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

Abstract

Men with epilepsy are known to have reduced fertility. Whether this is drug-induced or a result of the epilepsy itself is still under debate. Few studies have been carried out on semen from men with epilepsy. The aim of the present study was first to investigate possible drug-specific effects of long-term treatment with either valproate or carbamazepine on semen quality and testicular size, and secondly to see whether the results in epilepsy patients differed from healthy fertile males. Men with epilepsy, 20-40 years old, having used either valproate (n = 16) or carbamazepine (n = 20) for >2 years, were included. The semen data of healthy fertile men without epilepsy in the same age group (n = 90) were used as controls. The semen was examined according to WHO (1999). No significant differences in semen quality were seen between men receiving either valproate or carbamazepine. However, semen from the valproate-treated, as opposed to the carbamazepine-treated, differed from controls with regard to tail abnormalities. Absolute testicular size was not significantly different between the two treatment groups. However, after correcting for changes in body mass index (BMI), the testicular size/BMI ratio was lower in the valproate-treated patients. The valproate-treated patients gained significantly more weight than the carbamazepine-treated patients after start of current medication. No differences between the patient groups were found in terms of libido/potency or number of pregnancies fathered. When comparing all epilepsy patients with healthy fertile males, there was a significant reduction in the percentage of rapidly progressive motile sperms in the semen from epileptic patients. The semen from men with epilepsy also showed significant differences from the controls regarding neck and head abnormalities of the spermatozoa.

Momordica cochinchinensis (L.) Spreng: Aril Extract Prevents Adverse Reproductive Parameters of Male Rats Induced with Valproic Acid

“…Particularly, VPA causes adverse effects of male reproductive parameter in human and animals. Previous studies have shown that the testosterone levels and semen qualities of epileptic men being treated with VPA significantly decreased (Herzog, 2008;Bauer et al, 2004;Isojärvi et al, 2004;Roste et al 2003). Bauer et al have suggested that such adverse effects involved male infertility.…”

Seminal fluid analysis and testicular volume in adults with epilepsy receiving valproate

“…AED can also directly act on the HPG axis or on peripheral hormones and induce various reproductive or sex hormonal abnormalities [7]. Moreover, long-term use of AED has been shown to reduce sperm quantity and quality and affect spermatogenesis, resulting in infertility [8][9][10][11][12][13]. Disturbances in reproductive hormones and gonadal morphology have been observed in patients with epilepsy and in non-epileptic animals on AED [14,15].…”

“…Disturbances in reproductive hormones and gonadal morphology have been observed in patients with epilepsy and in non-epileptic animals on AED [14,15]. Studies on AED including CBZ [10,12], PHT [8] and VPA [9,11,13] reported drug-related side effects which include abnormal sperm morphology, reduced motility, lower sperm count, and reduced testicular volume. It has been suggested that semen quality may be deleteriously affected as (1) a result of direct toxic effect of AED on the gonads [14][15][16] HPG axis with abnormalities of sex hormones (such as testosterone) which are essential for normal sperm [17], and (3) a result of carnitine deficiency associated with some AED particularly VPA [18,19] and to lesser extent others, including CBZ, PHT and PB [20].…”

Epilepsy in men: The effect of the disease and its therapy on reproductive endocrine functions

“…n Effekte auf die Spermiogenese Zusätzlich zu einer indirekten Beeinflussung der Sexualhormone über die Induktion des hepatischen Enzymsystems können Antiepileptika vermutlich auch auf anderem Weg direkt an den Testes wirken und so die Testosteronsynthese sowie die Spermiogenese negativ beeinflussen [26]. Tierexperimentelle Studien zeigten unspezifische Spermienveränderun-gen bei Gabe unterschiedlicher Antiepileptika [27,31].…”