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Erik Taubøll

Publications and source records attributed to Erik Taubøll.

18 recordsLinked to original sources
PubMed2006

[Epilepsy and pregnancy--drug use, seizure control, and complications].

BACKGROUND: There is insufficient knowledge about the effect of epilepsy and epilepsy treatment on pregnancy, and vice versa. The European Registry of Antiepileptic drugs and Pregnancy (EURAP) was therefore established in 1999. We here present the results from the Norwegian part of the study, with emphasis on attack control, use of antiepileptics and folate, presence of status epilepticus, attacks in connection with birth and complications in the pregnancy. MATERIAL AND METHOD: The study is prospective and observational. The women are offered 5 consultations, 3 during pregnancy and 2 after birth. RESULTS: As of September 2005, 296 pregnancies in 263 Norwegian women were included. In 220 pregnancies (74 %), the women were treated with a single antiepileptic drug, most often carbamazepine. In 187 pregnancies (63 %), the women were seizure free. In those with seizures, 17 % had an increase in seizure frequency during pregnancy and 15 % had a decrease. Convulsive status epilepticus associated with delivery occurred in 1 % of the women and seizures associated with the delivery in 2.7 %. The consequences for the mother and the child were not as serious as previously reported. The frequency of complications during pregnancy and the sectio rate did not differ significantly from the average population. INTERPRETATION: Most women with epilepsy go through pregnancy and delivery without complications. Specialists should only follow up those with a suboptimal seizure control. The slightly increased teratogenic risk can be reduced by giving these women extra folate before the conception.

Adolescent↗
PubMed2006

Onset of epilepsy and menarche--is there any relationship?

PURPOSE: Women with epilepsy have increased frequency of reproductive health problems compared to women without epilepsy. In puberty, reproductive hormonal changes during sexual maturation may affect epilepsy and induce the debut of seizures as indicated in some studies. On the other hand, epileptic activity affects sex hormone function, which may induce alterations in pubertal endocrine maturation and thereby menarche age. We wanted to investigate the relation between epilepsy and menarche age in a larger population of female epilepsy patients. METHODS: A retrospective, questionnaire study of a cohort of 265 female outpatients from three Norwegian hospitals and 142 controls, aged 18-45 years was conducted. Parameters regarding epilepsy and reproductive health issues were registered. Perimenarche was defined as 2 years before and 2 years after the year of menarche. RESULTS: There was a significantly higher frequency of patients with epilepsy debut between 10 and 18 year compared to 0-9 years (p<0.01). There was, however, no significant difference in occurrence of epilepsy debut in the perimenarche period compared to the 5 year periods before and after perimenarche, and no significant difference in epilepsy debut in the year of menarche compared to the 5 years before or after. Menarche age was not significantly different in those with epilepsy debut before or after menarche. Epilepsy type (idiopathic generalised or partial) did not influence the menarche age. CONCLUSIONS: The study did not confirm the former observations of clustering of epilepsy debut at menarche or in the perimenarche period or alterations in menarche age in girls with epilepsy. However, onset of epilepsy is more frequent in the adolescent years (10-18), than in childhood (0-9).

Adolescent↗
PubMed2006

Comparison of reproductive effects of levetiracetam and valproate studied in prepubertal porcine ovarian follicular cells.

PURPOSE: Long-term valproate (VPA) treatment has been associated with reproductive endocrine disorders characterized by hyperandrogenism and polycystic changes in the ovaries in women with epilepsy. Levetiracetam (LEV) is a promising, new antiepileptic drug that may represent an alternative to VPA for many patients. Here the effect of LEV and VPA on basal and gonadotropin-stimulated steroid secretion from prepubertal porcine ovarian follicular cells was compared and the conversion of testosterone to estradiol is measured. METHODS: Ovarian follicles were obtained from prepubertal pigs. Follicular theca and granulosa cells were cocultured and different concentrations of LEV or VPA added to the control or gonadotropin-stimulated cultures. RESULTS: VPA, but not LEV, caused a significant increase of LH-stimulated testosterone secretion and decreased FSH-stimulated estradiol secretion. VPA decreased conversion of testosterone to estradiol in both basal and FSH-stimulated cultures, while LEV only decreased testosterone to estradiol conversion after FSH stimulation and only at the highest, nontherapeutic drug concentration. Both drugs increased basal testosterone secretion at therapeutic drug levels. VPA also reduced basal estradiol secretion, while LEV decreased basal estradiol secretion only at nontherapeutic drug levels. CONCLUSION: Both LEV and VPA affect endocrine function in the prepubertal ovary. But while VPA alters both basal and gonadotropin-stimulated testosterone and estradiol secretion at therapeutic drug concentrations, LEV only affects basal hormone secretion at this concentration level. The possibility that LEV could be an alternative treatment to VPA if reproductive endocrine problems emerge in adult women, is discussed. However, extrapolation to the clinical situation is problematic and particular emphasis is placed on the need for further studies.

