Portal de Periódicos da CAPES

Evidence of a Possible Direct Action of Danazol on the Human Ovary

1983; Informa; Volume: 62; Issue: 2 Linguagem: Inglês

10.3109/00016348309155789

1600-0412

Ariel Milwidsky, Norma F. Besch, Paige K. Besch, Raymond H. Kaufman,

Hormonal Regulation and Hypertension

Strong evidence is presented that Danazol might exert a direct action on the human ovary by binding to receptor-like receptors for progesterone and testosterone, in concentrations well within the pharmacological range of the treated patient. The possible significance of this finding in understanding Danazol's mode of action is discussed.The purpose of this study was to assess the ability of Danazol to bind to high affinity binders for progesterone and testosterone in the cytosol of the human ovary in vitro. Ovaries from women ranging in age from 28-40 years were prepared and used in competition analyses which demonstrated the ability of Danazol to displace testosterone as well as dihydrotestosterone (DHT), from the androgen high affinity binders, and to displace progesterone and R5020, a synthetic compound with high affinity for progesterone receptors, from the progesterone high affinity binder. Use of the recommended dose of 800 mg/24 hours of Danazol for conditions such as endometriosis can lead to significant displacement of progesterone and testosterone by Danazol, assuming that the high affinity binders are not in direct contact with follicular fluid containing much higher levels of progesterone and androgens. Examination of the ovary of a patient treated with Danazol 800 mg/day for 1 year prior to oophorectomy disclosed both the high affinity binder for androgens and the high affinity binder for progesterone that were found in the ovarian cystosol of nontreated patients, proving that longterm treatment with Danazol did not abolish the high affinity binders for either steroid and that a direct action of Danazol at the ovarian level is conceivable. The progesterone and androgen high affinity binders may play a role in ovarian function, hormone production, and ovulation. Danazol binding to them would probably interfere with their normal functioning.