Sex Hormones, Gonadotropins and Prolactin in Male Epileptic Subjects in Remission: Role of the Epileptic Syndrome and of Antiepileptic Drugs

Abstract

Sex steroid peripheral pattern, pulsatile luteinizing hormone (LH) secretion, gonadotropin and prolactin responses to LH-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) were studied in 35 male epileptics treated with phenobarbital (PB), carbamazepine (CBZ), or phenytoin (PHT), and in age-matched healthy males. Idiopathic generalized epilepsy (IGE) was diagnosed in 12 cases and partial epilepsy (PE) in 23 cases. Patients were seizure-free and did not show EEG abnormalities at repeated controls in the last 5 years, so that interfering effects of seizures were possibly excluded. The aim of the study was to evaluate both the role of epileptic syndromes and of antiepileptic drugs on the endocrine function. Changes in sex hormone binding globulin, total and free testosterone, dihydrotestosterone and Δ4-androstene-dione were found to be independent of the epileptic syndrome type. The LH response to LHRH was lower in PB-treated PE than in IGE subjects on the same drug regimen. An impairment of LH pulsatility with respect to controls was found in PE but not in IGE patients taking PB. Among antiepileptic drugs, PHT is associated with higher sex hormone binding globulin and estradiol and lower free testosterone and dihydrotestosterone levels. PB and CBZ, but not PHT, blunt the LH response to exogenous LHRH in PE. Prolactin responses to TRH were consistently enhanced in PE subjects treated with CBZ or PHT.

Serum Sex Hormones Are Altered in Patients with Chronic Temporal Lobe Epilepsy Receiving Anticonvulsant Medication

“…We might speculate that other binding proteins might be increased, this causing lower levels of free testosterone. The concomitant finding of decreased free testosterone and an increased SHBG level was previously reported (28,29). The increase of SHBG levels is atrributed to AED therapy, which leads to liver-enzyme induction (4,18).…”

“…Controversial data have been published that document normal, as well as elevated, estradiol concentrations in such patients (29,38). Impairment of libido or sexual potency is often reported by men with epilepsy (1,4,9).…”

Effects of valproate and carbamazepine monotherapy on neuroactive steroids, their precursors and metabolites in adult men with epilepsy

“…It appears that besides the effects of AEDs, some of these consequences might be rather connected with epilepsy than with the effect of AEDs as also indicated by our results. Changes in SHBG, total and free testosterone, dihydrotestosterone and androstenedione appear to be independent of the epileptic syndrome type [56]. VPA belongs to the group of enzyme non-inducing drugs and the data in the literature shows that VPA therapy does not significantly influence testosterone levels in men [38,[42][43][44][45][46][47]51] and has no effect on SHBG levels [38,44,46,47,51].…”

Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate

“…Valproic acid (VPA) has also been found to be an effective antiepileptic drug (AED) in epilepsy (3,4). Although these AEDs are well tolerated, many effects on endocrine function have been reported in literature (5)(6)(7)(8). The effect of these two AEDs on serum thyroid hormone concentrations has been controversial: CBZ therapy can decrease the serum thyroid hormone levels, but generally serum thyrotropin-releasing hormone (TSH) concentrations remain normal except in a small percentage of patients who show increased TSH levels (9,12).…”