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New Health Concerns About Testosterone

April 7th, 2009 · No Comments

Nearly all of the educational material relating to the use of testosterone or other anabolic steroids (AAS) relates to possible adverse (negative) side effects. The field has been dominated by dogma and speculation for decades, as the number of AAS users is limited. Generally they are healthy young adult men; use is commonly moderate in regards to dose and duration; and the culture of AAS use is not conducted openly due to legal and social consequences. Posters hang in locker rooms and speakers aim their lasers at PowerPoint presentations to focus upon the reasons not to use AAS. Educational programs regarding the risks involved with AAS use are important, as adults should be fully informed before making a decision regarding the use of powerful hormonal drugs, especially at doses exceeding the normal physiologic range.

Unfortunately, as most programs are targeted at adolescents who should not have access to AAS, the message is often focused upon the more extreme and dangerous practices of irresponsible and risk-taking youth. Further, many of the organizations involved in “steroid education” are funded through grants or donations; a more dramatic message of the risks and inflating the number and youth of users increases the urgency in creating emotional and financial support for anti-doping agencies. This bias is transmitted to the public as the media depends on “authoritative sources” for news.

AAS users were subjected to a misinformation campaign during the 1980s and 1990s. Prescription drugs, such as AAS, include a package insert which describes in tiny print how the drug works, signs of adverse effects and how the drug should be administered. Ideally, the information is based upon science and clinical trials. Sadly, pharmaceutical companies inserted a statement near the beginning of each package insert of AAS that stated “anabolic steroids have not been shown to enhance athletic ability.” This blatant attempt at deception failed as AAS produce obvious gains in strength, mass and aggression— all components that tie directly to improved performance in many sports; also, many users were not performance athletes, but bodybuilders or people seeking to improve their appearance, so the statement was not a deterrent; additionally, as government enforcement increased, the majority of AAS originated from Mexican and Chinese sources and did not include a package insert. Not only did athletes and bodybuilders continue to use AAS, but they also lost all faith and trust in medical professionals and government agencies.

Little legitimate research has been performed on AAS use at concentrations that would provide anabolic responses in healthy adult males. Universities and other research institutions would not allow scientists to provide controlled amounts of AAS in supraphysiologic doses (higher than the normal range of testosterone produced by the body) to subjects. Instead, research either involved replacement doses of testosterone or even subphysiologic (lower than normal) doses; these studies provided no relevant information. Other studies were allowed that followed AAS users during their own self-selected and self-purchased cycles. The downside to this is that the drug use pattern varies greatly between subjects in the same study and black-market drugs vary considerably in purity, making the results difficult to interpret. The end result? AAS users remain in the dark about AAS risks and benefits, as well as threshold values defining the therapeutic range (the range in which benefits occur and risks are minimal).

Recently, there has been an increase in studies examining AAS users or providing healthy young adult men or older men supraphysiologic testosterone. Controlled studies have been consistent in showing benefits in healthy young men using up to 600mg/week of testosterone enanthate with no significant adverse effects.1,2 Long-term hormone replacement surveys have been published showing therapeutic benefits without significant adverse effects for periods of several years using newer formulations, such as topical gels or long-acting testosterone esters.3-5 Also, certain negative associations are being challenged, such as the relationship between testosterone and new prostate cancer (testosterone can promote the growth of existing prostate cancer).

New Findings
Yet, not all is sunny in androgen-land. New evidence using more sensitive tests and imaging technologies are revealing potential risks of supraphysiologic (higher than normal doses, such as used by a bodybuilder to increase muscle mass) androgen use. The most interesting research relates to potential changes in heart function and the cardiovascular system. Long-standing concerns mentioned in medical journals are changes that AAS cause in good and bad cholesterol, as well as triglycerides (fats) in the blood.7,8 These changes have been noted in individual reports and small case series, but the findings are not consistent. Remember, AAS is a large group of similar drugs but there remain very important differences among the individual drugs; some are easily aromatized, others resist conversion to estrogen; some become more androgenic after reacting with the enzyme 5alpha-reductase, others become less so; many are 17alpha-alkylated to be taken orally which increases the risk of liver problems; some are released rapidly, which creates huge swings in androgen concentrations…others are released slowly over days or weeks, etc. Further, as underground or black-market use of AAS involves no medical screening or supervision, it is probable that many people have used the drugs who may have had a pre-existing condition that predisposes one to a negative response.

Nonetheless, there is some risk that long-term use of AAS, especially at supraphysiologic levels, may increase the risk of atherosclerosis (blockage of the arteries that increases the risk of heart attack, stroke, etc.), especially in people who are already at risk due to family history or who have high levels of bad cholesterol or triglycerides off-cycle. Of course, there have been challenges that the actual AAS-associated risk is overstated as cholesterol and triglyceride levels quickly return to baseline levels off-cycle; thus an otherwise healthy person would incur little, if any, additional risk from cyclical use of AAS over the long-term.9 The question remains unanswered due to the lack of research support in this area.
The putative (assumed) effect of AAS on atherosclerosis has been noted for some time, as has another putative cardiovascular effect, high blood pressure. Anyone who has had much exposure to AAS-users has seen users who become bloated and develop a reddish-hue to their skin tone (if they have a fair skin complexion). Though it is rarely reported, some individuals develop an increase in blood pressure on-cycle. At times, this increase can escalate to dangerous levels, which increase the risk of rupturing a blood vessel in a vital organ like the brain or potentially kidney damage if the condition goes unnoticed or untreated for a long time. High blood pressure also strains the heart, which is a unique type of muscle. Under a higher stress load, heart muscle enlarges, just like the biceps or pecs do with weightlifting. Interestingly, AAS users see a greater degree of enlargement than non-AAS using bodybuilders, suggesting that the heart is either under greater stress and/or the heart muscle hypertrophy is enhanced by AAS. While a larger, stronger heart may sound like a good thing, the degree of hypertrophy (growth) can become too great to allow the heart to pump blood efficiently and the pattern of muscle growth may impede the flow of blood into the circulation (concentric v. eccentric cardiac hypertrophy).
A recent review published in the journal Kidney & Blood Pressure Research attempts to clarify the effect of testosterone on blood pressure.11 The authors discuss the complex interaction of testosterone on the physiology that may influence blood pressure, concluding that though testosterone protects against, as well as promotes, high blood pressure, the net effect [they conclude] is that testosterone promotes hypertension. The paper presented both supportive and contradictory research to its credit, but relies heavily upon animal research and hormonal treatment of transsexuals (genetically female patients (women) undergoing surgical and hormonal conversion to become men). In spite of the breadth of its research, the dependency of the review on animal and female testosterone exposure makes it difficult to consider the conclusion as final. The authors acknowledged as much in the conclusion, “However, findings of experimental trials are often species specific and cannot simply be applied to the human organism.”11

