A 30-day preclinical safety evaluation study of recombinant human follicle-stimulating hormone in female rhesus monkeys.

The objective of this study was to identify potential target organs for toxicity of recombinant human follicle stimulating hormone (r-hFSH) in female rhesus monkeys and to establish a no observed adverse effect level (NOAEL). In all, 24 female rhesus monkeys (Chinese origin, weighing 3.4-5.2 kg, approximately 5 years of age) received repeated subcutaneous (sc) r-hFSH at doses of 10, 60, and 300 IU/kg per d or vehicle once daily for 30 days followed by a 15-day recovery period. Endometrial hyperplasia and dermal edema in the external genitals were found in some animals at 300 IU/kg per d. Pharmacologic-related multiple cystic follicles were found in all r-hFSH-treated groups. A weak, anti-FSH antibody response was detected at the end of treatment in animals administered 60 and 300 IU/kg per d. These results indicate that the primary effects of r-hFSH in female rhesus monkeys were related to its pharmacological activity on the reproductive system. The NOAEL was considered to be 60 IU/kg per d.