valporate side effects--abstracts

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VALPORATE ASSOCIATED WITH WEIGHT GAIN

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EDITORIAL COMMENT: It's not clear why weight gain occurs in about

half of patients receiving valproate. This report demonstrates that

59% of women on valproate were obese and that 64% had polycystic

ovaries, hyperandrogenism, or both. As well, polycystic ovaries

occurred in about two-thirds of women who become obese on valproate.

The authors suggest that the over-representation of polycystic

ovarian syndrome among valproate-treated women with epilepsy may be

attributed to the associated weight gain and the resultant endocrine

concomitants of insulin. What is unclear is why valproate-treated

obese women develop polycystic ovaries more commonly than obese,

normal, control subjects. Moreover, this complication occurs even in

lean valproate-treated women. This work raises several unanswered

questions. It's not possible to conclude that valproate is

contraindicated in women of childbearing age. Further studies may be

warranted.

Obesity and endocrine disorders in

women taking valproate for epilepsy

(ANN NEUROL 1996;39:579-584) JOUKO I.T. ISOJÄRVI, MD, PHD, TIMO

LAATIKAINEN, MD, PHD, MIKAEL KNIP, MD, PHD, ARTO J. PAKARINEN, MD,

PHD, KAISA T.S. JUNTUNEN, MD, VILHO V. MYLLYLÄ, MD, PHD, OULU,

FINLAND

We recently reported the frequent occurrence of polycystic ovaries

and hyperandrogenism in women taking valproate for epilepsy,

especially when the medication was started before the age of 20

years. In the present study we evaluated the association of obesity

and hyperinsulinemia with valproate-related polycystic ovaries and

hyperandrogenism in women with epilepsy. Sixty-five women

participated in the study. Twenty-two received valproate monotherapy

and 43 received carbamazepine monotherapy. In addition to clinical

examination, vaginal ultrasonography was performed to determine

ovarian size, and the concentrations of serum sex hormones, insulin,

insulin-like growth factor 1, and the insulin-like growth factor-

binding proteins 1 and 3 (IGFBP-1) and IGFBP-3) were measured. Fifty-

nine percent of the women on valproate were obese, and in a

retrospective analysis an indisputable weight gain (mean, 21 kg;

range, 8-49 kg) was found in 50% of the women taking valproate.

Fourteen (64%) of the women on valproate had polycystic ovaries,

hyperandrogenism, or both. These women were obese, and in addition to

elevated serum androgen levels, they had high concentrations of

fasting serum insulin and low levels of serum insulin-like growth

factor-binding protein 1. Valproate therapy for epilepsy is

associated with weight gain during treatment in approximately 50% of

women patients. The weight gain can be progressive, and is associated

with hyperinsulinemia and low serum levels of insulin-like growth

factor-binding protein 1, which may lead to hyperandrogenism and

polycystic ovaries.