A controlled study of danazol for the treatment of karyotypically normal spontaneous premature ovarian failure.

OBJECTIVE

To determine if the immunomodulatory and gonadotropin-suppressing properties of danazol would improve follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure.

DESIGN

Prospective, double-blind, crossover trial.

SETTING

Tertiary care research institution.

INTERVENTIONS

Two intervention phases lasting 4 months each: one phase during which patients received a standardized estrogen and progestin replacement regimen and one phase during which each patient received a twice daily 400 mg oral dose of danazol.

PATIENTS

Fifty-two patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 21 to 39 years.

MAIN OUTCOME MEASURES

We measured serum E2 and P levels weekly during the 2 months after each intervention. We defined a serum E2 > 50 pg/mL (184 pmol/L) as evidence of ovarian follicle function and a P > 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation.

RESULTS

Of the 46 patients who completed the study, danazol did not significantly enhance ovarian follicle function or the chance of ovulation. Eight patients ovulated after danazol and four patients ovulated after estrogen and progestin. The power to detect a 30% and a 5% ovulation success rate with therapy was 0.80 and 0.90, respectively. Overall, 30 of 46 women (65%) demonstrated ovarian follicle function and 10 women (21%) ovulated.

CONCLUSION

We were unable to demonstrate a statistically significant benefit from the immunomodulatory and gonadotropin-suppressing effects of danazol in patients with karyotypically normal spontaneous premature ovarian failure. These patients often have spontaneous remission. Thus, controlled studies are required to determine the effectiveness of treatments for this condition.