Adjuvant gonadotropin-releasing hormone analogues for chemotherapy induced premature ovarian failure in premenopausal women

Chemotherapy has significantly improved the prognosis for patients with cancer and some non-cancerous conditions. This treatment, however, is associated with ovarian toxicity. Factors which may affect the risk level of chemotherapy-induced ovarian damage include the patient's age and type of chemotherapy regime. Gonadotropin-releasing hormone (GnRH) analogues, which are artificial hormone derivatives, can protect the ovaries by suppressing the gonadotrophin hormone, which stimulates ovary function and decreases blood flow, making them less sensitive to the chemotherapy drugs.

Included studies in this review showed that injections of GnRH agonists protected menstruation and ovulation after chemotherapy, whereas intranasal administration of GnRH agonists had no protective effect. The use of GnRH agonists therefore should be considered in women of reproductive age who are treated with chemotherapy and should be given throughout the course of chemotherapy treatment.

Authors' conclusions: 

The use of GnRH agonists should be considered in women of reproductive age receiving chemotherapy. Intramuscular or subcutaneous GnRH analogues seem to be effective in protecting ovaries during chemotherapy and should be given before or during treatment, although no significant difference in pregnancy rates was seen.

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Background: 

Chemotherapy has significantly improved prognosis for patients with malignant and some non-malignant conditions. This treatment, however, is associated with ovarian toxicity and gonadotropin-releasing hormone (GnRH) analogues may have a protective effect on the ovaries. The mechanism of action of GnRH is based on suppression of the gonadotropin levels to simulate pre-pubertal hormonal milieu and decrease utero-ovarian perfusion.

Objectives: 

To assess the efficacy and safety of GnRH analogues given before or in parallel to chemotherapy to prevent chemotherapy-related ovarian damage in premenopausal women with malignant or non-malignant conditions.

Search strategy: 

We searched the Cochrane Gynaecological Cancer Group Specialized Register (up to July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2011); MEDLINE (1950 to July 2011); EMBASE (1980 to July 2011); and the Chinese Biomedicine Database (CBM) (1976 to July 2011).

Selection criteria: 

Randomized controlled trials (RCTs), in all languages, which examined the effect of GnRH analogues for chemotherapy-induced ovarian failure in premenopausal women, were eligible for inclusion in the review.

Data collection and analysis: 

The review authors independently extracted data and assessed trial quality using the Cochrane risk of bias tool. We analyzed binary data using risk ratios (RRs) with 95% confidence intervals (CI) and for continuous data, we used the standardized mean difference (SMD) to combine trials. As there was substantial difference in the types of chemotherapy used, we applied the random-effects model in our analyses. We contacted study authors for additional information.

Main results: 

Included studies in this review showed that intramuscular/subcutaneous administration of GnRH agonists was effective in protecting menstruation and ovulation after chemotherapy (resumed menses: RR 1.90, 95% CI 1.30 to 2.79; amenorrhoea: RR 0.08, 95% CI 0.01 to 0.58; ovulation: RR 2.70, 95% CI 1.52 to 4.79), whereas intranasal administration of GnRH agonists had no protective effect on ovaries (resumed menses: RR 0.75, 95% CI 0.33 to 1.72; ovulation: RR 1.13, 95% CI 0.20 to 6.24). Pregnancy rates were not significantly different between groups (intramuscular/subcutaneous GnRH agonist: RR 0.21, 95% CI 0.01 to 4.09; intranasal GnRH agonist: RR 0.41, 95% CI 0.02 to 8.84). Ultrasound antral follicular count (AFC) was not significantly different between groups (SMD 1.11, 95% CI 0.32 to 1.90).

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