Update on Male Hormonal Contraception: Is the Vasectomy in Jeopardy?

GJ Manetti and SC Honig


Int J Impot Res. 2010;22(3):159-170. 

In This Article

Medroxyprogesterone Acetate (MPA and Depot MPA)

Since the 1970s, the contraceptive efficacy of MPA has been studied.[58] Unlike studies on testosterone monotherapy, there are few randomized, multicenter, large population studies evaluating efficacy of testosterone/progestin preparations.[59]

A review of MPA/testosterone preparations showed that only 67% of patients receiving MPA with different testosterone preparations achieved azoospermia.[60] The 1993 WHO study comparing testosterone alone and 19-nortestosterone with depot MPA showed consistent azoospermia in 95.6 and 97.8%, respectively, in 90 Indonesian men.[61] On the basis of this data, it was not clear if the effect was from testosterone alone or combination therapy. Subsequent studies in 55 men with testosterone implants and depot MPA showed suppression to <1 million sperms per ml in 94% of patients with no pregnancies in this suppression subgroup.[62] Median time to counts returning to 20 million sperms per ml was 5 months, but return to baseline numbers was much longer, suggesting an accumulation of drug in adipose tissue. These studies were conducted in the Asian population only. Recently, two papers reporting on the same group of patients studied 38 men with testosterone gel and depot MPA for sperm suppression and evaluated patient acceptability of this combination.[63,64] Over 90% of patients had sperm suppression <1 million per ml, but acceptability was low, with only 45% saying they would use it if commercially available, one-third of the patients said it would interfere with their daily routine and questionnaire data showing mild changes in overall satisfaction with sexual activity and ejaculatory function. Interestingly, a subgroup of patients received GnRH antagonist, but there was no additive effect in terms of sperm suppression. A recent study by the same group looked at factors that might differentiate azoospermic groups from nonazoospermic groups.[55] Amory et al. performed a retrospective analysis of male hormone contraceptive studies and found that end of treatment INSL-3 levels were significantly increased in the nonazoospermic subgroup.[55] INSL-3 is a peptide hormone that appears to be almost exclusively produced by Leydig cells and can be relatively easily measured in serum by immunoassay. Although the exact role/function of INSL-3 remains unclear, administration of this substance to mice has been shown to prevent apoptosis of male germ cells in the setting of FSH/LH deficiency.[65] However, although INSL-3 may be a useful target for refining treatment, further investigation is still required to better understand and corroborate this interesting association between INSL-3 and nonazoospermic men and its potential application to the development of a hormonal contraceptive for men.


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