Gonadotropin suppression for the treatment of karyotypically normal spontaneous premature ovarian failure: a controlled trial.
OBJECTIVE
To determine if gonadotropin suppression improves ovarian follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure.


METHODS
Prospective, double-blind, placebo-controlled, crossover trial.


METHODS
Tertiary care research institution.


METHODS
Two intervention phases lasting 4 months each: one placebo phase, and one treatment phase during which each patient received daily subcutaneous injections of 300 micrograms of the gonadotropin-releasing hormone agonist (GnRH-a) deslorelin. During both phases, patients took a standardized estrogen (E) replacement regimen.


METHODS
Twenty-six patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 18 to 39 years.


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


RESULTS
The GnRH-a therapy did not significantly enhance recovery of ovarian follicle function or the chance of ovulation. The power to detect a 40% and a 33% ovulation success rate with therapy was 0.95 and 0.83, respectively. We found evidence for ovarian follicle function in 11 of 23 women (48%), and 4 women (17%) ovulated.


CONCLUSIONS
Patients with karyotypically normal spontaneous premature ovarian failure treated with E replacement did not benefit from the additional gonadotropin suppression achieved with GnRH-a. Because these patients have a significant possibility of spontaneous remission, attempts to induce ovulation should be limited to controlled trials designed to determine safety and effectiveness.
Nelson
L M
LM
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Kimzey
L M
LM
White
B J
BJ
Merriam
G R
GR
D000328:Adult; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D007621:Karyotyping; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D011374:Progesterone / Q000097:blood; D011446:Prospective Studies; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives
D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; C066438:deslorelin