Effect of clomiphene citrate on ovarian, endometrial, and cervical histologies in a rat model.
OBJECTIVE
To examine the effect of clomiphene citrate (CC) on the ovarian, endometrial, and cervical histologies in a rat model.


METHODS
The rats (n = 40) were randomly assigned to 4 treatment groups: CC 50 (repetitive doses of 0.2 mg CC); CC 100 (repetitive doses of 0.4 mg CC); CC 200 (repetitive doses of 0.8 mg CC), and control (repetitive doses of normal saline). Each study group received its CC dose intraperitoneally in 2 ml saline for 5 days and the controls received 2 ml saline only. Each treatment cycle was repeated six times. Six months later the rats were euthanized. Their ovaries, uterine horns, and cervices were removed and examined for histologic changes.


RESULTS
We found no significant difference in the number of follicles and corpora lutea of the study groups (p > 0.05). The numbers of granulosa, theca, and luteal cells of the CC 100 and CC 200 groups were significantly higher than those of the CC 50 group and controls (p < 0.05). There was no important finding related to pre-malign and malign changes in ovarian, endometrial and cervical samples of the control and CC 50 groups. Focal atypia and atypical mitoses were noted in 2 cases of granulosa cells in the CC 100 and CC 200 groups.


CONCLUSIONS
We did not find an association between the use of CC and ovarian, endometrial, and cervical neoplasms; nevertheless, we noticed an increase in granulosa, theca and luteal cells with high doses of CC, which may be a risk factor for granulosa, theca, and luteal cell tumors.
Ozdemir
Ismail
I
Department of Obstetrics and Gynecology, Abant Izzet Baysal University, Duzce School of Medicine, Duzce, Turkey. drismailozdemir@yahoo.com
Ustundag
Nil
N
Guven
Aysel
A
Duran
Bulent
B
Demirci
Fuat
F
D000818:Animals; D002584:Cervix Uteri / Q000033:anatomy & histology* / Q000187:drug effects*; D002996:Clomiphene / Q000009:adverse effects / Q000494:pharmacology*; D003338:Corpus Luteum / Q000187:drug effects; D004717:Endometrium / Q000033:anatomy & histology* / Q000187:drug effects*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000139:chemically induced; D010053:Ovary / Q000033:anatomy & histology* / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013799:Theca Cells / Q000187:drug effects
D002996:Clomiphene