Complications?
Another androgen-related factor that complicates blood flow and raises the potential risk for life-threatening blood clots is the blood itself. Most people think of blood as a liquid since that is the form most often encountered. However, when viewed under a microscope, blood is seen to contain a number of cells, including red blood cells that carry oxygen, white blood cells involved with immune function and platelets that help with clotting. Normally, the red blood cells (which are solid particles) do not take up more than half of the space in the blood vessels. When there are too few red blood cells, less oxygen is available and people feel fatigued, a condition called anemia. Having too many red blood cells can also be a problem, as the blood becomes thick and tends to clot in smaller vessels. Instead of flowing like water, the blood moves sluggishly like maple syrup. “Thick” blood (erythrocytosis) increases the risk of stroke and other dangerous blood clots. Erythrocytosis is the most common adverse event reported in men receiving testosterone therapy and is particularly worrisome among elderly men, as was evidenced in a recent study published in the Journal of Clinical Endocrinology and Metabolism.12 Young adult and middle-aged men receiving testosterone enanthate tolerated up to 600mg/week without any significant problems. However, men 60-75 years of age experienced a significant rate of erythrocytosis at 600mg/week; lower doses up to 300mg/week were well tolerated. However, even younger users should still exercise caution, as the study revealed that the peak in erythrocytosis is later at high doses.

As mentioned earlier, not only are the arteries and circulation of the blood potential targets of androgen action, the heart itself can be affected by AAS. Studies have shown AAS users to have larger hearts than non-using bodybuilders or sedentary people and there is some concern that the degree and pattern of the heart enlargement may predispose AAS users to a greater risk of ischemia (poor delivery of oxygen to the working heart muscle) or conduction abnormalities (the heartbeat is regulated by an electrical signal that transmits through the heart and scarring in the heart muscle can interfere with the signal).13,14 Interestingly, some studies suggest these changes may be reversible.14,15 However, the contribution of AAS may be overstated, as a recent study in the New England Journal of Medicine identifies 10 genes that are associated with cardiomyopathy and early ventricular hypertrophy in children.16 Athlete’s heart and sudden cardiac death in young athletes is a major concern regardless of AAS use.17 Clearly, AAS appear to have an anabolic effect on heart muscle as well, so properly screening individuals is necessary to minimize risks.

One last concern that will be discussed in this article is the function of the heart. Even as the structure of the heart is changed due to the combined hypertrophic effect of exercise and AAS, so too is the way the heart muscle works. Initially, no change in heart function was noted in early studies comparing users to non-users.18 However, advances in technology are allowing cardiologists (heart doctors) to view and measure heart function with greater resolution. As a result, slight changes are being picked up and reported. The significance of these discrete changes remains to be determined, as they are only detectable using high-powered scans and do not appear to be related to exercise tolerance or classical measures of heart function. Specifically, the change noted is a slowing in diastolic relaxation, meaning the heart is slower to relax after “squeezing” to pump the blood out of the heart.14,19,20 The relaxation phase is the time when the heart refills to pump the next pulse of blood. If this was to become exaggerated, the heart would pump less blood with less force, exercise tolerance would drop and the health, even survival of the individual could be compromised. Thankfully, the subjects in one study who measured exercise tolerance showed AAS-using exercisers exceeded the sedentary control subjects, even though non-AAS-using subjects outperformed the AAS users.14

What is the take-home message from this growing body of data? Simply that the depth of knowledge regarding AAS use remains shallow and uncertain. Much of the blame lies on the shoulders of the numerous administrations who have ignored the therapeutic potential of testosterone and other AAS, as well as the public exposure to illicit use, not only failing to fund important clinical research, but impeding research through the disincentive challenges of social, legal and regulatory scorn.

For the person using testosterone or AAS, these studies exemplify the strong need to follow the medical literature and be as informed as possible about the possible risks of AAS use. Thus far, there has not been an epidemic of AAS users dropping dead, but the increase in premature heart disease and deaths among bodybuilders, wrestlers and other entertainers is worrisome. Unfortunately, many of these cases involved the abuse of recreational drugs, making it difficult to determine how much AAS may have contributed. Adults considering the supraphysiologic use of AAS need to be aware that these powerful drugs could have a number of seemingly insignificant adverse effects in the short term that could collectively present a serious challenge to one’s health over the long term. Hopefully, further research will emerge that will clarify these issues and give those interested in AAS use the information necessary to minimize risk and make an informed decision.

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