Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease.
BACKGROUND
Our objective was to develop a new animal model for the study of polycystic ovaries by using the non-steroidal aromatase inhibitor, letrozole.


METHODS
Thirty four rats were divided into four groups, including a control group of 10 rats that received vehicle only (1% aqueous solution of carboxmethlycellulose [CMC]) once daily orally (p.o.) and three treatment groups of eight rats each that were administered letrozole at concentrations of 0.1 or 0.5 or 1 mg/kg p.o. dissolved in 1% CMC (2 mL/kg) once daily. The treatment period was 21 days. During this period, vaginal smears were collected daily for estrus cycle determination. On the day subsequent to last letrozole dose administration, rats were killed; uteri and ovaries were then excised and weighed. Serum hormone levels and histologic changes in ovaries were examined.


RESULTS
When compared to control group, ovaries from study groups showed high incidence of subcapsular ovarian cyst and capsular thickening together with incomplete luteinization and decreased number of corpora lutea. Letrozole treatment brought about dose-dependent suppression of uterine weight despite having no significant effect on ovarian weight. Although serum estradiol and progesterone levels were reduced in a dose-dependent manner, testosterone levels were elevated as were levels of luteinizing hormone (LH). Serum follicle-stimulating hormone (FSH) levels were markedly increased at higher doses of letrozole (0.5 and 1.0 mg/kg), contrary to low dose of letrozole (0.1 mg/kg) at which slight decrease was observed.


CONCLUSIONS
Despite the fact that this is not a fully convincing model for the study of polycystic ovaries or of polycystic ovary syndrome (PCOS) as a whole, this animal model in several ways is similar to the human polycystic ovary syndrome.
Kafali
Hasan
H
Departments of Obstetrics and Gynecology, School of Medicine, Harran University, Sanliurfa 63100, Turkey. hasankafali@hotmail.com
Iriadam
Mehmet
M
Ozardali
Ilyas
I
Demir
Nurettin
N
D000818:Animals; D047072:Aromatase Inhibitors; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006728:Hormones / Q000097:blood; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology*; D006080:Ovarian Follicle / Q000473:pathology; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000139:chemically induced* / Q000473:pathology*; D011863:Radioimmunoassay; D051381:Rats; D012680:Sensitivity and Specificity; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D006728:Hormones; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; D005640:Follicle Stimulating Hormone