Hormone replacement therapy with estrogens may reduce lamotrigine serum concentrations: A matched case-control study

Area of Science:

• Pharmacology
• Endocrinology
• Clinical Pharmacy

Background:

• Lamotrigine (LTG) is an antiepileptic drug primarily metabolized by glucuronidation.
• Estrogens, particularly ethinyl estradiol (EE) in hormonal contraceptives, are known to induce the glucuronidizing enzyme, leading to reduced LTG serum concentrations.
• Limited and conflicting data exist regarding the interaction between estrogens used in hormone replacement therapy (HRT) and LTG.

Purpose of the Study:

• To investigate the potential interaction between estrogens used in HRT and LTG serum concentrations.
• To compare the effect of HRT with estrogens on LTG levels to that of EE-containing contraceptives.

Main Methods:

• Retrieved LTG serum concentration data from a therapeutic drug monitoring database.
• Identified users of HRT and EE, matched with controls for age and dose, excluding those with interacting comedications.
• Calculated LTG serum concentration-to-dose ratios (CDRs) and compared groups using the Mann-Whitney U test.

Main Results:

• Both HRT users (n=79) and EE users (n=200) exhibited significantly lower mean LTG CDRs compared to their respective matched controls (n=158 and n=400).
• The observed reduction in LTG CDRs suggests a decrease in serum LTG concentrations in individuals using HRT with estrogens.

Conclusions:

• Estrogen-containing HRT may lead to reduced serum concentrations of lamotrigine.
• This finding has implications for managing epilepsy patients on LTG who also use HRT, suggesting potential need for dose adjustments.