Testosterone: Cardiovascular Myths and Benefits

I enjoy writing educational essays in this website to hopefully provide interesting reading material to my patients. 
 
I have previously written essays that include an overview of issues pertaining to prevention and how to achieve well-being. Included was an introductory essay of how your body’s natural hormones play important roles throughout life in maintaining the strength and well- being of your body. 
 
Over the past year I have taken a number of educational seminars and study in the area of optimizing your own body’s hormones to help improve health and well-being.
 
I’d like you all to know that I have recently written the exam and passed with flying colors and am now certified in this interesting area.
 
Following is an essay overviewing the benefits as well as the myths pertaining to testosterone therapy. This essay is derived from numerous peer review papers in the medical literature which convey significant benefit of testosterone therapy, and this essay will also touch upon some of the negative papers that achieved much media attention and conveyed significant misperceptions about this subject. 
 
I recently gave this talk at Cardiovascular Conference to the Department of Cardiology at Hoag Memorial Hospital.
 
 
WHAT IS TESTOSTERONE?
 
 Testosterone is a hormone secreted by the ovaries, the adrenal glands, and the testes. The “Normal Range” is portrayed at about 250 to 900 pg/ml. This is an arbitrary setting based on up to 20 men in the 50 to 80 year old range. The ranges would be considerably higher in the healthy 20 to 30 year old group: consider about 500 to 2000!
Depletion of testosterone with aging (testosterone deficiency) includes symptoms of diminished libido, sense of vitality, erectile dysfunction, reduced muscle mass and bone density, mood change, depression, and anemia.
 
CONFUSION AND MISPERCEPTIONS ABOUT TESTOSTERONE:
 
There are 2 papers in the medical literature written in 2013, and 2014 that received enormous media attention. These have determined to be very flawed papers, written with very faulty statistical design and flawed methods and conclusions. They both initially suggested that there was an increase in cardiac events such as heart attacks and strokes, but further analysis demonstrated incorrect interpretation of the numbers and incorrect conclusions. In fact 29 societies and 50 international experts have called for the retraction of these papers. One paper has had to make 3 corrections with apologies, and when re-done it actually showed that testosterone lowered the percentage of adverse cardiovascular events. The second paper had no control group, and in fact, it was based on merely handing out a testosterone prescription and did not assess whether the men were actually taking it!
 
 
One of the big confusions is that doctors think that testosterone increases the risk of clotting and what it does to the blood. This is simply not true.
 
The confusion is many doctors think that testosterone can cause a blood disorder called Polycythemia, which can increase the risk of clotting. This is because Polycythemia causes an increase in hemoglobin and hematocrit, (red blood cells) as well as an increase in white blood cell count and increase in platelets. It is the increase in platelets that causes the increase risk of clotting. 
 
Testosterone at high levels may increase the level of hemoglobin and hematocrit (red blood cells which carry oxygen to your cells)! This is something called “erythrocytosis”. Testosterone does not increase the level of white cells nor platelets and therefore does not increase the risk of clotting.
 
 In fact, over 200,000,000 people on the Planet Earth may have “erythrocytosis” because they live at over 7,000 feet above sea level and they don’t have an increased risk of clotting. In fact, the US Olympic athletes often train in Colorado at elevation in order to boost their hemoglobin and hematocrit!  It is not uncommon for the Sherpas who carry heavy loads in the Himalayas to have very elevated hemoglobin and hematocrit. They do not have an increased risk of blood clots.
 
Since those two studies, more than a dozen clinical trials and observational studies have provided additional information, with none demonstrating increased cardiovascular risk. On the contrary, several of these studies have suggested that testosterone therapy may be cardioprotective. Following are some examples:
 
PUBLICATIONS ON THE BENEFITS OF TESTOSTERONE:
 
A recent paper published in the Journal of Cardiovascular Pharmacology and Therapeutics by Traisch in 2017 compared a group of higher cardiovascular risk men treated with testosterone versus placebo: 360 men treated versus 296 on placebo;  a 10 year follow-up. The treated group had a significant lower incidence of death, heart attacks and stroke than the placebo group. Also noted was a reduction in waist circumference, and body weight, improvement in lipid profile and reduction of blood glucose.
In fact, the placebo group had 26 nonfatal heart attacks and 30 nonfatal strokes and the testosterone treated group had none. There were 21 deaths in the placebo group: 19 cardiovascular events including 5 heart attacks, 4 strokes, 7 heart failures, 2 thromboembolism, 1 Pulmonary embolism. There were 2 deaths in the testosterone treated group: 1 person died after a surgical procedure, and 1 person died in a car accident.
 
