Parkinson's disease in women

PARKINSON'S DISEASE IN WOMEN

by Susan M. Rubin, MD

UNTIL RECENTLY LITTLE HAS BEEN WRITTEN REGARDING THE EFFECT THAT GENDER HAS ON THE DEVELOPMENT AND MANAGEMENT OF PARKINSON'S DISEASE. CURRENT RESEARCH HAS FOCUSED MAINLY ON THE IMPACT THAT SEX HORMONES HAVE ON THE DEVELOPMENT OF PARKINSON'S DISEASE. LESS HAS BEEN WRITTEN ON THE IMPACT THAT PARKINSON'S DISEASE HAS ON MENSTRUATION, PREGNANCY AND MENOPAUSE. THIS ARTICLE WILL REVIEW THE MOST RECENT INFORMATION ON BOTH THE AFFECT THAT PARKINSON'S DISEASE HAS ON WOMEN AND THE IMPACT THAT GENDER HAS ON PARKINSON'S DISEASE.

While Parkinson's disease is usually thought of as a disease of the elderly, approximately 3-5% of women diagnosed with this disorder are under the age of 50. A large number of these women are still experiencing regular menstrual cycles. Studies that have reviewed the effect of hormone fluctuations and menstruation on Parkinson's disease have noted an impact of the menstrual cycle on disease control. During menstruation women described increasing Parkinsonian symptoms, decreasing medication responsiveness and increased "off" times. They also complain of increased fatigue, cramps and heavier menstrual flow. This can lead to occasional humiliating self-care issues due to worsening dexterity.

Premenstrual symptoms of depression, bloating, weight gain and breast tenderness also appear to increase in intensity in women who note a variation in their symptom control with menstruation. Usually these symptoms improve after menstruation but will reoccur with each cycle. A small sample of women in the studies used birth control pills. They reported that they had less intense fluctuations in their symptom control but more research needs to be done before recommendations can be made. However, it is important to recognize that these fluctuations occur so that women can be prepared for the changes in control. The use of regular exercise and relaxation techniques can help decrease symptoms and improve coping abilities.

There have been only a limited number of pregnancies to women with Parkinson's disease reported. The data has been divided into the impact that pregnancy has on Parkinson's disease and the effect that Parkinson's disease has on pregnancy. There is an increase in both motor and non-motor symptoms during pregnancy although it is rarely significant enough to impact the women's overall level of functioning. Non-motor symptoms (such as fatigue, constipation and depression) seem to improve after delivery but any progression of motor symptoms (rigidity, slowness of movement and tremor) usually persists. While data has shown that increasing length of estrogen exposure (the amount of time from puberty to menopause) decreases the risk of developing Parkinson's disease, increasing amount of time spent pregnant seems to increase the risk of developing Parkinson's disease. This seems contradictory but may be due to differences in the effect that estriol (the pregnancy form of estrogen) and estradiol (the menstrual form of estrogen) have on the disease.

The main concern of pregnant women with Parkinson's disease is the risk of birth defects from antiparkinson's medications. The dopamine agonists, bromocriptine and pergolide (Permax), are considered relatively safe during pregnancy but make it impossible to breast feed because they block milk production. The remainder of the antiparkinson's medications carries a category C rating, meaning that animal studies suggest some risk but human studies are not available or have not confirmed that risk. The data on Levodopa with or without carbidopa (Sinemet) suggests some risk in animal studies but there were no reported birth defects in newborns in the small number of pregnancies reviewed. Amantadine is the only antiparkinson's medication that has resulted in heart malformations in babies with first trimester exposure. There were no reports of major malformations with the use of Selegiline (Eldepryl) and there is no data available so far on the COMT inhibitors.

Women with Parkinson's disease do not have trouble with fertility but can have changes in self-image that lead to social avoidance and difficulty with sexual intimacy. This can lead to decreased pregnancy rates and sexual dysfunction. Women who do become pregnant must then face the challenge of caring for a child postpartum. The American Parkinson Disease Association offers resources and helpful staff to provide information and support regarding pregnancy and parenting issues related to PD. Establishing a support system and planning are critical to being an effective parent, especially if you have a progressive disease.

It has been noted that women are more likely to develop Parkinson's disease later than men and usually when they are postmenopausal. Basic science research with rats has shown that there is an increase in the slow decline in dopamine producing cells coincident with menopause. Use of hormone replacement in rats that have had their ovaries removed seems to reverse that increase. However, studies in women have had contradictory results showing only partial or no benefit from hormone replacement. This may be due to the timing of the hormone replacement, since the animal studies have shown a difference in benefit based on the timing of the hormone supplementation. The rats who received hormone supplements within 10 days of having their ovaries removed had no increase in the loss of dopamine producing cells, while rats that did not receive estrogen until 30 days later did lose cells more rapidly. They did not see any benefit from the supplements in the rats who received them later.

The few studies that have compared the impact of hormone replacement therapy on disease progression have been mildly positive. Women on hormone replacement reported more "on" time and lower UPDRS functionality scores than non-estrogen users. Unfortunately the number of women studied is too low to support the use of hormone replacement in women with Parkinson's disease at this time. The benefits still need to be weighed against the risks recently reported in the Women's Health Initiative study.

In conclusion, we are beginning to understand the impact of sex hormones on the development and progression of Parkinson's disease. Recent studies suggest that there is an inverse relationship between lifetime estrogen exposure and the risk of developing Parkinson's disease. It has also been shown that fluctuations in hormone levels will result in changes in disease control and result in the need for changes in symptom management during menstruation, pregnancy and menopause. Hopefully, we will gain further understanding in the future which will lead to new treatment options for women with Parkinson's disease.

Susan M. Rubin, MD, Clinical Instructor and Director, Women's Neurology Center, Glenbrook Hospital, Glenview IL.

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