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ABSTRACT: To evaluate the outcome of epilepsy and later reproductive endocrine health in girls who had epilepsy during puberty, using a population-based controlled study.
Sixty-nine patients (88%) and 51 control subjects (94%) of previously identified cohorts of 78 girls with epilepsy and 54 healthy control girls participated in this study (initial age 8 to 18.5 years, at follow-up 12.5 to 25.8 years). Thirty-five of the patients were initially taking valproate (VPA), 17 carbamazepine, and 17 oxcarbazepine as monotherapy. Most of the patients (61%) were off medication. All the subjects were examined clinically, the medical and menstrual histories were obtained, ovarian ultrasonography was examined, and serum reproductive hormone concentrations were analyzed.
There were no significant differences in laboratory or clinical findings between the patients off medication and the control subjects. Postpubertal patients on medication had higher serum testosterone (1.9 nmol/L, SD 0.7 nmol/L) and androstenedione (18.8 nmol/L, SD 15.2 nmol/L) levels than patients off medication (1.4 nmol/L, SD 0.5 nmol/L, and 9.5 nmol/L, SD 2.6 nmol/L) or control subjects (1.4 nmol/L, SD 0.5 nmol/L, and 10.2 nmol/L, SD 3.2 nmol/L) (all comparisons p < 0.02). All patients still on VPA had elevated serum androstenedione levels. Polycystic ovary syndrome was 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).
Epilepsy during pubertal maturation does not affect reproductive endocrine health in female subjects who discontinue the medication before adulthood. However, an increased prevalence of endocrine disorders is detected if the patients remain on antiepileptic drugs, especially VPA, until adulthood.
Neurology 03/2004; 62(3):445-50. · 8.31 Impact Factor
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ABSTRACT: Long-term treatment with valproate (VPA) or carbamazepine (CBZ) may induce reproductive endocrine disorders in patients with epilepsy.
Serum concentrations of reproductive hormones were studied in 17 women and 22 men with recently diagnosed epilepsy before they started either VPA or CBZ medication, and 1 and 3 months later.
No weight gain or clinical signs of hormonal disorders were observed during the follow-up. The mean serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin (SHBG) increased, and dehydroepiandrosterone sulfate (DHEAS) decreased, in women starting VPA. Serum testosterone levels increased in half of the women on VPA. Serum concentrations of progesterone and dehydroepiandrosterone increased, and gonadotropins decreased, in men on VPA during the follow-up. Serum SHBG levels increased and DHEAS decreased during the first months of CBZ treatment in both sexes. In addition, the free-androgen index decreased in men after starting CBZ.
Hormonal changes occur after only 1 month's use of VPA or CBZ. VPA-treatment seems to be associated with increased serum androgen levels, but the profile of hormonal changes appears to be different in women than in men. The use of CBZ, in turn, was associated with increased SHBG concentrations and thus with diminished sex steroid function in both sexes. The women with increased serum testosterone levels in the early phase of VPA medication may be at increased risk for VPA-related endocrine disorders later during treatment.
Neurology 09/2001; 57(3):440-4. · 8.31 Impact Factor
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J I Isojärvi,
E Taubøll,
A J Pakarinen,
J van Parys,
J Rättyä,
H F Harbo,
P O Dale,
B C Fauser,
L Gjerstad,
R Koivunen,
M Knip,
J S Tapanainen
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ABSTRACT: Polycystic ovaries and menstrual disturbances seem to be common among women taking valproate for epilepsy. The purpose of the present study was to assess the frequency of valproate-related metabolic and endocrine disorders in different groups of women with epilepsy.
Seventy-two women with epilepsy and 52 control subjects from centers in three European countries (Finland, Norway, and the Netherlands) participated in the study. Thirty-seven of the women with epilepsy were taking valproate monotherapy and 35 carbamazepine monotherapy.
The frequency of polycystic ovaries or hyperandrogenism, or both, among valproate-treated women with epilepsy was 70% (26 of 37) compared with 19% (10 of 52) among control subjects (P <0.001). They were found in 79% (11 of 14) of obese and 65% (15 of 23) of lean women on valproate, and in 20% (7 of 35) of carbamazepine-treated women. The obese valproate-treated women with polycystic ovaries or hyperandrogenism, or both, had hyperinsulinemia and associated unfavorable changes in serum lipid levels consistent with insulin resistance.
