Premature ovarian failure in women with epilepsy.

PURPOSE: Women with epilepsy (WWE) have an increased risk for several reproductive endocrine disorders that may affect their fertility. The incidence of premature ovarian failure (POF) in women with epilepsy has not been systematically studied. This study examined the incidence of POF in women with epilepsy. METHODS: Fifty consecutively evaluated cognitively normal women with epilepsy, aged 38-64 years, whose seizures began before age 41 years, were interviewed for symptoms of perimenopause and menopause. Endocrine studies, performed in women aged 45 years or younger at the time of evaluation, included serum follicle-stimulating hormone (FSH; done on menstrual cycle day 3 in menstruating women), inhibin A levels when FSH was normal, thyroid-stimulating hormone (TSH), prolactin, and, in menstruating women, menstrual cycle day 20 serum progesterone level. Nonsurgical premature menopause was defined as secondary amenorrhea of >12 months' duration with FSH levels of >14 International Units (IU) in women younger than 42 years. Premature perimenopause was defined by the presence of one or more of the following: somatic perimenopausal symptoms; change in previously regular menstrual cycles without evidence of other reproductive endocrine disturbance; and FSH level of >14 IU or inhibin A level of <7 pg/ml. Similarly aged neurologically normal women seen in the menopause and sleep clinics served as control subjects. Statistical analysis included Fisher's exact test, Kruskal-Wallis test, t test, and multivariate logistic regression analysis with significance set at p < 0.05. RESULTS: Seven (14%) of 50 women with epilepsy had nonsurgical premature perimenopause (six of seven) or menopause (one of seven), compared with three of 82 control (p=0.042). Five of 41 women with localization-related epilepsy (LRE) had POF compared with two of nine women with primary generalized epilepsy (PGE; p=0.595). Mean age of POF was 39.6 years (range, 37-42 years). Seizure duration, age at seizure onset, seizure severity and lateralization, smoking history, age of menarche, body mass index and incidence of depression was not statistically different between women with and without POF. There was no statistically significant association between POF and antiepileptic drugs (AEDs). Women with POF were more likely to have had catamenial exacerbation of their seizures than were women without POF (p=0.02). CONCLUSIONS: Women with epilepsy have an increased risk for developing POF. This finding should be considered in counseling women with epilepsy on family planning.

Functional activation of punch-cultured magnocellular neuroendocrine cells by glutamate receptor subtypes.

To provide a simple means to isolate and study the cellular functions of small groups of neurons, we developed a modified 'punch' culture procedure that facilitates acute and long-term in vitro physiological studies. Primary 'punch' cultures of magnocellular neuroendocrine cells (MNCs) from the supraoptic nucleus (SON) were established and the basic physiological effects of subtype-specific glutamate receptor agonists were characterized. MNCs from the punch cultures established a mature morphology in culture with extensive outgrowth of axons and varicosities. After 8 days, a single cultured SON punch produced an average of 10.0 +/- 2.1 pg AVP and contained an average of 222 +/- 53 vasopressin-neurophysin immunoreactive cells. Patch clamp recordings from MNCs demonstrated the presence of N-methyl-D-aspartate (NMDA)-sensitive and DL, alpha-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA)-receptors. Stimulation of metabotropic receptors with 1S,3R ACPD induced acute or gradual increases in intracellular calcium. NMDA, AMPA and metabotropic receptors all contributed to the secretion of vasopressin from the punch cultures with an agonist rank order potency of: NMDA (10 microM) > AMPA (1 microM) = 1S,3R ACPD (100 microM) > kainate (10 microM). This culture preparation should be useful for cellular studies of small groups of neuroendocrine and other cells.