A series of papers called the Testosterone Trials showed at 2 year of follow up, 8 heart attacks in the placebo group, and 1 heart attack in the testosterone treated group. There were improvements in cholesterol levels, blood sugar levels, blood pressure, heart rate, weight, waist circumference...and these were added benefits in addition to the presence of statins.
Another paper showed an 8 year weight loss of 17-24% with testosterone therapy comparing favorably to the 10 year weight loss of 14%-25% seen with bariatric surgery.
 
The Testosterone Trials were published in the New England Journal of Medicine in 2016. They were a set of 7 double blind placebo-controlled trials at 12 sites. The studies were built around inclusion criteria of sexual function, physical function and vitality in 790 men over the age of 65. These men had issues of obesity, high blood pressure, diabetes, some were smokers, and a number even had previous heart attacks: they were considered to be a high risk group. 
 
Androgel, a fairly weak commercial product was used and more or less doubled the testosterone levels from around 230 to 250 to about 500 ng/dL (nothing stellar!).
The testosterone group versus placebo group showed improved sexual desire, increase in sexual activity, and improved erectile function. There was improvement in walking distance and duration. There was an improvement in energy, mood, reduction in depression; improved muscle strength and bone density. Over 2 years, cardiovascular events including heart attack, stroke, and death due to cardiovascular cause were 9 in the testosterone treated group and 16 in the placebo group. (3 deaths in the testosterone group, 7 in the placebo group.)
 
SO WHAT DO WE KNOW ABOUT THE BENEFITS OF TESTOSTERONE?

1. Numerous studies have shown that testosterone therapy reduces waist circumference, body fat mass, blood pressure, and blood glucose. It increases lean body mass, insulin sensitivity, and improvement in the lipid (cholesterol) profile. Since obesity, dyslipidemia (bad cholesterol numbers), insulin resistance, metabolic syndrome, hypertension, and diabetes are well established cardiovascular risk factors, ANY therapeutic modality that improves these risk factors should be expected to reduce cardiovascular risk.
2. Testosterone administration results in increased muscle mass, strength endurance, and exercise tolerance. There a decrease in subcutaneous and visceral fat. There is enhanced psychological status and enhancement of well-being. There is an increase in lean muscle mass, and improvement in bone density. There is improvement in skin tone. There is improvement in libido and sexual performance.
3. Testosterone offers protection to the cardiovascular system, the neurological system, the musculoskeletal system, the vascular system, the immune system. It prevents against deterioration of muscle, ligaments, joints, tendons, bones and skin. It protects against insulin resistance, metabolic syndrome, and diabetes by decreasing visceral fat
4. It decreases pro-inflammatory proteins that cause further deterioration of atherosclerosis. It protects against dementia.

 
In fact, testosterone is banned in the Olympics and professional sports due to the fact that it improves strength, it increases muscle mass, it increases endurance, and it may therefore improve athletic performance.
  
TESTOSTERONE IN WOMEN:
 Testosterone for women has the same beneficial effects as it has for men.
It improves well-being, energy, strength and endurance. It improves body composition, decreases visceral and subcutaneous fat, and improves bone density. It maintains muscle mass which helps maintain better metabolism. This is beneficial for prevention of diabetes and heart disease. It may improve sexual function and increases orgasmic ability. It increases collagen in skin with increased skin thickness, improved texture, decrease in wrinkles and decrease in fat deposition and cellulite. 
It is indicated for any woman who wants to improve health, wellness, strength, confidence aesthetics, metabolism, fat loss, sexual function, and breast cancer protection.
It is contraindicated in pregnancy, planned pregnancy, breast feeding, and physician resistance!
  
HOW TESTOSTERONE IS SUPPLIED:

1. There are commercial creams that tend to be lower in delivery capability because the percentage mixed in cream is of a lower concentration.
2. There are compounded bioidentical creams that may be applied to skin that deliver higher concentrations.
3. There are injections that deliver higher concentrations but there is a peak and trough effect with levels that go up and down.
4. There are pellets that are surgically placed under the skin that can last for over 3 months.

 
My preference is with the compounded creams because they are well absorbed, maintain higher and consistent levels without a “peak and trough” effect.
 
CONCLUSION:
 When the full literature is reviewed and studied, the overwhelming trend is very much in favor that testosterone at a minimum does not harm in terms of cardiovascular risk, and indeed there is an abundance of evidence that it offers significant benefit to cardiovascular risk factors, and outcomes. The 2 papers that suggested a negative interaction have been highly criticized and found to be flawed in their presentation, analysis, and conclusions. There are several dozen papers in the literature that show significant benefit. Additionally, are the added benefits of well-being, energy, libido, sexual function, muscle mass, diminished fat, skin tone, improved bone density. 
 
This is a hormone that is intrinsic to both males and females. It offers benefits to both.
 
However, only males have prostates and this is another area where misinformation and confusion abound in the relationship of testosterone to prostate cancer. I will next go into a full discussion of this topic-something the medical community at large does not know much about- in my next blog, which will follow shortly.