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Danazol: endocrine pharmacology and therapeutic applications.

Abstract
The options for the medical management of endometriosis have been expanded by the introduction of the synthetic steroid, danazol. The results of large clinical studies suggest that danazol treatment produces significant improvement in the symptoms, signs, and laparoscopic findings of endometriosis. The original studies of the pharmacology of danazol concluded that danazol was a strong antigonadotrophin with mild androgenic effects and no other hormonal properties. Recent studies which emphasize the molecular pharmacology of danazol suggest that this steroid has direct effects on hypothalamic-pituitary function, multiple classes of steroid receptors, gonadal steroidogenesis, and endogenous steroid metabolism. These studies demonstrate that: (1) danazol prevents the midcycle surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH); (2) danazol does not significantly suppress basal LH or FSH in gonadally intact human beings; (3) in castrated animals danazol can prevent the compensatory increase in LH and FSH; (4) danazol binds to androgen, progesterone, and glucocorticoid receptors; (5) danazol does not bind to estrogen receptors; (6) danazol binds to sex hormone-binding globulin and corticosteroid-binding globulin; (7) danazol inhibits multiple enzymes of steroidogenesis; (8) danazol increases the metabolic clearance rate of progesterone; and (9) metabolites of danazol are hormonally active. Given the complex pharmacology of danazol it is inappropriate to continue to refer to danazol as a "selective antigonadotrophin."U
AuthorsR L Barbieri, K J Ryan
JournalAmerican journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 141 Issue 4 Pg. 453-63 (Oct 15 1981) ISSN: 0002-9378 [Print] UNITED STATES
PMID7025640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)
Chemical References
  • Enzyme Inhibitors
  • Gonadotropins, Pituitary
  • Pregnadienes
  • Receptors, Steroid
  • Progesterone
  • Estradiol
  • Danazol
Topics
  • Animals
  • Binding, Competitive (drug effects)
  • Cats
  • Danazol (adverse effects, metabolism, pharmacology, therapeutic use)
  • Endometriosis (drug therapy)
  • Enzyme Inhibitors (pharmacology)
  • Estradiol (metabolism)
  • Female
  • Gonadotropins, Pituitary (blood)
  • Humans
  • Hypothalamo-Hypophyseal System (drug effects)
  • In Vitro Techniques
  • Infertility, Female (drug therapy)
  • Male
  • Metabolic Clearance Rate (drug effects)
  • Pregnadienes (pharmacology)
  • Progesterone (metabolism)
  • Pseudopregnancy (drug therapy)
  • Rabbits
  • Rats
  • Receptors, Steroid (drug effects)
  • Thyroid Gland (drug effects)
  • Uterine Neoplasms (drug therapy)

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