The Canadian Men’s Health Foundation has issued comprehensive new guidelines on the diagnosis and management of testosterone-deficiency syndrome in response to confusion in the literature about whether this syndrome even exists and whether testosterone-replacement therapy is safe.
Prior to developing the new guidelines, the Canadian Men’s Health Foundation carried out a survey of Canadian physicians that suggested many are uncomfortable dealing with testosterone deficiency and uncertain about how to manage the condition.
“This was not surprising to someone like me, who has been interested in this subject for years, as a lot of the literature is very contradictory and there are very important differences of opinion in the management of testosterone-deficiency syndrome,” guideline chair Alvaro Morales, MD, from the department of urology, Queen’s University, Kingston, Ontario, said in a podcast with CMAJ. The journal published the new guidelines October 26.
“Testosterone deficiency can occur at any age, but we are dealing mostly with men in whom there is decreasing testosterone production, who are most likely over the age of 45,” Dr Morales noted in the podcast.
Sexual symptoms and fatigue are the earliest and most common symptoms of testosterone deficiency; other symptoms include increased visceral fat and decreased lean-muscle mass; loss of facial, axillary, and pubic hair; and depressed mood, irritability, and inability to concentrate.
“Ideally, we should see at least some of the changes on physical examination that are induced by lower levels of testosterone production,” observed Dr Morales.
Diagnosis and Treatment Options
Total testosterone levels should be measured in men suspected as having the syndrome, with serum samples taken in the morning or within 3 hours of waking in the case of shift workers.
On confirmation that total testosterone levels are low, the choice of testosterone replacement should be decided between physician and patient and may include short-acting injectable testosterone, oral testosterone undecanoate, transdermal testosterone patches or gels, and axillary transdermal testosterone solution 2%.
“The goal of testosterone treatment is to improve symptoms of testosterone deficiency and to achieve levels of testosterone in the mid-normal range for healthy young men at between 14 and 17.5 nmol/L,” the task-force authors write.
“Monitoring is an integral and mandatory part of the management of hypogonadism,” guideline authors also stress.
For example, they recommend that testosterone levels be assessed at 3 and 6 months after initiation of treatment and then annually thereafter. They also recommend physicians assess both prostate-specific antigen and hematocrit at baseline and at 3 and 6 months and then again annually thereafter.
Lack of or an inadequate response to testosterone replacement should call for changes in the form of delivery, the dose, or the frequency of administration.
As to how many months to continue with the testosterone trial, “it depends on what the main manifestations of the patient’s testosterone deficiency are,” Dr Morales noted.
For example, physicians used to think men with sexual manifestations of the syndrome would respond within the first 3 months of treatment, but it may take 6 to 12 months for sexual symptoms to respond and 1 to 2 years for other manifestations of the syndrome such as decreased muscle mass.
What About Prostate Cancer and Heart Disease?
The task force concluded that patients with stable cardiovascular disease (CVD) may be candidates for testosterone therapy as long as physicians discuss the risk and benefits of the treatment with them.
Patients who have been successfully treated for prostate cancer and who have developed testosterone deficiency can also be treated according to the guidelines, although they need to be carefully monitored.
Guideline authors also found a role for testosterone therapy in testosterone deficiency associated with alterations in body composition, metabolic issues, and in chronic illnesses such as HIV infection and depression.
In contrast, men who have only erectile dysfunction and no other manifestations of testosterone deficiency should be investigated only after a trial of phosphodiesterase type 5 (PDE-5) inhibitors has failed.
“Not all men with testosterone deficiency are candidates for treatment,” Dr Morales cautioned. Some have contraindications to testosterone therapy, while for others, the severity of the deficiency may not be troubling enough to warrant treatment.
“If a patient is not prepared to participate in a schedule of monitoring after you start him on treatment, I don’t think he should be considered for treatment either,” Dr Morales added.
What Levels Call for Treatment?
According to editorialist Geoffrey Hackett, MD, Heartlands Hospital, Birmingham, United Kingdom, contended that the lack of a specific total testosterone value below which physicians should intervene is unhelpful.
“If you had cholesterol guidelines with no values, it would be very difficult to guide physicians to the point where they would know they need to intervene,” Dr Hackett said.
“And one of the dangers with these new guidelines is that you need a combination of symptoms with biochemical abnormalities to make the diagnosis, but the symptoms are all vague, and then if you make the biochemical abnormality vague, you are getting to a situation where treatment is going to be an eminence-based diagnosis, where only an eminent physician can say a man has this condition or not,” he said.
The European Association of Urology and the International Society for Sexual Medicine both hold that men with a total testosterone level of less than 8 nmol/L will usually benefit from treatment, and that a testosterone trial may be indicated for men with levels between 8 and 12 nmol/L if they have significant symptoms. Such levels, argued Dr Hackett, “do, at least, provide a basis for primary-care management.”
As for the duration of a testosterone trial, in Europe, the most common type of testosterone used is a long-acting injectable administered every 12 weeks.
“If a testosterone trial only lasts 3 months, patients have had at the most two injections, and we know that it’s with the fourth injection that we reach a steady state,” Dr Hackett observed. “So I suggest that clinicians consider a minimum of 6 months when assessing treatment response.”
Dr Hackett also did not agree that men with diabetes or the metabolic syndrome receive only PDE-5 inhibitors for erectile-dysfunction therapy and not testosterone replacement.
“Most patients with diabetes have sexual symptoms, but they also have vascular and neuropathic disease, and unless you treat both of these simultaneously, you are not going to get a satisfactory outcome for these patients,” he said.
“Testosterone deficiency is also very prevalent in men with the metabolic syndrome, and all the meta-analyses show that these men do very well with testosterone replacement because their low testosterone is a consequence of their metabolic problems.”
Dr Hackett added that men are likely to get only one trial of testosterone therapy, “so it is vital that we do it properly and expose them to sustained levels of testosterone for an adequate period to achieve maximal benefit.”