Should this be the Case, Estrogen Therapy should improve Cognition and Motor Function of...



Ram S. Bhatt, PhD., Chief Science Officer


Is there a Gender Difference in the Integrity of the Blood-Brain Barrier (BBB)?

“Should this be the case, estrogen therapy should improve cognition and motor function... ”

Blood-Brain Barrier: Let us first dive into understanding what the blood-brain barrier (BBB) is. The BBB is an intricate web of tightly packed endothelial cells held together by strings known as proteins. It plays a critical role in protecting the brain from blood-borne pathogens, viruses, bacteria, chemicals, proteins, and cancer cells, etc. Like a security guard the BBB selects what can go into the brain or not. It allows essential nutrients to enter the brain but blocks nearly 98% of all drugs. While drugs such as L-Dopa, Tylenol, Advil, etc. are permitted to cross the BBB these drugs are incapable of altering the disease course. These drugs merely treat symptoms for a short while and stop working thereafter. Nearly 100% of drugs that can potentially cure brain diseases are not able to cross the BBB; hence our world is facing an epidemic of neurodegenerative diseases. Global estimates are that more than one billion individuals are affected by different forms of neurodegenerative diseases. US alone has about 6 million Alzheimer’s (AD) patients, 1.1 million Parkinson’s (PD) patients, ~1.0 million multiple sclerosis, and ~ 63,000 motor neuron disease patients. Unless technologies are immediately developed that can safely and without compromising the BBB and can deliver disease altering/curing drugs across the BBB the world is likely to face epidemics that are far worse than COVID-19 within the next 2–3 decades.

Gender Difference in the Integrity of the BBB: There are some speculations, albeit too early and not validated, that there exists a sex difference in the integrity of the BBB. For example, more men seem to have Parkinson’s disease than women; in 3:2 ratios. Speculation is women are protected by estrogen from getting Parkinson’s. Should this be the case, estrogen therapy should improve cognition and motor function of treated patients. Unfortunately, clinical trials have shown to have no effect of estrogen replacement therapy on AD [J. Steroid Biochem. Mol. Biol, 142, 99 (2014)]. Although estrogen appears to delay Parkinson’s onset in women, there are no clear differences in disease progression of men and women. It, therefore, won’t be wise for women or men to start taking estrogen replacement therapy. The wise thing would be to consult the neurologist or Movement Disorder Specialist.

Next month we will discuss the effect of aging on the BBB integrity, so please stay tuned.

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Updated: August 16, 2017