Animals↗
PubMed2005

Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy.

It is well known that epilepsy, antiepileptic drugs (AEDs), and the reproductive system have complex interactions. Fertility is lower in both men and women with epilepsy than in the general population. Moreover, reproductive endocrine disorders are more common among patients with epilepsy than among the population in general. These disorders have been attributed both to epilepsy itself and to use of AEDs. The use of the liver enzyme-inducing AEDs phenobarbital, phenytoin and carbamazepine increases serum sex hormone-binding globulin (SHBG) concentrations in both men and women with epilepsy. Over time, the increase in serum SHBG levels leads to diminished bioactivity of testosterone and estradiol, which may result in diminished potency in men and menstrual disorders in some women, and thus to reduced fertility. Liver enzyme-inducing AEDs also reduce the efficacy of oral contraceptives. Valproic acid medication may have effects on serum androgen concentrations and it reduces serum follicle stimulating hormone levels in men with epilepsy. However, the clinical significance of valproic acid-related reproductive endocrine changes in men is unknown. On the other hand, in women, use of valproic acid appears to be associated with a frequent occurrence of reproductive endocrine disorders characterised by polycystic changes in the ovaries, high serum testosterone concentrations (hyperandrogenism) and menstrual disorders. These disorders are especially common among women who have gained weight during valproic acid treatment. There are some discrepancies regarding the reported occurrence of reproductive endocrine disorders in women taking valproic acid for epilepsy. However, most studies also including patients receiving valproic acid for other reasons than epilepsy, and studies in different non-epileptic animal models, have shown an association between valproic acid medication and hyperandrogenism and related reproductive endocrine disorders. From a practical point of view, the length of the menstrual cycles and bodyweight should be monitored in women with epilepsy after commencement of treatment with valproic acid. A serum testosterone assay is helpful in following the possible biochemical endocrine changes. Ultrasonography of the ovaries (preferably transvaginal) is indicated if clinical assessment and serum testosterone measurement imply that there is a clinically significant valproic acid-related reproductive endocrine problem. That would be the case if the menstrual cycles were irregular or prolonged (usually >35 days) and serum testosterone levels elevated, especially with associated weight gain. The endocrine effects of the new AEDs have not been widely studied. However, it seems they may offer an alternative if reproductive endocrine problems emerge during treatment with the older AEDs.

Anticonvulsants↗
PubMed2004

Antiepileptic drugs inhibit cell growth in the human breast cancer cell line MCF7.

Several antiepileptic drugs (AEDs) are associated with anti-cancer activity. At the same time, many AEDs alter endocrine function with phenytoin (PHT) and phenobarbital (PB) causing-reduced free fractions of sex-steroid hormones, while VPA induces hyperandrogenism. Changes in sex-steroid hormone levels are known to affect apoptosis in endocrine tissue. The aim of the study was to investigate the influence of the antiepileptic drugs PHT, PB, VPA and lamotrigine (LTG) on estrogen-stimulated cell growth of human breast cancer cells (MCF-7), and to evaluate whether this effect could be related to a direct estrogen receptor (ER) binding. VPA reduced cell growth at therapeutically relevant concentrations; half-maximum effect of VPA on cell growth was 230 microM. PHT (100 microM) and PB (10 microM) reduced cell growth by 47 and 21%, respectively. None of the drugs had affinity to isolated estrogen receptors, and excess of estrogen was not able to abolish the growth inhibition provoked by VPA. However, sub-therapeutic concentrations of VPA (100 microM) mimicked estrogen by inducing cell growth (11%) in an estrogen-depleted medium, an effect that was abolished by adding an estrogen receptor antagonist. In conclusion; the estrogen receptor appear to be indirectly activated by sub-therapeutic concentrations of VPA, but therapeutic concentrations of VPA inhibits cell growth by mechanisms that do not seem to involve the estrogen receptor or estrogen stimulation.

