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  • Title: Inhibition of spermatogenesis in men using various combinations of oral progestagens and percutaneous or oral androgens.
    Author: Guerin JF, Rollet J.
    Journal: Int J Androl; 1988 Jun; 11(3):187-99. PubMed ID: 2970439.
    Abstract:
    Eight men (experiment 1) requesting male contraception received a daily oral dose of 20 mg medroxyprogesterone acetate (MPA) combined with 125 mg percutaneous dihydrotestosterone (DHT). Three months later the mean sperm count was only diminished slightly; the replacement of DHT for four men by percutaneous testosterone at the same concentration led to a dramatic fall in sperm count. For 6-18 months all men were treated with MPA plus percutaneous testosterone (250 mg daily). The latter dose restored physiological levels of plasma testosterone. Follicle-stimulating hormone levels were inhibited more severely than in the DHT-treated group, whereas LH levels were variable. Azoospermia was achieved and maintained in six cases; two men were oligozoospermic and in one case a moderate secondary rise in the sperm count was observed. Twelve volunteers (experiment 2) received a daily oral dose of either 5 or 10 mg norethisterone acetate plus percutaneous testosterone (250 mg daily). All of them achieved azoospermia within 2 months, but two subjects later exhibited a partial restoration in sperm count. Follicle-stimulating hormone and LH levels were inhibited more severely than in the first experiment. The sperm count and gonadotrophin levels returned to initial values within 6 months after cessation of the treatment in both experiments. No side-effects were noted concerning blood parameters, libido or body weight. However, several female partners had elevated levels of plasma testosterone. In experiment 3 (13 volunteers), percutaneous testosterone was replaced by oral testosterone undecanoate (160 mg daily). Only seven men were azoospermic and most of them had lowered levels of plasma testosterone. Thus, the combination of percutaneous testosterone and oral progestagens appears to be the most convenient for male hormonal contraception. In 3 successive experiments, the efficacy of various combinations of progestagens and androgens for male contraception was tested and compared. In the 1st experiment, 8 men received a daily oral dose of 20 mg medroxyprogesterone acetate (MPA) combined with 125 mg percutaneous dihydrotestosterone (DHT). After 3 months of this regimen, the mean sperm count was not significantly reduced. Thus DHT was replaced with percutaneous testosterone (250 mg/day) for 6-18 months. This move resulted in a dramatic fall in sperm count. Azoospermia was achieved in 6 cases and 2 men were oligozoospermic. In the 2nd experiment, 12 male volunteers received a daily dose of either 5 or 10 mg norethisterone acetate and 250 mg percutaneous testosterone. Azoospermia was achieved within 2 months by all 12 subjects, but 2 men later demonstrated a partial restoration in their sperm count. This regimen inhibited follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels more severely than was the case in the 1st experiment. In the 3rd experiment, percutaneous testosterone was replaced by 160 mg/day of oral testosterone undecanoate. Only 7 of the 13 volunteers in this experiment achieved azoospermia and most had lowered levels of plasma testosterone. The sperm count and gonadotropin levels returned to initial values within 6 months after cessation of treatment in these experiments and there were no significant side effects in terms of blood parameters, libido, or body weight. Overall, this research indicates that a combination of progestagens and androgens administered daily without injections induces satisfactory inhibition of spermatogenesis. If a fully active, nontoxic oral androgen were to become available as a substitute for percutaneous administration, hormonal male contraception could achieve more widespread acceptability.
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