While the number of men seeking testosterone treatment has tripled over the past decade, many patients who need hormone replacement for a testosterone deficiency are not receiving it.1 When low T occurs because of poor functioning testes or a tumor on the pituitary gland, for example, the result may be hypogonadism.
Recognizing this trend has led to the publication of guidelines for the diagnosis and management of testosterone deficiency in men by the American Urological Association1 (AUA) and an updated best practice recommendation from the Endocrine Society.
“The use of testosterone therapy has increased dramatically in relatively healthy men without a clear indication of testosterone deficiency (low T), while other men in need of testosterone therapy fail to receive it due to clinician concerns regarding cardiovascular events or the development of prostate cancer,” says John P. Mulhall, MD, director of the Male Sexual and Reproductive Medicine Program at Memorial Sloan Kettering Cancer Center in New York City, and lead author of the AUA guideline.
“One goal of the AUA guideline is to outline criteria to determine who has a bona fide testosterone deficiency, how to evaluate and determine who should be treated,” he tells EndocrineWeb.
Similarly, the Endocrine Society updated their best practices guidance for testosterone therapy in men with hypogonadism, a form of testosterone deficiency.
These clinical recommendations were prepared in response to a “much higher quality of evidence published in recent years about testosterone deficiency and a wider availability of high quality assays for measuring testosterone levels, which had been a problematic issue,” said Shalendar Bhasin, MD, professor of Medicine at Harvard Medical School, and director of Men’s Health, Research Program at Brigham and Women’s Hospital, in Boston Massachusetts, who led the work on the Endocrine Society project.
How Does Low Testosterone Differ from a Hormonal Deficiency?
Testosterone—a hormone produced primarily in testicles but also to a lesser extent by the ovaries and adrenal cortex—is essential for a variety of physical, cognitive, sexual, and metabolic functions in men. This sex hormone usually peaks in adolescence and early adulthood. As men age, the ability to produce testosterone begins to decline such that testosterone levels begin to drop about 1 to 3 percent a year beginning around age 40 years.
This natural decline, however, does not imply that a man is testosterone deficient or a candidate for testosterone therapy.1,2 A deficiency in this hormone only occurs in cases where there is a low level of testosterone along with specific symptoms or signs.
“Testosterone deficiency is a very specific clinical condition that is defined by the presence of a set of specific signs and symptoms that occur as a result of decreased production of testosterone by the testes in men,” says Dr. Bhasin. “It’s extremely important that testosterone is used only as Food and Drug Administration-approved treatment for this condition.
“What’s been happening over the past couple of years is that there has been a rise in off-label use of testosterone to treat a variety of age-related conditions and symptoms that don’t qualify as a testosterone deficiency,” he says.
Diagnosing and Testing for Hypogonadism
Outside of age, there are “myriad causes for testosterone deficiency,” Dr. Mulhall adds. “They include testicular dysfunction, chemotherapy or radiation to testes, or loss of the testes,” he said. Then there are secondary testosterone deficiencies, genetic disorders, Kleinfelter syndrome, pituitary disorders, steroid use, opioid use, diabetes, and obesity.
While testosterone supplementation is being used to treat low hypoactive sexual desire, a type of sexual dysfunction, in women, “we don't know if it's a bona fide condition,” says Dr. Bhasin. It’s been plausible but remains only a hypothesis that hasn’t been proven definitively.
According to the recommendations issued by both the Endocrine Society and AUA,1,2 before a diagnosis of testosterone deficiency can be made, patients must demonstrate both a low testosterone levels and show signs and/or symptoms of the condition.
Signs and Symptoms Signaling a Problem:2,3
Red flag symptoms:
Low sex drive
Difficulty with erection
Low sperm count
Unexplained loss of hair
Low bone density
Testicular atrophy (changes in testes)
Diminished lean muscle mass
Increased body fat
Elevated hemoglobin A1c
Osteopenia or low trauma bone fracture
Problems sleeping (insomnia)
Difficulty concentrating, lack of motivation, depression
When and How Should a Low Testosterone be Treated?
“Testosterone replacement shouldn't be used to treat a naturally occurring, age-related decline in this hormone or simply for a low T number,” says Dr. Bhasin, “but if a man has a testosterone deficiency or classical hypogonadism, the benefits of treating the condition with testosterone is favorable and outweighs any risks.”
According to Dr. Bhasin, over the last two to three years there has been greater availability of high quality lab providing good results for testosterone levels, which until recently has been a problematic when trying to make a firm diagnosis.
To confirm the existence of low testosterone requiring treatment, the patient should have two separate blood tests on nonconsecutive days in the early morning (testosterone levels fluctuate during the day and are highest in the early hours) that are analyzed by reliable laboratories certified by the Centers for Disease Control and Prevention, Dr. Bhasin told EndocrineWeb.
A normal range for testosterone levels is 300 ng/dL to 1,000 ng/dL, with the Endocrine Society considering low testosterone below 263 ng/dL, says Dr. Bhasin.
Your doctors should also determine if you (your spouse) shows signs or symptoms of a testosterone deficiency. One problem with the symptoms for testosterone deficiency is many are “incredibly nonspecific” Dr. Mulhall cautions, which is why getting accurate testosterone levels is vital.
“If a man had a testosterone level less than 220 and shows signs of osteopenia, the testosterone is low because the patients has bone density loss,” says Dr. Mulhall, “but you can’t just go on the number alone.”
Monitoring, Managing, and Follow-Up Care
Both sets of guidelines stress the importance of monitoring T levels during treatment to make sure the hormone falls within a desired range and to check the status of other health conditions such as sex, heart and bone health.
“While the number of men using testosterone has increased, it’s concerning that about 20 to 25 percent of men who go on testosterone never get their levels double checked before treatment, and a percentage of men who go on testosterone who don’t get their levels checked at all while they’re on the treatment,” says Dr. Mulhall.
There are a number of health reasons to monitor testosterone treatments. For example, low testosterone is a risk factor for cardiovascular events, but “giving a patient [supplemental] testosterone cannot be said to definitively raise or lower the risk for cardiovascular issues,” Dr. Mulhall says.
While testosterone replacement therapy does not cause prostate cancer, Dr. Bhasin notes that increasing testosterone could raise PSA levels, which may lead to an increased risk for prostate cancer, particularly in the 30% of men over 70 years of age who may have with an early stage prostate that has not yet become detectable.4
“One important goal of monitoring testosterone levels is to minimize the risk of unnecessary biopsies,” he adds.
Know the Health Warnings of T Supplementation
When it comes to treatment, there are a variety of forms of testosterone—from gels to adhesive pellets to injections—that can be administered to men.
However, you should be aware that patients who use transdermal gels to restore normal T levels should be careful to avoid any risk of transferring testosterone gels to women and children.4 Covering the shoulders or upper arms where the gel has been applied is sufficient to protect against accidental exposure of this hormone to others.
From a reproductive standpoint, both professional organization guidelines note that men who are trying to conceive should not receive testosterone treatments because it impairs sperm production.
“Even when testosterone replacement is stopped, there will be a period of time during which it will take sperm production a while to recover,” says Dr. Mulhall.
“There’s no magic to diagnosing or treating testosterone deficiency,” says Bhasin. “Like any other condition it’s really important to have accurate measurements and be rigorous in the diagnosis and a major concern has been starting treatments without an appropriate diagnosis.
“The result has been that half the people never refill their prescriptions and about three quarters of men given a testosterone prescription will not be using testosterone after the first year,” he said. “It's a bona fide condition that is under diagnosed and over treated.”