Testosterone Replacement Therapy… is it the new FOUNTAIN OF YOUTH?

Drug commercials promise men with low testosterone relief from decreased sex drive, loss of energy, and moodiness. It appears the message has hit home as use of testosterone replacement therapy has skyrocketed over the last 10 years.

The number of men over age 40 prescribed treatment for “low T” has tripled since 2001, according to a study published this June in JAMA Internal Medicine that tracked prescriptions of more than 10 million men from one of the nation’s largest health insurers. Use of testosterone therapy has increased from 0.81% of men in 2001 to 2.9% in 2011.

The increase in prescriptions was seen in men of all age groups. And of the four forms examined — topical gel, skin patch, oral forms, and injectables — the use of testosterone gel had the highest boost in prescriptions with more than a fivefold jump.

“We believe this trend has been driven, in large part, by direct-to-consumer marketing campaigns targeting middle-aged men, the rapid expansion of clinics specializing in the treatment of low testosterone, and the development of new drugs and improved delivery mechanisms, particularly transdermal gels,” explains Jacques Baillargeon, PhD, of the University of Texas Medical Branch at Galveston, who was the study’s lead author.

Martin Miner, MD, clinical associate professor of Family Medicine and Urology at the Warren Alpert School of Medicine at Brown University, agrees there has been a huge spike in testosterone use but adds that one issue highly resonant with clinicians who prescribe the therapy is that today’s baby boomers want to remain more active as they age.

“They are replacing joints, stenting arteries, and enjoying arduous exercise,” Miner says. “Testosterone replacement therapy improves mobility in aging men, improves lean body mass, muscle mass, and bone strength.” Miner led another recent study appearing in Postgraduate Medicine that observed men who took 1% testosterone gel for 12 months.

Testosterone therapy is specifically approved to treat abnormally low testosterone levels associated with symptoms and signs caused by low testosterone, a condition known as male hypogonadism. Blood tests determine whether testosterone levels are in the normal range, generally 300 to 1,000 ng/dL, but what’s “normal” may differ depending on the laboratory that conducts the test, according to The Endocrine Society’s Clinical Guidelines. Testosterone levels decline about 1% – 2% each year as men age, the guidelines report. And some studies estimate that almost 14 million men in the U.S. over the age of 45 have below normal testosterone levels.

A Rush to Prescribe?

The recent spike in prescriptions has some questioning whether physicians are becoming too eager to give men the replacement therapy. Are male patients just looking for the fountain of youth? Is testosterone becoming the latest sex-enhancing drug?

In the JAMA Internal Medicine study, researchers found that hypogonadism, in fact, was not the only diagnosis driving the prescription of replacement therapy. Only half of the men were diagnosed with hypogonadism. Diagnosis of fatigue made up 34%, erectile dysfunction 31%, and psycho-sexual dysfunction was nearly 12%. What’s more, the study reported that a quarter of the men did not have their levels tested before they were prescribed the hormone.

These facts contradict The Endocrine Society’s Clinical Practice Guidelines that recommend testosterone treatment only in men with “consistent symptoms and signs and unequivocally low serum testosterone levels.”

Karen Herbst, PhD, MD, associate professor at the University of Arizona, says that because testosterone testing is not a routine test done during an annual exam, men need either to have some signs or symptoms that would prompt the provider to measure the testosterone level or they have to ask to be measured themselves.

“I think if a man came in and said ‘I’m more fatigued now than I was before, my libido is a little bit down, and my erections aren’t as hard,’ those three things would definitely prompt a provider to measure it,” says Herbst.

Weighing the Risks

Safety information on the popular topical gel warns users about the potential risk to their female partners and children who may come into contact with testosterone remaining on the skin surface of the application site of the gel. It’s a danger that worries many of its users.

The risk to family members is a definite concern, says Herbst. “If my patients choose the gel, the next thing I do is explain how to avoid transferring,” she explains.

Herbst says that although prescribing information cautions users to avoid contact for at least an hour, she tells patients to boost the wait time up to four hours and gives strict instructions on wearing t-shirts and washing hands after applying.

Transferring is not the only concern. For men who choose testosterone skin patches, irritation is a common complaint, as is pain at the injection site for those who take testosterone injections.

Research studies have investigated the risks using all forms of testosterone therapy and the well-known list of potential side effects include increased risk of prostate cancer, swelling, enlarged breasts, worsening of sleep apnea, and blood clots.

“There are a number of side effects with testosterone including erythrocytosis, so we monitor their hemoglobin or their hematocrit,” says Herbst.

A 2010 systematic review published in the Journal of Clinical Endocrinology and Metabolism of 37 randomized, controlled studies found testosterone replacement did cause an increase in hemoglobin, hematocrit, and PSA and a decrease in HDL cholesterol.

Infertility is also a concern for young men because another common side effect of therapy is lowered sperm count. Glenn Braunstein, MD, Cedars-Sinai’s vice president of Clinical Innovation, says a reduction in testicular size is another consequence.

“It is important in evaluating a male with infertility associated with oligospermia or azoospermia to ask about testosterone or anabolic steroid use,” says Braunstein. “If a patient who initially had normal testicular function has used exogenous androgens, it often takes three months and some times even up to a year for normal testosterone and sperm production to recover.”

In efforts to preserve fertility in young men with hypogonadism, many doctors are turning to alternative medications to testosterone (see sidebar left).

Observing the Benefits

While there are several risks of testosterone replacement, the therapy has proven beneficial for many men. In their study, Miner and his colleagues found men on testosterone therapy had positive health outcomes after one year of use.

The researchers followed more than 800 men, between the ages of 21 and 85, who used either 5 or 10 grams of testosterone gel per day. The men had significant improvements in sexual function and mood after three months. By 12 months, their body mass indexes, waist circumferences, and glucose levels improved as well. And while there was a significant increase in the mean PSA levels over 12 months, the researchers concluded the changes were “well within guidelines.”

“PSA changes with testosterone are rather negligible and are based on the degree of testosterone deficiency present,” Miner explains. “Usually, if PSA rise does not exceed 0.4 ng/ml, men do not usually experience an exacerbation of their lower urinary tract symptoms.”

A 2013 randomized, controlled study in the Journal of Clinical Endocrinology and Metabolism also found men over age 60 who used testosterone gel had improved fat mass and upper body strength after 12 months compared with the placebo group.

Yet, the controversy over the therapy continues. Experts emphasize that all the benefits and risks of testosterone therapy are unknown due to the lack of large-scale, long-term clinical trials. Many in the field are anticipating more answers next year, however, with the conclusion of The Testosterone Trial, an National Institue on Aging (NIA)-sponsored randomized, doubleblind, placebo-controlled study being conducted in 800 men, aged 65 and older, from 12 cities across the U.S. The trial promises to determine if testosterone gel treatment (vs. placebo) will improve their walking, vitality, sexual function, memory, blood count, and cardiovascular risk. Participants will be followed for one year during the trial and followed up for one additional year.

— Fauntleroy is a freelance writer in Carmel, IN, and a regular contributor to Endocrine News.

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