Testosterone: The New Anti-Aging Wonder Drug?

by Rebecca Shatsky, MD 2011 | shatsky@myhousecallmd.com

Since the advent of Viagra, the field of Men’s Health seems to have grown by leaps and bounds. Topics that were once taboo like erectile dysfunction and low libido are now being addressed and treated more effectively than ever before. However, while the field has seen its successes recently, there are still a number of questions that are just beginning to receive the attention they deserve as valid medical issues. One of the most hotly debated topics currently is testosterone deficiency and replacement. Historically, testosterone was used in high doses as an anabolic steroid by athletes and body builders, a practice that was banned in 1990 due to various sports industry scandals. Recently, however, questions have arisen as to whether low doses of testosterone might be helpful for middle aged and elderly men whose testosterone levels have begun to decline due to aging or chronic disease. There are already million dollar ad campaigns plastered all over popular magazines encouraging men to ask their doctors about “low T.”  It’s clear that drug companies are hoping testosterone replacement will be the next big blockbuster moneymaker, but is it the right treatment for those with low testosterone?

While testosterone deficiency is finally receiving recognition as a serious medical condition, testosterone replacement therapy, like all medical therapies, is not without risk (and for certain groups of men it may be downright dangerous).  Before you make any decisions on testosterone replacement, we at House Call, MD want to provide you the most recent research to guide your decision. We’ll give you the lowdown on what causes low testosterone, review who is at risk for low T and outline the potential risks and benefits of treatment.

What causes low testosterone?

Testosterone belongs to a group of hormones called androgens. Androgens are responsible for normal growth and development of male reproductive organs, including the penis, testicles, scrotum, prostate, and seminal vesicles. Androgens, and testosterone in particular, also function to produce what we call “secondary sex characteristics” which include body hair, musculature, fat distribution and development of mature vocal cords.

Production of testosterone occurs primarily in the testes. The production of testosterone by the testes is regulated by the hypothalamus and pituitary in the brain in a complex hormone feedback pathway called the Hypothalamus-Pituitary-Gonadal (HPG) axis. When the body fails to produce adequate levels of testosterone to support sexual function, muscle mass and secondary sex characteristics, we call this hypogonadism. Hypogonadism (also known as androgen deficiency) can be caused by a problem anywhere along the HPG axis.

Testosterone production in men increases rapidly at the onset of puberty and then appears to decrease steadily after age 45. Some have described the decrease in testosterone production with aging as “male menopause,” or more fittingly “andropause.” However, unlike female menopause, the decline in male testosterone production and overall androgen sensitivity happens so gradually that most men are not affected by the change.

Decreased levels of testosterone in the adult male can have a variety of negative affects on your body including decreased size of the testes, loss of body hair, reduced sexual desire, erectile dysfunction, decreased muscle mass, depression, reduced bone density and infertility…all the unfortunate effects of aging that men dread. On the other hand, many men have low blood testosterone levels and have no signs or symptoms at all, throwing a wrench in the debate over the effects of “low T.”

Who is at risk for low testosterone?

Recent research has indicated that certain groups of men are more likely to suffer from testosterone deficiency than others. Specific groups identified include men suffering from obesity, high blood pressure, type II diabetics, high cholesterol, osteoporosis, prostate disease, COPD or HIV (2).

The actual prevalence of hypogonadism is difficult to determine because past studies have used different criteria to diagnosis the condition. One of the largest studies on the topic (published in International Journal of Clinical Practice) evaluated 2146 men over the age of 45 for serum total testosterone and found the prevalence of low serum testosterone to be 38.7%.  That’s a lot of men.  According to this study, which only evaluated serum testosterone levels without correlating them to symptoms nearly 4 out of every 10 men over the age of 45 has low testosterone (5). However, data suggests that when the diagnosis includes both symptoms of hypogonadism (low libido being the most commonly reported symptom) as well as low blood total testosterone, the prevalence is actually much lower – between 12 and 15% (1). This data indicates that a large proportion of men with low blood testosterone are asymptomatic, which raises the question of whether they should be treated or not.

When should low testosterone be treated?

