Ovarian dysfunction in patients with gestational trophoblastic neoplasia treated with short intensive courses of etoposide (VP-16-213).

The effect of oral Etoposide (VP-16-213) on the ovarian function in 22 patients with residual gestational trophoblastic disease was studied by serial weekly measurement of serum follicle stimulating hormone (FSH), 17 beta-estradiol (E2), progesterone (P) and prolactin (PRL), and monitoring of the menstrual patterns during and after drug treatment. Multiple courses of VP-16-213 at a dosage of 200 mg/m2 X 5 days were given 1 week apart. Following an average dose of 5.0 gm, five young patients developed transient ovarian failure for a mean period of 2.4 months and two elderly patients developed permanent ovarian failure (total incidence, 7/22, 31.8%) as evidenced by hypergonadotropic, hypoestrogenic amenorrhea. In addition, two patients each developed anovulatory cycles and hypomenorrhea. VP-16-213 should therefore be regarded a potent gonadotoxic drug and these hitherto unreported side effects should be recognized when the drug is used in menstruating females.