Abstracts

Rationale: Clinical decision making which contraceptive regimen is optimal for an individual woman with epilepsy often is a challenging tasks when taking care of women with epilepsy. The interactive potential of antiepileptic drugs and hormonal contraceptives needs to be taken into account. Ethinylestradiol (EE) induces the uridine 5-diphosphate-glucuronosyltransferase (UGT) 1A4, the key enzyme in LTG metabolism. Thus the use of EE containing hormonal contraceptives (COCs, vaginal ring or patch) causes clinically relevant serum-concentration (SC) reduction of LTG of approx. 50% that may be accompanied by worsening of seizure control. A new combined oral contraceptive containing dienogest (DNG) and estradiol-valerate (E2/Val) instead of ethinylestradiol (EE) in a multiphasic regimen was recently approved in many European countries and the USA. After oral administration E2/Val is immediately cleaved to 17?-estradiol (E2) and valeric acid. Compared to EE, E2/Val has lesser impact on various hepatic pathways including SHBG induction. Thus it seemed reasonable to assume that this new COC would cause a lesser UGT-induction and lesser drop of LTG-SC than conventional COCs containing EE.Methods: We prospectively evaluated LTG-SC in 6 women with epilepsy on a stable LTG dose (100-1200 mg/d; SC 2.8-23 mg/l). Four patients switched from a COC containing 30mcg EE and 2mg DNG(n=3) or 0,125mg LNG(n=1) to the new COC (E2/Val+DNG multiphasic 26/2 regimen). In 2 women taking no hormonal contraception the new COC (E2/Val+DNG) was added. Follow up included measurement of E2, progesterone, LH and FSH and sequential vaginal ultrasound measurements in order to assess ovarian function.Results: Switching from a conventional EE COC to E2/Val+DNG incrased LTG trough-levels by 61-109%. LTG daily dose had to be reduced in 2 patients. SC-fluctuations during the day were diminished and tolerability was improved in 2 patients. Adding E2/Val+DNG as the first hormonal contraceptive changed LTG trough-levels by -17 to +6% with no impact on seizure control or tolerability. None of the 6 patients ovulated, no progesterone surge occurred, there was some spotting in 3/6 patients.Conclusions: Our preliminary observations indicate that E2/Val containing COCs decrease LTG-SC to a much lesser extent than conventional EE containing COCs. However, moderate dosage adjustments of LTG may still be necessary if a patient is started on the new E2/Val COC. Larger studies are needed to verify this effect. Compared to EE-containing hormonal contraceptives the new COCs containing estradiol may be a better contraceptive option for women with epilepsy treated with LTG.