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.


METHODS
Prospective, double-blind, crossover trial.


METHODS
Tertiary care research institution.


METHODS
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.


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


METHODS
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.


CONCLUSIONS
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.
Anasti
J N
JN
Section on Gynecologic Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-0010.
Kimzey
L M
LM
Defensor
R A
RA
White
B
B
Nelson
L M
LM
D000328:Adult; D018592:Cross-Over Studies; D003613:Danazol / Q000627:therapeutic use*; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007621:Karyotyping; D007986:Luteinizing Hormone / Q000097:blood; D010053:Ovary / Q000187:drug effects / Q000503:physiopathology; D016649:Primary Ovarian Insufficiency / Q000188:drug therapy* / Q000235:genetics; D011446:Prospective Studies; D012016:Reference Values
D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003613:Danazol