Many adolescent and young adult female cancer survivors are at increased risk of premature menopause (that is, menopause occurring before age 40 years). This also leads to reduced fertility and the ability to have offspring. While these effects of cancer treatment on female health may not be life-threatening, they are a major source of distress to cancer patients and their families, both in the short- and long-term. Currently, options to help adolescent and young adult females "preserve" their fertility are limited. This includes freezing and storing embryos, oocytes (unfertilized "eggs"), and a piece of the ovary itself. However, these options are not available to many patients because of cost, scheduling, and other considerations. Therefore, identifying more readily available options for fertility preservation is important. One possibility is the use of a class of drugs called gonadotropin-releasing hormone analogs (GnRHa). Currently, there is information from young breast cancer patients that GnRHa may help with fertility preservation. However, the benefit of GnRHa in women diagnosed with other cancers is unclear. Nevertheless, oncology providers are sometimes using these drugs in women diagnosed with other cancers. As treatment for breast cancer differs from that of other cancers, more information on whether GnRHa can help preserve fertility for other cancer patients is needed.

The proposed study will be a "pilot" or preliminary study to see if we can conduct a clinical trial of a commonly used GnRHa called triptorelin in girls and women with newly diagnosed cancers other than breast cancer. We propose to enroll 60 participants under the age of 40 years across the U.S. and Canada. Half the patients will be randomly chosen to receive triptorelin and the other half will not. Although 60 patients will not be enough to definitively test the effect of triptorelin on ovarian health, information from this pilot study will be important to determine if a larger study can be done, and how many patients would be needed for that larger study. Lessons that will be learned from the proposed pilot study include how readily cancer treatment centers and eligible cancer patients are willing to participate. Among participants, we will learn how many are able to complete study blood draws and questionnaires over the entire 2+year study period. Study data include several blood measurements of ovarian function over 2+ years. Study data also include questionnaires that will ask participants about symptoms that triptorelin can cause, changes to their menstrual patterns, quality of life, attitudes toward reproductive issues, and information on future pregnancies and births. Together, this information will help researchers develop a larger randomized clinical trial that can definitively test if triptorelin can help newly diagnosed girls and young women with cancer better protect their reproductive health. The data from this pilot study would also become part of this larger future study. Results from the proposed pilot study and any future larger study can change how adolescent and young adult female cancer patients are treated in the future. Even if triptorelin is found not to be helpful, that knowledge will also be important as many young women currently are being offered GnRHa without knowing if these medications help preserve fertility.

In summary, reproductive health issues are a major source of distress among cancer survivors soon after diagnosis, during active treatment, and long afterwards. More effective ways to help female adolescent and young adult cancer patients preserve their fertility are needed. The proposed project will address this issue, and by doing so, may potentially improve mission readiness among military personnel (active-duty or Veterans) or their dependents undergoing cancer therapy.