As people age, they often encounter new health problems. One of the challenges for men and women growing older is how these changes are dealt with, including navigating the world of treatment options that are often available.
Low testosterone can lead to erectile dysfunction, reduced sexual desire and infertility.
When men get older, many notice significant differences in their sex drive, weight, emotion and energy levels. These changes, often occurring when men reach their late 40s and early 50s, have prompted comparison with the female menopause.
Sometimes these changes are attributed to reduced levels of testosterone – the male sex hormone produced predominantly by the testes. Men with reduced testosterone levels can experience benefits with testosterone therapy, with many physicians able to prescribe replacement testosterone in the form of injections, patches, pellets and gels.
However, the use of testosterone therapy is fiercely debated – particularly when low testosterone levels are associated with age – with clinicians concerned about when treatment is appropriate and what its risks and benefits are.
In this Spotlight feature, we have a look at circumstances that might warrant the use of testosterone therapy and investigate different viewpoints from both sides of the current debate.
The ‘male menopause’
One major aspect of the debate is how the drop in testosterone is discussed. In many news stories, the terms “male menopause” and “andropause” are used on account of the fact that most of the symptoms associated with declining testosterone levels are similar to those caused by the female menopause.
Low testosterone can lead to changes in sexual function, including reduced sexual desire, erectile dysfunction and fewer spontaneous erections. Other physical changes that can occur include increased body fat, decreased bone density and hot flashes.
Emotional changes can also occur, such as a decrease in motivation and self-confidence, as can sleep disturbances such as insomnia.
However, the timeframe over which these changes occur is a major difference between what is experienced by women and many men. Whereas the female hormone levels fall over a short period of time, male testosterone levels typically decline gradually over a period of many years.
Dr. Abraham Morgentaler, an associate clinical professor of urology at Harvard Medical School in Boston, MA, told Medical News Today that the terms are problematic in that they set up a parallel with the female menopause that is obviously incorrect. However, he believes the terms do have some use.
“On the other hand, what is valuable about these terms is that they convey to the public a condition that has strong similarities to something they already know, making it easier to understand,” he explained.
Testosterone levels decline in men as they grow old as part of the aging process, typically falling by around 1% each year after men enter their 30s. However, testosterone levels can also fall as part of a disease known as hypogonadism, caused by a problem with the testicles or pituitary gland.
Central to the debate over using testosterone therapy to treat perceived symptoms of hypogonadism is whether or not observed biological changes are a result of a decline in hormone concentrations caused by reproductive system pathology or merely the result of aging (aging-related hypogonadism) or other conditions, such as thyroid problems and alcohol use.
Testosterone therapy can reverse the effects of hypogonadism. However, the use of testosterone therapy in otherwise healthy men who are experiencing symptoms caused by reduced levels of testosterone is subject to passionate debate.
“Unfortunately, passion clouds our ability to assess the evidence on testosterone objectively,” warns Dr. Morgentaler in an article published on Medscape.
Is testosterone therapy dangerous?
Dr. Morgentaler believes that testosterone treatment can benefit patients reporting symptoms associated with reduced levels of testosterone even when there is no documented cause for hypogonadism, such as a pituitary tumor.
“Deficiencies of hormones, such as testosterone, produce certain symptoms,” he writes. “The effect is the same whether an underlying cause is identified or not. Imagine limiting antihypertensive therapy to the minority of men with known causes. This makes no sense.”
An argument for limiting testosterone therapy is a perceived risk of cardiovascular events among men receiving testosterone. Earlier this year, the US Food and Drug Administration (FDA) updated testosterone product labels to detail a possible increased risk of heart attacks and stroke.
Supporters state that testosterone therapy is a proven effective treatment and that cardiovascular risks are overstated.
The FDA recommend that physicians should only prescribe testosterone therapy for men with low testosterone levels caused by disorders of the testicles, pituitary gland or brain that cause hypogonadism.
Prior to this announcement, however, Dr. Morgentaler and colleagues conducted a systematic review of available literature on testosterone and cardiovascular risks.
They found only four studies reported negative concerns while many others suggested several positives, including reduced mortality, increased exercise capacity and improvement in cardiovascular risk factors such as fat mass.
In summary, the researchers concluded that there is no convincing evidence of increased cardiovascular risks with testosterone therapy and, on the contrary, there could be a beneficial relationship between cardiovascular health and normal testosterone levels.
“Although no large, long-term controlled studies have definitively determined risk, the weight of evidence right now strongly favors the [cardiovascular] benefits of having a normal serum testosterone concentration, whether achieved naturally or with testosterone therapy,” Dr. Morgentaler writes.
Overall, there is evidence demonstrating that testosterone therapy can improve symptoms – both sexual and nonsexual – in most men, and Dr. Morgentaler holds that general health may also be improved in symptomatic users.
“Testosterone therapy is good medicine for the appropriate patient,” he writes. “There is value in identifying men who are testosterone-deficient, and offering them a trial of treatment. For the good of men, it is high time to restore the primacy of science to the field of testosterone deficiency.”
