Does danazol affect fertility in man? Does it have teratogenic effects?

Fråga: Does danazol affect fertility in man? Does it have teratogenic effects?

Sammanfattning: Danazol can cause reduction in spermatogenesis and change in sperm morphology which may result in infertility in man. Dose and duration of treatment should be considered and patient should be followed with regular sperm analysis.

There is no information about teratogenicity of danazol when it is taken by a male patient. Even in woman, there is no recorded teratogenic effect of danazol use before the 8th week of gestation.

Svar: Danazol is an anabolic steroid derived from ethinyltestosterone. It is mostly used in endometriosis, fibrocystic breast disease and hereditary angioedema.

Androgenic and antigonadotrophic effect on the pituitary-ovarian axis can be observed in high doses like more than 800 mg daily (1). Both danazol and ethinyltestosterone, a metabolite of danazol, are responsible for this adverse effect of the drug. Danazol inhibits steroid synthesis in rat ovary, testis, and adrenal glands, in vivo (1).

A number of reports have described the inadvertent use of danazol during the pregnancy resulting in pseudohermaphroditism in female fetuses (2, 3) but not in male fetuses. There has been no case of virilization if the drug is discontinued before the 8th week of gestation which is the onset of androgen receptor sensitivity (2) and there is no information about any teratogenic effect of danazol when it is used by a male patient. On the other hand, administration of danazol to male patient caused a reduction of sperm count (4-5). Especially danazol plus testosterone preparations caused a severe reduction in spermatogenesis in man (4).

In a case report (5), 34-year-old male hereditary angioedema patient was treated with danazol, 400 mg daily. Five month later, azospermia and abnormal sperm morphology were observed. Sperm analysis became normal nine weeks after the discontinuation of the treatment. Treatment with epsilon-aminocaproic acid did not cause any sperm abnormality in this patient.

The level of spermatogenesis inhibition was clarified experimentally in adult rats (6). Danazol suppressed serum concentrations of gonadotrophins and inhibited proliferation of spermatogonia and primary spermatocytes in adult rats (6).