Steroids - The Unknown Side Effect?

They May Help You Live Longer

  steroids are the most widely used performance-enhancing drug. Elite bodybuilders have been using anabolic steroids to build muscle mass and strength for quite some time now.¹In fact, the use of anabolic steroids has likely increased over time, as one study investigating their use by competitive bodybuilders showed that 77 percent of the respondents reported using anabolic steroids. While anabolic steroid use is very high among topflight bodybuilders, the truth is the vast majority of steroid users are not elite bodybuilders or professional athletes, but rather, individuals simply wanting to look leaner and more muscular. In fact, steroid use in America has become quite the public health problem, with roughly 3 million individuals in the United States having utilized these drugs.²

Muscle-Building Impact of Steroids

The reason for the widespread consumption of anabolic steroids is they do, indeed, vigorously enhance muscle growth and strength. The primary anabolic effect from anabolic steroid use is caused when the steroid molecule binds and activates the steroid receptor within the muscle cell, which alters the shape of the steroid receptor. The change in shape of the activated steroid receptor causes it to translocate into the nucleus of the muscle cell, where it can directly bind to DNA— triggering the production of certain protein molecules within the muscle cell that have the ability to increase muscle growth and strength. For instance, one of the target proteins synthesized in response to anabolic steroid use is the muscle protein follistatin, which directly blocks the negative effects of the muscle-depleting molecule myostatin, which ultimately results in muscle growth.³

Adverse Side Effects From Steroid Use

The positive influence on muscle growth from anabolic steroid use does not come without negative side effects, as anabolic steroids also trigger protein synthesis in non-muscle cells, such as the prostate, which promotes the unwanted enlargement of the prostate gland— increasing the probability of developing prostate cancer. Anabolic steroids have also been shown to dramatically impair cardiac function by pathologically increasing cardiac muscle hypertrophy, which decreases the capacity of the heart to pump blood throughout the body.⁴In addition to the undesirable effects of anabolic steroids on the function of cardiac tissue, steroids— particularly the 17-alpha-alkylated anabolic steroids like Anadrol⁵— reduce the levels of high-density lipoprotein cholesterol (the “good cholesterol”) while increasing low-density lipoprotein cholesterol levels (the “bad cholesterol”), which is a well-established blood lipid profile associated with cardiovascular disease.⁶

Juiced-Up Telomeres Fights Illness and Increases Life Span

So, how is it possible for anabolic steroids to increase life span when they have been connected to all of these life-threatening diseases? Well, as previously mentioned, anabolic steroids directly influence gene expression by activating the steroid receptor, which turns on the expression of many different genes. One of the many genes that can be cranked up by anabolic steroids is the gene for an enzyme called telomerase— which, in certain cases, can improve health and increase life span.

The improved well-being associated with telomerase function occurs because telomerase maintains the length of the end segments of every chromosome in your body. These end regions of your chromosomes— known as telomeres— become shorter every time a cell divides, which happens readily, and telomerase maintains its length as best as it can for as long as it can. However, over time, telomerase is simply unable to maintain the complete telomere length— as shortening of the telomeres caused by cell division eventually outpaces the telomere-replenishing activity of telomerase, gradually resulting in shorter telomeres. Eventually, telomeres shrink to a length that causes enough of a genetic insult that cells die, which ultimately leads to a decline in tissue function, organ function and overall health as we grow older.

In addition to the normal shortening of the telomere, some individuals have genetic defects that exacerbate telomere erosion— causing a more rapid decrease in telomere length, triggering certain diseases such as bone marrow failure, live cirrhosis and pulmonary fibrosis.⁷ As previously mentioned, certain anabolic steroids improve telomere length, providing a potential therapeutic for telomere-related diseases. In fact, one study by Townsley et al. showed that subjects genetically prone to shorter telomeres had a significant increase in telomere length after being orally administered the anabolic steroid danazol.⁷ Danazol, by the way, was a steroid used by male bodybuilders many decades ago because of its anti-estrogen qualities. At any rate, the results of this study clearly indicate that certain anabolic steroids may be able to mitigate disease resulting from eroded telomeres by increasing telomere length— and because shorter telomeres reduce life span, perhaps anabolic steroids could also increase life span by increasing telomere length.

Telomere Length Has to Be Just Right

Well, it turns out, just like everything else in biology, the influence of anabolic steroids on health and longevity isn’t that straightforward. While there is plenty of evidence that shorter telomeres have been associated with many premature aging diseases⁸ and, to the contrary, longer telomeres in white blood cells reduce the likelihood of dying from certain cancers⁹, too much telomerase activity from anabolic steroid use generating longer telomeres can be just as deleterious to your health as telomeres that are too short.

That is because excessive telomerase function can actually help cancer cells survive¹⁰, as cancer cells are extremely susceptible to cell death triggered by short telomeres. That is because cancer cells divide a lot, making them prone to shorter telomeres that could trigger the cancer cell to die. Therefore, if one triggers telomerase activity by taking certain anabolic steroids, one might increase the length of telomeres in certain cancer cells— improving their viability, likely resulting in more cancer growth.

So, to reduce the risk of cancer and improve overall health and longevity, it seems that we need an intermediate level of telomerase activity. Thus, the capacity of certain anabolic steroids may improve the health of those with telomere-shortening diseases, and these potent muscle-building drugs will likely increase telomere length in healthy individuals— excessively improving the probability of developing life-threatening diseases such as cancer, and ultimately reducing the ability to live a long and healthy life.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

References:

1. Michel G and Baulieu EE. Androgen receptor in rat skeletal muscle: characterization and physiological variations. Endocrinology 1980;107, 2088-2098.

2. Pope HG Jr, Wood RI, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev 2014;35, 341-375.

3. Simental JA, Sar M, et al. Transcriptional activation and nuclear targeting signals of the human androgen receptor. J Biol Chem 1991;266, 510-518.

4. Benten WP, Lieberherr M, et al. Testosterone induces Ca2+ influx via non-genomic surface receptors in activated T cells. FEBS Lett 1997;407, 211-214.

5. Ceballos G, Figueroa L, et al. Acute and nongenomic effects of testosterone on isolated and perfused rat heart. J Cardiovasc Pharmacol 1999;33, 691-697.

6. Bhasin S, Woodhouse L, et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab 2005;90, 678-688.

7. Townsley DM, Dumitriu B, et al. Danazol Treatment for Telomere Diseases. N Engl J Med 2016;374, 1922-1931.

8. Gomes NM, Ryder OA, et al. Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination. Aging Cell 2012;10, 761-768.

9. Willeit P, Willeit J, et al. Telomere length and risk of incident cancer and cancer mortality. Jama 2010;304, 69-75.