Granulosa cell tumors and menopausal hormone therapy: A narrative review

Adult granulosa cell tumors (GCT) are rare sex cord stromal tumors of the ovary, characterized by distinct histologic features and the near ubiquitous presence of a recurrent somatic mutation in the FOXL2 gene. Although GCT have a favorable prognosis compared to other ovarian cancer subtypes, recurrences typically occur later than other ovarian cancers; usually between 4-8 years after initial diagnosis. Once recurrence is diagnosed, cure through surgery is rare and few effective systemic therapies exist. The median age at GCT presentation is between 46-50 years old, and many cases occur in premenopausal women. GCT are hormonally active tumors, with many of the tumors secreting estrogen. Hormone receptors, including progesterone and estrogen receptors are often expressed in these tumors. Younger GCT patients who undergo the recommended surgical staging procedure, experience premature surgical menopause, which is associated with vasomotor symptoms, increased risk of osteoporosis and cardiovascular events as well as reduced cognitive and sexual functioning. Menopausal hormone therapy (MHT) mitigates these risks and is recommended for individuals with premature menopause. In GCT patients, most guidelines caution against MHT use, due to perceived risk associated with the hormonally and endocrinologically active nature of these tumors. This narrative review outlines the hormonal nature of GCT and summarizes and synthesizes the evidence relating to possible safety and risk of MHT use in GCT patients.