Testing Testosterone Treatments

 

Whatever is in this water, it isn’t testosterone

Ponce de Leon is said to have been looking for the Fountain of Youth when he explored Florida. That’s only a myth. Now there’s a new myth, that testosterone supplements are a Fountain of Youth for aging men. Men are urged to get their testosterone levels checked if they have any of a long laundry list of vague symptoms. Anti-aging clinics promote testosterone supplementation in many forms: prescription, bioidenticals from compounding pharmacies, natural remedies, testosterone boosters, and precursors. There are highly inflated estimates of the number of men who need supplementation, often relying on broadened criteria for diagnosis or non-standard lab tests. Testimonials abound: “My depression symptoms disappeared in 20 minutes when I started using Androgel.” (That one’s particularly hard to believe. Suggestion can be powerful.)

Until recently, evidence for the benefits of testosterone supplements was scanty, and there was concern about increased cardiovascular and prostate risks and other side effects. A 2013 study found that while testosterone was clearly indicated for younger men with classic hypogonadism caused by known diseases, , a general policy of testosterone replacement in all older men with age-related decline in testosterone levels was not justified. In 2003 an Institute of Medicine panel called for a set of coordinated clinical trials to determine whether testosterone would benefit older men who had low testosterone levels for no known reason other than age and who had clinical conditions to which low testosterone might contribute. The results of those trials are starting to come in. The findings to date were covered in an article in the New England Journal of Medicine in February 2016.  The full text is available online.

Background

Testosterone levels rise at puberty and peak in the late teens and early twenties. Then they decline by about 1% a year. Declining levels are a natural consequence of aging. With age, men have decreases in strength, mobility, sexual function, and energy. Are those decreases due to lower testosterone levels or due to the aging process itself? Wouldn’t it be great if we could prevent many of the consequences of aging by simply keeping testosterone at the levels found in young men? That’s a nice dream, but the reality is otherwise.

Early studies showed that testosterone increases muscle mass. That’s why some athletes, even young men with normal testosterone levels, have used it, sometimes in massive doses. It is on the list of drugs banned from the Olympics. There were inconsistent results from studies of the effects of testosterone on other measures like increased physical performance, sexual function, and energy.

The Testosterone Trials

 The Testosterone Trials set out to resolve the inconsistencies in the evidence. They are a coordinated set of double-blind, placebo-controlled trials being carried out at 12 sites. They were designed to address seven outcomes: sexual function, vitality, physical function, cognitive function, anemia, bone density, and cardiovascular status. The first three of those have been completed.

The trials were large and well designed. Selection of subjects was stringent. They had to be 65 or older, to have testosterone levels below the normal range for men 19-40 years of age, to have symptoms related to predetermined outcomes, and to have none of a long list of contraindications (like high risk of prostate cancer or cardiovascular disease or severe depression). Only 1.5% of those screened were eligible and enrolled. Inclusion in the Sexual Function Trials had several more requirements including self-reported decreased libido. Inclusion in the Physical Function Trial required self-reported difficulty walking or climbing stairs and a gait speed of less than 1.2 m per second on the 6-minute walk test. The Vitality Trial required self-reported low vitality and a score of less than 40 on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACT) scale. They were randomized into two groups and treated with either testosterone gel (Androgel) or a placebo gel with an identical appearance. The Androgel dose was adjusted to keep the serum testosterone levels in the normal range for men aged 19-40. The dose of placebo gel was changed simultaneously to maintain blinding.

The results

There were modest improvements in sexual function but they tended to wane after several months and were not as robust as with Viagra-type drugs. There were small gains in physical performance and in indexes of mood and depression; overall vitality was no better than with placebo. No major toxic effects were observed, although hemoglobin and prostate-specific antigen (PSA) levels were affected. The study was too short and too small to rule out negative outcomes for prostate or cardiovascular health.

As summarized in the accompanying editorial,

The results show that testosterone therapy did yield certain benefits, but at this point their clinical importance is uncertain. Therapy was not a panacea, and the findings alone might be insufficient to support a decision to initiate testosterone therapy in symptomatic older men.

