The decision to prescribe testosterone replacement therapy or not

It seems like every day in the office I see at least one man concerned about testosterone deficiency.  If you look at the symptoms of testosterone deficiency most of us have one or more of these symptoms at least some of the time.  Fatigue, depression, weight gain, lack of energy, reduced sex drive, loss of physical strength, and moodiness are all described as symptoms typical of testosterone deficiency. Making the issue even more difficult it the controversy over whether testosterone levels in the lower third of the range reported as normal is in fact normal, or whether some of these men also have symptoms of testosterone deficiency.

Testosterone deficiency is also felt to be more prevalent in patients with several common medical conditions.  These include diabetes, chronic pain, metabolic syndrome, inflammatory arthritis, COPD, and advanced renal disease.  Most if not all of these problems can cause many of the symptoms also associated with testosterone deficiency.

Making the decision of whether to prescribe testosterone replacement therapy or not more vexing is that we know little about the long term effects of testosterone replacement.  We do know that some men on testosterone replacement therapy develop in increased number of red blood cells called polycythemia.  This can require cessation of testosterone therapy because polycythemia can lead to stroke and other serious complications. We don’t know if long term testosterone therapy is associated with more or less atherosclerotic heart disease, prostate enlargement or cancer.  Really we don’t know much at all about the very long term consequences.

This all is reminiscent of the wings in expert opinion on hormone replacement therapy (HRT) in women for treatment of menopause over the last couple of decades.  Consensus of opinion was to treat all women at menopause with HRT  unless there was a specific reason to avoid therapy to prevent vascular and bone disease until data showed otherwise. Now most experts recommend to try to avoid HRT except for short term treatment of severe menopausal symptoms as evidence of HRT hazards including breast cancer and  cardiovascular disease became documented.

Estimates of the prevalence of testosterone deficiency range from 2.8% to 39% in various population with the higher number being in populations with conditions like diabetes, chronic pain, etc.

In summary we are really left to decide on a case-by-case basis whether to start men on testosterone replacement therapy.  In cases where the testosterone levels are very low and the symptoms are typical I feel pretty good about starting therapy. In cases where testosterone levels are only modestly low or are at the low end of normal but symptoms are present it is much less clear when therapy is indicated.  I often feel like my arm is being twisted by some men desperate for some help with their symptoms, and we have to decide on the risk-benefit balance best for them.

When therapy is indicated the route of administration of testosterone, transdermal testosterone as a gel or patch vs. intramuscular (IM) injection is the next decision.  A big factor in making this decision is the high cost of all the branded transdermal products ($330 per month for Androgel on, others similar) which have the advantage of not requiring IM injections and steadier daily dosing. The much less expensive IM shots with the discomfort and risk of IM administration and the peaks and troughs of testosterone levels are often used to reduce cost of therapy.

I look forward to more research on the long term safety, benefits and risks of testosterone deficiency therapy.  I’m confident there is a lot we don’t know.  I suspect the answers will be slow in coming and surprising whatever they show.  Stay tuned but don’t hold your breath.  This research is not likely to be funded by Big Pharma, and I don’t know of any current long term not-for-profit studies underway.

Edward Pullen is a family physician who blogs at

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