Estrogen and Parkinson's: What's the Connection?

Bret S. Stetka, MD; Kara M. Smith, MD


June 25, 2014

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Editor's Note: While attending the American Academy of Neurology 66th Annual Meeting, held in Philadelphia, Pennsylvania, from April 26 through May 3, 2014, Medscape interviewed Kara M. Smith, MD, a fellow in the Department of Neurology at the University of Pennsylvania Perelman School of Medicine in Philadelphia, about her study[1] looking at the potential protective role of estrogen in Parkinson disease (PD).

Medscape: Can you give us some background on your study?

Dr. Smith: My study is about the neuroprotective effects of estrogen and sex hormones in PD. We know that PD is much more common in men than in women, and women who have a higher lifetime exposure to estrogen have a lower risk for PD. When women do get PD, it tends to be later in life after menopause, when they have lower levels of estrogen.

So there seemed to be a connection epidemiologically that was then looked at in animal models. I did a systematic review of these studies to evaluate the evidence for and against the neuroprotective effects of estrogen and related compounds.

Medscape: What did you find?

Dr. Smith: There were about 238 results in my literature search, and I focused on the articles about neurotoxin-mediated animal models of PD, including MPTP, methamphetamine, and 6-OHDA. Overall, there is consistent evidence that certain estrogen compounds, particularly 17-beta estradiol, globally appear to be neuroprotective. When these compounds were given to animals before they were exposed to the toxin, they didn't experience death of dopaminergic neurons in the substantia nigra, or decreasing levels of dopamine in the striatum in general. In addition, there was evidence that these animals didn't have the same motor problems as the untreated animals.

Medscape: Can you speak to the potential mechanism through which estrogen might be neuroprotective?

Dr. Smith: It seems that the effects are mediated through the estrogen receptor itself. So there's the potential that if we find compounds that modulate the estrogen receptor in the brain without causing some of the concerning systemic effects that estrogen replacement therapy is associated with, then this could be an effective neuroprotective approach in humans.

Medscape: Had prior evidence shown an association between estrogen and dopamine metabolism?

Dr. Smith: There are some examples of primates in which an oophorectomy was associated with a decrease in dopamine, which could be reversed by replacing estrogen. So dopamine did seem to protect dopamine neurons in the brain.

Medscape: Do you see this as ultimately leading to human trials of estrogen therapy?

Dr. Smith: I think that's certainly down the line. But one problem is that the animal models aren't quite the same as idiopathic PD in humans. And again, there are concerns about balancing the benefits with the systemic side effects of estrogen and sex hormones. There may be ways in which we can develop compounds to get around those problems. Maybe more advanced animal models will better allow us to see the risks and benefits for humans.


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