Polycystic ovary syndrome characteristics and clinical controversies
Download
1 / 61

Polycystic Ovary Syndrome: - PowerPoint PPT Presentation


  • 458 Views
  • Updated On :

Sponsored by ACCESS Medical Group Department of Continuing Medical Education Funded by an unrestricted educational grant from Abbott Laboratories. Polycystic Ovary Syndrome: Characteristics and Clinical Controversies. PCOS Overview, History, and Epidemiology.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Polycystic Ovary Syndrome: ' - LeeJohn


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Polycystic ovary syndrome characteristics and clinical controversies l.jpg

Sponsored by

ACCESS Medical Group

Department of Continuing Medical Education

Funded by an unrestricted educational grant from Abbott Laboratories.

Polycystic Ovary Syndrome: Characteristics and Clinical Controversies


Slide2 l.jpg

PCOS

Overview, History, and Epidemiology


Polycystic ovarian syndrome pcos overview l.jpg
Polycystic Ovarian Syndrome (PCOS)Overview

  • PCOS is a complex endocrine disorder affecting women of childbearing age characterized by increased androgen production and ovulatory dysfunction

  • PCOS is the leading cause of anovulatory infertility and hirsutism

  • Women with PCOS have an increased risk of miscarriage, insulin resistance, hyperlipidemia, type 2 diabetes, cardiovascular disease, and endometrial cancer

Bauer J, et al. Epilepsy Res. 2000;41:163-167.

Dunaif A, et al. Annu Rev Med. 2001;52:401-419.

Franks S. N Engl J Med. 1995;333:853-861.


Pcos and stein leventhal syndrome l.jpg
PCOS and Stein-Leventhal Syndrome

  • PCOS was first identified by Stein and Leventhal in 1935

  • They described a group of women who were obese and infertile, with enlarged ovaries with multiple cysts

  • Few of these original features are now considered consistent findings in PCOS

Stein IF, Leventhal ML. Am J Obstet Gynecol. 1935;29:181-191.

Dunaif A, et al. Annu Rev Med. 2001;54:401-419.


Prevalence of pcos in various populations of women l.jpg
Prevalence of PCOS in Various Populations of Women

With oligomenorrhea*

With amenorrhea*

Unilateral temporolimbic epilepsy†

Idiopathic generalized epilepsy‡

Primary generalized epilepsy†

Reproductive-age (4% to 12%)§

Untreated epilepsy‡

Valproate-treated epilepsy‡

Carbamazepine-treated epilepsy‡

0

15

30

45

60

75

90

Prevalence of PCOS, %

*Franks s. N Engl J Med. 1995;333:853-861.

†Herzog AG, et al. Epilepsia. 2001;42:311-315.

‡Duncan S. Epilepsia. 2001;42(suppl 3):60-65.

§Dunaif A, et al. Annu Rev Med. 2001;52:401-419.


Slide6 l.jpg

PCOS

Characteristics


Pcos national institutes of health diagnostic criteria l.jpg
PCOS: National Institutes of Health Diagnostic Criteria

  • Presence of ovulatory dysfunction, polymenorrhea, oligomenorrhea, or amenorrhea

  • Clinical evidence of hyperandrogenism and/or hyperandrogenemia

  • Exclusion of other endocrinopathies (eg, Cushing syndrome, hypothyroidism, late-onset congenital adrenal hyperplasia

Duncan S. Epilepsia. 2001;42(suppl 3):60-65.


Clinical features of pcos menstrual irregularity l.jpg
Clinical Features of PCOSMenstrual Irregularity

  • May appear at puberty with a delayed menarche followed by the onset of irregular periods or as the breakdown of a previously regular cycle

  • Anovulation is usually chronic and presents as oligomenorrhea or amenorrhea

Duncan S. Epilepsia. 2001;42(suppl 3):60-65.

Ernst CL, et al. J Clin Psychiatry. 2002;63(suppl 4):42-55.

Lobo RA, et al. Ann Int Med. 2000;132:989-993.


Clinical features of pcos hyperandrogenism l.jpg
Clinical Features of PCOSHyperandrogenism

  • Symptoms may include hirsutism, acne, male pattern balding, and/or male distribution of body hair

Acne

Hirsutism

Lobo RA, et al. Ann Intern Med. 2000;132:989-993.