Anticonvulsants↗
PubMed2003

[Epilepsy and genetics].

The inheritance of epilepsy has been known since antiquity. Twin studies have shown that genes are important, particularly in primary generalised epilepsies, although the overall risk of epilepsy in offspring of parent with epilepsy is only approximately 6%. Many different protein structures control the normal activation of a brain neurone, and genes are responsible for the structure of these proteins. Mutations can lead to the characteristic pathological activation of epileptic neurones. Monogenic epilepsies may be related to changes in structures of importance for neuronal activation, e.g. the Na channel, the K channel, the GABA-A receptor, and in an acetylcholine receptor. A mutation has been demonstrated in a gene possibly related to brain development. Most likely, many primary epilepsies are polygenic. Epilepsy is also a part of many other genetic diseases. Susceptibility genes may be of importance for the development of certain epilepsies. De novo mutations may also occur. Studies in families with epilepsy may lead to the discovery of more monogenic epilepsies. Comparison between large populations of patients and controls is necessary in order to identify susceptibility genes in non-familiar epilepsy. The new knowledge of genetic aspects of epilepsy will bring improvements in diagnostics and treatment.

Brain↗
PubMed2003

[Treating epilepsy].

Epilepsy is not one single disease but a major symptom in a wide variety of brain disorders, hence better referred to as the epilepsies. Treating epilepsy requires expert knowledge about the disorders themselves and the various treatment options. The basis for optimal treatment is a correct diagnosis of the patient's type epilepsy and identification of seizure-provoking factors. The need for chronic drug treatment must be weighted against possible side effects. Several different drugs may be effective for a given type of seizure or epilepsy but drug effectiveness must be considered in relation to interactions and possible adverse effects. Even with optimal drug treatment, only about two thirds of patients achieve complete seizure control. In selected cases surgical treatment is very effective and should be considered in all patients who do not achieve seizure control within two years after having tried relevant antiepileptic drugs in optimal concentrations.

Adult↗
PubMed2003

[Women and epilepsy].

Women with epilepsy have several gender-specific problems, first of all related to pregnancy and childbirth. They do, however, also meet with several other, less well-recognised specific problems. Many women have a marked change in seizure frequency in relation to their menstrual cycle, and menstrual disorders and polycystic ovaries induced by the use of antiepileptic drugs (AEDs), or by the condition itself, are more frequent in women with epilepsy. Cosmetic side effects of AEDs including weight gain, hair loss and skin problems can significantly reduce compliance in drug treatment and thus affect seizure frequency. Enzyme-inducing AEDs reduce the effectiveness of oral contraceptives and may lead to unplanned pregnancies. A higher incidence of sexual problems in women with epilepsy has also been reported. In menopause, the seizure frequency may change in parallel with the endocrine changes and some AEDs may facilitate the development of osteoporosis. Better understanding and awareness of these problems among patients and health care professionals can relieve many of the gender-specific problems in women. The goal is to tailor the treatment to the needs of the individual woman.

Anticonvulsants↗
PubMed2003

[Pregnancy and birth in women with epilepsy].