Polycystic ovaries and related hyperandrogenism are frequently encountered in both obese and lean women taking valproate for epilepsy. The use of valproate is associated with risk factors for cardiovascular disease in obese women.
The American Journal of Medicine 09/2001; 111(4):290-6. · 5.43 Impact Factor
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ABSTRACT: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy.
Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, gamma-glutamyl-transferase (GGT) and antibody (ab) assays was obtained.
Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in men taking CBZ or OCBZ. Forty-five percent of men taking CBZ and 24% of men taking OCBZ had serum T4 and/or FT4 levels below the reference range. However, no correlations were found between T4 or FT4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)-ab and/or thyroglobulin (TG)-ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal.
Serum thyroid hormone concentrations are low in CBZ- or OCBZ-treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function.
Epilepsia 08/2001; 42(7):930-4. · 3.96 Impact Factor
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ABSTRACT: To evaluate changes in serum electrolyte balance and underlying regulatory mechanisms in 10 male patients with epilepsy 2 and 6 months after replacing long-term carbamazepine (CBZ) monotherapy with oxcarbazepine (OCBZ) monotherapy. Arginine vasopressin (AVP) is thought to be most important underlying mechanism of CBZ-related hyponatremia via direct or kidney tubular mechanisms. Furthermore, AVP is as well hormonally regulated by the renin-angiotensin-aldosterone system and atrial natriuretic peptide (ANP).
The medication of the patients was changed from CBZ to OCBZ. Serum electrolytes, creatinine, albumin, aldosterone, and the N-terminal fragment of ANP (NT-proANP) concentrations were measured before and 2 and 6 months after the change in the medication.
The mean serum sodium level diminished after the medication was changed. Serum sodium levels decreased below the reference range in two (20%) patients during OCBZ medication. Serum sodium levels decreased altogether in four patients, and remained unaltered in six patients. Serum aldosterone levels increased in the six patients whose serum sodium concentrations did not decrease, but no increase was found in the patients with decreased sodium levels during OCBZ medication. Serum NT-proANP levels decreased in all patients.
Serum sodium levels decrease after replacing CBZ with OCBZ. The low serum NT-proANP concentrations appear to reflect the decreased serum sodium levels, but a compensatory aldosterone response may prevent the development of hyponatremia in some patients during OCBZ medication.
Epilepsia 07/2001; 42(6):741-5. · 3.96 Impact Factor
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Epilepsia 04/2001; 42(3):305-10. · 3.96 Impact Factor
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ABSTRACT: Valproate (VPA) medication is associated with development of polycystic ovaries, menstrual disorders and hormonal changes in women with epilepsy. We sought to determine if changes in the ovaries also occurred in an animal model without epilepsy, and whether this effect could be related to a carcinogenic effect expressed by overexpression of p53. A potentially alternative antiepileptic drug, lamotrigine (LTG), was evaluated simultaneously. To this end, female Wistar rats were fed perorally with VPA 400 mg/kg/day (n = 15), VPA 600 mg/kg/day (n = 20), LTG 10 mg/kg/day (n = 15) or control solution (n = 15) for 90-95 days. There was a significant, dose-dependent increase in the number of follicular cysts, reduction in the number of corpora lutea and reduction of ovarian weight in the VPA group. No ovarian pathology was observed in the LTG group. In neither of the groups were morphological changes seen in other organs, nor was there any overexpression of the tumor suppressor gene p53 found. An alternative antiepileptic drug, LTG, showed no ovarian pathology, and there were no light microscopic changes in other organs, or evidence of pathologic p53 overexpression in the LTG-treated animals.
Experimental and Toxicologic Pathology 03/2001; 52(6):545-52. · 2.78 Impact Factor
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ABSTRACT: Recent observations have indicated that reproductive endocrine disorders are common among women taking valproate (VPA) for epilepsy, but it is not known whether respective abnormalities develop in men taking VPA for epilepsy. Carbamazepine (CBZ) may induce endocrine disorders in men with epilepsy, but the endocrine effects of oxcarbazepine (OXC) are not known.
Reproductive endocrine function was evaluated in 90 men taking VPA (n = 21), CBZ (n = 40), or OXC (n = 29) as monotherapy for epilepsy and in 25 healthy control men.
