Primary ovarian insufficiency associated with lenvatinib therapy in a patient with hepatocellular carcinoma: A case report

Abstract

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. The present report describes a case of ovarian insufficiency in a young woman caused by tyrosine kinase inhibitor lenvatinib. The 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 indicated 4.40 mIU/ml luteinizing hormone (LH), 5.2 mIU/ml follicle-stimulating hormone (FSH) and age-equivalent hormone values. Amenorrhea occurred after the start of administration, and 48 days later, the LH level was 41.8 mIU/ml and the FSH level was 44 mIU/ml, indicating a decrease in ovarian function. The patient underwent hepatectomy, and 49 days after the end of lenvatinib administration, the LH level had improved to 4.5 mIU/ml and the FSH level had improved to 2.5 mIU/ml. After the hepatectomy, the patient began to have regular menstrual cycles once again. Ovarian toxicity has not been recognized as a side effect of lenvatinib. However, the present report describes primary ovarian insufficiency considered to be caused by this 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.

Keywords: hepatocelluler carcinoma; lenvatinib; oncofertility; ovarian insufficiency; tyrosine kinase inhibitor.

Figure 1.

Computed tomography scanning images before surgery. (A) Large liver tumor in the right lobe. (B) Three-dimensional fusion image showing the relation between the hepatic tumor, veins and portal veins.

Figure 2.

Changes in LH and FSH levels over the administration period of lenvatinib. Blood sampling times are indicated by the numbers 1–7: 1, 2 days before administration of lenvatinib; 2, 48 days after starting lenvatinib administration; 3, 111 days after starting lenvatinib administration and 13 days after ending lenvatinib administration; 4, 147 days after starting lenvatinib administration and 49 days after ending it; 5, 257 days after starting lenvatinib administration and 159 days after ending it; 6, 380 days after starting lenvatinib administration and 282 days after ending it; and 7, 482 days after starting lenvatinib administration and 384 days after ending it. FSH, follicle-stimulating hormone; LH, luteinizing hormone.

Figure 3.

Numerous types of tyrosine kinase receptor expressed on the surface of endothelial cells on tumor blood vessels are suppressed by lenvatinib. VEGFR is expressed in follicles and suppressed by lenvatinib. FGFR, fibroblast growth factor receptor; PDGFR, platelet-derived growth factor receptor; RET, rearranged during transfection; KIT, tyrosine-protein kinase; VEGFR, vascular endothelial growth factor receptor.