madman
Super Moderator
OFF-LABEL USE AND MISUSE OF TESTOSTERONE, GROWTH HORMONE, THYROID HORMONE, AND ADRENAL SUPPLEMENTS: RISKS AND COSTS OF A GROWING PROBLEM
ABSTRACT
Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Testosterone therapy is often promoted to men for the treatment of low energy, lower libido, erectile dysfunction, and other symptoms. Growth hormone is used in attempts to improve athletic performance in athletes and to attenuate aging in older adults. Thyroid hormone and/or thyroid supplements or boosters are taken to treat fatigue, obesity, depression, cognitive impairment, impaired physical performance, and infertility. Adrenal supplements are used to treat common nonspecific symptoms due to “adrenal fatigue,” an entity that has not been recognized as a legitimate medical diagnosis. Several factors have contributed to the surge in off-label use and misuse of these hormones and supplements: direct-to-consumer advertising, websites claiming to provide legitimate medical information, and for-profit facilities promoting therapies for men’s health and anti-aging. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks. For example, the risks of growth hormone abuse in athletes and older adults are unknown due to a paucity of studies and because those who abuse this hormone often take supraphysiologic doses in sporadic intervals. In addition to the health risks, off-label use of these hormones and supplements generates billions of dollars of unnecessary costs to patients and to the overall health-care system. It is important that patients honestly disclose to their providers off-label hormone use, as it may affect their health and treatment plan. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, growth hormone, thyroid hormone, and adrenal supplements.
EXECUTIVE SUMMARY
1. Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone (GH), thyroid hormone, and adrenal supplements.
2. Testosterone therapy is indicated for the treatment of primary and secondary male hypogonadism. GH is approved by the U.S. Food and Drug Administration (FDA) for use in children and adults with GH deficiency. Thyroid hormone is indicated for the treatment of primary and secondary hypothyroidism. Glucocorticoids are indicated for the treatment of adrenal insufficiency and a wide array of inflammatory diseases.
3. “Adrenal fatigue” is an unrecognized entity that supposedly is due to the overuse of the adrenal glands, which may lead to a general sense of unwellness, fatigue, body aches, nervousness, sleep disturbances, digestive problems, weight gain, and a multitude of other nonspecific symptoms.
4. Many patients seek treatment for common nonspecific symptoms such as fatigue, low energy, poor sleep, weight gain, and lower libido. Unfortunately, some clinics and websites lead people to believe that their symptoms are attributable to a deficiency of a hormone and that treatment with this hormone will improve or eliminate their symptoms.
5. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks.
6. Dietary supplements do not undergo rigorous premarket safety and effectiveness testing and may contain undeclared pharmaceuticals.
7. Practitioners should undergo appropriate training to interpret laboratory test results in a more comprehensive way than simply checking whether a value falls within the reference range. There are many causes of abnormal laboratory results that are not due to hormonal deficiency or excess.
8. Patients should disclose to their providers off-label hormone use as it may affect their overall health, diagnostic testing, and treatment plan.
9. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, GH, thyroid hormone, and adrenal supplements.
CONCLUSION
Off-label use and misuse of testosterone, GH, thyroid hormone, and adrenal supplements have become increasingly prevalent. Many patients seek treatment for common nonspecific symptoms such as fatigue, low energy, poor sleep, weight gain, and lower libido. Unfortunately, some clinics and websites lead people to believe that their symptoms are attributable to a deficiency of a hormone and that treatment with this hormone will eliminate their symptoms. While it is true that aging and chronic diseases are associated with a decline in serum concentrations of testosterone and GH, there is no scientific evidence to support prescribing these hormones for anti-aging purposes. Physicians and other health-care professionals should therefore only prescribe testosterone, GH, thyroid hormone, and glucocorticoids to patients with clearly established diagnoses of male hypogonadism, GH deficiency, hypothyroidism, adrenal insufficiency, and other conditions where these medications are an accepted standard treatment.
