Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine
Stanford University, Stanford and Neuropace, Mountain View, CA 94043, USA. Annals of Neurology
(Impact Factor: 9.98).
08/2008; 64(2):200-11. DOI: 10.1002/ana.21411
To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy.
Female individuals with epilepsy and regular menstrual cycles were eligible for this prospective study. Participants were randomized to 12 months of valproate (n = 225) or lamotrigine (n = 222) therapy. Serum androgen levels were measured every 3 months. Urinary pregnanediol glucuronide levels were measured weekly for two 3-month periods. The primary end point was development of PCOS components (ie, hyperandrogenism or ovulatory dysfunction). A post hoc analysis was conducted in women more than 2 years after menarche (177 lamotrigine, (HA) 186 valproate) to exclude OD the confounding effect of puberty.
More women in the valproate group than the lamotrigine group developed (OD) in the prospective (54% valproate, 38% lamotrigine; p = 0.010) and the post hoc (HA) analyses (36% valproate, 23% lamotrigine; p = 0.007). More women in the valproate group than the lamotrigine group developed PCOS (9 vs 2%; p = 0.007). Development of HA was more frequent with OD valproate than lamotrigine among those initiating treatment at age younger than 26 years (44% valproate, 23% lamotrigine; p = 0.002) but was similar if treatment was started at age 26 years or older (24% valproate, 22% lamotrigine).
Development of HA occurred more frequently with valproate than lamotrigine, especially if medication was started at age younger than 26 years.
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ABSTRACT: ABSTRACT ABSTRACT ABSTRACT ABSTRACT ABSTRACT Epilepsy is recognized as the commonest,serious neurological disorder in the world. Women with epilepsy (WWE) experience several gender-related physical and social problems. They constitute high obstetric risk because of reduced fertility,risk of seizures during pregnancy, and complications of pregnancy. Hormonal and other factors can alter the pharmacokinetics of antiepileptic drugs (AED) during pregnancy and puerperium. Antenatal exposure to AEDs, particularly at higher dosage and in polytherapy, increases the risk of fetal malformation. Recent reports raise the possibility of selective developmental language deficits and neurocognitive deficits with antenatal exposure to AEDs. There are concerns regarding the effect of traces of AEDs that pass to the infant during breast-feeding. The pre conception management,is the cornerstone for epilepsy care in WWE. A careful reappraisal of each case should ascertain the diagnosis, the need for continued AED therapy,selection of appropriate AEDs, optimization of the dosage, and prescription of folic acid. During pregnancy, the fetal status needs to be monitored with estimation of serum a-feto-protein and ultrasound screening for malformations. The dosage of AEDs can be adjusted according to clinical requirement and blood levels of AEDs. Several institutions recommend,oral vitamin K toward the end of pregnancy when enzyme inducing AEDs are prescribed because the latter may potentially predispose the new born to hemorrhagic
Available from: Andrew G Norman
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ABSTRACT: We measure the dipole moment of InGaAs/GaAs self-assembled quantum dots by investigating the propagation of femtosecond light pulses interacting resonantly with the ground to excited state transition. The measurement involves coupling light into a waveguide containing quantum dots in the core and time resolving the output. The advantages are increased interaction length with the weakly absorbing quantum dots and observation of the decay of light pulses over successive cavity round trips. The large uncertainty in waveguide coupling efficiency that has hindered the determination of the absolute dipole moment in similar experiments' does not affect our results.
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ABSTRACT: Epilepsy, bipolar disorder, and migraines are common disorders that are often associated with disturbances in menstrual function in adolescent girls. Women with untreated epilepsy are more likely to have irregular menstrual cycles than are nonepileptic controls, indicating that the disease itself plays a role in the etiology of these reproductive abnormalities. In addition, many girls with these disorders require chronic maintenance treatment with agents that may perturb the hypothalamic-pituitary-ovarian axis. Valproate is a highly effective antiepileptic drug used widely to treat epilepsy, bipolar disorder, and migraines. Valproate induces features of the polycystic ovary syndrome (PCOS) in approximately 7% of women. Girls with epilepsy, and possibly bipolar disorder, appear particularly susceptible to developing PCOS features on valproate, perhaps on account of the relative immaturity of their hypothalamic-pituitary-ovarian axes. Antipsychotics are highly effective drugs used widely to treat adolescents with bipolar disorder, psychotic disorders, and behavioral disturbances. Some, but not all of the antipsychotic, induce hyperprolactinemia, which may result in oligo- or amenorrhea. Prolonged amenorrhea in association with hyperprolactinemia incurs significant risks for bone health in adolescent girls. Because of the potential reproductive health risks associated with use of specific antiepileptic drugs and selective antipsychotics, these agents are vital treatments for adolescents with severe illnesses. Use of these agents should be considered and weighed against the risk of using alternative agents, which have their own side effects, or not treating these serious neurologic and psychiatric disorders.
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