Antiepileptic drugs alter reproductive endocrine hormones in men with epilepsy

Abstract

Disturbances of reproductive endocrine hormones are more often found in men with epilepsy than in the general population. There is an ongoing debate whether this can be attributed to chronic use of antiepileptic drugs or to the epilepsy itself. The aim of the present study was to evaluate the degree of endocrine disturbances in men with epilepsy compared with healthy controls, and to investigate whether there was a drug-specific effect of valproate (VPA) or carbamazepine (CBZ). Men with epilepsy, 20-40 years old, having used either VPA (n = 16) or CBZ (n = 19) as monotherapy for >2 years were included and compared with age-matched controls. Men with epilepsy (VPA + CBZ) had significantly lower FSH values and higher C-peptide values compared with controls. Regarding possible drug-specific effects, the VPA treated patients had significantly higher dehydroepiandrosterone (DHEAS) levels and lower FSH and LH concentrations compared with the controls, whereas there were no differences in testosterone, testosterone/sexhormone-binding globulin (SHBG) ratio or androstenedione levels. Men on VPA also had significantly lower free carnitine/total carnitine, which may have implications for sperm motility, and also higher insulin and C-peptide concentrations. The CBZ treated patients had significantly lower testosterone/SHBG ratio than the controls. Compared with the CBZ treated patients, men on VPA had significantly higher DHEAS concentrations and lower levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) as well as a lower free carnitine/total carnitine ratio. A marked age dependency was found in all three groups regarding several of the endocrine hormones. In conclusion, drug-specific endocrine effects of VPA and CBZ were found in men with epilepsy. Long-term VPA treatment leads to significant changes in DHEAS, FSH, LH, insulin, C-peptide and carnitine ratio. Long-term CBZ treatment leads to significant lower testosterone/SHBG ratio. A strict age matching were found to be of importance in the evaluation of endocrine function in men.

Treatment Effects Of Onion (Allium cepa) And Ginger (Zingiber officinale) On Sexual Behavior Of Rat After Inducing An Antiepileptic Drug (lamotrigine)

“…Then rats were kept in glass cages in pairs and they were filmed by cameras for 1 hour in darkness. This information (erection, ejaculation and cup) was recorded (23).…”

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

“…Concerning the effects of valproate (VPA) on the levels of steroids and related substances, except Røste et al [42], who found higher LH levels in VPA treated male patients than in the control group, most authors did not find an effect of VPA on the LH levels [38,[43][44][45].…”

“…Although, some studies reported no effect of VPA on FSH levels [38,43], most studies found lower FSH levels in VPA treated patients than in controls [42,46] or even suppression of FSH by VPA therapy [44,45]. In addition, no effect of VPA on the LH/FSH ratio was reported by Stephen et al [47].…”

“…Most authors found a positive correlation between CBZ treatment and gonadotropin levels [42][43][44]48,49], but there are also studies reporting no significant effect [38,50].…”

Valproic Acid Alters GnRH-GABA Interactions in Cycling Female Rats

“…Furthermore chronic treatment with VPA has been associated with a variety of endocrine related side effects, suggesting that VPA acts at multiple levels within CNS. VPA administration decreases secretion of anterior pituitary hormones such as luteinizing hormone (LH) and follicle stimulating hormone (FSH) (Roste et al 2005). Increase in mean serum levels of serum hormone binding globulin (SHBG) ) is another reported side effect of VPA medication.…”