These findings may be used to support treatment of elderly men with very low testosterone levels. But they may not apply to younger men, those with not-so-low testosterone levels, those with risk factors for prostate and cardiovascular disease, those without symptoms, or those with symptoms not studied in the trials.

Oversell

Solvay Pharmaceuticals mounted an aggressive campaign to sell its Androgel, claiming that 13 million men suffered from low testosterone, 90% of them undiagnosed.  In reality, only 0.1 percent of men in their forties, 0.6 percent in their fifties, 3.2 percent in their sixties, and 5.1 percent of men in their seventies would meet the criteria for the diagnosis of androgen deficiency.  Never mind. At a chain of Low-T centers, a man can walk in, have his blood drawn, and get his first testosterone injection 30 minutes later. They promise to boost energy, decrease body fat, irritability and depression, and even claim that research has found that testosterone can solve long-term health issues like Alzheimer’s and heart disease. One man was offered a free workup; when he protested that he felt fine, they told him he only “thought” he felt fine.

There are testosterone doctors like Paul Campion, who was first treated and then recruited by Cenegenics. He and his patients plan to take testosterone for life. He charges $5000 for an initial visit and then $1000 a month, with lab tests every 3 months. His aim is to promote well-being, not to treat disease. He says “Testosterone is ridiculously powerful…I can tell you from experience, the feeling of well-being, of focus, and of masculine energy are massively increased. It’s like you’re back to being 35.”

A Harvard urologist named Abraham Morgentaler wrote the book Testosterone for Life. He says

Men have symptoms that are related or possibly related to a deficiency of a hormone and if the symptoms are bothersome, then the men will undergo a trial of treatment and it is often but not always successful…This is what we do in medicine. There is nothing that’s different.

No, that’s not what we do in scientific medicine. What we do is compare the success of treatment to the success of placebo, because we know that a simple trial of treatment may deceive doctors and patients when it is followed by improvement that is not due to the treatment itself.

An FDA investigation found that fully half of men taking testosterone hadn’t been diagnosed with the disease hypogonadism, and a quarter of them were given hormones without a previous blood test.

Natural remedies

Naturopaths use saliva and other non-standard tests to diagnose androgen deficiency, and they treat it with lifestyle and dietary modification, nutrient supplementation, and herbal remedies like Korean ginseng, tribulus, saw palmetto, damiana, oat seed, and liquorice. The evidence for this approach is lacking.

Joseph Mercola of mercola.com also advocates raising testosterone levels by natural means. He recommends zinc, vitamin D, limiting sugar, consuming organic dairy products, high intensity interval training, and controlling stress with Emotional Freedom Technique (rhythmically tapping designated spots on the body with the fingertips). There is some evidence that low zinc levels are associated with low testosterone levels, but zinc deficiency is rare and the other recommendations are not likely to be helpful.

Conclusion

The other four studies in the Testosterone Trials (on cognitive function, anemia, bone density, and cardiovascular status) are still in progress, and we can look forward to learning more from them. At present, all we can conclude is that for men over 65 who have the specific symptoms studied, who are at low risk of prostate and heart disease, and who have testosterone levels below 275 ng per deciliter, raising testosterone levels to the normal range for men aged 19-40 has modest benefits. There is no good evidence to support treatment for men younger than 65, men with higher levels of testosterone, men at higher risk of prostate and heart disease, and men with other symptoms or no symptoms. The risks remain uncertain. The side effects are not limited to the patient himself: if women or children come into contact with testosterone gel or to a man’s unwashed hands after he has applied it, it can cause hair growth, menstrual irregularity, and premature puberty. It has even been reported to cause aggressive behavior in pets.

There is no evidence to support using bioidentical hormones from compounding pharmacies, natural remedies, testosterone boosters, or precursors like DHEA.

Clearly, a lot of men are taking these products for indications that are not evidence-based. An article in Atlantic likened it to a “mad T party.”  Let’s guard against turning a natural phenomenon of aging into a disease. Testosterone may be useful when prescribed appropriately for symptomatic androgen deficiency, but it is clearly no Fountain of Youth; the hype has far exceeded the reality.

from Science-Based Medicine http://ift.tt/1pGZmce