COMMENTARY

Can Gonads Be Protected During Chemotherapy?

Peter Kovacs, MD, PhD

Disclosures

January 19, 2016

Protecting Ovaries During Chemotherapy Through Gonad Suppression: A Systematic Review and Meta-analysis

Elgindy E, Sibai H, Abdelghani A, Mostafa M
Obstet Gynecol. 2015;126:187-195

Cancer in Reproductive-age Women

Annually, about 800,000 new cases of cancer are diagnosed among women in the United States. As a result of improved diagnostic tests, diagnosis at an earlier stage is now a reality for many of these cancers. Cancers that were at one time more commonly identified in older women are now being diagnosed in reproductive-age women. In the 20- to 39-year age group, breast cancer, cervical cancer, leukemia, colorectal cancer, and central nervous system cancer are the five leading causes of cancer death.[1]

Treatment of earlier-stage cancer may be more specific, effective, and less destructive, leading to improved survival and better quality of life upon completion of therapy.[1] Cancer therapy usually requires a combination of surgery and chemotherapy, with or without radiation therapy. Such rapidly dividing cells as cancer and germ cells are sensitive to both chemotherapy and radiation therapy, and gonadal dysfunction can be induced.[2]

The degree of gonadal dysfunction associated with cancer treatment depends on many factors, including the patient's age. Older women and those with already reduced ovarian capacity are most likely to develop gonadal failure as a result of cancer treatment.[3]

Gonadal failure has two consequences. Women can become infertile and lose the opportunity to reproduce with their own eggs, or they can become hypoestrogenic. This may be desired with certain types of cancer (eg, estrogen receptor–positive breast cancer) but can have a negative effect on quality of life. These issues need to be addressed, preferably before initiating cancer therapy.[4] One method of preserving reproductive capacity is believed to be protecting ovarian function during chemotherapy.

This meta-analysis evaluated the potential benefits of gonadotropin-releasing hormone analogue (GnRHa) treatment in the prevention of gonadotoxic effects of chemotherapy.

Study Summary

This meta-analysis includes findings from 10 randomized controlled trials involving 907 patients who underwent different types of chemotherapy for a variety of cancers. The median age of the patients was 35 years, and the median duration of follow-up was 24 months.

Resumption of menstrual cycles was observed in 320 of 468 (68%) women who received GnRHa and 263 of 439 (60%) who did not. This difference was not statistically significant (risk ratio, 1.12; 95% confidence interval, 0.99-1.27; P =.07). Of the 10 studies in this meta-analysis, four found a benefit of GnRHa during chemotherapy, whereas six did not.

When different types of cancers were analyzed, no significant benefit was found of GnRHa coadministration among women undergoing chemotherapy for breast cancer, lymphoma, or ovarian cancer. Furthermore, when age was considered, no benefit was seen in women older than 40 years vs those younger than 40 years.

Measures of ovarian capacity (baseline follicle-stimulating hormone level, anti-Müllerian hormone level, or antral follicle count) and pregnancy rates upon completion of chemotherapy did not significantly differ between women exposed and those not exposed to GnRHa during chemotherapy.

On the basis of this meta-analysis, GnRHa co-treatment had no significant impact on rates of resumption of ovarian function among reproductive-age women undergoing chemotherapy.

Viewpoint

Multiple studies with conflicting results have evaluated the use of GnRHa to prevent follicle loss during chemotherapy.[5,6] It is believed that the suppressed state of the follicles, the reduced blood supply to the ovaries, or direct ovarian effects through GnRHa receptors may render the ovaries more resistant to chemotherapy-induced damage. However, such benefits are not supported by this meta-analysis, despite a seemingly favorable trend. This could be owing to differences among the study participants or to a genuine lack of effect.

GnRHa-induced amenorrhea still may be beneficial, because chemotherapy often induces adverse changes in the blood count and the lack of menstrual blood loss could therefore be desirable. On the other hand, hypoestrogenism will induce vasomotor symptoms and urogenital atrophy and could further compromise the already lower quality of life during chemotherapy.

Current evidence does not support the routine use of GnRHa to prevent follicle loss during chemotherapy. It may be offered, however, to avoid menstruation during the course of chemotherapy. Further trials should evaluate the effect of GnRHa co-treatment in various age groups and various types of cancer to seek potential benefits.

Abstract

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