The effect of anticonvulsant drugs on the development of male rats and their fertility.

Abstract

SUMMARY Albino male rats were injected with diphenylhydantoin, carbamazepine, valproic acid or clonazepam for three months immediately after weaning. Following the treatment the fertility of the rats was tested by caging them with proestrus females and recording impregnations. The males were decapitated and their sex organs weighed. Epididymal sperm content and motility rate were recorded. A decrease in the prostate weight was found in the valproic acid and the carbamazepine treated rats. Epididymal weights were found decreased only in the valproic acid treated rats. These rats had diminished sperm content and sperm motility and their fertility was decreased. Carbamazepine treated rats had a lowered epididymal sperm content which did not affect their fertility.A large battery of anticonvulsant drugs is available for the treatment of epilepsy. Since this condition involves long term use of drugs and since epilepsy tends to start in childhood, it is essential to study the effect of such drugs on the development of the reproductive tract and on sexual maturation. The purpose of this study was to follow the growth curves of rats who were treated immediately after weaning for three months with commonly used anticonvulsant drugs such as diphenylhydantoin, carbamazepine, valproic acid and clonazepam and to record the activity of the reproductive system. Material and methodsAlbino male rats of original Wister stock were used. Following weaning, three weeks postpartum, they were given the dose by daily subcutaneous injection. Doses were diphenylhydantoin, eleven rats, 2 mg/100 g body weight; clonazepam, eleven rats, 0 18 mg/100 g body weight; valproic acid, ten rats, 3-0 mg/100 g body weight. The doses selected were high clinical ones multiplied by the factor of metabolic rate. Control groups of ten rats were injected with 0-1 saline subcutaneously. Nine rats were injected with carbamazepine, 2 mg/100 g body weight, dissolved in propylene glycol. Body weights were recorded weekly. Following three months of treatment the rats were tested for fertility as described previously.' The last drug injection was administered two days prior to necropsy; methods are given elsewhere. 2 values are reported as means + SE.Significance of differences were calculated using Student's t test. Differences in fertility rates were compared using the Fisher exact probability test. ResultsThe effect of treatment on the growth curves are given in the figure.

Alterations in semen parameters in men with epilepsy treated with valproate or carbamazepine monotherapy

“…, 2001). In accordance with this, animal studies have shown altered semen quality after use of different anticonvulsants including phenytoin, carbamazepine and valproate (Cohn et al. , 1982; Taneja et al.…”

Morphological changes in the testis after long-term valproate treatment in male Wistar rats

“…A drug-specific effect of valproate also gains some support from the study by Cohn et al 11 in which male rats received different antiepileptic drugs for a period of 3 months. Both carbamazepine treated and valproate treated rats had diminished sperm content, but the valproate treated animals were the only ones with significantly decreased fertility.…”

“…Sexual dysfunction, including reduced potency and hyposexuality is seen in as much as 38-71% of men with epilepsy [1][2][3][4] . This may, at least in part, be due to longterm use of AEDs which have been shown to induce disturbances in sex hormone levels 2,[5][6][7][8][9] and also to reduce sperm quality 5,[10][11][12][13] . These effects have so far not been related to specific drugs.…”

Influence of photoinhibition on GABA and glutamic acid levels, and on glutamate decarboxylase activity in the testis and epididymis of the golden hamster

“…Our laboratory previously described GABAergic regulation of gonadal activity (Ritta et al, 1987). O n the other hand, GABA A-type binding sites were described on the plasma membrane of spermatozoa (Erdo & Wekerle, 1990), and some authors have reported a direct effect of GABA on sperm viability and motility (Person et al, 1990;Cohn et al, 1982). GABA in reproductive tissues could be derived from different sources: uptake from the bloodstream or peripheral innervation (Erdo & Amenta, 1986;Leader et al, 1992), synthesis from putrescine via the diamine-oxidase or monoamine-oxidase pathway (Seiler, 1980;, and synthesis de novo from glutamic acid via GAD activity (Persson et al, 1990;Tillakaratne et al, 1992).…”