WITHDRAWN: Kinin-enhancing drugs for unexplained subfertility in men

Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility. One suggested treatment for idiopathic oligo- and/or asthenospermia is the administration of kallikrein (kallidinogenase), a kinin-releasing enzyme (or kininogenase). Although the kinin system may also be involved in the regulation of spermatogenesis in vivo, a clear mechanism of action is missing. Multiple suggestions on how an increase in kinin levels in the genital tract influences spermatogenesis at the testicular levels have been made by various authors.

To determine whether treatment of the male with drugs enhancing kinin levles increases pregnancy rates among couples where failure to conceive has been attributed to idiopathic oligo- and/or asthenospermia. Effects on sperm parameters and sex hormones were studied as secondary outcomes.

The Cochrane Subfertility Review Group specialised register of controlled trials was searched.

SIxteen RCTs on the therapeutic use of androgens (clomiphene citrate or tamoxifen) in subfertile men were identified. Six trials were excluded.

All data were extracted by the first author. Unclear issues were resolved by consensus with the senior author (RL). Data was combined for meta-analysis using Peto odds ratios for dichotomous data or weighted mean difference for continuous data.

X AUTHORS' CONCLUSIONS: This review does not provide conclusive proof of effectiveness. The benefit on pregnancy rates suggested by observational studies and low quality controlled trials is not confirmed by more rigorous trials. A modest effect on sperm motility is technically possible but was again not confirmed in the better quality trials. The clinical significance of a modest increase in sperm motility is uncertain. Untill effectiveness is proven, kallikrein should only be used in the context of clinical trials.