madman
Super Moderator
The deluge of advertisements marketing erectile dysfunction medications and testosterone products has empowered many older men to seek medical help for their sexual and genitourinary problems. As a reflection of this historical transition toward increased attention on men’s sexual health, men’s health clinics have sprung up across the United States; concomitantly, testosterone prescription sales increased from about $100 million US dollars in the year 2000 to nearly $2.7 billion in 2013. Today, a majority of testosterone prescriptions are written for men aged 40–64 years (1) even though testosterone is not approved by the US Food and Drug Administration (FDA) for age-related decline in testosterone. Citing the lack of data on long-term benefits and risks of testosterone treatment in older men with an age-related decline, the FDA has sounded the alarm over the growing off-label use of testosterone (2). Experts have debated whether prescribing testosterone to older men with testosterone deficiency is disease mongering or whether subsets of older men with testosterone deficiency might benefit from testosterone treatment. Fortunately, several recent randomized controlled trials (RCTs) have provided important information on the efficacy and short-term safety of testosterone treatment in older men (3–9). This Viewpoint synthesizes data from epidemiologic studies and RCTs and offers a perspective on a patient-centric approach to treatment decisions in older men with testosterone deficiency based on an individualized assessment […]
*Epidemiological evidence
*Placebo-controlled trials
*Potential risks of testosterone treatment
Testosterone treatment of older hypogonadal men is associated with a low frequency of adverse events (4–9). The adverse effects of testosterone treatment include acne, erythrocytosis, growth of metastatic prostate cancer reduced sperm production, and increased risk of detecting subclinical prostate cancer (ref. 1 and Figure 1). Erythrocytosis is the most frequent adverse event associated with testosterone treatment. Testosterone treatment does not worsen lower urinary tract symptoms of obstructive sleep apnea. No adequately powered trial of sufficiently long duration has been conducted to determine the effects of testosterone on the risk of prostate cancer or major adverse cardiovascular events (MACE). Retrospective analyses of electronic medical records and meta-analyses of RCTs have yielded inconclusive results. No consistent relationship exists between testosterone levels and prostate cancer risk, and the rates of prostate cancer in the carefully selected men who were included in RCTs have been low. A Mendelian randomization analysis found that genetically determined testosterone level is associated with increased risk of prostate cancer (12); conversely, men with Klinefelter syndrome have decreased prostate cancer risk. These data suggest that long-term testosterone exposure could increase the risk of prostate cancer. An ongoing large cardiovascular safety RCT (TRAVERSE Trial, NCT03518034) in hypogonadal men, age 45–80 years, at increased cardiovascular the risk will provide definitive information on the effects of long-term testosterone treatment on MACE and other efficacy and safety outcomes.
*An individualized approach to treatment decision
Testosterone treatment of older men with symptomatic testosterone deficiency offers some clinical benefits (e.g., improvement of sexual symptoms in men with low libido, correction of anemia) and is associated with a low frequency of adverse events. However, because of the lack of evidence of long-term safety and limited evidence of long-term efficacy, testosterone treatment of all older men with low testosterone levels is not justified.
Instead, an expert panel of the Endocrine Society recommended that “testosterone therapy should be offered on an individualized basis ... in men >65 years who have symptoms or conditions suggestive of testosterone deficiency (e.g., low libido or unexplained anemia) and consistently low testosterone” (25).
The decision to offer testosterone treatment to older men with low testosterone levels should be guided by an individualized assessment of potential benefits and risks (Figure 1): (a) evaluate whether the patient has clear evidence of testosterone deficiency; (b) weigh the burden of symptoms/conditions against the potential benefits and the uncertainty of long-term harm; and (c) ascertain whether a patient has conditions, such as prostate cancer, erythrocytosis, heart failure, or a hypercoagulable state that would increase the risk of harm.
Older men considering testosterone treatment should undergo evaluation for prostate cancer risk. Prostate cancer screening and monitoring have some risks. The burden of symptoms, patient preferences, and risk tolerance should be weighed against the uncertainty of benefits and risks, the burden and risks of monitoring, and the cost. Finally, a shared decision to initiate testosterone treatment should be accompanied by a standardized monitoring plan to optimize the benefit-to-risk ratio
*Epidemiological evidence
*Placebo-controlled trials
*Potential risks of testosterone treatment
Testosterone treatment of older hypogonadal men is associated with a low frequency of adverse events (4–9). The adverse effects of testosterone treatment include acne, erythrocytosis, growth of metastatic prostate cancer reduced sperm production, and increased risk of detecting subclinical prostate cancer (ref. 1 and Figure 1). Erythrocytosis is the most frequent adverse event associated with testosterone treatment. Testosterone treatment does not worsen lower urinary tract symptoms of obstructive sleep apnea. No adequately powered trial of sufficiently long duration has been conducted to determine the effects of testosterone on the risk of prostate cancer or major adverse cardiovascular events (MACE). Retrospective analyses of electronic medical records and meta-analyses of RCTs have yielded inconclusive results. No consistent relationship exists between testosterone levels and prostate cancer risk, and the rates of prostate cancer in the carefully selected men who were included in RCTs have been low. A Mendelian randomization analysis found that genetically determined testosterone level is associated with increased risk of prostate cancer (12); conversely, men with Klinefelter syndrome have decreased prostate cancer risk. These data suggest that long-term testosterone exposure could increase the risk of prostate cancer. An ongoing large cardiovascular safety RCT (TRAVERSE Trial, NCT03518034) in hypogonadal men, age 45–80 years, at increased cardiovascular the risk will provide definitive information on the effects of long-term testosterone treatment on MACE and other efficacy and safety outcomes.
*An individualized approach to treatment decision
Testosterone treatment of older men with symptomatic testosterone deficiency offers some clinical benefits (e.g., improvement of sexual symptoms in men with low libido, correction of anemia) and is associated with a low frequency of adverse events. However, because of the lack of evidence of long-term safety and limited evidence of long-term efficacy, testosterone treatment of all older men with low testosterone levels is not justified.
Instead, an expert panel of the Endocrine Society recommended that “testosterone therapy should be offered on an individualized basis ... in men >65 years who have symptoms or conditions suggestive of testosterone deficiency (e.g., low libido or unexplained anemia) and consistently low testosterone” (25).
The decision to offer testosterone treatment to older men with low testosterone levels should be guided by an individualized assessment of potential benefits and risks (Figure 1): (a) evaluate whether the patient has clear evidence of testosterone deficiency; (b) weigh the burden of symptoms/conditions against the potential benefits and the uncertainty of long-term harm; and (c) ascertain whether a patient has conditions, such as prostate cancer, erythrocytosis, heart failure, or a hypercoagulable state that would increase the risk of harm.
Older men considering testosterone treatment should undergo evaluation for prostate cancer risk. Prostate cancer screening and monitoring have some risks. The burden of symptoms, patient preferences, and risk tolerance should be weighed against the uncertainty of benefits and risks, the burden and risks of monitoring, and the cost. Finally, a shared decision to initiate testosterone treatment should be accompanied by a standardized monitoring plan to optimize the benefit-to-risk ratio
