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.

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Fourteen patients with Idiopatic Addison's disease (IAD) were studied in order to detect a possible subclinical hypothyroid state. All were clinically euthyroid with normal serum thyroxine (T4) and serum 3,5′,3′-triiodothyronine (T3). Eleven had circulating thyroid microsomal antibodies in blood. The mean basal serum TSH was significantly higher than that of the control group but only three patients had values above the upper normal range. The mean value of serum T4 was decreased as compared to that of the normal persons, while serum 3,3′,5′-triiodothyronine was elevated. 7.5 mU bovine thyrotrophin per kilogram body weight injected intravenously caused a rise in serum T3 not different from the response in normals. However, as well increasing serum TSH as increasing microsomal antibody titer correlated significantly to decreasing thyroidal release of T3. Our results suggest that clinically euthyroid patients suffering from IAD might have a beginning thyroidal insufficiency because of a progressive immunological damage of the thyroid.