Partial and Generalized Seizures Affect Reproductive Physiology Differentially in the Male Rat

Summary: Purpose: Reproductive dysfunction and endocrine disorders occur frequently among men with epilepsy. This study tested the hypothesis that focal limbic seizures and generalized seizures may both contribute to reproductive dysfunction.

Methods: The rat kindling model was used to mimic focal limbic seizures. Kindling electrodes were placed in the basolateral amygdala. Male rats were either intact, gonadectomized (GDX) or GDX + testosterone (T) replaced and then kindled. Controls were left intact and sham-kindled. Maximal electro-convulsive shock (MES) treatment was used to model generalized seizures, by using eight stimulations, one every other day, for 2.5 weeks. Animals were killed either 3 h or 6 weeks after MES treatment to determine short- and long-term effects.

Results: Kindled seizures resulted in an increase in serum testosterone, estradiol, and prolactin in intact males, accompanied by a significant increase in testis, epididymis, and pituitary weight, as well as a significant decrease in prostate weight. MES treatment caused a short-term reduction in serum testosterone and testis, epididymis, and prostate weight. All parameters were restored to control values within 6 weeks of the last MES seizure, with the exception of pituitary weight and serum prolactin, which remained significantly elevated 6 weeks after MES treatment.

Conclusions: Our results indicate that both focal limbic (amygdaloid) seizures and generalized MES seizures disturb normal reproductive physiology in the male rat. Amygdaloid-kindled seizures have mixed effects on different parameters of reproductive function, whereas MES seizures induce a transient hypogonadal state. These results suggest that reproductive dysfunction in men with epilepsy may result from seizure-related interference with the normal functions of the hypothalamic-pituitary-testicular axis.