Can Lamictal (lamotrigine) cause hypogonadism in males?

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Can Lamictal Cause Low Testosterone in Males?

Lamotrigine (Lamictal) does not cause low testosterone or hypogonadism in men and is considered weight-neutral and endocrine-neutral among antiepileptic drugs.

Evidence from Antiepileptic Drug Studies

The most comprehensive evidence comes from direct comparative studies of antiepileptic drugs and their endocrine effects:

  • Lamotrigine has not been shown to result in endocrine side effects, distinguishing it from enzyme-inducing antiepileptic drugs like phenobarbital, phenytoin, and carbamazepine, as well as from valproate 1.

  • In a controlled study of 85 men with epilepsy, bioactive testosterone levels in men taking lamotrigine were comparable to untreated controls and significantly higher than those taking carbamazepine or phenytoin 2.

  • Among men with epilepsy on lamotrigine, only 12% had bioactive testosterone below the control range, compared to 48% on carbamazepine and 28% on phenytoin 2.

  • Sexual function scores in the lamotrigine group were equivalent to controls and significantly better than enzyme-inducing antiepileptic drugs 2.

Mechanism: Why Lamotrigine Differs

The key distinction lies in lamotrigine's pharmacologic profile:

  • Lamotrigine does not induce liver enzymes, unlike carbamazepine and phenytoin, which increase sex hormone-binding globulin (SHBG) concentrations 1, 3.

  • Elevated SHBG from enzyme-inducing drugs leads to lower bioactive testosterone and estradiol over time, causing sexual dysfunction and reduced fertility 1.

  • Lamotrigine is classified as weight-neutral, avoiding the metabolic disruptions associated with valproate that can affect testosterone through different mechanisms 3.

Guideline Context on Drug-Induced Hypogonadism

According to the 2025 European Association of Urology guidelines on male hypogonadism, drug-induced causes include 4:

  • Antiandrogens (cyproterone acetate, spironolactone, flutamide, bicalutamide)
  • 5α-reductase inhibitors (finasteride, dutasteride)
  • Estrogen receptor blockers
  • Aromatase inhibitors
  • Drugs that increase SHBG (notably anticonvulsants—but this refers specifically to enzyme-inducing agents)

Lamotrigine is conspicuously absent from these lists of medications causing hypogonadism.

Clinical Implications

  • If a male patient on lamotrigine presents with symptoms of low testosterone (reduced libido, erectile dysfunction, fatigue), investigate other causes rather than attributing it to the medication 5.

  • Common alternative explanations include obesity, metabolic syndrome, type 2 diabetes, chronic illness, opioid use, or age-related decline 4.

  • Switching from enzyme-inducing antiepileptic drugs to lamotrigine may actually improve testosterone levels and sexual function in men with epilepsy 2.

Important Caveat

While lamotrigine itself doesn't cause hypogonadism, epilepsy as a condition is independently associated with reproductive dysfunction in both treated and untreated patients 3, 2. In the comparative study, 20% of untreated men with epilepsy had low sexual function scores, though this was still better than those on carbamazepine (32%) or phenytoin (24%), and worse than lamotrigine (4%) 2.

References

Research

Effects of Treatment on Endocrine Function in Patients with Epilepsy.

Current treatment options in neurology, 2005

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Laboratory Testing for Male with Low Libido

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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