
- Psychiatric Times Vol 18 No 5
- Volume 18
- Issue 5
Investigating Polycystic Ovary Syndrome in Women With Bipolar Disorder
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, and it may manifest as mood disturbances in those affected. How can this medical condition be treated in women who have bipolar disorder?
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age (Franks, 1995). It is defined as an increase of serum testosterone levels (
Cardinal clinical characteristics of PCOS are hirsutism, acne and alopecia.
The fundamental defect in PCOS is unclear, but theories implicate dysfunction of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes and related neurochemical systems.
Regardless of treatment,
In 1993, Isojrvi et al. reported increased menstrual disturbances, polycystic ovaries and hyperandrogenism in women with
A more recent report investigated the role of obesity in the relationship between endocrine disorders and women taking valproate for epilepsy (Isojrvi et al., 1996). Treatment of epilepsy with valproate has been associated with weight gain in approximately 50% of female patients (Dinesen et al., 1984; Egger and Brett, 1981). Isojrvi et al. (1996) found this weight gain to be related to hyperinsulinemia and low serum levels of insulin-like growth factor-binding protein 1, which may lead to hyperandrogenism and PCOS.
Further, Isojrvi et al. (1998) proposed that valproate induces a metabolic syndrome in women with epilepsy, which results in obesity, hyperinsulinemia, lipid abnormalities, and polycystic ovaries or hyperandrogenism. Replacement of valproate with lamotrigine (Lamictal) in these patients resulted in a significant decrease in body weight and a normalization of serum hormone and lipid levels after six months. After one year, the total number of women with polycystic ovaries decreased from 11 to seven.
Although seemingly reversible, endocrine and metabolic consequences of PCOS may include coronary heart disease, hypertension, diabetes and cancer. The importance of these consequences and their clinical implications have stimulated further investigation of the effect of anticonvulsants on female reproductive function. In addition, clozapine (Clozaril) and olanzapine (Zyprexa) have been implicated in glucose dysregulation, although head-to-head studies are lacking.
Thus far, an association between treatment of
We investigated reproductive function in 22 female outpatients, ages 18 to 45, who were taking lithium or divalproex sodium (Depakote) for a DSM-IV diagnosis of BD (Rasgon et al., 2000). We did not find any biochemical or radiological (ultrasound) evidence of PCOS in this sample, unlike Isojrvi et al. (1993). In that 1993 study, the length of exposure to divalproex was approximately seven years, compared to approximately three years in our study. The mean dose for bipolar patients in our study, however, was somewhat higher than in women with epilepsy in the 1993 Isojrvi et al. study.
It is possible that PCOS-like changes occur in association with divalproex sodium only after years of exposure, and a false negative result was obtained in the current study due to a relatively short length of exposure and small sample size. Alternatively, the PCOS-like changes in the epilepsy group could be due to epilepsy per se, or a therapy-epilepsy interaction. The impact of both length and timing of exposure to divalproex on reproductive functioning requires further study with larger sample sizes, longitudinal designs and longer lengths of exposure.
In our cross-sectional study, all patients taking lithium and 70% of women taking divalproex sodium reported some type of menstrual dysfunction (Figure 2), which preceded the diagnosis of BD in many cases. Thus, our preliminary findings suggested that women with BD have a high prevalence of menstrual disturbances independent of therapeutic agent used and, in some cases, preceding the onset of BD. Our findings, as well as those of Isojrvi et al. (1993), indicated a need for a longitudinal, controlled evaluation of reproductive function in women taking mood stabilizers.
At this time, we continue to study the prevalence of PCOS in women with BD receiving mood stabilizers across the five sites within the Stanley Foundation Bipolar Network. In addition, we have started a longitudinal, two-year study of the effects of mood stabilizers and atypical antipsychotics now used in the treatment of BD on metabolic (body mass index, insulin resistance) and female reproductive endocrine function. This study will help to identify the population at risk for the development of endocrine dysfunction and metabolic disturbances upon treatment with mood stabilizers and atypical antipsychotics.
References:
References
1.
Dinesen H, Gram L, Andersen T, Dam M (1984), Weight gain during treatment with valproate. Acta Neurol Scand 70(2):65-69.
2.
Egger J, Brett EM (1981), Effects of sodium valproate in 100 children with special reference to weight. Br Med J (Clin Res Ed) 283(6291):577-581.
3.
Franks S (1995), Polycystic ovary syndrome. [Erratum appears in N Eng J Med 333(21):1435.] N Engl J Med 333(13):853-861 [see comment].
4.
Herzog AG, Seibel MM, Schomer D et al. (1984), Temporal lobe epilepsy: an extrahypothalamic pathogenesis for polycystic ovarian syndrome? Neurology 34(10):1389-1393.
5.
Isojärvi JI, Laatikainen TJ, Knip M et al. (1996), Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol 39(5):579-584 [see comment pp559-560].
6.
Isojärvi JI, Laatikainen TJ, Pakarinen AJ et al. (1993), Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 329(19):1383-1388.
7.
Isojärvi JI, Rattya J, Myllyla VV et al. (1998), Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol 43(4):446-451.
8.
Mattson RH, Cramer JA (1985), Epilepsy, sex hormones, and antiepileptic drugs. Epilepsia 26(suppl 1):S40-S51.
9.
O'Donovan C, Graves J, Kusumakar V (1999), Prevalence rates of self-reported menstrual abnormalities and clinical hyperandrogenism of women taking divalproex for bipolar mood disorder. Abstract No. 89. Presented at the Third International Conference on Bipolar Disorder. Pittsburgh; June 17-19.
10.
Pasquali R, Casimirri F (1993), The impact of obesity on hyperandrogenism and polycystic ovary syndrome in premenopausal women. Clin Endocrinol (Oxf) 39(1):1-16.
12.
Pierpoint T, McKeigue PM, Isaacs AJ et al. (1998), Mortality of women with polycystic ovary syndrome at long-term follow-up. J Clin Epidemiol 51(7):581-586.
13.
Rasgon NL, Altshuler LL, Gudeman D et al. (2000), Medication status and polycystic ovary syndrome in women with bipolar disorder: a preliminary report. J Clin Psychiatry 61(3):173-178.
Articles in this issue
over 24 years ago
The Politics of Health Care: What Will a New Administration Bring?over 24 years ago
Book Review Editor Retiresover 24 years ago
Injectable Atypical Antipsychotics Recommendedover 24 years ago
Movement Disturbances Associated With SSRIsover 24 years ago
PTSD Treatment Improves Youths'Academicsover 24 years ago
Decreasing Suicide in Schizophreniaover 24 years ago
Parenteral Antidepressants: Is America Ready?over 24 years ago
Investigating SAM-e for DepressionNewsletter
Receive trusted psychiatric news, expert analysis, and clinical insights — subscribe today to support your practice and your patients.