cyproterone and Abnormalities--Drug-Induced

Topics: Abnormalities, Drug-Induced; Aminoglutethimide; Androgen Antagonists; Androstenes; Animals; Cattle; Cell Differentiation; Cyproterone; Dogs; Female; Guinea Pigs; Hydroxysteroid Dehydrogenases; Indenes; Ketosteroids; Male; Naphthalenes; Nitriles; Pregnancy; Pyridines; Rabbits; Rats; Testis; Testosterone; Wolffian Ducts

Topics: Abnormalities, Drug-Induced; Adult; Androgen Antagonists; Cyproterone; Cyproterone Acetate; Drug Combinations; Ethinyl Estradiol; Female; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Trimester, First

Pregnant mice were treated with a single subcutaneous injection of either cyproterone acetate (CA) or medroxyprogesterone acetate (MPA). In the first experiment the animals received 5-900 mg/kg of the hormone before implantation (day 2 of pregnancy). CA treatment on day 2 caused a dose-dependent decrease in fetal weight and a significant dose-dependent increase in the rates of cleft palate and urinary tract abnormalities. Exencephaly and heart abnormalities were also significantly more frequent, but this increase was not dose-dependent. MPA treatment on day 2 was followed by sporadic increases in dead and resorbed fetuses, a decrease in fetal weight and an increase in the rates of cleft palate, and malformed or abnormally developed fetuses. None of these effects, however, was dose-dependent. In the second experiment the mice were given one single injection (30 mg/kg) of CA or MPA on any one of days 1-12 of gestation. Treatment with CA on one day between days 1 and 12 revealed that the specific sensitivity for abnormalities of the urinary tract was on days 5 and 6, for the respiratory tract on days 8 and 9, and for cleft palate on days 10 and 11. Treatment with MPA on one day between days 1 and 12 only revealed a high rate of respiratory and urinary tract abnormalities on day 9. After treatment with MPA cleft palate was again significantly more frequent in all treated groups, however, days of peak sensitivity were not detected. The long half-life of CA (60 hours) explains the teratogenic effect of high doses of this progestin after treatment on day 2 and also the pattern of abnormal development found after treatment with a single dose of CA on one of the days between day 1 and day 12.

Topics: Abnormalities, Drug-Induced; Animals; Cleft Palate; Contraceptive Agents, Male; Cyproterone; Cyproterone Acetate; Dose-Response Relationship, Drug; Embryonic Development; Female; Fetal Death; Gestational Age; Heart Defects, Congenital; Medroxyprogesterone; Medroxyprogesterone Acetate; Mice; Pregnancy; Respiratory System Abnormalities; Skull; Urinary Tract

1. Malformations and functional disturbances of the male genitalia may be caused by teratogens. 2. A short review of the prenatal development points out the possible sites of action. 3. In animals some distinct teratogens produce typical malformation syndromo spermatogenetic cells. Cyproteronacetat, an antiandrogen, suppresses the development of the accessoric genital organs and produces an external feminisation. 4. In man, cryptorchidism, agenesis of the spermatic tracts, anorchia and hypospady are known as non-hereditary malformations. 5. The teratogenic etiology of some disturbances of the spermatogenesis is discussed.. In males, malformations of the exterior genitalia, and perhaps sperm absence or malfunction, can be traced to teratogenic disturbances. In rats, Busulfan administered in pregnancy can cause destruction of gonocytes and lack of spermatogenesis in adult male rats. Cyproterone acetate taken in pregnancy interferes with development of the Wolff passages, so that adult male rats lack the accessory genitals and suffer from exterior feminism. Other toxics possibly responsible for damage to the prenatal male genital system include antiandrogens, estrogens, testosterone, cytostatics, antimetabolites, antibiotics, and tranquilizers. In man cryptorchidism or testicle dystopis is accessible to therapy if treated early by administration of 250-500 E/Woche human chorionic gonodotropin 10 times a week, or later by operation to relocate the testicles. Spermatogenic disturbances occur in 1% of the male population and are extremely difficult to treat. Testicle aplasia may be treated with androgen substitution and epispadia and hypospadia may be improved by operative procedures. The rare cases of anochia, aphallia, and agenisis of spermatic tracts do not respond to treatment.

Topics: Abnormalities, Drug-Induced; Adult; Busulfan; Cryptorchidism; Cyproterone; Female; Genitalia, Male; Humans; Hypospadias; Infant, Newborn; Infertility, Male; Male; Pregnancy; Spermatogenesis

Topics: Abnormalities, Drug-Induced; Animals; Cesarean Section; Cyproterone; Dihydrotestosterone; Female; Fetus; Injections, Subcutaneous; Male; Mammary Glands, Animal; Mice; Pregnancy; Testosterone

Topics: Abnormalities, Drug-Induced; Androgen Antagonists; Animals; Cyproterone; Estrogens; Female; Gestational Age; Labor, Obstetric; Mice; Oxytocin; Pregnadienes; Pregnancy; Pregnancy, Animal