The U.S. Food and Drug Administration (FDA) has issued a cautionary alert regarding prescription testosterone products that the agency has approved only for men with low testosterone levels due to certain medical conditions. Testosterone is a male hormone essential for growth and development of male sex organs and for maintenance of secondary male characteristics, such as facial hair. FDA-approved testosterone formulations include gels, solution, skin patch, intramuscular injection, pellets implanted under the skin, and a buccal system applied to the upper gum or inner cheek.
The FDA notes that in the past five years, use of testosterone replacement therapy has increased significantly, from 1.3 million patients in 2009 to 2.3 million patients in 2013 receiving testosterone product prescriptions. They report that currently, approximately 70 percent of men receiving testosterone prescriptions through retail pharmacies are between the ages of 40 and 64, and that neither benefit nor safety of these medications have been established for the treatment of age-related low testosterone levels, even in cases when a patient’s symptoms appear to be related to low testosterone levels.
Testosterone levels can decrease naturally as a man ages, and sometimes to levels lower than the normal range found in young, healthy men. Aging men may also experience hormone-related signs and symptoms such as decreased energy levels and problems with sexual function. However, the FDA says it’s uncertain as to whether these are caused by lowered testosterone levels or are simply a part of the normal aging process, leaving the matter of whether there’s a need to replace testosterone in these aging men unsettled.
The FDA points out that while a conclusive diagnosis of hypogonadism requires laboratory evidence of low testosterone levels measured on at least two separate mornings, in one health plan database reviewed, approximately 20 percent of men who received testosterone prescriptions filed no insurance claims for testosterone levels laboratory testing.
Consequently, the agency is requiring that manufacturers of all approved prescription testosterone products revise labeling in order to clarify the extent of approved use of these medications. The FDA is also requiring these manufacturers to provide additional information in their labeling regarding possible increased heart attacks and strokes risk for patients taking testosterone, and says health care professionals should prescribe testosterone therapy only for men with low testosterone levels that result from medical conditions such as disorders of the testicles, pituitary gland, or the part of the brain called the hypothalamus that controls testosterone production by the testicles that can cause hypogonadism (low testosterone) that have been confirmed in laboratory testing. Manifestation of these disorders may include testicular failure of the to produce testosterone due to genetic problems, or damage caused by chemotherapy or infection.
The FDA says it has become aware of testosterone being used extensively in efforts to relieve symptoms in men presenting with low testosterone levels with no apparent cause other than normal aging — a cohort for whom benefits and safety of testosterone use have not been established.
Additionally, based on available evidence from published studies and expert input from an Advisory Committee meeting, the FDA has identified potential increased cardiovascular risk associated with testosterone use revealed in some studies that included aging men treated with testosterone, some of which reported increased heart attack, stroke, or death risk associated with testosterone treatment, although others did not.
Pursuant to these findings, the FDA is taking the precaution of requiring labeling changes for all prescription testosterone products to reflect a potentially greater risk of heart attack and stroke associated with testosterone use, noting that health care professionals should also make patients aware of this possible risk when determining whether to start or continue a patient on testosterone therapy.
In addition, the regulatory agency is requiring approved testosterone product manufacturers to conduct a well-designed clinical trial that can more clearly address the question of whether increased risk of heart attack or stroke exists among users of these products or not. The FDA is encouraging these manufacturers to pool efforts on a collaborative clinical trial, although they will be permitted to work separately if they prefer.
It is also recommended that patients using testosterone seek immediate medical attention if symptoms of a heart attack or stroke manifest such as: chest pain, shortness of breath or trouble breathing, weakness in one part or one side of the body, or slurred speech.
A list of FDA-approved testosterone products can be found by searching for testosterone at Drugs@FDA.
U.S. Food and Drug Administration (FDA)