Does your patient really need testosterone replacement?
Or has he been made to think so by direct-to-consumer advertising? Here’s how to properly screen patients and when to recommend treatment.
PRACTICE RECOMMENDATIONS
› Confirm suspected hypogonadism by getting 2 serum testosterone levels at least one month apart prior to initiating testosterone replacement therapy. B
› Consider testosterone replacement therapy when there is both laboratory and clinical evidence of hypogonadism. B
› Offer testosterone replacement to older men (≥65 years) with hypogonadism only after talking to them about the risks and benefits. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Testosterone replacement raises issues of abuse and CV risk
On October 25, 2016, the US Food and Drug Administration (FDA) approved class-wide labeling changes for all prescription testosterone products, alerting prescribers to the agent’s abuse potential and the serious cardiac and mental health adverse outcomes that have been reported as a result of such abuse. In addition, the FDA is revising the Abuse and Dependence section to include new safety information regarding the risks associated with abuse of testosterone and other anabolic androgenic steroids.18
Prior to this announcement, the FDA had mandated in 2015 that product labels include information about a possible increased risk of myocardial infarction (MI) and stroke in people using testosterone. This warning was based on 2 published studies that showed increased cardiovascular risk.19,20 However, a third larger study showed no increase in risk.21 All 3 of these studies were retrospective and had methodologic limitations, including differing baseline testosterone levels, insufficient documentation of baseline levels, and inadequate monitoring of response to therapy.
A recent statement by the American Association of Clinical Endocrinologists and the American College of Endocrinology in response to the older FDA warning cites the need for randomized controlled trials (RCTs) to elucidate whether an association exists between testosterone replacement and cardiovascular risk.22
Of note, researchers have shown that androgen deprivation therapy (ADT) in patients with prostate cancer impacts cardiovascular risk factors (ie, it increases body fat and decreases lean body mass, increases total cholesterol, and increases insulin resistance and risk of diabetes). ADT may also be associated with increased cardiovascular mortality, although data are conflicting.23
Investigators have shown that testosterone replacement positively affects certain risk factors for cardiovascular disease (CVD) including increasing lean muscle mass and improving laboratory values associated with the metabolic syndrome.24 A large retrospective cohort study of male veterans with documented low total testosterone levels who received their medical care at the Veterans Health Administration (VHA) found that those who received testosterone replacement and achieved normal testosterone levels had lower all-cause, cardiovascular, and stroke mortality than controls.21 The men who did not achieve normal testosterone levels also had lower all-cause mortality (but significantly less than those with normalization of serum testosterone levels), but no change in stroke or cardiovascular mortality.
Since this study was retrospective, there were significant limitations, including unknown baseline characteristics of patients in each group. The CVD risks associated with testosterone therapy in middle-aged and older men should be discussed by physicians and their patients on an individual basis. Some experts believe that patients who have had an MI, revascularization, or a stroke within the past 6 months are not good candidates for replacement therapy.25
Until there are better data from prospective RCTs, it may be prudent to make sure that traditional CVD risk factors including smoking, hypertension, hyperlipidemia, and diabetes have been assessed and are appropriately managed in men prescribed testosterone replacement.
Testosterone helps with ED in certain cases
Testosterone deficiency is associated with sexual dysfunction in men, including decreased libido and erectile dysfunction (ED). About 20% to 40% of men with ED will have low testosterone, although replacement does not always improve the condition.2
Current guidelines do not recommend testosterone replacement to treat ED or sexual dysfunction in the absence of a low serum testosterone level and recommend evaluating for other causes of sexual problems in men.3 In one study, men who did not have documented hypogonadism received testosterone replacement therapy for sexual dysfunction including ED or ejaculator dysfunction. These patients saw no improvement in symptoms.26
CORRESPONDENCE
J. Andrew Hoover, MD, Department of Family and Community Medicine, Lancaster General Hospital, 540 North Duke Street, Lancaster, PA 17604; jhoover4@lghealth.org.
