance) and can provide good gonadotrophin and spermatogenic suppression.
Bisdichloro acetyldiamine: This acts by reversible inhibition of conversion of Vitamin A to retinoic acid in the testis, essential for meiotic phase in spermatogenesis. Though being a rapidly effective method than the hormonal approach, because of its ‘ant-abuse’-type reaction in human beings is not considered a viable alternative till the reaction can be eliminated.
Bromodomain testis-specific protein inhibitors (BRDT): BRDTs are very important in the chromatin remodeling and usually expressed during the sperm maturation. Thus, BRDT inhibitors serve the purpose of contraception but still in the preclinical testing stage.
Lonidamine with anti spermatogenic characteristics has got significant side effects (testicular pain, liver dysfunction) and lesser efficacy.