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Movement Disorders in Women: a Review

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Movement Disorders in Women: a Review REVIEW CME Movement Disorders in Women: A Review Marcie L. Rabin, MD, Claire Stevens-Haas, Emilyrose Havrilla, Tanvi Devi, BS, and Roger Kurlan, MD* Atlantic Neuroscience Institute, Overlook Medical Center, Summit, New Jersey ABSTRACT: The field of women’s health devel- contraceptives and hormone-replacement therapy), oped based on the recognition that there are important have significant implications for women with movement sex-based differences regarding several aspects of disorders. Understanding this biological sex-specific medical illnesses. We performed a literature review to information can help improve the quality and individuali- obtain information about differences between women zation of care for women with movement disorders and and men for neurological movement disorders. We may provide insights into neurobiological mechanisms. identified important differences in prevalence, genetics, VC 2013 International Parkinson and Movement Disorder clinical expression, course, and treatment responses. In Society addition, we found that female life events, including menstruation, pregnancy, breast feeding, menopause, and medications prescribed to women (such as oral Key Words: movement disorders; women; gender The field of women’s health evolved from the recog- We conducted a Medline literature search for the nition that a number of medical conditions differ in years 1970 to 2013, focusing on the most common presentation, course, and therapeutic response between movement disorders along with the key words gender, women and men. It is known that distinct physiologi- sex, women, female, estrogen, progesterone, hor- cal and anatomical differences occur in a variety of mones, menstruation, pregnancy, breastfeeding, and organ systems, depending on whether an individual menopause. Resulting articles were reviewed and are has two X chromosomes or one X and one Y chromo- summarized below, organized according to the type of some. Furthermore, it has been recognized that there movement disorder. We have focused on sex differen- are important interactions between disease states and ces in prevalence, genetics, clinical expression, and uniquely female life events, such as menstruation, course treatment; on the influence of female life pregnancy, and menopause. The Institute of Medicine events, such as menstruation, pregnancy, lactation, has recommended exploration of the biological contri- and menopause; and on medication for women, butions of sex to human health.1 It is well known by including oral contraceptives and hormone- neurologists that there are clear sex differences and replacement therapy. Following the recommendations specific women’s issues in a variety of neurological of the Institute of Medicine, we use the term “sex” as conditions, such as headache, pain, stroke, and epi- opposed to “gender.” Sex is the classification of either lepsy. Although women’s issues have been mentioned male or female based on reproductive organs and widely in the literature on neurological movement dis- functions assigned by chromosomes. Gender encom- orders, this is the first review article that attempts to passes one’s self and social identity as either male or synthesize the information. female, which is rooted in biology but also shaped by ------------------------------------------------------------ environment.1 *Correspondence to: Dr. Roger Kurlan, Atlantic Neuroscience Institute, Overlook Medical Center, Summit, NJ 07902; [email protected] Parkinson’s Disease Relevant conflicts of interest=financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online ver- A decreased rate of Parkinson’s disease (PD) among sion of this article. women has been reported in many prevalence and Received: 11 July 2013; Revised: 25 September 2013; Accepted: 1 incidence surveys, and this difference persists across October 2013 2 Published online 22 October 2013 in Wiley Online Library age groups. These results have been confirmed in two (wileyonlinelibrary.com).DOI: 10.1002/mds.25723 published meta-analyses, which reported age-adjusted Movement Disorders, Vol. 29, No. 2, 2014 177 RABIN ET AL. male-to-female incidence ratios of 1.46 and 1.49.3,4 edly experience more violent dreams, causing them to The prevalence of PD was approximately two-fold kick out or fight, whereas women have less aggressive lower for women than for men in the Northern Cali- behavior but more disturbed sleep.21 In patients with fornia population study and in the Italian longitudinal PD residing in nursing homes, it was observed that study.3,5 The latter study reported a prevalence rate of women more often had wandering behavior and 8.8 to 9.9 cases per 100,000 for women compared reported more