Twelve men (57%) taking VPA had increased serum androgen levels. The mean serum level of androstenedione was high in patients taking VPA. Serum levels of dehydroepiandrosterone sulfate were low, and serum concentrations of sex hormone-binding globulin (SHBG) were high in men taking CBZ. The endocrine effects of OXC seemed to be dose-dependent, because serum hormone levels were normal in patients with low OXC doses (< 900 mg/day), but serum concentrations of testosterone, gonadotropins, and SHBG were high in patients with a daily OXC dose > or = 900 mg.
VPA increases serum androgen concentrations in men with epilepsy. The endocrine effects of CBZ and OXC were different, because CBZ appears to decrease the bioactivity of androgens, whereas OXC does not.
Neurology 01/2001; 56(1):31-6. · 8.31 Impact Factor
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ABSTRACT: The increased prevalence of autoantibodies in patients with epilepsy has been traditionally regarded to be a consequence of antiepileptic drugs. The purpose of this study was to measure autoantibodies in well-defined groups of patients with seizures to determine the effects of epilepsy and antiepileptic medications on the presence of autoantibodies.
We studied the frequency of antinuclear antibodies, anti-beta2-glycoprotein I antibodies, and anticardiolipin antibodies in 50 patients with therapy-resistant localization-related epilepsy, 50 patients with generalized epilepsy syndromes, 52 patients with a newly diagnosed seizure disorder but no antiepileptic medication, and 83 healthy controls.
Compared with controls, newly diagnosed patients had a significantly greater prevalence of immunoglobulin (Ig) G class anticardiolipin antibodies (21% versus 7%); the prevalence was 14% in patients with localization-related epilepsy and 8% in patients with generalized epilepsy. The prevalence of IgM class anticardiolipin antibodies was significantly greater in all seizure groups (60% in localization-related epilepsy, 42% in generalized epilepsies, and 33% in newly diagnosed patients) compared with controls (7%). Antinuclear antibodies were significantly more common in newly diagnosed patients (21%) and localization-related epilepsy (24%) compared with controls (12%). When patients with generalized epilepsy (8%) were used as the reference group, antinuclear antibodies were also significantly more frequent in localization-related epilepsy (relative risk [RR] = 2.9, 95% confidence interval [CI]: 1.1 to 8.2) and newly diagnosed seizures (RR = 3.4, 95% CI: 1.2 to 9.3). There were no consistent associations between autoantibodies and specific antiepileptic medications.
The prevalence of autoantibodies is greater in patients with epilepsy, including newly diagnosed seizure disorder. The increased prevalence of autoantibodies is more strongly associated with epilepsy than with antiepileptic drugs, perhaps indicating that immune dysregulation may be commonly associated with epilepsy.
The American Journal of Medicine 01/2001; 109(9):712-7. · 5.43 Impact Factor
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ABSTRACT: To measure interictal cardiovascular autonomic functions in patients with either refractory or well-controlled temporal lobe epilepsy (TLE).
For autonomic assessment, heart rate variation during normal and deep breathing, Valsalva maneuver, and tilting were measured in 19 patients with chronic refractory TLE, 19 patients with well-controlled TLE, and 38 age- and sex-matched healthy control subjects. Blood pressure responses to tilting and isometric work also were evaluated.
Heart-rate (HR) variation during normal breathing (p = 0.006) and tilting (p = 0.043) was lower in patients with refractory TLE than in control subjects. Heart-rate response to tilting (p = 0.036) was also lower in patients with well-controlled TLE than in control subjects. Blood-pressure responses showed no differences between the patients and the control subjects. Patients taking carbamazepine (CBZ) medication had decreased HR responses to deep breathing (p = 0.046) and to tilting (p = 0.014) compared with the control subjects.
Refractory TLE seems to be associated with dysfunction of the cardiovascular autonomic regulation, manifesting as impaired HR responses to certain stimuli. Interictal autonomic dysfunction is seen in patients with well-controlled TLE as well, but it may be more evident in patients with refractory epilepsy. CBZ medication may also be associated with altered autonomic cardiac control.
