Androgens and Parkinson's Disease
Written by Ben Bunting: BA(Hons), PGCert. Sport & Exercise Nutrition. British Army Physical Training Instructor.
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Androgens are important for the development and maintenance of healthy brains. They also play a role in the progression of neurodegenerative and neuropsychiatric disorders.
In men, testosterone decreases with age and causes a range of symptoms associated with Parkinson's disease (PD). Replacement of low testosterone levels improves non-motor symptoms in some PD patients.
Testosterone
A recent study from Rush University Medical Center in Chicago suggests that a sudden decline in testosterone may be linked to the increase in Parkinson's disease (PD) among men. This sudden decrease in hormone levels can lead to tremors, loss of balance and limb stiffness, and reduced facial expression.
Testosterone is a male hormone that regulates sexual development and function during adolescence. It also stimulates the production of sperm. It is secreted by the testicles, and it's regulated by signals from the brain and pituitary gland.
Low testosterone levels in men are a condition called "testosterone deficiency syndrome", "low-T", "andropause" or "hypogonadism" This can happen as you get older, and it can cause a number of problems.
It's important to have your blood tested for testosterone levels to see if you have low testosterone or a related condition. This can help you get treatment for it and other conditions that can be treated with testosterone, such as prostate cancer.
Your doctor will need to take some blood samples from your arm, a vein in your neck, or a vein in your stomach. These tests can be done quickly and are very safe. You can ask your provider if it is necessary to fast for some of these tests, as this can reduce the risk of side effects.
Testosterone helps the deelopment of tendons and ligaments, and it increases bone growth. It also helps muscle protein synthesis.
Many men have high levels of testosterone when they are young and healthy. But this naturally declines as men age, usually once they have hit 30 years old.
Hormone replacement therapy can help treat a number of symptoms in patients with PD, including fatigue, slowed movement and balance, mood changes, decreased libido, and increased pain. It also can improve quality of life. It can be used in conjunction with deep brain stimulation (DBS) or other PD treatments.
However, there are risks associated with testosterone replacement therapy, as such these will be discussed with a medical professional prior to any prescribed course.
Estrogen
Estrogens play a central role in the development of many human physiological processes, including reproduction, cardiovascular health, bone integrity, cognition and behavior. In addition, estrogens are essential for the proper functioning of the brain and spinal cord. In particular, they are thought to regulate the function of the renin-angiotensin system (RAS) in the brain and the production of nitric oxide and hydrogen peroxide free radicals in the body.
Although the mechanisms of the neuroprotective effects of estrogen have not been fully elucidated, it has been shown that it can protect neurons against selective death by 6-hydroxydopamine (THDA) or by oxidative stress. This is done by promoting the formation of nitric oxide or hydrogen peroxide-sensitive endoplasmic reticulum membranes, and it can also inhibit the synthesis of THDA and 6-OHDA from the adenylyl cyclase pathway.
In addition, it has been found that estrogens can decrease apoptosis and prevent the degeneration of dopaminergic neurons in the substantia nigra in mice with PD-like symptoms. This has been demonstrated both in pre-treatment of cultured dopaminergic neurons with estrogen via time-release capsules and in vivo.
The role of estrogens in humans has been studied in a number of clinical and epidemiologic studies, where it has been found that women who are more exposed to estrogen prior to menopause tend to have less severe Parkinson's disease symptoms than those who do not. In addition, it has been found that postmenopausal hormone replacement therapy can reduce the risk of developing PD in those who are already diagnosed with the condition.
However, these benefits of estrogens need to be weighed against the risks associated with taking HRT. For example, a recent study has found that there is an increased risk of cardiovascular diseases and stroke in postmenopausal women who are treated with hormone replacement therapy. The Women's Health Initiative (WHI) trial has also shown that women with a history of venous thromboembolism are more likely to have a stroke or a heart attack when they are on hormone replacement therapy. These findings may suggest that hormone therapy should be used only in patients with a known cardiovascular risk profile.
Bioidentical Hormone Replacement Therapy (BHRT)
Hormones are special chemicals produced by our body’s glands, ovaries in women and testicles in men that tell all the cells in the body what to do and how to do it. They control the functions of our organs, such as the heart and brain. These hormones are so important that they can cause serious health issues if their levels drop too low or are out of balance.