The American Association of Clinical Endocrinologists (AACE) strongly recommends that board-certified endocrinologists diagnose GH deficiency and adrenal insufficiency, as these conditions are uncommon diagnoses that require a high level of expertise in endocrinology. Testing protocols for these conditions can be complex. While the diagnoses of male hypogonadism and hypothyroidism do not necessarily need to be confirmed by endocrinologists, practitioners who prescribe testosterone and thyroid hormone need to have adequate knowledge about these conditions and understand the potential risks of related therapies. Practitioners should have training to interpret lab results in a more comprehensive way than simply checking whether a testosterone or TSH value falls within the reference range. There are many causes of abnormal laboratory results that are not due to hormonal deficiency.
When evaluating patients who have been prescribed testosterone, GH, thyroid hormone, and/or adrenal supplements by other providers, it is important to confirm that the diagnosis was firmly established. This may involve reviewing the patients’ outside test results prior to starting hormone therapy and/or discontinuing treatment in order to reassess the endocrine axis. For patients in whom repeat testing does not confirm their initial suspected diagnoses, clinicians should collaborate with other members of the patients’ health-care team to consider other potential explanations and etiologies for their unexplained symptoms. For example, many obese men have fatigue secondary to undiagnosed obstructive sleep apnea.
General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, GH, thyroid hormone, and adrenal supplements. Table 1 summarizes the approved indications, unproven claims, and potential risks and adverse effects of the hormones described and glucocorticoids. Patients can be directed to reputable online educational resources, including the Endocrine Society’s Hormone Health Network and AACE’s Disease State Resources (123,124). Many leading health systems, such as the Mayo Clinic and Cleveland Clinic, also have online resources for patients (125,126). Clinical practice guidelines are also available for clinicians on the diagnosis and treatment of androgen deficiency, GH deficiency, hypothyroidism, and adrenal insufficiency (10,23,49,50,122).
Given the increase in off-label use and misuse of testosterone, GH, thyroid hormone, and adrenal supplements, it is important that reputable medical organizations and journals work together to increase awareness of this topic among the general public, as well as among the medical community. Given the rise of health-care costs associated with tests and medications, practitioners should strive to be good stewards of the health-care system by minimizing the ordering of unnecessary tests and medications. Treatment recommendations should be based upon well designed scientific studies. Finally, we should always keep in mind one of the most important principles of medicine, which is to do no harm.
ABSTRACT
Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Testosterone therapy is often promoted to men for the treatment of low energy, lower libido, erectile dysfunction, and other symptoms. Growth hormone is used in attempts to improve athletic performance in athletes and to attenuate aging in older adults. Thyroid hormone and/or thyroid supplements or boosters are taken to treat fatigue, obesity, depression, cognitive impairment, impaired physical performance, and infertility. Adrenal supplements are used to treat common nonspecific symptoms due to “adrenal fatigue,” an entity that has not been recognized as a legitimate medical diagnosis. Several factors have contributed to the surge in off-label use and misuse of these hormones and supplements: direct-to-consumer advertising, websites claiming to provide legitimate medical information, and for-profit facilities promoting therapies for men’s health and anti-aging. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks. For example, the risks of growth hormone abuse in athletes and older adults are unknown due to a paucity of studies and because those who abuse this hormone often take supraphysiologic doses in sporadic intervals. In addition to the health risks, off-label use of these hormones and supplements generates billions of dollars of unnecessary costs to patients and to the overall health-care system. It is important that patients honestly disclose to their providers off-label hormone use, as it may affect their health and treatment plan. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, growth hormone, thyroid hormone, and adrenal supplements.
EXECUTIVE SUMMARY
1. Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone (GH), thyroid hormone, and adrenal supplements.
2. Testosterone therapy is indicated for the treatment of primary and secondary male hypogonadism. GH is approved by the U.S. Food and Drug Administration (FDA) for use in children and adults with GH deficiency. Thyroid hormone is indicated for the treatment of primary and secondary hypothyroidism. Glucocorticoids are indicated for the treatment of adrenal insufficiency and a wide array of inflammatory diseases.
3. “Adrenal fatigue” is an unrecognized entity that supposedly is due to the overuse of the adrenal glands, which may lead to a general sense of unwellness, fatigue, body aches, nervousness, sleep disturbances, digestive problems, weight gain, and a multitude of other nonspecific symptoms.