Epilepsia 02/2000; 41(1):42-7. · 3.96 Impact Factor
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ABSTRACT: Long-term valproate treatment is associated with polycystic ovaries and endocrine disorders in women with epilepsy. The mechanisms responsible for these effects are unknown, but both the epilepsy itself and the drug per se may be of importance. The aim of this study was to investigate possible effects of the drug on gonadal structure and function in animals with no epileptic disorders. Three groups, each of 15 female Wistar rats, were fed perorally with a valproate mixture (50 mg / kg or 200 mg / kg) or control solution once daily for 90 days, giving mean valproate concentrations within the normal human range. A significant, 20% increase in ovary weight was found in both low- (P = 0.027) and high- (P < 0.001) dose animals together with a significantly increased number of ovarian follicular cysts. Mean serum testosterone concentration was significantly reduced in both low- and high-dose animals. There was a non-significant trend towards reduced estrogen levels, while progesterone levels were unchanged. Even if the hormonal changes are somewhat different from those in humans, the findings demonstrate that changes in gonadal structure and endocrine function also occur in intact animals indicating a drug-specific effect. Our findings encourages further studies using animal models to elucidate possible mechanisms involved in the endocrine side-effects of antiepileptic drugs.
Seizure 01/2000; 8(8):490-3. · 1.80 Impact Factor
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ABSTRACT: Valproate is effective for treatment of a variety of seizure types both in adults and in children with epilepsy, but it induces obesity and polycystic ovaries in a considerable proportion of adult women, particularly when the medication is started before the age of 20. In the present study we evaluated reproductive endocrine function in 41 girls, 8 to 18 years old, taking valproate for epilepsy and in 54 healthy control girls. Among the girls taking valproate, 16 were prepubertal, 11 were pubertal, and 14 were postpubertal, and the corresponding numbers were 20, 13, and 21 in the control group. The mean serum testosterone concentrations of prepubertal, pubertal, and postpubertal girls taking valproate were significantly higher than those of the control girls at the same pubertal stage. Hyperandrogenism, defined as serum testosterone levels higher than the mean + 2SD in the control girls at the same pubertal stage, was seen in 38% of prepubertal, 36% of pubertal, and 57% of postpubertal girls taking valproate. In addition, postpubertal girls taking valproate were more obese than the controls and the mean serum insulin-like growth factor binding protein-1 concentration of pubertal and postpubertal hyperandrogenic girls taking valproate was lower than in valproate-treated girls without hyperandrogenism. Valproate may induce hyperandrogenism in girls with epilepsy during the sensitive period of pubertal maturation, and the frequency of hyperandrogenism increases with pubertal development. This emphasizes the importance of careful endocrine observation of girls taking valproate for epilepsy.
Annals of Neurology 05/1999; 45(4):444-50. · 11.09 Impact Factor
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ABSTRACT: Antiepileptic drugs (AEDs) have endocrine effects that may interfere with growth and sexual maturation in children. The aim of this study was to evaluate the effects of AEDs on growth and pubertal development in girls with epilepsy.
Forty girls taking valproate (VPA), 19 girls taking carbamazepine (CBZ), and 18 girls taking oxcarbazepine (OXC) for epilepsy and 49 healthy control girls participated in the study, which included a cross-sectional clinical examination when the girls were 8 to 18 years old and a longitudinal growth analysis from the age of 1 year.
VPA, CBZ, or OXC did not affect linear growth or pubertal development in girls with epilepsy. However, the patients taking VPA gained weight, and an increase in relative weight was seen in girls who started their medication before as well as during puberty. The body mass index of the VPA-treated girls (19.8 +/- 4.8 kg/m2) was higher than that of the control girls (18.0 +/- 2.5 kg/m2) at clinical examination. The weight of the girls taking CBZ or OXC for epilepsy was similar to that of the control girls. Plasma insulin-like growth factor-I (IGF-I) levels were higher in girls treated with CBZ and OXC than in the control girls, but AEDs did not affect fasting serum insulin, IGF-binding protein-1, or IGF-binding protein-3 concentrations in girls on VPA, CBZ, or OXC medication during the period of exposure (average 2.8, 4.1, and 1.9 years, respectively) in this study.
AEDs do not seem to have any adverse effects on linear growth or sexual maturation in girls with epilepsy. VPA-related weight gain can be seen already in prepuberty and it is not associated with hyperinsulinemia in these young patients. The clinical significance of high circulating concentrations of IGF-I in patients taking CBZ or OXC remains to be defined.
