Low dose gossypol for male contraception.

AIM: To ascertain whether the side effects of gossypol, hypokalemia and irreversibility, could be avoided on dose reduction. METHODS: Seventy-seven male volunteers were divided into 3 groups: control (22 cases), 10 mg gossypol (29 cases) and 12.5 mg (26 cases). Serum levels of testosterone, FSH and LH were measured by RIA and potassium by flame photometry. Sperm counts and motility were examined before and regularly after treatment for the evaluation of contraceptive efficacy. RESULTS: The average sperm density and motility started to decrease significantly by the end of month 2 of medication and gradually reached the infertility levels (< 4 million/mL) in both treated groups. After that the 10 mg group was asked to take the same dose every other day for up to a total observation period of 16-18 months for the maintenance of infertility. Subjects in the 12.5 mg group did not take gossypol any more so as to observe the length of the loading dose required, but in a few, a maintenance dose of 12.5 mg every other day was instituted for a few more months. In both treated groups, none of the spouses was pregnant during the maintenance dose period. Serum levels of potassium, FSH, LH and testosterone were not significantly changed and not a single volunteer complained of myoasthenia. After cessation of drug administration, the semen data returned to pretreatment levels. CONCLUSION: A regimen with 10 or 12.5 mg of gossypol as the daily loading dose and 35 or 43.75 mg as the weekly maintenance dose could induce infertility in male volunteers without developing hypokalemia or irreversibility.

Effects of tripchlorolide on the epididymides and testes of rats.

AIM: To further evaluate the antifertility effects of tripchlorolide, a derivative of triptolide produced at the extraction procedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and possible mechanisms of action. METHODS: In male rats, tripchlorolide was given by oral garage at a dose of 50 micrograms.kg-1.d-1 for 5 weeks, fertility was assessed by mating tests, and biochemical indices and light microscopic observation of the epididymides and testes were also performed. RESULTS: Administration of tripchlorolide at 50 micrograms.kg-1.d-1 for 3 weeks did not influence the fertility of male rats, but 5-week treatment rendered the rats infertile. The density and motility of spermatozoa collected from cauda epididymides were reduced significantly. The epididymal weights, as well as the L-carnitine concentration and alpha-glucosidase content in the epididymal fluid were decreased. There were no significant differences in alpha-glucosidase and acid phosphatase (ACP) in caput epididymal homogenates between the control and the experimental rats. Obvious morphological changes were observed in the epididymal spermatozoa, mainly including head and tail separation or acrosome curving. Sloughed spermatids were found in the seminifeous and epididymal tubules. In testicular homogenates, tripchlorolide had no influence on the lactate dehydrogenase-C4 (LDH-C4) and hyaluronidase activities. No apparent lesions were observed in the seminiferous and epididymal epithelium. CONCLUSION: At the dose level employed, tripchlorolide has a significant effect on the fertility in male rats and the primary sites of action may be spermatids and testicular and epididymal spermatozoa.

[Antifertility effect of the implant containing 16-methylene-17 alpha-acetoxy-19-norprogesterone (ST-1435)].

The silastic capsules containing ST-1435 (0.5, 1, 2, 4, 6 or 8 mg) showed "burst effect" with a peak value of 4-15 micrograms.h-1 after incubation in vitro. A constant release rate was gradually approached within 1-2 wk. After the capsules were subcutaneous implanted or vaginally administrated, the rats manifested diestrus within 24-48 h. The normal estrus cycles and fertility were restored as soon as the release rate of implants decreased to 10 micrograms.d-1 in vitro. ST-1435 did not inhibit the superovulation induced by PMSG and HCG in immature female rats, but blocked the ovulation induced by LHRH in mature rats.

[Endocrine activity of pseudolaric acids A and B and their effects on sex hormones, prostaglandins, uteri, and fetuses].

Two novel diterpendoids, pseudolaric acids A and B (PA, PB) first isolated from the root of Pseudolarix kaempferi Gorden in China, have been reported to possess significant antifertile activities in rats, hamsters, rabbits, and dogs. The present study demonstrated that neither PA nor PB had estrogenic and antiestrogenic activities, they also did not inhibit deciduous formation. When an effective dose of PB 30 mg.kg-1 was given on d 6 of pregnancy and the hormonal determinations were done on d 8 and d 12 of pregnancy, the progesterone, estradiol and prostaglandins E, F levels in plasma and the uterine prostaglandin E, F levels were not significantly reduced vs those of the control rats. The human uterus was used as the experimental material in vitro. PA and PB 200 micrograms.ml-1 cultural medium (McCoy's 5a medium) damaged only a part of the decidual and trophoblast cells. In partially depolarized isolated uterine smooth muscles of early pregnant rats, PA and PB caused a decline in the contractile tension. A low dose of PB 2 mg.kg-1.d-1 was given ig on d 6-12 of pregnancy in rats caused the body weight and the length of fetuses and the placental weight value significantly lower than those of the control. Thus, ischemia due to the vasoconstrictor effect is probably of great, and sometimes of supreme, importance.