Abstract Introduction Epilepsy is one of the most common neurologic conditions worldwide, affecting approximately 5 million people globally every year. Many with this diagnosis rely on lifelong medications for seizure prophylaxis, which involve complex mechanisms of action with various hormones. The myriad of therapeutic side effects and the debilitating nature of this disease process make sexual dysfunction a common occurrence, with low libido, arousal, and orgasm being the primary complaints for 30-67% of female patients with epilepsy. Prioritizing quality of life from a biopsychosocial perspective is imperative – the need for investigating diverse treatment options for sexual dysfunction in these female patients becomes increasingly evident. Objective This study aims to discuss the available treatment options for sexual dysfunction in females with diagnosed epilepsy. Methods A systematic review in the PubMed database that spanned between January 2015 and November 2022 was executed. Six authors independently and thoroughly screened titles, abstracts, and full-text articles. They assessed the relevant medical literature that acknowledged the presence of female sexual dysfunction and explicitly stated treatment options for patients who have epilepsy. MeSH advanced key terms used to refine the search include: [“epilepsy”], [“female sexual dysfunction”], AND [“treatment”]. Results The published articles (n = 26) that fit the inclusion criteria were reviewed. The pathophysiology behind sexual dysfunction in patients with epilepsy is multifactorial. Seizure activity preferentially occurring in the temporal and frontal lobes alters several fundamental functions of the brain and nervous system, including the HPA axis and the release of gonadal hormones. Furthermore, anti-epileptic drugs target complex substrates that influence the limbic system, hypothalamus, pituitary, endocrine glands, as well as steroid and protein synthesis and metabolism in the liver and adipose tissue. Specifically, drugs documented to correlate with sexual dysfunction negatively are valproate, topiramate, and gabapentin. Agents such as lamotrigine, oxcarbazepine, and levetiracetam are reported to result in fewer sexual side effects and may even have a protective role against sexual dysfunction. Non-pharmacological approaches such as treating underlying comorbidities, addressing psychosocial variables, and mindfulness-based cognitive therapy have also proven significantly beneficial in treating and preventing adverse sexual outcomes. Conclusions Sexual dysfunction, secondary to epilepsy-induced seizures or anti-epileptic drug management, is not adequately explored and treated. The body of literature supports treating sexual dysfunction in females with epilepsy from a multidimensional standpoint; however, there remains a lack of thorough discussion on treatment options tailored to female pelvic anatomy. Going forward, continued research on how the pathologic consequences of epilepsy affect sexual function, unrelated to the use of anti-epileptic drugs, could enhance the prevention and comprehensive management of female sexual dysfunction in this population. Additionally, evaluating the effectiveness of topical estrogens, 5-HT1a agonists/5HT2a antagonist like Flibanserin, and melanocortin receptor agonists like Bremelanotide in female patients with epilepsy and other neurologic disorders may aid in the understanding of this relationship and spark further discussion. Sexual dysfunction and related symptoms have a devastating impact, indicating the need for this research, standardized guidelines, and a wide array of biopsychosocial treatment options. Disclosure No
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