Use of progestins in male contraception

@article{Nieschlag2003UseOP,
  title={Use of progestins in male contraception},
  author={Eberhard Nieschlag and Michael Zitzmann and Axel Kamischke},
  journal={Steroids},
  year={2003},
  volume={68},
  pages={965-972}
}

Hormonal approaches to male contraception: Approaching reality

Male hormonal contraception: concept proven, product in sight?

A better understanding of the endocrine and genetic regulation of spermatogenesis is necessary and may allow for new treatment paradigms, as the development of an effective, consumer-friendly male contraceptive remains challenging.

Male contraception: A realistic option?

  • M. WenkE. Nieschlag
  • Biology, Medicine
    The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception
  • 2006
This review illustrates the principle of hormonal male contraception and gives an overview of current trials aiming at the development of a marketable hormonal contraceptive for men, finding that scrotal and non-scrotal testosterone patches, orally administered testosterone undecanoate and testosterone gels are generally well tolerated and provide stable testosterone levels in the normal range.

Direct effect of progestogen on gene expression in the testis during gonadotropin withdrawal and early suppression of spermatogenesis.

Analysis of expression of genes in the normal human testis reflecting steroidogenesis, Sertoli cell function, and spermatogenesis after short-term gonadotropin withdrawal and the effects of activating testicular progesterone receptors provides evidence for direct progestogenic effects on the testis.

The Leydig Cell as a Target for Male Contraception

Control of testicular steroidogenesis and gametogenesis represents the main target of hormonal male contraception and hormonal fertility regulation through the Leydig cell provides the most promising method for men who wish to control their fertility.

Depot testosterone with etonogestrel implants result in induction of azoospermia in all men for long-term contraception.

The combination of three etonogestrel implants with depot testosterone results in rapid and consistent suppression of spermatogenesis, which can be maintained for up to 1 year and may be a suitable approach for a long-acting male hormonal contraceptive.

Male Hormonal Contraception: Where Are We Now?

Hormonal male contraception clinical trials began in the 1970s. The method is based on the use of exogenous testosterone alone or in combination with a progestin to suppress the endogenous production

Effects of testosterone and levonorgestrel combined with a 5alpha-reductase inhibitor or gonadotropin-releasing hormone antagonist on spermatogenesis and intratesticular steroid levels in normal men.

A similar high testicular:serum gradient exists for E2 and T in normal men, and 8 wk of gonadotropin suppression markedly reduces iTT, with 5alpha-reduced androgens and E2 levels decreasing to a much lesser degree.

Would male hormonal contraceptives affect cardiovascular risk?

  • M. Zitzmann
  • Medicine, Biology
    Asian journal of andrology
  • 2018
Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk, however, as all trials have been relatively short (< 3 years), a final statement regarding the cardiovascular safety of hormonal male contraceptive, especially in long-term use, cannot be made.

Norethisterone enanthate has neither a direct effect on the testis nor on the epididymis: a study in adult male cynomolgus monkeys (Macaca fascicularis).

Short-term NETE treatment has neither a direct effect on the testis nor on the epididymis in this nonhuman primate model and its contraceptive effects appear to be exerted exclusively through gonadotropin suppression.
...

References

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The results of the first clinical trial with TB for male contraception indicate a different hormonal equilibrium and probably different susceptibility to feedback regulation of the responders compared to the nonresponders.

Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception.

It is demonstrated that etonogestrel implants with depot testosterone provide effective suppression of spermatogenesis with reduced metabolic effects and are, therefore, a promising approach to the development of long-acting yet reversible male contraception.

An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations.

This study documents the high efficacy of TU in combination with NET and confirms that this dose and mode of application is as effective as the previously reported regimen containing 1000 mg TU + 200 mg NETE im every 6 wk.

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Although only 5 of 11 volunteers reached the target sperm counts (<3 million/mL), the study shows that a self-applicable hormonal male contraceptive could be developed.

Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism.

The combination of oral progestogens with low dose T is a promising approach to achieve effective reversible male contraception and was highly effective in suppressing pituitary-testicular functions in adult men.

Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men.

This combination of oral desogestrel with depot testosterone maintains physiological testosterone concentrations with consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men and therefore has many of the properties necessary for a contraceptive preparation for men.

Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception.

Combination treatment with NETE showed suppression of spermatogenesis comparable with results using testosterone esters in combination with GnRH antagonists or cyproterone acetate, but had more favorable injection intervals and better efficacy.

Suppression of spermatogenesis in man induced by Nal-Glu gonadotropin releasing hormone antagonist and testosterone enanthate (TE) is maintained by TE alone.

It is concluded that sperm counts suppressed with GnRH antagonist plus T can be maintained with relatively low dose TE treatment alone and the concept should be explored further in the development of effective, safe, and affordable hormonal male contraceptives.

Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach.

It is concluded that combination hormonal therapy with T plus a progestogen might offer a reversible male contraceptive approach with a more rapid onset of action and more reliable induction of both azoospermia and severe oligOSpermia than T alone.

Effects of testosterone plus medroxyprogesterone acetate on semen quality, reproductive hormones, and germ cell populations in normal young men.

It is concluded that the addition of DMPA hastens the onset of FSH/LH suppression, correlating with a more rapid impairment of spermatogonial development, but in the longer term, neither germ cell number nor sperm count differed.