title: Modeling perimenopause in Sprague-Dawley rats by chemical manipulation of the transition to ovarian failure.
abstract: Various age-related diseases increase in incidence during perimenopause. However, our understanding of the effects of aging compared with hormonal changes of perimenopause in mediating these disease risks is incomplete, in part due to the lack of an experimental perimenopause model.  We therefore aimed to determine whether manipulation of the transition to ovarian failure in rats via the use of 4-vinylcyclohexene diepoxide (VCD) could be used to model and accelerate hormonal changes characteristic of perimenopause. We examined long-term (11 to 20 mo), dose-dependent effects  of VCD on reproductive function in 1- and 3-mo-old female Sprague-Dawley rats. Twenty-five daily doses of VCD (80 or 160 mg/kg daily compared with vehicle alone) depleted ovarian follicles in a dose-dependent fashion in rats of both ages, accelerated the onset of acyclicity, and caused  dose-dependent increases in follicle-stimulating hormone that exceeded those naturally occurring with age in control rats but left serum levels of 17β-estradiol unchanged, with continued ovarian production of androstenedione. High-dose VCD caused considerable nonovarian toxicities  in 3-mo-old Sprague-Dawley rats, making this an unsuitable model. In contrast, 1-mo-old rats had more robust dose-dependent increases in follicle-stimulating hormone without evidence of systemic toxicity in response to either VCD dose. Because perimenopause is characterized by an increase  in follicle-stimulating hormone with continued secretion of ovarian steroids, VCD acceleration of an analogous hormonal milieu in 1-mo-old Sprague-Dawley rats may be useful for probing the hormonal effects of perimenopause on age-related disease risk.
authors: Department of Medicine, College of Medicine, The University of Arizona, Tucson, Arizona, USA.
authors: Jennifer B
authors: JB
authors: Frye
authors: Ashley L
authors: AL
authors: Lukefahr
authors: Laura E
authors: LE
authors: Wright
authors: Sam L
authors: SL
authors: Marion
authors: Patricia B
authors: PB
authors: Hoyer
authors: Janet L
authors: JL
authors: Funk
mesh_terms: D000818:Animals; D001835:Body Weight; D053138:Cyclohexenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D010053:Ovary / Q000187:drug effects*; D047648:Perimenopause; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation; D014753:Vinyl Compounds / Q000494:pharmacology
chemical_list: D053138:Cyclohexenes; D014753:Vinyl Compounds; C012606:4-vinyl-1-cyclohexene dioxide