PEDIATRICS 04/1999; 103(3):588-93. · 4.47 Impact Factor
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ABSTRACT: All the benzodiazepines (BZDs) in clinical use have the capacity to promote the binding of the major inhibitory neurotransmitter, gamma-amino-butyric acid (GABA), to sub-types of GABA receptors which exist as multi-subunit ligand-gated chloride channels. Thus, the BZDs facilitate the actions of GABA in the brain. The BZDs in use as antiepileptic drugs are diazepam, clonazepam, clobazam, nitrazepam, and lately, also lorazepam and midazolam as emergency therapy. The BZDs have a wide-spectrum of proven clinical efficacy in the prevention of different kind of seizures. Clonazepam and clobazam, as well as nitrazepam in some cases, can be useful as an adjunct treatment in refractory epilepsies. However, the clinical use of BZDs for the prophylactic treatment of epilepsy is associated with two major problems which have limited the long-term use of these drugs: the potential for side-effects, especially sedative effects, and the high risk of development of tolerance. Despite the limitations of BZDs in the prophylactic treatment of epilepsies, these drugs play a prominent role in clinical practice in the emergency management of acute seizures and status epilepticus. Diazepam, clonazepam and lorazepam are all considered first-line agents in the emergency management of acute seizures and status epilepticus. Furthermore, the value of midazolam as an emergency therapy in epilepsy has been increasingly recognized in recent years.
Journal of Intellectual Disability Research 01/1999; 42 Suppl 1:80-92. · 1.88 Impact Factor
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ABSTRACT: We recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism associated with weight gain and hyperinsulinemia in women taking valproate for epilepsy. The purpose of this study was to evaluate the risks related to valproate-induced hyperinsulinemia and their reversibility after discontinuing the medication. Sixteen women with valproate-related polycystic ovaries or hyperandrogenism participated in the study. Vaginal ultrasonography was performed, and endocrine and lipid parameters were measured. Thereafter, lamotrigine was substituted for valproate and the patients were observed for 12 months. Twenty-four healthy age-matched women served as control subjects. Twelve women completed the 12-month follow-up. While still on valproate they had centripetal obesity with associated hyperinsulinemia and unfavorable serum lipid profiles. The body-mass index and fasting serum insulin and testosterone concentrations decreased during the first year after replacing valproate with lamotrigine whereas the HDL-cholesterol/total cholesterol ratios increased from 0.17 +/- 0.06 to 0.26 +/- 0.05. The total number of polycystic ovaries in these women decreased from 20 during valproate medication to 11 one year after replacing valproate with lamotrigine. Valproate induces a metabolic syndrome with centripetal obesity, hyperinsulinemia, lipid abnormalities, and polycystic ovaries/hyperandrogenism in women with epilepsy. These valproate-related risks can be reduced by substituting lamotrigine for valproate.
Annals of Neurology 05/1998; 43(4):446-51. · 11.09 Impact Factor
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ABSTRACT: To evaluate the interictal autonomic nervous system function in 84 patients with epilepsy: 37 with newly diagnosed, previously untreated epilepsy, and 47 patients receiving long-term carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA) monotherapy, or CBZ plus PHT, or CBZ plus VPA for their seizure disorder.
We assessed autonomic control of the cardiovascular regulatory system by standardized cardiovascular reflex tests measuring changes in heart rate (HR) and blood pressure (BP) at rest and after certain stimuli.
The HR and BP responses were similar to those of control subjects in patients with newly diagnosed epilepsy. However, HR variation during normal breathing and maximum systolic BP increase in isometric work were diminished in patients, who had been treated with antiepileptic drugs (AEDs) for epilepsy for a long time. Diminished HR responses to the Valsalva maneuver were noted in patients receiving CBZ as monotherapy and during deep breathing in patients receiving CBZ combined with PHT or VPA. Furthermore, patients receiving CBZ had diminished BP responses in isometric work. When analyzed in relation to epilepsy type, suppressed HR responses in normal breathing were associated with primary generalized epilepsy (PGE), whereas diminished BP responses in isometric work were associated with partial epilepsy. Two patients with recently diagnosed partial epilepsy and 1 patient receiving long-term CBZ monotherapy for partial epilepsy had two abnormal cardiovascular response test results.