More than 90 % of all women with epilepsy who take antiepileptic drugs (AEDs) will undergo normal pregnancies and give birth to children free of birth defects, though mothers on AEDs have two to three times higher incidence of malformations. Uncertainty exists regarding which AEDs are the most teratogenic. Valproate and carbamazepine have been associated with neural tube defects and phenytoin with cleft lip/palate and heart and urogenital defects. All women taking valproate and carbamazepine are advised to take 4 mg/day of folic acid at least one month before pregnancy and during the first trimester. Other women with epilepsy in fertile age are recommended to take 0.4 mg/day. Vitamin K 10 mg/day should be given the last 4 weeks to women on liver enzyme-inducing AEDs. During pregnancy, ultrasound should be performed around weeks 12 and 17. Amniocentesis for a-fetoprotein should be offered at week 15 to women using valproate and carbamazepine. Most women with epilepsy do not experience any change in seizure frequency during pregnancy and have normal vaginal deliveries. Use of monotherapy, lowest effective dose and retard formulations of AEDs, are advised during pregnancy. A seizure during labour is very rare, seen in 1-2 % of cases. Breast-feeding is encouraged for most AEDs, although barbiturates and benzodiazepines may have sedative effects on the infant. Pregnancy is generally safe in women with epilepsy, but preconception counselling and close collaboration during the pregnancy between the gynaecologist and the neurologist is warranted.

Abnormalities, Drug-Induced↗
PubMed2003

[What is epilepsy?].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed2003

Gonadal morphology and sex hormones in male and female Wistar rats after long-term lamotrigine treatment.

Drug-induced disturbances in reproductive hormones and gonadal morphology have been observed both in patients with epilepsy and in non-epileptic animals. Less is known about the influence of newer antiepileptic drugs including lamotrigine on reproduction. Lamotrigine is now increasingly used both in epilepsy and psychiatric disorders. Sixty-five Wistar rats were fed by gastric tube either 5 mg kg(-1) lamotrigine solution (males=15, females=20) or 0 (vehicle control, males=15, females=15) twice daily for 90 days. In males, no significant differences were found in body or testicular weight. Testicular atrophy was observed in one control animal and in two of the rats receiving lamotrigine. No morphological changes were seen in the other organs investigated (liver, kidney, pancreas, brain, lymphatic tissue, heart). None of the animals showed over-expression of p53. No significant differences were observed between the control rats and the male rats receiving lamotrigine regarding testosterone, FSH and LH. In females, no changes in ovarian morphology or alterations in other tissues were observed. Serum testosterone, FSH, LH, insulin and progesterone remained unchanged in the lamotrigine treated animals, while serum estrogen was significantly reduced.

Animals↗
PubMed2003

Do women with epilepsy have increased frequency of menstrual disturbances?

PROBLEM: Menstrual disorders, reduced fertility and sexual problems seem to be more frequent in women with epilepsy than in the general population. Most investigations concerning menstrual disturbances in epilepsy patients, however, are small and based on selected materials. We therefore wanted to investigate the frequency of menstrual disturbances in a large, unselected population of epilepsy patients. METHODS: A retrospective, questionnaire study of a cohort of female outpatients, aged 18-45 was conducted. Each patient chose a close female friend who served as control, to optimise matching regarding age and lifestyle. RESULTS: Answers were received from 265 patients and 142 controls. Menstrual disturbances were more frequent in patients with epilepsy (48.0%) than in controls (30.7%) (P=0.004). Menstrual disturbances were more frequent in patients on polytherapy versus monotherapy (P=0.049) and more frequent in patients with high seizure frequency (>5seizures/year) compared to patients with a lower seizure frequency or those seizure free (P=0.006). The frequency of menstrual disturbances was higher in patients on valproate compared to carbamazepine monotherapy (P=0.045). CONCLUSION: This investigation confirms that women with epilepsy have an increased frequency of menstrual disturbances compared to women without epilepsy. In women with high seizure frequency and in those on polytherapy, the frequency of menstrual disturbances are further increased. The highest frequency of menstrual disturbances occurred in women using valproate.

Adolescent↗
PubMed2003

Valproate inhibits the conversion of testosterone to estradiol and acts as an apoptotic agent in growing porcine ovarian follicular cells.

