One of the most commonly used chemotherapy drugs, cyclophosphamide, can lead to ovarian failure and loss of fertility, a tragic consequence of cancer treatment that has led researchers world-wide in search of a solution. The risk of chemotherapy to induce premature menopause is well-documented, and depends largely on the patient’s age, as well as the type and dose of chemotherapy. The risk of premature menopause (i.e. permanent amenorrhea) following cytotoxic chemotherapy is 50% in women aged 35-50, and as high as 85% in women over the age of 40 [Wong et al., 2012].
Goserelin is a superagonist (i.e. analog) of gonadotropin-releasing hormone (GnRH) [also known as luteinizing hormone-releasing hormone (LHRH)] and has shown promise in recent research as an agent that may help to preserve fertility for pre-menopausal women with early-stage breast cancer. In essence, goserelin achieves a reversible post-menopausal state. It reversibly reduces sex hormone levels (such as estradiol) to nil, effectively causing ovarian cycling to halt, which is thought to protect the follicles against damage by cytotoxic chemotherapy.
Until recently, there was little evidence to strongly support the use of GnRH agonists to preserve ovarian function during cytotoxic chemotherapy, with studies showing conflicting results [Moore et al., 2015; Urruticoechea et al., 2007]. An international phase 3 study (POEMS/S0230), published in the New England Journal of Medicine in March 2015, reported on the co-administration of goserelin and chemotherapy in women aged 18-49 with hormone receptor-negative breast cancer, with promising results. This study looked at rates of ovarian failure (defined as cessation of menstrual periods and levels of follicle stimulating hormone (FSH) comparable to those seen post-menopause) in the two randomized study groups: the goserelin group (goserelin + chemotherapy), and the chemotherapy-alone group. As is standard, goserelin was administered every 4 weeks via subcutaneous injection, with the first injection given 1 week prior to initiation of chemotherapy [Moore et al., 2015; Wong et al., 2012; Urruticoechea et al., 2007].
The authors reported a statistically significant difference in rates of ovarian failure, with 22% of women in the chemotherapy-alone group having ovarian failure, compared to only 8% in the goserelin group [Moore et al., 2015]. This demonstrates that women given goserelin injections in conjunction with chemotherapy are 64% less likely to experience ovarian failure, and are also more likely to achieve successful pregnancy [Cancer Intelligence, ASCO, 2014]. The results of this recent study by Moore et al. are promising and encouraging, and confirm those of previous studies that indicate an LHRH agonist given concomitantly with chemotherapy protects ovarian function. It should be noted, however, that this study reports on concurrent administration of goserelin + chemotherapy for hormone receptor-negative breast cancers only. Further research is needed to explore the safety and efficacy of using GnRH analogues to preserve fertility in hormone receptor-positive breast cancer. [Moore et al., 2015].
Other options for assisted reproduction and fertility preservation for young women are limited, and include embryo or oocyte cryopreservation which are typically costly, invasive, and can result in significant delays in cancer treatment. In contrast, reversible ovarian ablation with goserelin is a fairly simple, low-cost alternative that does not cause treatment delay, nor does it require a male partner [Urruticoechea et al., 2007]. Goserelin is thus an attractive fertility preservation method for young women with financial limitations and/or without a long-term male partner. Finally, GnRH agonists can also be used in combination with other methods of fertility preservation, further expanding women’s options.
Rachel Adilman received her Bachelor of Science in Anatomy & Cell Biology at McGill University. Rachel is a Vancouverite currently working at the BC Cancer Agency, where she conducts breast cancer research with Dr. Christine Simmons. She also works part-time as a medical office assistant for Dr. Sheina Macadam, and plans to attend medical school in the near future. Rachel has a keen interest in the field of oncofertility, and has been lucky enough to gain experience and exposure in this field by conducting research with Dr. Nancy Baxter, as well as by collaborating with the Canadian non-profit organization ‘Fertile Future’. Rachel is excited to further her work in this field as she pursues a career in medicine. In her spare time, Rachel loves to hike and explore the outdoors, travel, and curl up with a good book.