Tuesday, October 14, 2014

What can Parkinson’s disease teach us about sex differences?

You probably have heard of Parkinson’s disease, a neurodegenerative disorder that affects motor ability, usually in older people. It is known for causing symptoms such as tremors, slowing of movement, and muscle stiffness. People with Parkinson’s can also have many other symptoms, such as  anxiety, trouble sleeping, dementia, trouble swallowing, constipation, and depression [1]. Parkinson’s is linked to losing neurons in the brain that produce dopamine, a neurotransmitter that your body uses to signal between neurons, especially in pathways that involve motivation and reward seeking. The area of the brain that loses dopamine during Parkinson's disease is called the substantia nigra, which, unsurprisingly, helps control movement.

As you can see in the graph below, Parkinson’s disease is much more common in men than in women. Interestingly, a study conducted by Haaxma et al. has found that there are also sex differences in symptom progression [2]. According to this study, women are more likely to develop a tremor as their initial symptom, while men are more likely to develop rigidity first. This is important because tremor dominant Parkinson's is usually characterized by a slower and milder progression of the disease. The study also found that on average, women are about two years older when they are diagnosed, and more dopamine was lost in women before symptoms developed. 

Figure 1: Age and gender of Parkinson’s diagnosis in the U.K. Fewer women are diagnosed with Parkinson's and they tend to be diagnosed at a later age (bathnes). 


The researchers explained that these differences could be caused by a neuroprotective effect of a female sex hormone, estrogen. This means that the presence of estrogen helps prevent, or at least delay, the development of Parkinson's disease. Supporting this, they found that among women with children, the more children they had, the older the average age of diagnosis. Estrogen levels are extremely high during pregnancy, so more children means more estrogen exposure during the women's life. Also, the age of diagnosis correlated with a longer fertile life span (amount of time between first period and menopause). A longer fertile life span indicates that the women were exposed to a higher level of estrogen for more years, because estrogen levels decrease during menopause. Both of these findings could mean that more estrogen means more protection against Parkinson’s disease.

The neuroprotection of estrogen against parkinson’s disease points to a possible link of estrogen and dopamine activity, possibly by estrogen preventing toxins from being transported to the dopamine nerve terminal [3]. In fact, dopamine levels have been shown to be higher in female than in male rats [4]. Because dopamine is involved in pathways of reward seeking, arousal, and attention, this trend has been used to explain many sex differences, such as the fact that males have higher rates of ADHD and alcohol dependence. It’s good to remember that anything to do with the brain is probably too complex to attribute just to one hormone or neurotransmitter. Sex differences in Parkinson’s disease are probably way more complicated than just an estrogen-dopamine connection. However, it is important to study potential causes, however partial, because these can be used as targets in developing treatments.

Fun fact: If you are male, and are feeling jealous of estrogen’s neuroprotective effects against Parkinson’s, try drinking coffee. Caffeine intake has shown to decrease the likelihood of developing Parkinson’s in men (but not in women).

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1. Gillies, G.E., Pienaar, I.S., Vohra, S., and Qamhawi, Z. 2014. Sex differences in parkinson's disease. Front Neuroendocrinol 35: 370-384.

2. Haaxma, C.A., Bloem, B.R., Borm, G.F., Oyen, W.J., Leenders, K.L., Eshuis, S., Booij, J., Dluzen, D.E., and Horstink, M.W. 2007. Gender differences in parkinson's disease. J Neurol Neurosurg Psychiatry 78: 819-824

3. Dluzen, D.E. 2000. Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system. J Neurocytol 29: 387-399

4. Walker, Q.D., Rooney, M.B., Wightman, R.M., and Kuhn, C.M. 2000. Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry. Neuroscience 95: 1061-1070



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