Abstract # 87:

Scheduled for Friday, June 22, 2007 11:10 AM-11:25 AM: Session 8 (North Main Hall C/D) Symposium

Modeling the Perimenopausal Transition

S. E. Appt1, J. R. Kaplan1, T. B. Clarkson1 and P. B. Hoyer1,2
1Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem 27157, USA, 2University of Arizona
     Emerging evidence suggests that cardiovascular disease and osteoporosis originate premenopausally, especially during the several years (“the perimenopausal transition”) that immediately precede menopause. A nonhuman primate model of the perimenopausal transition would facilitate the investigation of this life stage and provide a model for testing interventions. Exposure of mice and rats to the chemical 4-vinylcyclohexene diepoxide (VCD), results in the selective destruction of ovarian primordial and primary follicles, resulting in a follicle deplete, stroma intact ovary. Mice and rats so treated display a hormone profile similar to that of menopausal women. In an initial attempt to translate these findings to monkeys, we treated four adult cynomolgus macaques intramuscularly with either vehicle or one of three doses of VCD (80, 160, or 250 mg/kg). There was a dose response, with no follicular changes at the low dose, a 50% reduction in primordial but not primary follicles at the middle dose, and almost complete elimination of both primordial and primary follicles at the high dose. Clinical health measures remained within normal range except for a transient mild increase in liver enzymes during treatment with 250mg/kg. Post mortem evaluations (nine months) revealed no gross organ lesions. These results demonstrate that the monkey ovary is susceptible to VCD and, as in rodents, primordial and primary follicles are selectively targeted.