Valproate-associated reproductive and metabolic abnormalities: are epileptic women at greater risk than bipolar women?
OBJECTIVE
Evidence indicates that valproate (VPA) may have an adverse impact on reproductive endocrine and metabolic functions in women with epilepsy. This study explores whether the association of VPA with reproductive endocrine abnormalities is applicable to women with bipolar disorder (BD) or is unique to women with epilepsy.


METHODS
Thirty female patients aged 18-40 years with a DSM-IV diagnosis of BD (15 on lithium monotherapy and 15 on VPA monotherapy or VPA in combination with lithium therapy) and 15 with idiopathic generalized epilepsy (IGE) on VPA monotherapy were evaluated for reproductive endocrine functioning and metabolic parameters.


RESULTS
The menarche age, mean length of menstrual cycle and mean length of menses were not significantly different between groups. None of the bipolar patients on lithium, three (20%) of the bipolar patients on VPA and seven (47%) of the epileptic patients on VPA reported menstrual disturbances. Hirsutism scores of the epilepsy group were significantly higher than those bipolar women, regardless of treatment. Serum total testosterone levels were significantly higher in patients (both with BD and with IGE) treated with VPA than in those treated with lithium. Serum FSH levels were significantly lower and LH-to-FSH ratio was significantly higher in patients with epilepsy than in patients with BD, regardless of treatment. The weight parameters and lipid values investigated did not differ significantly between the groups.


CONCLUSIONS
The study supports the conclusion that VPA may be associated with menstrual abnormalities and increased total testosterone levels in both bipolar and epileptic patients although women with BD did not show clinical features of hyperandrogenism (menstrual abnormalities, hirsutism and truncal obesity) as did frequently as women with epilepsy.
Akdeniz
Fisun
F
Department of Psychiatry, Affective Disorders Unit, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey. akdeniz@med.ege.edu.tr
Taneli
Fatma
F
Noyan
Ayşin
A
Yüncü
Zeki
Z
Vahip
Simavi
S
D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D004703:Endocrine System / Q000187:drug effects; D004827:Epilepsy / Q000150:complications*; D005260:Female; D006628:Hirsutism / Q000139:chemically induced; D006801:Humans; D008599:Menstruation Disturbances / Q000139:chemically induced*; D008659:Metabolic Diseases / Q000139:chemically induced*; D009765:Obesity / Q000139:chemically induced; D012307:Risk Factors; D013739:Testosterone / Q000097:blood; D014635:Valproic Acid / Q000009:adverse effects*; D015430:Weight Gain
D018692:Antimanic Agents; D013739:Testosterone; D014635:Valproic Acid