Polycystic ovary syndrome and antiepileptic drugs

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

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Polycystic Ovary Syndrome (PCOS)

• Irregular menstrual cycles
• Intermenstrual variation gt7 days
• Cycle duration gt35 or lt 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)

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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
24322-334
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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 200462 445-450
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Polycystic Ovary Syndrome (PCOS)

• Setting
• Oulu University Hospital (FIN)
• Methods
• Clinical examination (history)
• Ovarian ultrasonography
• Serum reproductive hormone concentrations

Mikkonen Neurology 200462 445-450
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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 lt 0.02).
• All patients still on VPA elevated serum
  androstenedione levels.

Mikkonen Neurology 200462 445-450
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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 200462 445-450
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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 200462 445-450
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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
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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
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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
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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
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Polycystic Ovary Syndrome (PCOS)

• Question
• PCOS (hyperandrogenism (testosterone gt 0.7 ng/ml)
  combined with oligomenorrhoea (cycle gt 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 gt1 AED, 19 without AED
• Follow up 6 months

Bauer Epilepsy Res. 2000 Sep41(2)163-7.
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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 Sep41(2)163-7.
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Polycystic Ovary Syndrome (PCOS)

• Conclusion
• PCOS in WW focal E not related to CBZ or VPA

Bauer Epilepsy Res. 2000 Sep41(2)163-7.
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Polycystic Ovary Syndrome (PCOS) in WWE on AED

• Problems
• Different definitions of PCOS used (w/o
  ultrasonography)
• Duration follow up
• Small numbers
• Selection bias

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Polycystic Ovary Syndrome (PCOS) in WWE on AED

• Overall conclusion
• Increased prevalence of endocrine disorders in
  patients on AEDs, especially VPA