What is the relationship between epilepsy and male infertility?

From the Guidelines

Epilepsy can significantly impact male fertility, and men with epilepsy should be evaluated and managed by a multidisciplinary team to minimize fertility impacts. The relationship between epilepsy and male infertility is complex, involving multiple mechanisms such as anti-epileptic drugs (AEDs) altering hormone levels, increasing oxidative stress, and disrupting the hypothalamic-pituitary-gonadal axis essential for normal sperm production 1. Men with epilepsy often have lower testosterone levels and higher estrogen levels, which can impair sperm production and contribute to sexual dysfunction. Seizures themselves can also disrupt the hormonal axis, while the psychological stress of living with epilepsy may contribute to sexual dysfunction.

Some key points to consider in the management of male infertility in epilepsy include:

• Medication management is crucial, with newer AEDs like lamotrigine, levetiracetam, and oxcarbazepine generally having fewer reproductive side effects 1
• Working with both a neurologist and reproductive specialist is recommended to optimize seizure control while minimizing fertility impacts
• Potential interventions include AED adjustment, hormone therapy if deficiencies are identified, and antioxidant supplements to improve sperm parameters
• Regular semen analysis can help monitor fertility status, and assisted reproductive technologies remain an option for those with persistent fertility issues despite treatment optimization 1

It is essential to note that the evidence on the relationship between epilepsy and male infertility is limited, and more research is needed to fully understand the mechanisms involved and the most effective management strategies. However, based on the available evidence, a multidisciplinary approach to management, including medication adjustment and reproductive specialist involvement, is recommended to minimize fertility impacts in men with epilepsy 1.

From the FDA Drug Label

There have been rare reports of impaired male fertility and/or abnormal spermatogenesis. Testicular atrophy occurred in rats receiving carbamazepine orally from 4 to 52 weeks at dosage levels of 50 to 400 mg/kg/day. Additionally, rats receiving carbamazepine in the diet for 2 years at dosage levels of 25,75, and 250 mg/kg/day had a dose-related incidence of testicular atrophy and aspermatogenesis In dogs, it produced a brownish discoloration, presumably a metabolite, in the urinary bladder at dosage levels of 50 mg/kg and higher. Relevance of these findings to humans is unknown

The relationship between epilepsy and male infertility is not directly established in the provided drug label. However, the label mentions rare reports of impaired male fertility and abnormal spermatogenesis associated with carbamazepine, a medication used to treat epilepsy.

• Key points:
  • Rare reports of impaired male fertility
  • Abnormal spermatogenesis
  • Testicular atrophy in animal studies
• The relevance of these findings to humans is unknown 2

From the Research

Relationship Between Epilepsy and Male Infertility

The relationship between epilepsy and male infertility is complex, with several factors contributing to the reduced fertility in men with epilepsy. Some of the key points to consider are:

• Men with epilepsy have reduced fertility, and antiepileptic drugs may affect semen quality 3.
• Certain antiepileptic drugs, such as valproate (VPA), carbamazepine (CBZ), and oxcarbazepine (OXC), have been associated with sperm abnormalities, including low sperm count, poor motility, and abnormal morphology 3, 4.
• VPA has been shown to be associated with testicular atrophy and reduced testicular volume in men with epilepsy 3.
• Switching from VPA to other antiepileptic drugs, such as levetiracetam (LEV) or lamotrigine (LMG), may improve sperm counts and parameters, increasing the chance of spontaneous conception 4.

Mechanisms of Antiepileptic Drug-Related Infertility

The mechanisms by which antiepileptic drugs contribute to male infertility are not fully understood, but several factors have been proposed:

• The use of liver enzyme-inducing antiepileptic drugs, such as phenobarbital, phenytoin, and CBZ, increases serum sex hormone-binding globulin (SHBG) concentrations, leading to diminished bioactivity of testosterone and estradiol 5, 6.
• VPA medication may have effects on serum androgen concentrations and reduces serum follicle-stimulating hormone levels in men with epilepsy 5, 6.
• The endocrine effects of antiepileptic drugs may be reversible, and discontinuation of the medication may improve fertility 6, 7.

Clinical Implications

The clinical implications of the relationship between epilepsy and male infertility are significant:

• Men with epilepsy should be counseled about the possibility of reduced fertility and the potential effects of antiepileptic drugs on semen quality 3, 7.
• Alternative antiepileptic drugs may be considered for men with epilepsy who are trying to conceive, particularly if they have abnormal sperm parameters while on VPA or other drugs associated with infertility 4, 7.
• Further research is needed to fully understand the mechanisms of antiepileptic drug-related infertility and to develop effective strategies for managing fertility in men with epilepsy.