Common endocrine abnormalities in pcos l.jpg
Common Endocrine Abnormalities in PCOS

  • Elevated luteinizing hormone (LH)

  • Increased LH/follicle-stimulating hormone (FSH) ratio

  • Elevated androgen levels

  • Decreased sex hormone binding globulin levels

Duncan S. Epilepsia. 2001;42(suppl 3):60-65.


Metabolic abnormalities in pcos l.jpg
Metabolic Abnormalities in PCOS

  • Hyperinsulinemia and insulin resistance

  • Insulin resistance may be independent of the effect of obesity

  • Decreased peripheral insulin sensitivity and consequent hyperinsulinemia may play an important role in the pathogenesis of PCOS

Franks S. N Engl J Med. 1995;333:853-861.

Hopkinson ZE, et al. BMJ. 1998;317:329-332.


Lipid and lipoprotein abnormalities in pcos l.jpg
Lipid and Lipoprotein Abnormalities in PCOS

  • Elevated LDL cholesterol

  • Elevated triglycerides

  • Decreased HDL cholesterol

  • Decreased apolipoprotein A-I

  • Impaired fibrinolytic activity

Lobo RA, et al. Ann Int Med. 2000;132:989-993.

Hopkinson ZE, et al. BMJ. 1998;317:329-332.


Reproductive sequelae of pcos l.jpg
Reproductive Sequelae of PCOS

  • PCOS is usually associated with varying degrees of infertility

  • It is a frequent cause of anovulatory infertility in women

  • The disorder often develops shortly after menarche, lasting for most of the reproductive life

Legro RS. Mol Cell Endocrinol. 2002;186:219-225.



Polycystic ovaries pco l.jpg
Polycystic Ovaries (PCO)

  • 10 subcapsular follicular cysts, 2-8 mm in diameter, arranged around a thickened ovarian stroma

  • While associated with increased hirsutism, elevated testosterone, and irregular menstrual cycles, PCO are not intrinsically pathologic

Ernst CL, et al. J Clin Psychiatry. 2002;63(suppl 4):42-55.


Polycystic ovaries not intrinsically pathologic l.jpg
Polycystic OvariesNot Intrinsically Pathologic

  • PCO occur in about 17% to 22% of the general female population

  • As many as 25% of women with a radiographic finding of PCO have no endocrine or menstrual irregularities

  • An isolated finding of PCO may be a normal variation and does not necessarily imply altered fertility

Ernst CL, et al. J Clin Psychiatry. 2002;63:(suppl 4):42-55.

Genton P, et al. Epilepsia. 2001;42:295-304.


Rates of pcos and pco in the general population and women with epilepsy l.jpg
Rates of PCOS and PCO in the General Population and Women With Epilepsy

Polycystic Ovarian Syndrome Expert Consensus Panel

40

35

30

All premenopausal women

25

Prevalence, %

20

Women with epilepsy

15

10

5

0

PCOS

PCO

Genton P, et al. Epilepsia. 2001;42:295-304.

Dunaif A, et al. Annu Rev Med. 2001;52:401-419.

Herzog AG, et al. Epilepsia. 2001;42:311-315.


Polycystic ovarian syndrome pcos versus polycystic ovaries pco l.jpg
Polycystic Ovarian Syndrome (PCOS) Versus Polycystic Ovaries (PCO)

  • PCOS: A metabolic disorder characterized by ovulatory dysfunction, hyperandrogenism, and exclusion of other endocrinopathies

  • PCO: The presence of multiple ovarian cysts 2-8 mm in diameter and increased ovarian stroma; this condition is not intrinsically pathologic

Duncan S. Epilepsia. 2001;42(suppl 3):60-65.



Theories of pcos development l.jpg
Theories of PCOS Development (PCO)

  • PCOS may be caused by interactions between

    • Genetic factors (eg, autosomal dominant transmission)

    • Endocrine factors (eg, increased LH/FSH ratio, increased insulin and androgen concentrations)

    • Metabolic factors (eg, increased insulin resistance, decreased SHBG)

    • Neurologic factors (eg, epileptic discharges)

    • Environmental factors (eg, anabolic steroids)

LH=luteinizing hormone; FSH=follicle stimulating hormone; SHBG=sex hormone binding globulin

Herzog AG, et al. Epilepsia. 2001;42:311-315.