PURPOSE: Long-term valproate (VPA) treatment has been associated with hyperandrogenism and polycystic ovaries in women with epilepsy. The exact mechanisms of action of the drug on sex steroid hormone function are still unsettled. The aim of the present study was to investigate the action of VPA on basal and gonadotropin-stimulated steroid secretion in porcine ovarian follicular cells and to measure the conversion of testosterone to estradiol. Second, the action of VPA on proliferation and apoptosis of follicular cells was investigated. METHODS: Small and medium follicles were obtained from pig ovaries on days 8-10 and 14-16 of the estrus cycle. Both follicular compartments, theca and granulosa cells, were cultured as a coculture resembling follicles in vivo. VPA in concentrations of 100 and 250 micrg/ml was added to the control or gonadotropin-stimulated cultures. RESULTS: VPA caused a significant increase in basal and luteinizing hormone (LH)-stimulated testosterone secretion from small follicles, whereas in medium follicles, an increased basal but decreased LH-stimulated testosterone secretion was found. VPA caused decreased basal and follicle-stimulating hormone (FSH)-stimulated estradiol secretion by small follicles, whereas only the higher concentration decreased estradiol secretion in medium follicles. The conversion of testosterone to estradiol by small follicles was decreased under the influence of VPA in testosterone-alone and in testosterone-plus-FSH-stimulated cultures, whereas this was seen at only the higher VPA concentration in medium follicles. VPA had no effect on cell proliferation and viability, whereas in a dose-dependent manner, VPA increased caspase-3 activity. CONCLUSIONS: VPA affected steroidogenesis in both unstimulated and gonadotropin-stimulated porcine ovarian follicular cells and inhibited the conversion of testosterone to estradiol. In addition, VPA may act as an apoptotic agent in both small and medium-sized follicles.

Animals↗
PubMedDate not supplied

Valproate irreversibly alters steroid secretion patterns from porcine follicular cells in vitro.

The aim of the present study was to investigate whether exposure of porcine ovarian follicular cells to clinically relevant concentrations of valproate affected steroid production in vitro and to which extent these effects were reversed by removal of the drug from the culture medium. Small and medium follicles were obtained from ovaries collected, respectively, at days 8-10 and 14-16 of the estrous cycle. Theca and granulosa cells were collected from follicles and co-cultured in one well. To show whether the effect of valproate was reversible, cells were cultured for 24, 48, or 72 h with valproate 100 or 250 microg/ml. The medium was then changed to fresh medium without drugs for an additional 24, 48, or 72 h. Valproate added to the culture medium caused a significant reduction of estradiol secretion with concomitant increase in both testosterone and progesterone secretion by small follicles. In medium-sized follicles, 100 microg/ml valproate was without effect on estradiol secretion while 250 microg/ml caused a small, but statistically significant decrease. The effects of valproate on steroid secretion patterns were irreversibly independent of concentration, exposure time, and time of restoration after drug exposure up to 72 h in both small and medium follicles. In conclusion, the present study demonstrated that even short-term valproate treatment disrupted follicular steroidogenesis in isolated ovarian follicular cells resulting in increased testosterone and progesterone and decreased estradiol secretion. It was not possible to reverse the steroidogenic effects of valproate by removing the drug from the cell cultures.

Animals↗
PubMedDate not supplied

Effects of chronic valproate treatment on reproductive endocrine hormones in female and male Wistar rats.

Valproate (VPA) has been claimed to induce endocrine disorders in both sexes in humans. There is sparse information regarding the mechanisms behind these disturbances. By using an animal model, we wanted to study the effect of valproate on hormonal function in non-epileptic rats. Female rats were given 0 (vehicle control, n=15), 200mg/kg (n=15), or 300 mg/kg (n=20) valproate twice daily by gavage for 90 days, resulting in mean valproate concentrations within the therapeutic range 4-6h after the last dose given. Serum testosterone concentrations remained unchanged, while estradiol levels were significantly reduced in both treatment groups, leading to significantly increased testosterone/estradiol ratios. Follicle stimulating hormone (FSH) levels remained unaltered in valproate treated rats, whereas the luteinizing hormone (LH) concentrations were reduced at the lowest valproate dose. Male rats received 0 (vehicle control, n=15), 200mg/kg (n=15), or 400mg/kg (n=20) valproate twice daily by gavage for 90 days, resulting in mean valproate concentrations within the therapeutic range 4-6h after the last dose. Serum testosterone levels were not significantly changed, but there was a highly significant increase in FSH and LH concentrations at the high dose. In conclusion, the study demonstrates a drug-induced effect of valproate on endocrine function in both male and female rats. The results indicate that the drug exerts its effect primarily at the gonadal level, although a centrally mediated effect cannot be ruled out.

Administration, Oral↗