Testosterone Replacement Therapy Benefits Mixed In Older Males


Testosterone replacement therapy can improve bone density and lower anemia in older men with low levels of the hormone, however it may also raise the risk of future adverse cardiovascular events, new research suggests.

The study found there was a 20% increase in arterial plaque among men aged 65 and older who received testosterone replacement therapy for a year. The work followed 138 men in the Testosterone Trials (TTrials), a National Institutes of Health (NIH) funded clinical research trial to determine if testosterone treatment of men aged 65 and older will help their walking, vitality, sexual function, memory, blood count and cardiovascular risk.

Testosterone was given as a gel in a pump bottle, and a placebo gel was given similarly. Men who received a placebo had a 1% rise in plaque volumes, while the men who received the testosterone treatments for a year had a 20% increase in total coronary and noncalcified plaque volumes as measured with coronary computed tomographic arteriography (CCTA).

Conflicting Conclusions

Primary author of the study Matthew J. Budoff, MD, a cardiologist who is an LA BioMed lead researcher, said:

“Heart disease remains the No. 1 cause of death in the U. S., and measuring coronary artery atherosclerosis has become a most effective method for evaluating cardiovascular risk. While physicians are increasingly prescribing testosterone replacement for their older male patients, recent studies had reached conflicting conclusions about the potential cardiovascular risks.

This finding of a significant increase in plaque volumes among men undergoing testosterone treatments indicates they may face a potentially increased risk of heart disease. However, longer-term research is needed to determine the actual risk."

Another study investigating testosterone therapy published in the same issue of JAMA found no indication of an increased risk for cardiovascular events for men with androgen deficiency. The men in this study were age 40 and older.

Men who used testosterone replacement therapy to treat symptoms of androgen deficiency had a 33 percent lower risk of cardiovascular events such as heart attacks and stroke compared to those who did not receive any hormone therapy. Of those who received testosterone replacement therapy, 8.2 percent had a heart attack or stroke during the study period.

The study evaluated 44,335 male patients at Kaiser Permanente medical centers in Northern and Southern California who had been diagnosed with androgen deficiency between January 1, 1999 and December 31, 2010. Of these, 8,808 men were treated with testosterone replacement therapy, while 35,527 were never dispensed testosterone.

Androgen Deficiency

Androgen deficiency in men is characterized by lower levels of male sex hormones, specifically testosterone, as well as symptoms that include loss of sexual desire, erectile dysfunction, breast enlargement or tenderness, hot flashes, reduced energy, irritability and depressed mood. Similar to women, men experience a normal decline in sex hormone levels beginning in their 30s.

The decline in men is gradual and occurs over a number of years. It is estimated that approximately one in 200 men under the age of 60 has testosterone levels below normal, but as many as two in 10 men over the age of 60 have low levels. Not all men with low testosterone levels have symptoms of androgen deficiency.

Symptoms related to androgen deficiency can be treated with testosterone replacement therapy given by injection, orally or topically. Some recent studies, however, have raised concerns that testosterone replacement therapy may increase the risk for cardiovascular events such as heart attacks and strokes.

Other studies report that low testosterone levels in older men are associated with increased cardiovascular risk and that testosterone replacement therapy may have cardiovascular benefits.

Budoff MJ, Ellenberg SS, Lewis CE, Mohler ER, Wenger NK, Bhasin S, Barrett-Connor E, Swerdloff RS, Stephens-Shields A, Cauley JA, Crandall JP, Cunningham GR, Ensrud KE, Gill TM, Matsumoto AM, Molitch ME, Nakanishi R, Nezarat N, Matsumoto S, Hou X, Basaria S, Diem SJ, Wang C, Cifelli D, Snyder PJ
Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone
JAMA. 2017;317(7):708-716. doi:10.1001/jama.2016.21043

Cheetham TC, An J, Jacobsen SJ, Niu F, Sidney S, Quesenberry CP, VanDenEeden SK
Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency
JAMA Intern Med. Published online February 21, 2017. doi:10.1001/jamainternmed.2016.9546

Last Updated on November 14, 2022