depressive symptoms,22 and they devel- with 13.0 to 19.0 cases per 100,000 for men.5 Age at oped depression more frequently as a side effect of onset appears to be later in women compared with treatment. It also should be noted that women with men. Two studies found consistently that age at onset PD are more likely to have certain medical comorbid- was approximately 2 years later for women.6,7 ities, such as osteoporosis and bone fractures, which A lower preponderance of PD in women and later may influence the course of their illness.23 age at onset could reflect differences in risk factor Some studies have identified sex differences related exposure, such as lower occupational exposure to to the treatment of PD. A difference has been observed environmental chemicals or a lower rate of head in the metabolism of levodopa (L-dopa), with a greater trauma. Alternatively, sex hormones or the sex chro- bioavailability in women.16 One review indicated that mosomes themselves could affect the expression of women are less likely than men to undergo surgical PD-related genes (epigenetics) or disease risk. treatments for PD,24 and another study found that the Although there is an increased risk of PD if a blood use of surgery was delayed in female patients.25 Some relative has the illness, there is no reported evidence of studies have reported that women with PD have better any difference if the relative is female or male.8 This outcomes than men after stereotactic surgical proce- suggests that sex does not influence hereditary factors. dures.25,26 Investigators in the Stalevo Reduction in Data supporting a potential protective role of endoge- Dyskinesia Evaluation PD (STRIDE) study analyzed nous estrogens come from research indicating that their data and observed that female sex was a risk lifetime reduction in estrogen levels (early menopause, factor for the development of both L-dopa-induced fewer pregnancies, hysterectomy=oopherectomy) dyskinesias and wearing-off motor fluctuations.27 appears to be a risk factor for the development of The influence of female life events on PD has PD.9-12 An analysis of potential environmental risk received some attention in the literature. One study factors for PD indicated that, among men, the absence examined how hormone fluctuations in women of coffee consumption, a history of head trauma, and affected their symptoms of PD.28 Although no sub- pesticide exposure were the strongest factors identi- stantial changes were observed during menstruation or fied; whereas, among women, anemia was the strong- menopause, a significant increase in PD symptoms was est factor.13 Women may have reduced access to identified while women were taking oral contracep- medical care, which could influence assessed age at tives.28 In another study that involved 19 women with onset. Two studies found higher baseline levels of PD, 17 reported regular, natural menstruation, and 15 dopaminergic activity in women compared with men, noted a significant worsening of menses-associated which might explain the later age at onset.7,14 pain and fatigue after disease onset.29 Two of those The clinical manifestations of PD reportedly differ patients required hysterectomy. Most of the women somewhat based on sex. At onset, compared with also noted a worsening of their PD symptoms during men, women are more likely to have a tremor- menstruation as well as an attenuated effect of their dominant phenotype of PD, which has been associated antiparkinsonian medications with increased off time. with a slower rate of decline.7 At equivalent points in The investigators believed that this clinical worsening the time course of the illness, it has been observed was caused in part by the low estrogen levels during that women have less severe symptoms, as assessed by menstruation, because low estrogen levels have been the Unified Parkinson’s Disease Rating Scale (UPDRS), associated with worsening of PD symptoms. This sug- suggesting that, in general, women do have a more gests that estrogen supplementation may help with slowly progressing course of PD.15 However, women symptomatic treatment of PD (see below). generally report greater disability and worse quality of Although pregnancy (when estrogen levels are high) life when surveyed.16 Women tend to have more drug- appears to be an uncommon event in women with PD, induced dyskinesias than men.17-19 it has been associated with either no change or a There are sex differences in cognitive and behavioral worsening of the illness.30 One case study described a aspects of PD. Women tend to perform better on woman aged 33 years with PD who experienced a cognitive testing.17 When treated with a dopamine substantial worsening of her symptoms during preg- agonist, women reportedly have fewer impulse control nancy; and, 15 months after delivery,
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