Like any medication, testosterone therapy has potential risks and benefits. For men suffering from severe hypogonadism (not just low blood levels), testosterone replacement therapy can improve libido and may increase strength and muscle mass. The development of increased muscle mass can be especially beneficial for men with diabetes, high blood pressure, high cholesterol and obesity (the constellation of signs frequently referred to as metabolic syndrome)(3).  However, the complex relationship between these diseases and low testosterone is still under investigation so, for now, the presence of metabolic syndrome alone is not an indication for testosterone replacement therapy.

What about the safety of testosterone replacement?  The safety of low dose testosterone therapy has recently been called into question. A new study in published in The New England Journal of Medicine in July 2010 linked testosterone replacement therapy to increased risk of cardiovascular events including heart attack and stroke.  The study, which compared the overall health of 3369 men receiving 6 weeks of testosterone replacement vs. a placebo actually had to be stopped because the treatment group (those receiving testosterone and not the placebo) had a very high rate of heart attack and stroke (6). There is debate about whether the increased risk of cardiovascular disease in this study can actually be attributed to testosterone therapy and not chance alone and the final verdict is still out.  The study clearly does tell us that we need more long term studies before testosterone replacement can become a standard therapy prescribed by primary care physicians without consultation from endocrinologists who specialize in the condition.

In addition to the potential cardiovascular risks, testosterone therapy is not currently recommended for men with a history of prostate cancer, with a first degree relative who suffered from prostate cancer or those considered to be high risk for the disease. The prostate is a testosterone-sensitive organ (meaning its activity and growth is affected by blood levels of testosterone) and while long-term studies are still inconclusive, it is possible that taking testosterone could further increase the incidence of prostate cancer.

Another question that has yet to be conclusively answered is whether testosterone replacement is actually an effective treatment for men with moderately low testosterone. One of the major confounding factors in the low testosterone debate is that the symptoms of low testosterone are extremely vague and the correlation between symptoms and blood testosterone levels is highly variable. While both testosterone injections and topical gels currently prescribed will increase levels of testosterone in your blood, the symptomatic relief patients receive from therapy does not always coincide well with those measured blood testosterone levels.  Very frustrating, we know.

Low T: The Take Home Message

As our population ages and the average lifespan increases, we are naturally seeing a push for research on improvements in the health and quality if life of our aging population. Even though women live an average of 5-7 years longer than men, research has focused primarily on hormone replacement therapy for the postmenopausal female. Only recently has the field of Men’s Health begun to grow and address common problems that affect the aging man and the specific issues that were previously underreported or thought to be a normal part of growing old.  It’s about time men spoke up!

According to the new 2010 Endocrine Society Guidelines, testosterone replacement therapy is currently indicated for men who suffer from both symptoms of hypogonadism and low measured morning total testosterone levels (2). The key here is that, given the conflicting data and potential risks, only significantly symptomatic males with proven low levels of testosterone should be treated.  Yes, it’s a little disappointing to hear that testosterone therapy is not the new anti-aging wonder drug that it has recently been publicized to be.  At the same time, the topic is definitely an open book with many chapters that have yet to be written.  Only time and carefully designed long-term research will determine what the futures holds for the treatment of low T.

Questions? E-mail the Author: shatsky@myhousecallmd.com

References

1. Araujo AB, O’Donnell AB, Brambilla DJ, et al. Prevalence and Incidence of Androgen Deficiency in Middle-Aged and Older Men: Estimates From the Massachusetts Male Aging Study. The Journal of Clinical Endocrinology & Metabolism. 2004;89:5920-5926.

2. Bhasin, S., et.al. Guidelines for Testosterone Therapy in Androgen-Deficient Men. The Journal of Clinical Endocrinology & Metabolism. 2010; 95(6):2536-2559.

3. Dhindsa S., Prabhakar S, et. al., Frequent Occurrence of Hypogonadotropic hypogonadism in Type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism. 2004;89(11):5462-5468.


4. Kelleher S, Conway AJ, Handelsman, DJ. Blood testosterone threshold for androgen deficiency symptoms. The Journal of Clinical Endocrinology & Metabolisim. 2004;89:3813-7.

5. Mulligan T,. Frick MR,. Zuraw QC,. Stemhagen A,. McWhirter C., Prevalence of Hypogonadism in Males Aged At Least 45 Years: the HIM Study. International Journal of Clinical Practice. 2006; 60: 762-769.

6. Wu, FC, A. Tajar, JM Beynon, SR Pye, and AJ Siman. “Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men.” The New England Journal of Medicine 363.2 (2010): 123-35.

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