男性不妊症に対するα<sub>1</sub>-blocker 療法の基礎的, 臨床的検討

Abstract

Clinical usefulness of the alpha 1-blocker and beta-stimulant combined therapy for idiopathic male infertility has already been reported by Yamamoto et al. But the same trial followed by us revealed only a slight effectiveness and substantial adverse effects due to beta-stimulation. The mechanism of the alpha 1-blocker and beta-stimulant combined therapy is not yet established. In order to investigate its mechanism, fundamental study of alpha 1-receptor assay in the specimens of testis and various parts of male accessory sex organs obtained at the time of operation was done in this study. In addition the usefulness of alpha 1-blocker therapy for idiopathic male infertility was also examined clinically. The tissues used in this study were obtained from patients with prostatic cancer (23 cases), benign prostatic hyperplasia (24 cases), bladder cancer (6 cases), chronic epididymitis (3 cases), azoospermia due to disorders of vas deferens (5 cases) and a vasectomized man. Tritium labeled bunazosin was used as the ligand. The crude membrane fraction was extracted from the sample, with or without phentolamine incubated for 20 min at 37 degrees C. Maximal binding sites (Bmax) and the dissociation constant (Kd) were obtained by Scatchard plot analysis. Twenty-two infertile men were treated by oral administration of alpha 1-blocker (bunazosin, 3 mg/day) for 24 weeks. The results were as follows: 1) Bmax in the testis, epididymis, vas deferens and prostate, expressed as fmol, per mg. protein, was 2.27 +/- 1.74, 16.62 +/- 6.19, 29.44 +/- 17.81, 27.77 +/- 12.0, respectively (mean +/- S.D.). 2) Bmax in the rete testis was relatively high among various parts of the testis and seminiferous tubules. 3) Overall effective rates of sperm density and the sperm motility were noted in 36% at 12 weeks and 60% at 24 weeks after the therapy. 4) There was no clinical effect in patients with azoospermia and a slight effectiveness in patients with elevated plasma gonadotropin levels. 5) Adverse effect was reduced to 9.1%. These results suggest that the alpha 1-blocker therapy for idiopathic male infertility is clinically useful and that the mechanism of the therapy is through the action on male accessory sex organs behind the testis.