Prolactin Secretion in Epileptic Subjects Treated with Phenobarbital: Sex Differences and Circadian Periodicity

Abstract

Circulating basal prolactin (PRL) levels were evaluated in 126 subjects of both sexes with partial or generalized epilepsy, who were treated with phenobarbital (PB) alone or in combination with either phenytoin or benzodiazepines. A significant increase in PRL levels was observed in male, but not in female, patients compared with a sex- and age-matched healthy volunteer group. Circadian PRL secretion, studied in six male epileptic patients on PB monotherapy and in nine normal subjects, showed comparable 24-h PRL mean values and a preserved PRL surge during the night in both groups; however, a statistically significant additional peak was found in male epileptic subjects during the late afternoon. The cosinor analysis of the data, used to evaluate PRL rhythmicity, showed a disruption of the 24-h periodicity in epileptic subjects, while the 12-h periodicity was maintained. These results indicate that central and/or peripheral mechanisms involved in PRL secretion control are more sensitive to PB alone or in combination with other antiepileptic drugs in male than in female subjects. However, the changes of PRL secretion we found were small and unrelated to the different clinical conditions.

Epileptic but Not Psychogenic Seizures Are Accompanied by Simultaneous Elevation of Serum Pituitary Hormones and Cortisol Levels

“…The patients of this study were treated with anticonvul sants; the results on the influence of these drugs on serum prolactin or thyrotropin levels in epileptic patients and healthy controls are controversial, in that treatment with phénobarbital, benzodiazepines, phenytoin, or a combina tion of these drugs is reported to increase, decrease or pro duce no change in the serum levels of these hormones [7,12,16,19,25,30,31,37], Therefore, lowering of prolactin may be due to epilepsy or to treatment, or both. The circadian prolactin profile of patients and controls [29] showed an ad ditional peak during the late afternoon, thus refuting the claim that this may be a specific reaction of epileptic pa tients [8].…”

“…It was shown earlier that epileptic patients have altered serum prolactin or thyrotropin levels compared to healthy subjects [8,17,28]; from the circadian prolactin profiles of healthy subjects and patients with seizures the nightly surge of the hormone was found to atte nuate till after 07:00 h in the morning. Hence nonadherance to strict timing of collecting blood could be one of the causes for the divergent results reported in the literature.…”

“…The re lease of prolactin and thyrotropin is stimulated by thyrotro pin-releasing hormone (TRH) (13] and inhibited by dopa mine [13,15,32], Norepinephrine, melatonin, and serotonin also influence the release of pituitary hormones [13,27,30,33]. A cortisol increase after seizure [8,19,21] was con sidered to be a 'nonspecific stress' response [II]. However, the actual mechanism is not clear.…”

Prolactin Levels in Sudden Unexpected Death in Epilepsy

“…Prolactin is known to rise in sleep (20) (when most cases of SUDEP occur) and with some AEDs (21)(22)(23)(24)(25)(26)(27)(28). Although it is possible that the increase in prolactin in three patients, in whom there was no clinical evidence of a seizure, might have been caused by sleep-related increase (29), overall these factors do not seem to have had much effect on prolactin measurements in the SUDEP and the control groups with epilepsy.…”

Current Issues on Epileptic Women

“…Seizures can disrupt cortical regulation of hypothalamic hormone release and disturbe the hypothalamic-pituitary system. Accordingly, endocrine disturbances in women due to epileptic activity include abnormal pituitary responses to GnRH [22], disturbance in the pulsatile release of pituitary LH [23, 24], abnormal concentrations of pituitary LH, and increased levels of pituitary prolactine [25,26]. A few mechanisms for these abnormalities have been reported.…”