Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyproterone acetate (CPA) has been discovered more than 25 years ago and it was the first antiandrogen suitable for clinical use. CPA inhibits the action of endogenous and exogenous androgens at all androgen target organs; these include the prostate, seminal vesicles, testes, and the vas deferens. However, this antiandrogen also antagonizes less sex-specific effects of androgens, for example ossification of the epiphyseal cartilage, sebaceous gland function and skin thickness. Indications for CPA: Prostate cancer, androgen induced disorders of the skin (acne, seborrhoea, hirsutism, alopecia), precocious puberty and sexual disorders in men. Concerning sexual deviations clinical trials started in 1966. CPA leads to loss of libido and the ability to achieve erection, followed by the inability to achieve orgasm, after about 14 days of treatment (100-200 mg daily orally or 300 mg weekly i.m.). These effects are reversed in the same order as the onset. About 75 to 80% of patients respond to this therapy. CPA is generally well tolerated. Tiredness, lack of drive, listlessness and depressive moods have been reported as non-specific side-effects. Slight gynecomastia occurs in about 20% of patients. There are no good alternatives in this indication. Pure antiandrogens are unsuitable, because these are unable to inhibit libido sufficiently. Tranquilizers are not very effective, high doses of estrogens are associated with severe (cardiovascular) side effects. Orchidectomy is an irreversible intervention, LHRH analogues are associated with hot flushes and the initial increase in testosterone (flare phenomenon).
 ...
PMID:Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience. 183 80

Most antiandrogens appear to act by binding to the androgen receptor and competitively inhibiting the binding of testosterone and cihydrotestosterone to the receptor. Focusing on those compounds which appear to inhibit androgen receptor mediated responses, this review discusses the chemistry of those antiandrogens which have been studied to the extent that their mechanism of action is at least partially understood, outlines the mechanism of androgen action as it is currently understood and suggests how antiandrogens might fit in with this mechanism, indicates the major metabolites of several important antiandrogens, and discusses the clinical applications of several antiandrogens. Cyproterone acetate has been studied extensively as a potential male contraceptive. Although it was recognized that 100 mg of cyproterone acetate per day inhibited spermatogenesis, that dose also reduced libido and potency. Following the administration of 10 or 20 mg of cyproterone acetate per day to 15 males for 26 weeks, the following observations were made: the number of motile sperm was reduced; the quality of their motion was impaired; and the ability of the sperm to penetrate cervical mucus was decreased. Sperm density was also suppressed, but neither it nor sperm motility were inhibited to the extent necessary for contraception. Antiandrogens have been demonstrated to be beneficial in treating 5 clinical syndromes or diseases: acne, seborrhea, hirsutism with or without menstrual abnormalities; precocious puberty; benign prostatic hypertrophy; cancer of the prostate; and sexual deviates. Since 3 of these conditions are very common, effective and safe treatment would have a large market. At this time, antiandrogens are widely used in Europe for treatment of seborrhea, acne, and hirsutism and a large Veterans Administration Cooperative Study in the US was approved but has not yet been funded to compare antiandrogens with other treatments for cancer of the prostate. Studies to assess antiandrogen interaction with other hormones or drugs have been limited. Side effects in the female have been best evaluated when cyproterone acetate was administered in combination with ethinyl estradiol. In 46 women followed over 317 cycles, side effects were similar to those reported with estrogen-progestin contraceptives. Administration of 10-20 mg of cyrproterone acetate per day to males caused no significant side effects, but 100 mg or more/day has caused loss of libido, impotence, gynecomastia, tiredness, weakness, decreased efficiency, weight gain, drying and desquamation of skin over the legs, and loss of hair on the trunk and pubic area.
 ...
PMID:Androgen antagonists in androgen target tissues. 620 9

76 women with virilizing features (68 women suffering from hirsutism and 8 from acne) were treated on average for 25 months according to different models of Androcur medication. Success of treatment was clinically assessed as good in 3/4 of the cases and slight in the remaining 1/4. However, treatment is more successful in cases of adrenal hirsutism than in idiopathic hirsutism. Moreover, success of treatment seems to be better in women below 35 than over 35 years of age. Side effects, mostly bleeding anomalies and fatigue, were found in 31 women; these must be attributed to the gestagenic component of cyproterone acetate. By contrast, 12 women showed positive side effects such as weight reduction, improvement in depression states and reversal of hair loss, which must be attributed to the antiandrogenic component. The selected continuation rate in all subjects was 86% and the unselected 72%, over a treatment period of 4.5 years. Furthermore, hormonal controls were carried out under treatment. These showed, on average, a depression of plasma androstendione of 17%, of total plasma testosterone of 47%, as well as an inhibition of the testosterone/sex hormone-binding globulin quotient of 58%. These inhibition effects speak in favour of alterations taking place in steroid metabolism. However, by inhibition of androgenic serum levels, the mechanism of cyproterone acetate is only assisted, while the main mechanism is based on peripheral receptor inhibition. Furthermore, as additional component in this action a slight increase in plasma binding capacity was found during combined cyproterone-oestrogen treatment.
 ...
PMID:[Long-term treatment of virilized women with cyproterone acetate (author's transl)]. 645 62