An empiric treatment for idiopathic oligozoospermia revisited: a 20-year investigative saga

A series of studies aiming at introducing an effective treatment for idiopathic oligozoospermia was conducted in a step-wise fashion spanning over a 20-year period. The concept was that co-administration of an accessory gland-stimulating androgen, testosterone undecanoate (40 mg t.i.d.) and the FSH raising anti-oestrogen tamoxifen citrate (10 mg b.i.d.) may improve sperm parameters. A prerequisite for such an effect was the demonstration that testosterone undecanoate had no suppressing action on pituitary-testicular axis. In this context, initial studies demonstrated no change in basal or stimulated gonadotrophin and testosterone secretion in short- or long-term protocols. Two subsequent trials with this combination showed a marked improvement of sperm parameters and pregnancy incidence, with a seasonal variation noted in response to treatment, this being higher during the cold seasons of autumn and winter. Regarding the mechanism of testosterone undecanoate's action, a recent study from our unit showed that its administration resulted in a marked rise of serum DHT levels. Because this steroid is an epididymal function promoter, it appears that its contribution in the combination is mediated mainly through its DHT raising effect. By and large, this empiric approach for the treatment of idiopathic oligozoospermia was satisfactorily documented after a 20-year investigative saga.