Ovulation suppression for endometriosis.
BACKGROUND
Endometriosis is the finding of endometrial glands or stroma in sites other than the uterine cavity. Endometriosis appears to be an estrogen dependent condition. This hormonal dependency has prompted the therapeutic use of ovulation suppression agents, in an effort to improve subsequent fertility.


OBJECTIVE
To determine the effectiveness of a) ovulation suppression with danazol, medroxy progesterone acetate, gestrinone, combined oral contraceptive pills and GnRH analogues versus placebo or no treatment and b) any of the above agents versus danazol, for the treatment of endometriosis-associated subfertility.


METHODS
We searched the Cochrane Menstrual Disorders and Subfertility Group trial register (searched 30 April 2002), the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 2, 2002), MEDLINE (January 1966 to December 1998), EMBASE (January 1985 to December 1997) and reference lists of articles. We also contacted manufacturers and researchers in the field.


METHODS
Trials comparing the interventions described above, were included if allocation to treatment was based on a random process. Six RCTs with seven treatment arms compared an ovulation suppression agent with placebo or no treatment. Ten trials were identified comparing a suppressive agent with danazol.


METHODS
Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. 2 x 2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using Breslow-Day X2.


RESULTS
The odds ratio for pregnancy following ovulation suppression versus placebo or no treatment was 0.74 (95%CI 0.48 to 1.15). These data were statistically homogeneous, despite the use of a variety of suppression agents. They suggest no statistically significant benefit from treatment. The odds ratio for pregnancy following all agents versus danazol, the most commonly used agent prior to the advent of gonadotropin releasing hormone agonists (GnRHa), was 1.3 (95% CI 0.97 to 1.76). When GnRHa and danazol were directly compared, the odds ratio for pregnancy across six trials, was similar to the summary statistic for all ten studies: 1.29 (95% CI 0.9 to 1.85). Again, this suggests no statistically significant difference between these interventions.


CONCLUSIONS
These results rule out a benefit of more than a 15% increase in odds, and do not justify the risk of side effects when used as therapy for endometriosis-associated subfertility.
Hughes
E
E
Rm HSC-4F7, Dept of Obstetrics & Gynecol, McMaster University, 1200 Main St West, Hamilton, Ontario, Canada, L8N 3Z5.
Fedorkow
D
D
Collins
J
J
Vandekerckhove
P
P
D003613:Danazol / Q000627:therapeutic use; D004715:Endometriosis / Q000150:complications* / Q000188:drug therapy; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology; D010060:Ovulation / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic
D004965:Estrogen Antagonists; D005300:Fertility Agents, Female; D003613:Danazol