Hormonal consequences of epilepsy and its treatment in men

Abstract

Purpose of review Epilepsy and anticonvulsant medications may substantially alter endocrine homeostasis, including the male reproductive hormonal system. Recent findingsSeizures in medial temporal lobe structures, through their connectivity to the hypothalamus, alter the secretion of gonadotropins. Levels of circulating bioavailable testosterone are affected by changes in the level of binding proteins, which in turn may be affected by seizure medications. The use of older generation medications which induce the cytochrome P450 system is associated with an increase in sex hormone binding globulin and lower bioactive testosterone. Sexual dysfunction, including decreased libido and decreased potency, and infertility, is seen commonly in men with epilepsy., However, its relation to sex hormone levels remains unclear. Co-morbid depression and anxiety may be important confounding factors. Testosterone and sexual function appear not to be affected by the newer generation (non-inducing) anticonvulsants. SummaryEpilepsy and its drug treatments are associated with alterations in hormonal and sexual function in men. Further study is needed to clarify the precise mechanisms behind these alterations, as some of the data conflict. More attention should be paid to this issue in male patients with seizures; when appropriate, treatment for psychiatric co-morbidity and switches in anticonvulsant therapy may be worth consideration.

Sex and hormonal influences on seizures and epilepsy

“…Both men and women with epilepsy often have altered reproductive function (Herzog et al, 1986a; Herzog et al, 1986b; Sivaraaman and Mintzer, 2011). Steroid hormone levels have been shown to change as a result of seizure activity.…”

Long-term effect of antiepileptic drug switch on serum lipids and C-reactive protein

“…We now have good evidence to demonstrate that each of these non-inducing drugs avoids the elevation of vascular risk markers — and possible promotion of atherosclerosis 1 — which occurs with the inducing AEDs. CBZ and PHT are also responsible for a plethora of other metabolic derangements, including alteration of vitamin levels 5,21 bone metabolism 22,23 , male reproductive function 24 , and many drug interactions 25 . In view of these findings, there is increasing reason to believe that the use of enzyme-inducing AEDs is problematic.…”

Gender issues in the neurobiology of epilepsy: A clinical perspective

“…The dysregulation of normal hormone patterns by these seizures, or even by epileptiform discharges that pass through the HPA, results in menstrual irregularity and anovulatory cycles leading to infertility, premature menopause (Harden et al, 2003;Bauer and Cooper-Mahkorn, 2008) and overall effects on libido and sexual function in both men and women (Sivaraaman and Mintzer, 2011;Morris and Vanderkolk, 2005). In addition, sleep and mood can be deleteriously affected by hormonal disruptions (Duncan et al, 2009;Zelená et al, 2011).…”

“…Modulation of neurotransmitters, specifically NMDA and glutamate in the case of estrogens and GABA A in the case of progesterone, set a state of excitation or inhibition. Androgen is metabolized to 17β estradiol (by aromatization) or androstenedione (by glucuronidation) and these metabolites have opposite effects on the excitability of cortex (Sivaraaman and Mintzer, 2011). It has even been proposed that some of these hormone metabolites, such as androsterone, which, like progesterone metabolites, modulates GABA receptors, may be protective against seizures (Kaminski et al, 2005;Frye, 2010).…”