ReviewReproductive health in patients with epilepsy
Introduction
Sexual behavior is regulated by the brain, through neural and neuroendocrine mechanisms [1]. Physiologic response to sexual interest, arousal and behavior requires functional cerebral cortex, brainstem, spinal cord, and autonomic nervous system, anatomically and functionally intact genital structures, and appropriate levels of pituitary and ovarian or testicular hormones [2]. Sex hormones are controlled through the feedback loops of the hypothalamus–pituitary–endocrine gland axis [2].
In women, gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus by GnRH-expressing neurons in varying frequency pulses during the menstrual cycle and regulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, through hypothalamus–pituitary–gonadal axis. Both gonadotrophins LH and FSH regulate steroid sex hormone synthesis from the ovaries [3].
In men, GnRH is secreted in a relatively constant frequency pulse regulating LH secretion, which in turn regulates testosterone secretion from Leyding cells. Gonadotropin-releasing hormone also regulates FSH secretion, the role of which in spermatogenesis has not been yet fully elucidated. However, it is evident that FSH is required for the maintenance of the Sertoli cell number and the normal sperm production [4].
The prevalence of epilepsy is 7.6 per 1000 population [5]; however, the prevalence of epilepsy particularly in people of reproductive age has not been accurately estimated. Epilepsy per se may cause functional alterations of hypothalamus–pituitary–gonadal axis, probably by affecting hypothalamus and pituitary gland through the limbic system and especially by affecting the pulse pattern of GnRH [6]. Antiepileptic drugs, in addition, may affect liver and gonads and cause sex hormone level disturbances [2].
The aim of the present study was to review existing knowledge of the interconnection between epilepsy and subfertility/infertility in both sexes.
Section snippets
Impact of epilepsy on female reproductive health
In an initial study [7] in 1994, married women with epilepsy had less chance to achieve a pregnancy compared to their married healthy siblings, and this possibility was not significantly associated with the age of epilepsy onset, the seizures type, and the family history of epilepsy. Very intriguing are the findings of a recent study [8] showing that females with epilepsy have the same rates of pregnancy, time to pregnancy, and live births when compared to healthy controls, after controlling
Impact of epilepsy on male reproductive health
In literature, there are studies supporting that males with epilepsy have fathered fewer [91], [92], or similar number of children [93], [94] compared to the general population.
Men with seizures during adulthood had fewer children compared to those who had seizure remission before adulthood [93] while men who achieved seizure remission before adulthood had similar number of children with healthy controls, according a cohort study from Finland [93]. The young age of epilepsy onset and the focal
Conclusions
Epilepsy’s general impact and the adverse reactions of antiepileptic drugs on reproductive health may cause subfertility and thus affect family planning.
The intriguing interaction between epilepsy, AEDs, and reproductive disorders suggests that reproductive function should be monitored closely as part of the care given to reproductive age patients with epilepsy.
Having seizures under control and selecting the appropriate medication, less detrimental to fertility, is a decision with potentially
Disclosure of conflicts of interest
None of the authors has any conflict of interest to disclose.
Ethical publication statement
We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Funding Statement
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Cited by (12)
Mechanisms linking neurological disorders with reproductive endocrine dysfunction: Insights from epilepsy research
2023, Frontiers in NeuroendocrinologyEpilepsy, sexual function, and mindfulness-based cognitive therapy
2023, Handbook of Cognitive Behavioral Therapy by Disorder: Case Studies and Application for AdultsEffects of treatment with clinically relevant valproate, carbamazepine, oxcarbazepine, topiramate, lamotrigine and levetiracetam on ovarian folliculogenesis in young rats
2022, Epilepsy ResearchCitation Excerpt :Treatment with valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPM), lamotrigine (LTG), and levetiracetam (LEV) has been associated with reproductive endocrine disorders during childhood, adolescence and adulthood in females with epilepsy (Cansu, 2010; Cansu et al., 2011; Hamed, 2008; Isojarvi, 2008; Ogunjimi et al., 2021; Pack, 2010). The most common disorders are hyperandrogenism (HA), decreased estrogen levels, polycystic ovary syndrome (PCOS), premature menopause, amenorrhea, oligomenorrhea, and ovulatory failure (Isojarvi, 2008; Isojarvi et al., 2005; Markoula et al., 2020; Morrell et al., 2002; Opaleke and Helmers, 2007; Sidhu et al., 2018; Verrotti et al., 2009). Although it is difficult to confirm whether or not these endocrine disorders are related to the use of Anti-seizure medications (ASMs) alone, endocrine-disrupting effects of ASMs, independent of epileptic activity, have also been noted in animal studies and cell culture studies (Daoud et al., 2004; Gurgen et al., 2012; Sveberg Roste et al., 2002; Tauboll et al., 1999, 2002).
Sex and gender differences in epilepsy
2022, International Review of NeurobiologyCitation Excerpt :These ASM hormonal effects have not been found to correlate with menstrual disorders or reproductive endocrine disorders in this population; however, it has been postulated to contribute to reduced libido (Morrell et al., 2005). Serum dehydroepiandrosterone sulfate (DHAES) concentrations have also been shown to be lower with the use of EIASMs, although the clinical implications of this is not well understood (Markoula et al., 2020; Svalheim et al., 2015). No significant changes in functional levels of serum LH, FSH, or prolactin have been demonstrated with the use of these medications.