Primary ovarian insufficiency associated with lenvatinib therapy in a patient with hepatocellular carcinoma

Abstract

Abstract Background: In recent years, the number of chemotherapy options for malignant tumors has increased due to the development of new drugs. In particular, the therapeutic effects of molecular-targeted drugs are, in some cases, more pronounced than those of conventional chemotherapy, and their introduction as a standard treatment is increasing. Due to the improved life prognosis, there are an increasing number of opportunities to consider fertility preservation for young patients. We report a case of ovarian insufficiency in a young woman caused by the tyrosine kinase inhibitor lenvatinib. Case presentation: A 25-year-old woman received lenvatinib 8 mg/day for 98 days as preoperative chemotherapy for hepatocellular carcinoma. Blood testing the day before starting lenvatinib administration showed the following: luteinizing hormone (LH) 4.40 mIU/ml, follicle-stimulating hormone (FSH) 5.2 mIU/ml, estradiol (E2) 57.4 pg/ml, and age-equivalent hormone values. Amenorrhea occurred after the start of administration, and 48 days later, LH was 41.8 mIU/ml and FSH was 44 mIU/ml, values indicating a decrease in ovarian function. Hepatectomy was performed on the patient, and 49 days after the end of lenvatinib administration, blood test values improved to LH 4.5 mIU/ml, FSH 2.5 mIU/ml, and age-equivalent hormone values. Later, she began to have regular menstrual cycles once again. Conclusions: Ovarian toxicity has not been recognized as a side effect of lenvatinib. However, amenorrhea and hypergonadotropinemia were observed in this patient after lenvatinib administration, as was primary ovarian insufficiencythought to be caused by the drug. Potential damage to ovarian function may need to be considered when molecular-targeted drugs with the same mechanism of action as lenvatinib are used in young women.