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Polycystic ovary syndrome and antiepileptic drugs

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Cycle duration 35 or 21 days. At least once in preceding 6 months ... Testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, free ... – PowerPoint PPT presentation

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Title: Polycystic ovary syndrome and antiepileptic drugs


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 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)

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
24322-334
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 200462 445-450
6
Polycystic Ovary Syndrome (PCOS)
  • Setting
  • Oulu University Hospital (FIN)
  • Methods
  • Clinical examination (history)
  • Ovarian ultrasonography
  • Serum reproductive hormone concentrations

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

Mikkonen Neurology 200462 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 200462 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 200462 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 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.
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 Sep41(2)163-7.
16
Polycystic Ovary Syndrome (PCOS)
  • Conclusion
  • PCOS in WW focal E not related to CBZ or VPA

Bauer Epilepsy Res. 2000 Sep41(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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