Duncan S. Epilepsia. 2001; 42(suppl 3):60-65.

Ernst CL, et al. J Clin Psychiatry. 2002;63(suppl 4):42-55.


Developmental origin of pcos l.jpg
Developmental Origin of PCOS (PCO)

  • During gestation, human chorionic gonadotrophin, LH, and genes regulating folliculogenesis and steroidogenesis may cause excess prenatal androgen

  • Postpubertally, hyperinsulinemia and LH hypersecretion augment ovarian steroidogenesis, leading to anovulation

Abbott DH, et al. J Endocrinol. 2002;174:1-5.


Association between weight gain and pcos l.jpg
Association Between Weight Gain and PCOS (PCO)

  • Up to 50% of women with PCOS are moderately obese or overweight

  • Obesity is usually the android type, with increased waist-to-hip ratios

  • When present, obesity worsens insulin resistance and increases the risk for diabetes and cardiovascular disease

Ernst CL, et al. J Clin Psychiatry. 2002;63(suppl 4):42-55.


Impaired ovarian function as a cause of pcos l.jpg
Impaired Ovarian Function as a Cause of PCOS (PCO)

  • PCOS may be caused by increased steroidogenic activity in the ovary

  • This increased activity may be a genetic defect in the ovary; the result is an ovary that secretes increased amounts of

    • Androstenedione (an androgen)

    • 17-hydroxyprogesterone (a steroid that is intermediate in the androgen pathway)


Insulin resistance and pcos l.jpg
Insulin Resistance and PCOS (PCO)

  • Increased insulin levels can stimulate androgen production

  • Insulin can stimulate adrenal steroidogenesis by enhancing sensitivity to adrenocorticotrophic hormone and increasing pituitary LH release

  • Insulin-lowering therapies can restore menstrual cycles in some anovulatory women with PCOS

  • Defects in insulin receptors have been found in up to half of women with PCOS

Dunaif A, et al. Annu Rev Med. 2001;52:401-419.

Earnst CL, et al. J Clin Psychiatry. 2002;63(suppl 4):42-55.


Polycystic ovarian syndrome genetic influences l.jpg
Polycystic Ovarian Syndrome (PCO) Genetic Influences

  • Evidence suggests a defect in ovarian and androgen biosynthesis that may interact with an insulin abnormality

  • A familial aggregation of hyperandrogenism is found in first-degree relatives of women with PCOS

  • PCOS appears to have an autosomal dominant inheritance pattern

Dunaif A, et al. Annu Rev Med. 2001;52:401-419.

Franks S. N Engl J Med. 1995;333:853-861.


Epilepsy and reproductive endocrine dysfunction l.jpg
Epilepsy and Reproductive Endocrine Dysfunction (PCO)

  • Epileptic discharges may affect secretion of GnRH

  • Seizures can cause hyperprolactinemia, which can elevate LH levels and support androgenization

  • Epilepsy and PCOS may be caused by a common factor, such as a dysfunction in neurotransmission or genetic vulnerability

Ernst CL, et al. J Clin Psychiatry. 2002;63(suppl 4):42-55.


Bipolar disorder and reproductive endocrine dysfunction l.jpg
Bipolar Disorder and Reproductive Endocrine Dysfunction (PCO)

  • Women with bipolar disorder have a high prevalence of menstrual disturbances independent of therapeutic agent used

  • This finding may indicate compromise in reproductive endocrine function prior to treatment

  • It may represent a marker for an underlying hypothalamic-pituitary-gonadal axis dysregulation

Rasgon NL, et al. J Clin Psychiatry. 2000;61:173-178.


Women with bipolar disorder have a high rate of menstrual abnormalities l.jpg
Women With Bipolar Disorder Have a High Rate of Menstrual Abnormalities

In a study by Rasgon et al,

  • 59% of women treated for bipolar disorder had long menstrual periods

  • 18% displayed oligomenorrhea

  • These findings are consistent with a previous report that menstrual abnormalities are common in women with bipolar disorder receiving mood stabilizers

Rasgon NL, et al. Bipolar Disord. (in press).


