BLOG: Estrogen and its beneficial effects

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It makes a difference in the recovery whether a woman or a man is afflicted by a spinal cord injury. Vieri Failli, biologist, gives some insights into the topic.

Already at my birth, I was destined to die earlier than half of the babies of my maternity ward. Simply due to the fact that I am male, I am expected to die about three years earlier than any woman born on the same day as me. This puzzling fact has been known for decades, but it is only recently that we have started understanding it. A common idea was that men are more abusive of their bodies. However, women are slowly catching up on bad habits such as smoking, drinking and overeating, and yet this gender difference in life expectancy is subsisting. In fact, female chimpanzees, gorillas, orangutans, and gibbons also consistently outlive the males of the group, and those species do not have issues with their lifestyle. There is clearly something deeper engrained in our biology, and although there are many potential mechanisms at play, one of the most important is probably the female sex hormone estrogen.

What is estrogen?
Translated from Greek as “producer of desire”, it is the primary female sex hormone, responsible for the development and regulation of the female reproductive system and secondary sex characteristics. While estrogens are present in both men and women, they are usually present at significantly higher levels in women of reproductive age. Estrogen occurs in three major naturally forms in the female body and its levels vary throughout the life of a woman.

Estrogen  plays not only vital roles in remodeling and regulation of the reproductive system but also contributes to cognitive function in the central nervous system. When compared with females, the estrogen is significantly low in males, and even at a very low level it has important roles in maintaining overall health in males. Estrogen is a multi-active hormone, and it takes care of many, many pathways. It is a powerful antioxidant and anti-inflammatory. It acts as a growth factor, promotes micro-vessel growth and improves blood flow. Thus, estrogen may be a multi-active neuro-protectant.

Estrogen and trauma
A large study done on more than 50.000 patients proved that women who have been severely injured are 14 percent more likely to survive than similarly injured men are. Similarly, estrogens seem to offer some degree of protection after traumatic brain injuries. Numerous laboratory studies, but also patient’s analysis proved that females recover much better than males after a traumatic brain injury.

Estrogen and spinal cord injury
Spinal cord injuries affect mostly men and the overall number of injuries is much lower than other type of traumatic injuries, so data in humans is not reliable. Studies in animals seem to prove that the beneficial effect seen in other conditions is also present after a spinal cord injury. Female have faster and larger amounts of locomotor recovery following spinal cord injury, when compared with their male counterparts. This means that without delivering any kind of treatment female animals will recover faster and better than male sustaining the same type of injury. It is as somehow females would be carrying their own and readily available treatment for spinal cord injury.

Estrogen as a medication
The effects of estrogen in nerve regeneration or protection have been studied throughout the last decade, and the results have shown the benefits of this hormone in different outcomes. Estrogen treatment improves recovery after traumatic brain injury, cerebral ischemia and peripheral nervous system lesions. Also in in both acute and chronic animal models of spinal cord injury, scientists could see that low doses of estrogen can significantly boost recovery

Estrogen – the mechanisms
Spinal cord injury is a complex event that involves several phases with many cellular mechanisms at play. After the initial injury, a wave of toxic chemicals released by the dying tissue and a localized inflammation create what is called the secondary injury that further extend the size of the damage. On top of this the blood-brain barrier, a membrane that isolates the brain from the circulating blood, gets disrupted and further aggravates the general picture.

Just as spinal cord injury activates multiple detrimental factors and pathways, the most mesmerizing fact about estrogen is that it is a multi-active therapeutic agent. Estrogen can inhibit the oxidative stress and block a whole cascade of toxic molecules while diminishing the localized inflammation. Estrogen can also promote the expression of molecules that will protect the neural and glial cells from death. Finally, estrogen prevents the breakdown of the blood-spinal cord barrier. These effects can be summarized as neuro-protective, since estrogen increases the chances of survival of the cells located within or near the injury site. However, estrogens also have the capacity to promote cell proliferation, cell growth and tissue re-vascularization so they might also play an active role in the recovery of locomotor function.

The dose makes the poison
Estrogens can easily pass the blood-brain barrier and diffuse across the cell membrane, so even variations in small amounts in the body can have dramatic results. While estrogen has its benefits, it must be carefully administered at an optimal dose; otherwise, it may cause a significant negative impact on the physiology of the host. Use of high dose of estrogens for a long time can be associated with risks of several cancers in females and can promote visible feminine characteristics in males.
Scientists were quick at using large amounts of estrogens while investigating their beneficial effect after injury. High doses of estrogens worked as a very effective anti-oxidant and showed high efficacy in the treatment of spinal cord injury in animals, which unfortunately developed later complications such as an increased number of tumors.

Finding the right balance
Recent studies proved that small amounts of estrogens treatment could promote recovery after spinal cord injury, making them suitable for potential clinical translation. Since tiny variations can trigger undesired side effects scientists are now taking a different approach. They are looking for another therapeutic agent that could enhance the beneficial effect estrogens. This would allow them to deliver small amounts of estrogens and keep any side effect at bay. Scientists are also trying to dissect the molecular action of estrogens to uncover new potential therapeutic targets that could generate new and safer treatment.

Estrogens show a great potential for promoting functional improvement after spinal cord injuries, but more research is needed before moving this therapy into a clinical trial. Thus, scientists in international research groups are actively searching for new synthetic or plant-derived natural product that could take advantage of this very mechanism.

Yours Vieri Failli

Vieri Failli is a Biologist and an insider in the field of spinal cord research.
Vieri Failli is a Biologist and an insider in the field of spinal cord research.