Background/Purpose: SLE is an autoimmune disease which predominantly affects women of childbearing age (age 20-40). Most of the medications used for treating SLE can adversely affect fertility, pregnancy, and fetal outcomes. Cyclophosphamide (CYC) is an immunosuppressive agent indicated for the treatment of severe SLE. The use of CYC cause ovarian insufficiency and lead to dormant primordial follicle activation and loss. Gonadotropin releasing hormone agonist (GnRHa) may preserve ovarian function by preventing early stage development of ovarian follicles from maturation. This may decrease the number of follicles that are vulnerable to chemotherapy.

There is conflicting data on whether GnRHa preserve ovarian function when given before cyclophosphamide. Furthermore, there are inconsistent guidelines from various professional societies regarding the administration of GnRHa for ovarian protection. We attempted to develop evidence-based practice guidelines for the use of GnRHa in SLE patients undergoing treatment with CYC.

Methods: We reviewed published literature on the use of GnRHa for ovarian protection by searching PubMed. The available evidence was discussed in multidisciplinary conferences for consensus building. The current guidelines and alternate option for ovarian preservation were also reviewed. The final document for evidence-based practice guidelines will be developed in future.

Results: ACR guideline and American Society of Clinical Oncology (ASCO) conditionally recommends GnRHa to prevent ovarian insufficiency while on IV CYC (Table 1). Five research studies showed a protective effect of GnRHa on ovarian preservation (Table 2). An in vitro study using CYC showed no ovarian protection with GnRHa. The studies from use of GnRHa in patients with breast cancer showed conflicting results on its efficacy for ovarian preservation.

Conclusion: Most of the studies done in autoimmune diseases had a smaller cohort with no uniform criteria for defining ovarian insufficiency and preservation. Three studies were retrospective chart reviews which poses selection bias. The data from in-vitro study done with the removal of ovarian tissue was not replicated in clinical trials. In the breast cancer studies, patients were on several types of chemotherapy and the dose of CYC was much higher as compared to studies done in autoimmune diseases. Side effects of GnRHa mimic a hypo estrogen state. The alternate options for ovarian preservation involve surgical options with ovarian stimulation which could pose a risk of disease flare or thrombosis in SLE.

The evidence for the use of GnRHa for ovarian preservation while on CYC is not robust, but it is the least invasive procedure. A review of the evidence should be presented to the patient in a shared decision-making process and be evaluated by a multi-disciplinary team. The effectiveness and safety of GnRHa in SLE needs to be studied prospectively in a much larger population with well-defined outcome measures.

TABLE 1

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/use-of-gonadotropin-releasing-hormone-agonist-for-ovarian-preservation-in-sle-patients-on-cyclophosphamide/