Increased insulin resistance in women with bipolar disorder l.jpg
Increased Insulin Resistance in Women With Bipolar Disorder Abnormalities

  • Insulin levels were measured in 42 women with bipolar disorder

  • Patients received at least 2 of the following: lithium, valproate, other anticonvulsants, or antipsychotics

  • 42% of women had insulin resistance

  • No difference was found in terms of which medication was used and the development of insulin resistance

  • Not clear if insulin resistance was due to treatment or bipolar disorder

Rasgon NL, et al. Poster presented at the American Psychiatric Association annual meeting, Philadelphia, Pa, May 18-23, 2002.


Pcos characteristics and causes l.jpg
PCOS AbnormalitiesCharacteristics and Causes

  • A complex disorder characterized by increased androgen production and ovulatory dysfunction

  • The leading cause of anovulatory infertility

  • Different from polycystic ovaries (PCO), a condition that is not intrinsically pathologic

  • Caused by interactions between genetic, endocrine, metabolic, neurologic, and environmental factors



Isoj rvi et al 1993 correlation between aeds and menstrual disturbances l.jpg

100 Abnormalities

90

80

70

60

50

40

30

20

10

0

Isojärvi et al 1993: Correlation Between AEDs and Menstrual Disturbances

N=238

Menstrual Disturbances, %

Carbam- azepine + Valproate

Valproate

Carbam- azepine

Other AEDs

AEDs=Antiepileptic drugs

Isojärvi JIT, et al. N Engl J Med. 1993;329:1383-1388.


Isoj rvi et al 1996 pco hyperandrogenism or both from valproate or carbamazepine l.jpg

100 Abnormalities

90

80

70

60

50

40

30

20

10

0

Isojärvi et al 1996: PCO, Hyperandrogenism, or Both From Valproate or Carbamazepine

PCO, Hyperandrogenism, or Both, %

Carbam- azepine

Control Group

Valproate

Isojärvi JIT, et al. Ann Neurol. 1996;39:579-584.


Isoj rvi et al 1993 and 1996 analysis l.jpg
Isojärvi et al 1993 and 1996: Analysis Abnormalities

  • In both studies

  • None of the women taking valproate with PCO met the NIH criteria for PCOS

  • There is a lack of pretreatment data regarding ovarian structure and function

  • Designs were cross-sectional and retrospective

Isojärvi JIT, et al. Ann Neurol. 1996;39:579-584.

Ernst CL, et al. J Clin Psychiatry. 2002;63(suppl 4):42-55.

Duncan S. Epilepsia. 2001;42(suppl 3):60-65.


Isoj rvi et al 1998 testosterone and insulin levels after switch from valproate to lamotrigine l.jpg
Isojärvi et al 1998: Testosterone and Insulin Levels After Switch From Valproate to Lamotrigine

*

125

12

VPA=Valproate LTG=Lamotrigine

100

*

10

§

§

§

8

75

Serum Testosterone, ng/dL

Serum Insulin, mU/L

6

50

4

25

2

0

VPA

Control

VPA

Control

LTG

6 mo

LTG

12 mo

LTG

6 mo

LTG

12 mo

LTG

2 mo

LTG

2 mo

*P<.05 compared with control subjects.

†P<.01 compared with valproate.

‡P<.05 compared with valproate.

§P<.001 compared with valproate.

Isojärvi JIT, et al. Ann Neurol. 1998;43:446-451.


Isoj rvi et al 1998 analysis l.jpg
Isojärvi et al 1998: Analysis Switch From Valproate to Lamotrigine

  • The decline in the number of cysts after the switch from valproate to lamotrigine was not significantly significant

  • Only obese women on valproate were chosen for the study; it was not randomized

  • Only 12 women completed the study after 4 withdrew (25% dropout rate)

  • Criteria for patient selection were not provided; possible selection bias cannot be evaluated

  • Switching medications may increase the risk of seizures in a controlled patient

Isojärvi JI, et al. Ann Neurol. 1998;43:446-451.

Dean JC, et al. American Epilepsy Society Annual Meeting, 2001.


