Does Keppra (Levetiracetam) affect menstrual cycles?

Does Keppra (Levetiracetam) Affect Menstrual Cycles?

Levetiracetam does not directly affect menstrual cycles through hormonal mechanisms, as it lacks cytochrome P450 enzyme-inducing properties and does not interact with hormonal contraceptives or endogenous reproductive hormones. 1, 2

Mechanism and Pharmacokinetic Profile

Levetiracetam has a unique mechanism of action that distinguishes it from enzyme-inducing antiepileptic drugs:

• Levetiracetam is minimally metabolized through pathways independent of the cytochrome P450 system, has no significant drug-drug interactions, and lacks enzyme-inducing potential. 1, 2
• The drug targets synaptic vesicle protein 2A (SV2A) and N-type calcium channels rather than affecting hormonal pathways. 1, 2
• Unlike traditional antiepileptic drugs (such as phenytoin, carbamazepine, or phenobarbital), levetiracetam does not reduce the effectiveness of hormonal contraceptives. 3

Clinical Context: Catamenial Epilepsy vs. Menstrual Disruption

It is critical to distinguish between levetiracetam's use for menstrual-related seizures versus causing menstrual irregularities:

• Levetiracetam has been successfully used as intermittent therapy specifically to treat catamenial epilepsy (seizures that worsen during menstruation), demonstrating that the drug works with—not against—the menstrual cycle. 4
• In five patients with catamenial epilepsy, intermittent levetiracetam treatment (0.5-0.75g twice daily) given 1 week before and after menstruation effectively controlled seizures without disrupting the menstrual cycle itself. 4

Contrast with Enzyme-Inducing Antiepileptic Drugs

The concern about antiepileptic drugs affecting menstrual cycles primarily applies to older, enzyme-inducing medications:

• Traditional antiepileptic drugs like carbamazepine, phenytoin, and phenobarbital can decrease the effectiveness of hormonal contraceptives and potentially affect endogenous hormone metabolism. 3
• These enzyme-inducing drugs may require alternative contraceptive methods or dosing adjustments, whereas levetiracetam does not. 3

Indirect Considerations

While levetiracetam itself does not affect menstrual cycles, clinicians should be aware of:

• Weight changes can indirectly affect menstrual regularity through metabolic effects, but levetiracetam is not associated with drug-induced weight gain. 2
• Any reported menstrual irregularities in patients taking levetiracetam should prompt evaluation for other causes (pregnancy, polycystic ovary syndrome, thyroid dysfunction, stress) rather than attributing them to the medication. 5

Practical Clinical Implications

• Women of reproductive age can use levetiracetam without concern for menstrual cycle disruption or reduced contraceptive efficacy. 1, 2
• No special monitoring of menstrual cycles is required when initiating or maintaining levetiracetam therapy. 2
• Levetiracetam represents an excellent choice for women with epilepsy who require reliable contraception, as it does not interfere with hormonal contraceptive methods. 3, 1