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Polycystic ovary syndrome and antiepileptic drugs

Polycystic ovary syndrome and antiepileptic drugs. CAT Marc de Krom 10-02-2005. zoektermen. polycystic ovar* AND antiepilept* : 37 polycystic ovar* AND population based: 51 polycystic ovar* AND general population : 83 14 duplicates of 171 157

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Polycystic ovary syndrome and antiepileptic drugs

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  1. Polycystic ovary syndrome and antiepileptic drugs CAT Marc de Krom 10-02-2005

  2. zoektermen • polycystic ovar* AND antiepilept* : 37 • polycystic ovar* AND population based: 51 • polycystic ovar* AND general population : 83 • 14 duplicates of 171 157 • #1 AND #2 or #1 AND #3: 0

  3. Polycystic Ovary Syndrome (PCOS) • Irregular menstrual cycles • Intermenstrual variation >7 days • Cycle duration >35 or < 21 days • At least once in preceding 6 months • Elevated serum levels testosteron or clinical signs hyperandrogenism (hirsutism, acne, obesity) • Ultrasonography: 8 or more subcapsular follicles (2-8 mm) in one or both ovaries (two dimensional plane)

  4. Polycystic Ovary Syndrome (PCOS) • A prospective longitudinal study with larger cohorts in newly diagnosed WWE or bipolar disorder is needed to definitively characterize the relationship between AEDs and PCOS… Rasgon N. : J Clin Psychopharmacol 2004; 24:322-334

  5. Polycystic Ovary Syndrome (PCOS) Patients: • 69 patients (88%) and 51 control subjects (94%) of previously identified cohorts of 78 girls with epilepsy and 54 healthy control girls (initial age 8 to 18.5 years, at follow-up 12.5 to 25.8 years). • 35 initially on VPA, 17 on CBZ, 17 on OCB (monotherapy). • 61% off medication Mikkonen Neurology 2004;62: 445-450

  6. Polycystic Ovary Syndrome (PCOS) Setting: • Oulu University Hospital (FIN) Methods: • Clinical examination (history) • Ovarian ultrasonography • Serum reproductive hormone concentrations Mikkonen Neurology 2004;62: 445-450

  7. Polycystic Ovary Syndrome (PCOS) RESULTS (1): • No differences in laboratory or clinical findings between patients off medication and controls • Postpubertal patients on medication higher serum testosterone and androstenedione levels than patients off medication or controls (p < 0.02). • All patients still on VPA: elevated serum androstenedione levels. Mikkonen Neurology 2004;62: 445-450

  8. Polycystic Ovary Syndrome (PCOS) RESULTS (2): • Polycystic ovary syndrome more common in patients on medication (38%; in 63% on VPA, in 25% on other medication) than in patients off medication (6%) or in controls (11%) (p = 0.005) Mikkonen Neurology 2004;62: 445-450

  9. Polycystic Ovary Syndrome (PCOS) CONCLUSIONS: • Epilepsy during pubertal maturation does not affect reproductive endocrine health in female subjects who discontinue the medication before adulthood • Increased prevalence of endocrine disorders in patients remaining on AEDs, especially VPA, until adulthood Mikkonen Neurology 2004;62: 445-450

  10. Polycystic Ovary Syndrome (PCOS) PURPOSE: • Effect epilepsy / AEDs on growth, pubertal development, and androgenic status in WWE (8 -18 y) METHODS: • 66 WWE, age mean 13.47 +/- 3.5 years and 40 female healthy age matched controls • Body length, - weight, staging pubertal maturation • Clinical manifestations hyperandrogenism • Testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, free androgen index • Transabdominal ultrasonic examination in 44 • Fasting serum insulin • Setting: University Hospital, Cairo, Egypt El-Khayat, H. A.Epilepsia 2004; 45(9):1106-1115

  11. Polycystic Ovary Syndrome (PCOS) RESULTS (1): Patients • Reduced mean height compared with controls (negatively correlated with duration epilepsy) • Increased frequency obesity, especially postpubertal girls on VPA (67%) also higher insulin levels • Increased frequency clinical hyperandrogenemia in different stages puberty • High testosterone and DHEAS in WWE (pubertal and postpubertal) • Hyperandrogenism (clinical and/or laboratory) most affected by the types of AEDs more frequently VPA compared to enzyme-inducing AEDs • PCOS in 18% El-Khayat, H. A.Epilepsia 2004; 45(9):1106-1115

  12. Polycystic Ovary Syndrome (PCOS) Results (2): No difference regarding types of seizures, degree of seizure control, type of AEDs, or insulin levels between patients with and those without PCOS El-Khayat, H. A.Epilepsia 2004; 45(9):1106-1115

  13. Polycystic Ovary Syndrome (PCOS) CONCLUSIONS: • Longer duration disease negatively correlated to body length in WWE • Postpubertal girls on VPA • more liable to obesity (increased incidence hyperinsulinemia) • clinical and/or laboratory evidence of hyperandrogenism more frequent in patients, especially VPA • High prevalence of PCOS, independent of AED or characteristics epilepsy El-Khayat, H. A.Epilepsia 2004; 45(9):1106-1115

  14. Polycystic Ovary Syndrome (PCOS) Question: PCOS (hyperandrogenism (testosterone > 0.7 ng/ml) combined with oligomenorrhoea (cycle > 35 days) or amenorrhoea) frequently seen in WWE on AEDs? Methods: Prospective cohort analysis premenopausal WW(focal)E Setting : University Hospital Bonn Patients: 93 of consecutive 150 women (aged 20-53 y; mean, 34.3 y), 38 monotherapy (18 VPA, 20 CBZ), 36 >1 AED, 19 without AED Follow up: 6 months Bauer Epilepsy Res. 2000 Sep;41(2):163-7.

  15. Polycystic Ovary Syndrome (PCOS) Results: PCOS in • 2 of 19 (10.5%) patients without AED • 4 of 38 (10.5%) of patients on monotherapy • in none of the patients on polypharmacy • Incidence of PCOS in VPA monotherapy (11.1%) similar to that CBZ monotherapy (10%) and to that in patients without AED Bauer Epilepsy Res. 2000 Sep;41(2):163-7.

  16. Polycystic Ovary Syndrome (PCOS) Conclusion: • PCOS in WW focal E not related to CBZ or VPA Bauer Epilepsy Res. 2000 Sep;41(2):163-7.

  17. Polycystic Ovary Syndrome (PCOS) in WWE on AED Problems: • Different definitions of PCOS used (w/o ultrasonography) • Duration follow up • Small numbers • Selection bias

  18. Polycystic Ovary Syndrome (PCOS) in WWE on AED Overall conclusion: • Increased prevalence of endocrine disorders in patients on AEDs, especially VPA

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