Testosterone concentrations in women with epilepsy treated with valproate or lamotrigine l.jpg
Testosterone Concentrations in Women With Epilepsy Treated With Valproate or Lamotrigine

100

Clinically Significant Elevation (>70 ng/dL)

90

80

70

60

Testosterone Level, ng/dL

50

40

30

20

10

0

Lamotrigine

Valproate

Taylor A, et al. [Poster] American Psychiatric Association Annual Meeting. May, 2001.


Taylor et al 2001 analysis l.jpg
Taylor et al 2001: Analysis With Valproate or Lamotrigine

  • Multicenter, international study (9 countries, 70 sites); 222 young women with epilepsy

  • Testosterone levels increased more in patients taking valproate, but both groups were well within normal range

  • Total cholesterol and LDL levels were lower in the valproate group

  • Insulin levels similar in both treatment groups

Taylor A, et al. [Poster] American Psychiatric Association Annual Meeting. May, 2001.


No association found between pcos and valproate or carbamazepine therapy l.jpg

Untreated With Valproate or Lamotrigine

Valproate

Carbamazepine

Polytherapy (0%)

No Association Found Between PCOS and Valproate or Carbamazepine Therapy

Incidence of PCOS, %

Treatment

Bauer J, et al. Epilepsy Res. 2000;41:163-167.


Bauer et al 2000 analysis l.jpg
Bauer et al 2000: Analysis With Valproate or Lamotrigine

  • Using NIH criteria for PCOS, investigators found no relationship between the administration of valproate, carbamazepine, or no treatment and the development of PCOS

  • Investigators concluded the study suggests manifestations of PCOS in women with focal epilepsy are not related to the administration of valproate or carbamazepine

Bauer J, et al. Epilepsy Res. 2000;41:163-167.


Reproductive endocrine disorders in epilepsy not associated with aeds l.jpg
Reproductive Endocrine Disorders in Epilepsy Not Associated With AEDs

100

Therapy

90

including

80

valproate

70

Therapy not

60

Women With a Reproductive Endocrine Disorder, %

including

50

valproate

40

30

Untreated

20

10

0

PCOS

PCO

Elevated Androgens

Irregular Menstrual Cycles

Bilo L, et al. J Clin Endocrinol Metab. 2001;86:2950-2956.


Bilo et al 2001 analysis l.jpg
Bilo et al 2001: Analysis With AEDs

  • In a study of women with epilepsy, no significant association was found between epilepsy type, AED used (valproate or other), and the development of reproductive endocrine disorders

  • Conclusion: the prevalence of disordered ovulation—especially PCOS—is increased in epilepsy, independent of AED use or type of seizure disorder

Bilo L, et al. J Clin Endocrinol Metab. 2001;86:2950-2956.


Valproate not associated with increased menstrual disorders pco or both l.jpg

100 With AEDs

90

80

70

60

50

40

30

20

10

0

Valproate Not Associated With Increased Menstrual Disorders, PCO, or Both

Valproate

Other AEDs

Rate, %

Menstrual Disturbances

Menstrual Disturbances and PCO

PCO

PCOS

*Other AEDs: carbamazepine, lamotrigine, primidone.

Luef G, et al. Epilepsy Res. 2002;48:91-102.


Luef et al 2002 analysis l.jpg
Luef et al 2002: Analysis With AEDs

  • Investigators noted that, in contrast with the studies of Isojärvi et al, they found no increased frequency of menstrual disorders in women receiving valproate (n=22) compared with women receiving carbamazepine or lamotrigine (n=21) after at least 2 years of treatment

  • A limitation of this study was its use of a small sample size and the cross-sectional study design

Luef G, et al. Epilepsy Res. 2002;48:91-102.


Larger study reaffirms no association between valproate and pco l.jpg
Larger Study Reaffirms No Association With AEDsBetween Valproate and PCO

100

N=105

90

80

Valproate

70

60

Carbamazepine

Incidence, %

50

40

30

20

10

0

Menstrual Disturbances

PCO

Luef G, et al. J Neurol. 2002;249:835-841.