Our results show that cardiovascular responses mediated by both the parasympathetic and sympathetic nervous system are diminished in patients with epilepsy. However, the changes appear to be clinically significant in only a few of them and appear to be associated with CBZ medication. Further studies are needed to detect the underlying complex interactions and clinical significance of autonomic nervous system dysfunction in patients with epilepsy.
Epilepsia 05/1998; 39(4):420-6. · 3.96 Impact Factor
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ABSTRACT: Basic haematologic parameters and serum gamma-glutamyl-transferase (GGT) activity were evaluated in a five-year prospective follow-up study of 25 patients with newly diagnosed epilepsy starting treatment with carbamazepine. In addition, we evaluated the effects of replacing carbamazepine by oxcarbazepine on these parameters, erythrocyte folate concentrations and serum vitamin B12 levels in 12 male patients with epilepsy. The mean white blood cell count (WBC) and red blood cell count decreased after 2 months carbamazepine therapy, and remained at this lower level during the first 5 years of medication. The mean erythrocyte volume (MCV) and the serum GGT activity increased progressively during carbamazepine treatment. The serum GGT activity decreased after replacing carbamazepine by oxcarbazepine indicating a normalization of the liver P450 enzyme system induction. Concomitantly, the erythrocyte folate concentrations and serum levels of vitamin B12 increased, and the WBC increased and MCV decreased. It is probable that the changes in folate metabolism and serum vitamin B12 concentrations are due to normalization of the liver P450 enzyme system induction after the change of medication. The haematologic changes during carbamazepine medication, and their normalization after replacing carbamazepine by oxcarbazepine are possibly related to changes in folate and vitamin B12 metabolism.
Seizure 07/1997; 6(3):207-11. · 1.80 Impact Factor
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ABSTRACT: 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.
Annals of Neurology 06/1996; 39(5):579-84. · 11.09 Impact Factor
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ABSTRACT: We determined changes in serum concentrations of thyroid hormones during carbamazepine (CBZ) therapy during a 5-year prospective follow-up study of 20 patients with newly diagnosed epilepsy. In addition, we evaluated the effects of replacing CBZ with oxcarbazepine (OCBZ) in 12 male patients with epilepsy in a 6-month prospective follow-up study. Circulating thyroxine and free thyroxine levels decreased after 2-month CBZ treatment and remained at a low level during the 5-year follow-up. There were no associated changes in serum thyrotropin (TSH) concentrations. When CBZ was replaced by OCBZ, the function of the liver's P450 enzyme system normalized, as shown by an increase in antipyrineT1/2, and a decrease in antipyrineCL. Serum total and free thyroxine levels increased, and thereafter serum TSH levels decreased. Indexes of diastolic heart function improved concomitantly, which may reflect subclinical hypothyroidism at the cellular level during CBZ treatment. We conclude that normal thyroid function can be restored in patients with epilepsy by replacing CBZ with OCBZ.
Epilepsia 09/1995; 36(8):810-6. · 3.96 Impact Factor
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ABSTRACT: We measured concentrations of serum sex hormones and sex hormone binding globulin (SHBG) in relation to regularity of the menstrual cycles in 8 women before carbamazepine (CBZ) treatment was initiated and after 1 and 5 years of CBZ therapy. In addition, we evaluated menstrual cycle regularity and related endocrine changes in 56 women receiving CBZ treatment for > 5 years. Serum SHBG levels increased, and serum concentrations of 17 beta-estradiol (estradiol) and estradiol/SHBG ratio decreased during CBZ treatment. Two of the 8 patients (25%) in the prospective study group developed menstrual irregularities during the first 5 years of therapy. In the cross-sectional study group of patients treated with CBZ for > 5 years, the frequency of menstrual disturbances was also 25.0% (14 of 56 patients). Concentrations of serum sex hormones and SHBG were measured in 13 women with menstrual disorders and in 11 randomly selected women with regular cycles. In most cases, menstrual disorders were associated with increased serum SHBG and decreased serum estradiol levels and low estradiol/SHBG ratio. Long-term CBZ treatment results in increased serum SHBG levels and decreased estradiol effect, which correlate with the frequency of menstrual disorders in CBZ-treated women with epilepsy.
Epilepsia 07/1995; 36(7):676-81. · 3.96 Impact Factor