This form of treatment is increasingly seen as valuable, by patients and clinicians alike. An estimated 2 million men in the US are currently being treated with testosterone, with the number of prescriptions rising steeply over the past decade.
In an article originally published in the Journal of the American Geriatrics Society, Dr. Thomas Perls and David J. Handelsman, PhD, describe the increases in prescriptions in detail:
“US pharmaceutical sales of testosterone increased from $324 million in 2002 to $2 billion in 2012, and the number of testosterone doses prescribed climbed from 100 million in 2007 to half a billion in 2012, not including the additional contributions from compounding pharmacies, Internet, and direct-to-patient clinic sales.”
Accusations of disease mongering
Dr. Morgentaler states that the reasons for this rise are an increased awareness of testosterone deficiency among health care providers and assuaged fears around an early association between testosterone therapy and prostate cancer.
Critics of testosterone therapy, however, believe that other forces are at work. In their paper, Dr. Perls and Prof. Handelsman state that 10- and 40-fold increases reported in the US and Canada are partly attributable to direct-to-consumer product advertising and lax consensus guidelines.
“We join others who characterize the mass marketing of testosterone coupled with the permissive prescribing of testosterone for common, nonspecific, aging-related symptoms as disease mongering of declines in testosterone with advancing age,” they write.
Critics believe that guidelines incorporating nonspecific symptoms such as increased weariness have been drawn up to increase the scope of testosterone therapy.
Dr. Perls, based in the Department of Medicine at Boston Medical Center, MA, told MNT that the evidence suggests that pharmaceutical marketing is the predominant reason that testosterone therapy has become as prevalent as it has, stating that aging-related hypogonadism did not exist as a condition to be diagnosed before 2000.
“It emerged once the pharmaceutical companies and other doctor and Internet-based entrepreneurs sensed a big profit opportunity by greatly expanding the market for testosterone by making up a new disease consisting of a decreased testosterone level […] combined with nonspecific common symptoms,” he said.
“Instead of the 0.5% of men previously noted by endocrinologists to have hypogonadism, there are now clinics and doctors claiming that 40-100% of men experience hypogonadism that merits testosterone replacement.”
Symptoms such as decreased sexual desire, depressed mood and decreased exertion tolerance can be the result of common problems such as obesity and smoking, which also cause a functional decline in testosterone.
“Replacing testosterone in these cases is medically inappropriate and, rather, steps should be taken to treat the underlying cause,” he said. In the example of obesity, more apt treatment methods include diet and exercise which do not carry the same risks as those identified by the FDA for testosterone therapy.
Co-author Prof. Handelsman, of the ANZAC Research Institute at the University of Sydney in Australia, believes that, at present, we do not know enough about naturally declining testosterone levels to automatically classify them as a deficiency. Regarding cases of testosterone decline in men not associated with reproductive medical disorders, Prof. Handelsman told MNT:
“In these situations lower circulating testosterone is not a deficiency at all. This thinking confuses a genuine deficiency state due to pathological reproductive system disorders with a normal functional, adaptive hypothalamic reaction to a systemic disease – which may be beneficial, neutral or harmful.”
Critics of the wide use of testosterone therapy believe that varying guidelines have been created that stretch the definition of hypogonadism to incorporate nonspecific age-related symptoms which in turn increase the scope of the treatment, making it easier for clinicians to prescribe.
“Without demonstrated underlying reproductive system pathology, a set of common complaints plus or minus a low serum testosterone cannot constitute ‘hypogonadism,'” write the authors.
The FDA currently require the demonstration of a pathological basis for growth hormone deficiency before a prescription for growth hormone can be dispensed. Dr. Perls and Prof. Handelsman believe that a similar demonstration of pathology should be required for the prescription of testosterone.
The debate continues
On the one hand, testosterone therapy is a form of treatment that can improve various symptoms experienced by some men as they grow older. On the other hand, testosterone therapy is a means to profit from disease mongering.
For supporters of testosterone therapy like Dr. Morgentaler, the results speak for themselves.
“Indeed,” he writes “one only needs to treat five symptomatic men with low testosterone values to become convinced: two will thank the physician profusely for restoring their sexuality and vitality, another two will report solid benefits, and one will not respond.”
Prof. Handelsman believes that further research is needed. “That point requires proper evaluation, not wild guesswork by pharma or single-issue proponents who have vested interests in such drug promotion,” he told MNT.
Both sides of the debate present their own evidence and refute that of the opposition, putting the lay person who lacks expertise in a tricky position when it comes to making a judgment.
The Mayo Clinic recommend discussing any signs and symptoms that could be attributed to a low testosterone level with a doctor. Being honest with health care providers, making healthy lifestyle choices and seeking help when feeling down are useful steps in tackling problems associated with aging and may help with any decision making about pursuing treatment.
It is likely that the debate surrounding testosterone therapy and aging-related hypogonadism will continue into the near future. For any patients affected by these topics, it would appear best to keep an open mind and listen to both sides of the debate while further research is conducted.
Written by James McIntosh