Luef et al 2002 analysis of larger study l.jpg
Luef et al 2002: With AEDsAnalysis of Larger Study

  • Investigators did not find an increase in menstrual disturbances or of the incidence of PCO in women with epilepsy treated with valproate (n=52) compared with women with epilepsy treated with carbamazepine (n=53)

  • The rate of PCO incidence in this study of women with epilepsy (27%) was comparable to the rate of PCO incidence in the general population (20%-30%)

Luef G, et al. J Neurol. 2002;835-841.


Women with bipolar disorder no pcos like changes with lithium or divalproex treatment l.jpg
Women With Bipolar Disorder: No PCOS-Like Changes With Lithium or Divalproex Treatment

Measurement Normal Range Li DVP Li + DPV

T, ng/dL 20-80 19.8 26.2 26.4

Bio T, ng/dL <5 3.3 4.5 5.4

DHEA, ng/dL 0.8-10.5 6.3 4.9 2.2

LH, mIU/mL 1.0-18.5 6.5 5.7 6.6

FSH, mIU/mL 2.5-8.0 6.9 4.9 4.5

Bio T=Bioavailable testosterone; DHEA =Dehydroepiandrosterone; DVP=Divalproex sodium; FSH=Follicle stimulating hormone; Li=Lithium; LH=Luteinizing hormone; T=Testosterone

Rasgon NL, et al. J Clin Psychiatry. 2000;61:173-178.


Rasgon et al 2000 analysis l.jpg
Rasgon et al 2000: Analysis Lithium or Divalproex Treatment

  • Women with bipolar disorder received divalproex (n=10), lithium (n=10), or both drugs (n=2)

  • At the beginning of the study, none of the women met the criteria for PCOS

  • All women were treated for >12 months; none developed PCOS

  • Women in the study reported high rates of menstrual disturbances, independent of therapeutic agent used, suggesting they may have had a compromised hypothalamic-pituitary-gonadal axis

Rasgon NL, et al. J Clin Psychiatry. 2000;61:173-178.


Association of epilepsy type aed and ovulatory function l.jpg
Association of Epilepsy Type, AED, and Ovulatory Function Lithium or Divalproex Treatment

  • Investigators studied the association of epilepsy syndrome category and AED (carbamazepine, phenytoin, phenobarbital, valproate, lamotrigine, or gabapentin) on ovulatory function

  • There was no association between AED used and anovulatory cycles; however, women with IGE who were taking or who had taken valproate within the last 3 years were at the highest risk for anovulatory cycles

  • There was no difference in rate of PCO by AED

Morrell MJ, et al. Ann Neurol. (In press).


Morrell et al 2002 analysis l.jpg
Morrell et al 2002: Analysis Lithium or Divalproex Treatment

  • The effects of the epilepsy syndrome could not be separated from the effects of AEDs; AED use was guided to some extent by the epilepsy syndrome

  • The study did not control for past AED exposure; a study of newly diagnosed women with epilepsy receiving AEDs de novo is needed to define drug effects

Morrell MJ, et al. Ann Neurol. (In press).


Menstrual abnormalities in women with bipolar disorder l.jpg
Menstrual Abnormalities in Women With Bipolar Disorder Lithium or Divalproex Treatment

50

45

40

35

30

Incidence, %

25

20

15

10

5

0

Valproate

No Valproate

Controls (0%)

O’Donovan C, et al. J Clin Psychiatry. 2002;63:322-330.


O donovan et al 2002 analysis l.jpg
O’Donovan et al 2002: Analysis Lithium or Divalproex Treatment

  • The data may have been distorted because the study relied on a mailed questionnaire that asked women to remember menstrual abnormalities in the past (recall bias)

  • Another major limitation of the study was that a large number of women did not answer the study questionnaires (participation bias)

O’Donovan C, et al. J Clin Psychiatry. 2002;63:322-330.


Long term valproate use in rhesus monkeys no effect on testosterone or lh levels l.jpg
Long-Term Valproate Use in Rhesus Monkeys: No Effect on Testosterone or LH Levels

Total Testosterone

100

2.0

90

Luteinizing Hormone

80

1.5

70

60

Total Testosterone, ng/dL

50

1.0

Luteinizing Hormone, ng/mL

40

30

0.5

20

10

0

0

Control

1st Trimester

2nd Trimester

Last Trimester

Valproate Treatment

Ferin M, et al. Poster presented at the American Epilepsy Society annual meeting; Seattle, Washington; December 6-11, 2002.


