Acute Anti-Ischemic Effect of Testosterone In Men With Coronary Artery Disease
I commonly recommend Testosterone Replacement Therapy (TRT) in appropriate patients for a number of reasons. However, many cardiologists, other physicians, and even some patients are concerned about possibly increasing the risk of cardiovascular disease. One thought is that men have a higher incidence of coronary artery disease which suggests a possible role with testosterone. However, some studies show endothelium-dependent relaxation is increased with testosterone. An article published in Circulation may help address some of these concerns.
According to the authors of this study, there is no direct evidence supporting the link between testosterone and coronary artery disease. They state that the only link between testosterone and coronary artery disease are indirect associations of body fat distribution and gender. Additionally, multiple studies demonstrate improvement in chest pain & post-exercise ischemia (ST depression) with testosterone.2-10 Another study demonstrated endothelium-independent arterial relaxation (rabbit) effects of testosterone.11 Therefore, it appears that testosterone has a protective effect in arterial tone and myocardial ischemia.
This study attempted to determine effects of IV testosterone therapy on exercise-induced myocardial ischemia in a population of men with known coronary artery disease.
14 patients ranging in age from 45 to 66 with known coronary artery disease of at least 70% arterial occlusion (identified by angiography) were enrolled. 5 of these patients had previous heart attacks and they were all taking medications to improve chest pain.
A baseline Bruce Protocol treadmill stress test was performed on all patients at baseline before any therapy was performed and showed at least 1mm ST-segment depression. There was a pharmacologic washout period to remove confounding results due to medications. Patients received either IV testosterone (2.5mg IV over 5 minutes) and performed a treadmill stress test 30 minutes later. The treadmill stress test was then repeated 2 days later at the same time of day receiving either IV testosterone or placebo again.
4 participants had a negative treadmill stress test after receiving testosterone meaning that they had less than 1mm ST-segment depression during the test. Recall that all participants had at least 1mm depression during their baseline treadmill stress test previously. The following table summarizes the results.
|Baseline & Placebo||Baseline & Testosterone|
|Stress test stopped due to worsening chest pain||10||6|
|Stress test stopped due to fatigue||4||8|
|Time (seconds) to ST-depression||471 + 210||579 + 204|
|Total exercise time (seconds)||541 + 204||631 + 180|
|Heart rate at onset of 1mm depression||123 + 14||135 + 12|
|Maximum ST-segment depression||2.1 + 0.4mm||1.7 + 0.3mm|
|ST-segment recovery time||215 + 34||168 + 48|
This study shows that testosterone administered IV improved ischemia during stress test in patients with coronary artery disease. The effect seemed to be greater in patients with low baseline testosterone. However, patients with ‘normal’ testosterone levels still seemed to benefit as well.
The authors provide a fairly comprehensive discussion in the original paper and may be worth the read.
- Rosano G, et al. Acute Anti-Ischemic Effect of Testosterone in Men with Coronary Artery Disease. Circulation. 1999;99:1666–1670
- Bonnel RW, Pritchett CP, Rardin TE. Treatment of angina pectoris and coronary artery disease with sex hormones. Ohio State Med J. 1941;37:554-556.
- Hamm L. Testosterone propionate in the treatment of angina pectoris. J Clin Endocrinol. 1942; 2:325-328.
- Lesser MA. The treatment of angina pectoris with testosterone propionate: preliminary report. N Engl J Med. 1942; 226:51-54.
- Lesser MA. The treatment of angina pectoris with testosterone propionate: further observations. N Engl J Med.1943; 228:185–188.
- Sigler LH, Tulgan J. Treatment of angina pectoris by testosterone. N Y State J Med.1943; 43:1424–1428.
- Strong GF, Wallace W. Treatment of angina pectoris and peripheral vascular disease with sex hormones. Can Med Assoc J.1944; 50:30–33.
- Waldman S. The treatment of angina pectoris with testosterone propionate. J Clin Endocrinol.1945; 5:305–317.
- Walker TC. The use of testosterone propionate and estrogenic substance in treatment of essential hypertension, angina pectoris and peripheral vascular disease. J Clin Endocrinol.1942; 2:560–568.
- Jaffe MD. Effect of testosterone cypionate on postexercise ST segment depression. Br Heart J.1977; 39:1217–1222.
- Yue P, Chatterjee K, Beale C, Poole-Wilson PA, Collins P. Testosterone relaxes rabbit coronary arteries and aorta. Circulation.1995; 91:1154–1160.
- Lesser MA. Testosterone propionate therapy in one hundred cases of angina pectoris. J Clin Endocrinol.1946; 6:549–557.