Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats.

PURPOSE: To assess estrogen-related changes in the redox status of the brain and liver proteins as well as the systemic oxidative stress in ovarectomised (OVX) rats METHODS: Twelve-week-old, sexually mature female Sprague-Dawley rats (200-250g) were randomly divided into four groups: The following treatment combinations were administrated daily to all in 0.05 ml 96% ethanol solution by gastric gavage. (1) Sham operation (2) OVX rats (3) OVX rats [0.02 mg/kg/day of 17beta-estradiol (E2) and 0.01 mg/kg/day of norethisterone acetate] (4) OVX rats [E2 (0.01 mg/kg/day) and drospirenon (0.02 mg/kg/day)]. Estrogen levels were determined using routine clinical-chemistry methods. We also measured protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH) and the other oxidative stress markers malondialdehyde (MDA) and glutathione (GSH). RESULTS: Ovariectomy resulted in abnormal elevation of plasma and tissue oxidative stress markers and changes in redox status of the proteins in tissue dependent manner. Supplementation of various estrogens combinations partially alleviated these abnormalities and restored redox homeostasis of proteins after the ovariectomy. Among the studied protein oxidation parameters, plasma and tissue PCO levels of the OVX rats were higher than those of the control groups (P < 0.01). Hormone replacement therapies (HRT) caused a decrease in PCO and MDA in both plasma and tissue of the OVX rats (P < 0.01). HRT in OVX rats decreased plasma MDA and increased liver and brain GSH (P < 0.01). Liver MDA levels of the Drospirenon-treated rats were lower than in the norethisterone acetate group (P < 0.01). On the other hand, Drospirenon increases brain GSH s more effectively than norethisterone acetate (P < 0.01). After bilateral oopherectomy, plasma and tissue T-SH levels decreased in the OVX group compared with control (P < 0.01). Norethisterone acetate increased plasma T-SH more effectively than Drospirenon (P < 0.05) CONCLUSIONS: The study showed the extent of oxidative protein damage (OPD) in this model of estrogen deficiency. The protective effect of estrogens against tissue specific OPD suggests that estrogens play an important role within the antioxidant defense systems in plasma, liver and brain. The exact molecular mechanisms leading to these findings are not yet completely known. Meanwhile, hormone replacement therapy for the prevention of OPD in a tissue specific manner may be required.

[Fears, knowledge, and need of counseling for women with epilepsy. Results of an outpatient study]. / Frauen mit Epilepsie: Befürchtungen, Wissen, Beratungsbedarf. Ergebnisse einer Querschnittstudie bei Patientinnen in ambulanter Behandlung.

BACKGROUND: Women with epilepsy are particularly affected by their condition and need therefore specific counseling and comprehensive information about issues related to contraception, pregnancy, hormone effects on seizure control, bone mineral density, etc. The primary aim of this study was to investigate the knowledge of women with epilepsy about their condition and their need for information and counseling. METHODS: A total of 365 women with epilepsy aged from 16 to 75 years of age took part in this prospective, cross-sectional study. All were treated by neurologists in private practice or outpatient clinics. The physicians distributed anonymous questionnaires to the women, who mailed them unsigned to the Society for Epilepsy Research. Sociodemographic and epilepsy-specific data of the women, their experiences and fears regarding partnership, family planning, pregnancy, care of children, and their self-rated and actual knowledge were assessed. RESULTS: Most women (80.9%) lived together with partners, and about half of the women (44.9%) had children. The majority of those with children were greatly worried during pregnancy about risks to their newborn child. They were afraid of potential handicaps (57.9%) and potential epileptic seizures of the child (52.5%) because of their own epilepsy or antiepileptic drugs. Another 39.0% had had great reservations about becoming pregnant. About every fifth woman (18.2%) stopped or reduced antiepileptic medication during pregnancy without consulting her doctor. Women who consciously abstained from having own children (n=87, 23.8%) often reported epilepsy-related reasons (e.g. risk of malformation caused by antiepileptic drugs, 40.8%). Epilepsy also affects the mother-child relationship. For example 40.8% of the women were worried that the child could be harmed during a mother's seizure and 36% reported that their seizures would frighten their children. About 56-66% of the epileptic women stated that they were well to very well informed about topics on contraception, pregnancy, prophylaxis of malformations, and heredity of epilepsies. The knowledge questionnaires revealed however considerable knowledge deficits. These were especially widespread concerning older women and epilepsy, e.g. antiepileptic drugs and osteoporosis, and more pronounced in older women (>50 years) and those with low school education. In all, self-rated and actual knowledge correlated only slightly (r=0.25). Of the women, 60% preferred personal counseling by their physicians. However, especially younger women wanted further information, primarily easy-to-understand brochures (32%) and educational courses (31%). CONCLUSION: Our results are in accordance with other studies from Great Britain and the U.S. They confirm that women with epilepsy have considerable deficits in epilepsy-specific knowledge and a great need of counselling and information.

[EURAP: the European Registry of Antiepileptic Drugs and Pregnancy]. / EURAP: Das europäische Register für Schwangerschaften unter Antiepileptika.

All old-generation antiepileptic drugs (AEDs) are considered to be teratogenic. In Germany, one out of 200 pregnant women (0.5%) is treated with AEDs for epilepsy. The risk of major malformations following exposure to AEDs during the first trimester of pregnancy is two to three times the rate reported in the general population, which is estimated at 2-3%. The risks associated with the treatment of epilepsy during pregnancy are therefore of major concern to all women of childbearing potential with epilepsy. Data on the comparative teratogenicity of these AEDs in humans are, however, conflicting, mainly due to inadequate sample sizes and other methodological shortcomings of previous studies. The teratogenic potential of newer AEDs is even less well known, which prevents a rational approach to AED treatment in women of childbearing potential. The European Registry of Antiepileptic Drugs and Pregnancy is a prospective international multicentre study of pregnancies with AEDs. In Germany the project was started in 2001 and so far more than 500 pregnancies have been enrolled. The enrollment rate is 4% of 4,000 pregnancies with AEDs reported annually.