Long term valproate use in rhesus monkeys glucose tolerance test l.jpg
Long-Term Valproate Use in Rhesus Monkeys: Glucose Tolerance Test

Glucose and insulin responses to glucose tolerance test the same in control and valproate-treated monkeys

Valproate

Control

Dextrose 0.1 g/kg

200

200

150

150

Insulin, U/mL

Glucose, ng/dL

100

100

50

50

0

0

10

0

5

15

20

25

35

-5

5

10

15

20

30

35

30

-5

0

25

Minutes

Minutes

Ferin M, et al. Poster presented at the American Epilepsy Society annual meeting; Seattle, Washington; December 6-11, 2002.


Ferin et al 2002 analysis l.jpg
Ferin et al 2002: Analysis Test

  • Long-term treatment (12-15 months) with valproate in monkeys was not associated with differences in testosterone or LH levels compared with a control group; both groups also had similar glucose and insulin responses to a glucose tolerance test

  • Examination of all 14 ovaries in valproate-treated monkeys showed no histological evidence of PCOS

  • The investigators concluded: “These results do not support the hypothesis that treatment with valproate per se is responsible for the induction of PCOS”

Ferin M, et al. Poster presented at the American Epilepsy Society annual meeting; Seattle, Washington; December 6-11, 2002.


Summary of literature on pcos and valproate l.jpg
Summary of Literature on TestPCOS and Valproate

  • There are no reliable data showing a greater prevalence of PCOS in women taking valproate

  • A careful analysis of Isojärvi’s findings shows that none of the women in key studies met the NIH criteria for PCOS

  • Valproate remains a first-line option for the treatment of women with epilepsy or bipolar disorder

  • Switching patients with epilepsy who are adequately controlled with valproate must be exercised with extreme caution

Ernst CL, et al. J Clin Psychiatry. 2002;63(suppl 4):42-55.

Genton P, et al. Epilepsia. 2001;42:295-304.

Dean JC, et al. [Poster] American Epilepsy Society Annual Meeting, 2001.



Pcos in women with epilepsy management goals l.jpg
PCOS in Women With Epilepsy TestManagement Goals

  • For reproductive endocrine disorders

    • Hyperandrogenism: hair removal, antiandrogens

    • Anovulation: clomiphene, gonadotropins

  • For metabolic and cardiovascular disease

    • Insulin resistance: insulin sensitizing agents

    • Elevated triglycerides and LDL, decreased HDL: statins and fibrates

    • Obesity: calorie restriction

Lobo RA, et al. Ann Int Med. 2000;132:989-993.

Franks S. N Engl J Med. 1995;333:853-861.


Failure to control seizures after switch from valproate to lamotrigine l.jpg
Failure to Control Seizures After Switch From Valproate to Lamotrigine

100

90

Seizures controlled with valproate

80

70

Seizures controlled with lamotrigine after switch

60

Seizure Control , %

50

40

JME=juvenile myoclonic epilepsy; GTCS=generalized tonic-clonic seizures; ABS=absence seizures; MJ= myoclonic jerks

30

20

10

0

JME

GTCS

ABS

MJ

Dean JC, et al. Poster presented at American Epilepsy Society Annual Meeting, 2001.


Effects of antiepileptic drugs on oral contraception efficacy l.jpg
Effects of Antiepileptic Drugs on Lamotrigine Oral Contraception Efficacy

Reduces Efficacy No Effect on Efficacy

Barbiturates Felbamate

Carbamazepine Gabapentin

Phenytoin Lamotrigine

Tiagabine Valproate

Topiramate

Oxcarbazepine

Morrell MJ. Neurology. 1998;51(suppl 4):S21-S27.

Hachad H, et al. Ther Drug Monit. 2002;24:91-103.


Pcos conclusions l.jpg
PCOS Lamotrigine Conclusions

  • PCOS is a serious reproductive endocrine disorder characterized by ovulatory dysfunction and hyperandrogenism

  • It needs to be distinguished from PCO, a condition that is not intrinsically pathologic

  • There are no reliable data showing a greater prevalence of PCOS in women treated with valproate or any AED

  • Treatment choices should be based on the most effective agent for controlling symptoms


ad