Symptoms of low hormones may include hot flashes, night sweats, and irritability. These symptoms can affect your quality of life and ability to function. If you are experiencing these symptoms, you should consult with your healthcare provider to see if hormone replacement therapy (HRT) could be helpful for you.
Bioidentical Hormone Replacement Therapy (BHRT) uses specialized hormones that are made to closely mimic the natural hormones that your body produces. These are a better choice than conventional hormone therapy because they do not have extra structural moieties that can change the receptor binding of your body’s natural hormones and lead to side effects.
This method of treating menopausal symptoms is safe and effective. In fact, a new study has shown that BHRT can reduce the frequency of hot flashes and night sweats in women. In addition, BHRT can also lower your irritability and emotional lability.
The treatment involves a quick in-office procedure to implant pellets that are slightly larger than a grain of rice. These pellets contain either estradiol or testosterone and dissolve inside your body over the course of a few months.
Unlike the other forms of hormone replacement, these pellets can provide consistent and healthy levels of hormones for a longer period than pills or patches do. Because they are pressed or fused into tiny solid cylinders, they avoid the fluctuations in hormone levels that other methods of delivery can cause.
Bioidentical hormones are made in a laboratory to closely match the chemical structure of your body’s own hormones. BHRT is an FDA-approved and safe option for women and men who are suffering from low hormones.
Other Hormones
Hormones are chemicals that circulate in the blood stream and send signals to different parts of the body. They play a vital role in homeostasis (constant internal balance), such as blood pressure and sugar regulation, fluid (water) and electrolyte balance, and body temperature.
They are made by specialist cells called endocrine glands. These glands secrete hormones into the bloodstream. The hormones are then passed on to other tissues, cells or organs.
The endocrine system contains a wide variety of glands. They include the hypothalamus, pituitary gland, gonads, adrenal glands, thyroid and parathyroid glands.
These glands are responsible for producing the hormones that control many of the body's functions and help regulate the body's response to stress and other stimuli. They are responsible for the control of appetite, sexual function and behavior, the body's temperature, sleep and many other processes.
In humans, hormones are released into the bloodstream and travel to specific target glands and cells to make them react in a certain way. Some of these hormones are derived from lipids (like testosterone, estradiol and progesterone) or amino acids. Others are peptides or proteins.
Adrenaline is a hormone that is produced by the adrenal glands and some of the central nervous system's neurons. It is a very important hormone as it helps to increase the metabolic rate, dilate the blood vessels and increase the heart's rate and speed.
It is also a key hormone for helping to deal with stress and the body's reaction to fear, pain and anxiety. It stimulates the production of norepinephrine and epinephrine and plays a major role in helping to respond to emergencies like when you are being attacked by a wild animal or during a car accident.
A recent study has found that a hormone that is produced by muscles during exercise may protect the brain cells of people with Parkinson's disease. This is important because it could slow the progress of the condition, which currently has no effective treatment options.
Conclusion
The occurrence of low testosterone levels is a well-recognized comorbidity in patients with Parkinson's disease (PD) that has not been associated with any significant improvement of motor or non-motor symptoms. Nevertheless, this condition has been treated in several cases with success by hormone replacement therapy.
The human androgen receptor transcriptionally activates tyrosine hydroxylase, a biosynthetic enzyme involved in dopamine synthesis. This mechanism has been shown to be relevant to PD because a loss of this enzyme has been linked to a greater risk of dementia and Alzheimer's disease (AD).
In addition, DJ-I likely serves as a transcriptional co-activator for androgen receptor 50'51. Moreover, DJ-I expression in SH-SY5 Y cells was able to accelerate the phosphorylation of AKT without increasing the expression of total AKT. Similarly, in SH-SY5 Y cells transfected with a construct encoding human androgen receptor, the presence of dihydroxytestosterone significantly increased the level of phosphorylated AKT compared to untreated controls.
The present invention provides methods for enhancing the expression of tyrosine hydroxylase. These methods include the administration of an androgen or an analog thereof, preferably one of the compounds of this invention. These methods can be used alone or in combination with other conventional therapeutics useful for the treatment of a neurodegenerative disease.
