Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women
Introduction
Reproductive endocrine disorders are common in women with epilepsy. Not surprisingly, birth rate is statistically reduced in such patients (Wallace et al., 1998). Explanations given for this finding include the impact of epilepsy (Herzog et al., 1986, Drislane et al., 1994, Bauer, 1996, Herzog, 1997) and anticonvulsant drugs (AED) (Isojärvi et al., 1993), resulting in an increased rate of anovulatory cycles consequently causing sterility (Cummings et al., 1995, Bauer et al., 1998).
Recently, the impact of valproate (VPA) on reproductive endocrine disorders has been discussed (Isojärvi et al., 1993, Isojärvi et al., 1996, Isojärvi et al., 1997, Isojärvi et al., 1998). It has been suggested that polycystic ovaries (PCO) and/or hyperandrogenism is a finding often detected in women with epilepsy treated with VPA, the association being most common in women with a body mass index (BMI) greater than 25 kg/m2 (Isojärvi et al., 1993, Isojärvi et al., 1996). These findings are not substantiated by other studies (Murialdo et al., 1997), and are at odds with the world-wide clinical experience of those who have treated women with the drug over many years (Genton et al., 2000). PCO and hyperandrogenism do not necessarily indicate a clinically relevant abnormal condition. PCO is found in about 20% of the general population, and polycystic ovary syndrome (PCOS) in only 4% of women (Clayton et al., 1992, Farquhar et al., 1994). Similarly, in women with epilepsy, PCO is a fairly common finding, but fully-blown PCOS occurs less frequently (Herzog, 1997).
The currently accepted definition of PCOS is an ovulatory dysfunction with clinical evidence of hyperandrogenism and/or hyperandrogenaemia, and exclusion of related disorders, such as those affecting adrenal or thyroid function (Adams et al., 1985). This definition specifically excludes the finding of PCO, multifollicular ovaries or hyperandrogenism in isolation. In the clinical setting, ultrasonography of a sufficient standard is not widely available for the diagnosis of PCO (Fox et al., 1991). Furthermore, to lead to confusion, PCO as defined by ultrasonographic studies may be present in normal women with ovulatory cycles and no hirsutism (Polson et al., 1987, Franks, 1995). Measurement of different hormones have been found to be predictive of PCOS confirmed by sophisticated ultrasonography in a research setting. For example, in testing for raised testosterone or luteinizing hormone and follicular stimulating hormone levels, a positive result was associated with 100% accuracy in the diagnosis of PCOS in women with functional oligomenorrhoea or amenorrhoea (Fox et al., 1991).
Since our study was to diagnose PCOS, ultrasonography was considered unnecessary. A combination of clinical and laboratory assessments was used in the evaluation of women with epilepsy in order to determine whether AEDs were associated with an increased risk of PCOS.
Section snippets
Patients and methods
From 150 women with focal epilepsy treated as out-patients at the Department of Epileptology, University of Bonn, 93 patients were included into the study; the other 57 patients were excluded because of (a) oral contraceptives, (b) menopause or (c) extra-temporal focal epilepsy. The patients were consecutively enrolled and followed-up for 6 months to establish menstrual cycle rhythm. Chronic anticonvulsant medication was maintained during this period.
The 93 women (aged between 20 and 53 years;
Results
The patients were receiving none (19 patients) or one AED (VPA in 18 patients, with mean daily dosage 1414 mg; carbamazepine (CBZ) in 20 patients, with mean daily dosage 1447 mg) or were treated with AED polytherapy (36 patients) including VPA plus an enzyme-inducing AED (n=11), VPA plus a non-enzyme-inducing AED (n=5), two enzyme-inducing AEDs (n=2), two non-enzyme-inducing AEDs other than VPA (n=2), and enzyme-inducing plus non-enzyme-inducing AEDs other than VPA (n=16).
In 60 patients
Discussion
All the patients in this study had chronic focal epilepsy, the majority were receiving long-term treatment with AEDs. If focal epilepsy affects the hypothalamic–pituitary axis (i.e. increases the LH-pulse frequency), it may cause testosterone-related hyperandrogenism (Herzog, 1997). Since testosterone is metabolised in the liver and VPA is an enzyme inhibitor, it has been argued that treatment with VPA could elevate serum testosterone levels (Herzog, 1996). Conversely, treatment with CBZ might
Acknowledgements
We would like to thank Dr Iris Damm for her help in data sampling.
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