Leupron or Zoladex for ovarian function preservation on chemotherapy – pro

The luteinising hormone-releasing hormone analogue goserelin (‘Zoladex’) suppresses ovarian oestrogen production in pre- and perimenopausal women. Goserelin is a biodegradable, sustained-release 3.6 mg depot that is administered by subcutaneous injection every 28 days.

Ovarian failure and infertility following adjuvant chemotherapy for early breast cancer are major concerns for some young women. Techniques for oocyte harvesting are associated with delay in starting treatment, potentially undesirable estrogen stimulation and a relatively low success rate. A recent publication looked at all evidence and presented a report an audit of experience with the luteinising hormone-releasing hormone agonist, goserelin, to achieve transient ovarian suppression during chemotherapy as a means of preserving ovarian function, and found it to not be aprticualrly effective. THis would be expected to be the case in a more advanced age, relevent to this case. The American Society of Clinical Oncology’s recommendations on fertility preservation in cancer patients (Lee, et al., 2006) stated that sperm and embryo cryopreservation are considered standard practice. On the other hand, the use of GNRH analogs or antagonists for testicular or ovarian suppression is considered investigational. ASCO guidelines state: “At this time, since there is insufficient evidence regarding the safety and effectiveness of GnRH analogs and other means of ovarian suppression on female fertility preservation, women interested in ovarian suppression for this purpose are encouraged to participate in clinical trials.” The guidelines also noted that there is insufficient evidence of the effectiveness of GnRH analogues in preventing chemotherapy-induced gonadal damage in men: “The efficacy of gonadoprotection through hormonal manipulations has only been evaluated in very small studies in cancer patients.”

A recent review says: “Although numerous studies in female patients undergoing chemotherapy indicate that GnRH analogs might be protective of ovarian function, none of the studies showing protection were prospective randomized clinical trials and thus they are inconclusive. Considering interspecies differences and similarities in the gonadal sensitivity to cytotoxic agents and hormones, mechanistic studies are needed to identify the specific beneficial effects of hormonal suppression in select animal models that may be applicable to humans. ”

In a review of the literature, Sonmezer and Oktay (2006) explained that there are a limited number of prospective studies of GNRH analogues in preventing chemotherapy-induced gonadal damage, “which are flawed because of short-term follow-up and/or because of lack of control subjects.” The review notes that “[i]n addition to the lack of consistent support from clinical studies, there is currently no biological explanation for who GNRHa [GNRH analogues] can affect ovarian reserve.” The authors concluded that “[i]n the absence of a prospective randomized study with sufficient power, we do not rely on ovarian suppression as an effective means of fertility preservation.”

However, more recently findings from a federally funded phase III clinical trial, S0230/POEMS, indicate that adding a hormone suppressing drug called goserelin to standard chemotherapy may be an effective method of preserving fertility among women with early-stage hormone receptor-negative breast cancer. These findings can be generalized to women with Hodgkins as well.

Senra JC, Roque M, Talim MCT, et al. Gonadotropin-releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2018; 51:77.

Ander Urruticoechea et al, Ovarian protection with goserelin during adjuvant chemotherapy for pre-menopausal women with early breast cancer (EBC) Journal Breast Cancer Research and Treatment Published online: 13 September 2007 http://www.springerlink.com/content/bg74271g146x8511/

Lee SJ, Schover LR, Partridge AH, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006;24(18):2917-2931.

Sonmezer M, Oktay K. Fertility preservation in young women undergoing breast cancer therapy. Oncologist. 2006;11(5):422-434.

Meistrich, Marvin L, Shetty, Gunapala Hormonal suppression for fertility preservation in males and females Reproduction 2008 136: 691-701

Moore HCF, Unger JM, Phillips KA, et al. Phase III trial (Prevention Of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 2, 2014; Chicago, IL. Abstract LBA505

Rodriguez-Wallberg KA, Oktay K. Fertility preservation during cancer treatment: clinical guidelines. Cancer Manag Res. 2014;6:105–117

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