4. Many patients seek treatment for common nonspecific symptoms such as fatigue, low energy, poor sleep, weight gain, and lower libido. Unfortunately, some clinics and websites lead people to believe that their symptoms are attributable to a deficiency of a hormone and that treatment with this hormone will improve or eliminate their symptoms.
5. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks.
6. Dietary supplements do not undergo rigorous premarket safety and effectiveness testing and may contain undeclared pharmaceuticals.
7. Practitioners should undergo appropriate training to interpret laboratory test results in a more comprehensive way than simply checking whether a value falls within the reference range. There are many causes of abnormal laboratory results that are not due to hormonal deficiency or excess.
8. Patients should disclose to their providers off-label hormone use as it may affect their overall health, diagnostic testing, and treatment plan.
9. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, GH, thyroid hormone, and adrenal supplements.
CONCLUSION
Off-label use and misuse of testosterone, GH, thyroid hormone, and adrenal supplements have become increasingly prevalent. Many patients seek treatment for common nonspecific symptoms such as fatigue, low energy, poor sleep, weight gain, and lower libido. Unfortunately, some clinics and websites lead people to believe that their symptoms are attributable to a deficiency of a hormone and that treatment with this hormone will eliminate their symptoms. While it is true that aging and chronic diseases are associated with a decline in serum concentrations of testosterone and GH, there is no scientific evidence to support prescribing these hormones for anti-aging purposes. Physicians and other health-care professionals should therefore only prescribe testosterone, GH, thyroid hormone, and glucocorticoids to patients with clearly established diagnoses of male hypogonadism, GH deficiency, hypothyroidism, adrenal insufficiency, and other conditions where these medications are an accepted standard treatment.
The American Association of Clinical Endocrinologists (AACE) strongly recommends that board-certified endocrinologists diagnose GH deficiency and adrenal insufficiency, as these conditions are uncommon diagnoses that require a high level of expertise in endocrinology. Testing protocols for these conditions can be complex. While the diagnoses of male hypogonadism and hypothyroidism do not necessarily need to be confirmed by endocrinologists, practitioners who prescribe testosterone and thyroid hormone need to have adequate knowledge about these conditions and understand the potential risks of related therapies. Practitioners should have training to interpret lab results in a more comprehensive way than simply checking whether a testosterone or TSH value falls within the reference range. There are many causes of abnormal laboratory results that are not due to hormonal deficiency.
When evaluating patients who have been prescribed testosterone, GH, thyroid hormone, and/or adrenal supplements by other providers, it is important to confirm that the diagnosis was firmly established. This may involve reviewing the patients’ outside test results prior to starting hormone therapy and/or discontinuing treatment in order to reassess the endocrine axis. For patients in whom repeat testing does not confirm their initial suspected diagnoses, clinicians should collaborate with other members of the patients’ health-care team to consider other potential explanations and etiologies for their unexplained symptoms. For example, many obese men have fatigue secondary to undiagnosed obstructive sleep apnea.
General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, GH, thyroid hormone, and adrenal supplements. Table 1 summarizes the approved indications, unproven claims, and potential risks and adverse effects of the hormones described and glucocorticoids. Patients can be directed to reputable online educational resources, including the Endocrine Society’s Hormone Health Network and AACE’s Disease State Resources (123,124). Many leading health systems, such as the Mayo Clinic and Cleveland Clinic, also have online resources for patients (125,126). Clinical practice guidelines are also available for clinicians on the diagnosis and treatment of androgen deficiency, GH deficiency, hypothyroidism, and adrenal insufficiency (10,23,49,50,122).
Given the increase in off-label use and misuse of testosterone, GH, thyroid hormone, and adrenal supplements, it is important that reputable medical organizations and journals work together to increase awareness of this topic among the general public, as well as among the medical community. Given the rise of health-care costs associated with tests and medications, practitioners should strive to be good stewards of the health-care system by minimizing the ordering of unnecessary tests and medications. Treatment recommendations should be based upon well designed scientific studies. Finally, we should always keep in mind one of the most important principles of medicine, which is to do no harm.
