The media was again splattered with bad news about testosterone therapy this week. On Wednesday, Jan. 29, 2014, Finkle and colleagues published a study in the journal Plos One that exhibited an increased risk of heart attacks in testosterone users in the first 90 days of therapy, and the risk was higher in men who had had a history of cardiovascular disease. There are many problems with the data in this study and others like it that have lead to attention-grabbing headlines about how treatment of low testosterone levels may put men at undue risk. Similar to a November 2013 JAMA study of testosterone risks that I reviewed in a prior post, this current study has multiple flaws that make its conclusions essentially meaningless. Neither study assessed testosterone levels of patients before and during therapy. There are other critical blood tests that should be done that were not being done during the treatment of the VA men or in the current study, including blood counts and estrogen levels. Higher red blood cell counts and higher estrogen levels are known issues that may occur in men given testosterone therapy. Without assessment of testosterone levels, red blood cell counts and estrogen levels prior to and during therapy, it is impossible to tell if a patient is a proper candidate for therapy and if they are tolerating the therapy well.
These newer studies have prompted some to ask for warnings on testosterone therapy and to educate their patients on possible increased risks of heart disease. Doctors are the ones who need more education here. Physicians should be educated on the possible issues they may encounter with patients on testosterone therapy, including higher levels of red blood cells and elevated levels of estrogen. Physicians should monitor their patients' blood cell counts and estrogen levels on testosterone therapy to assess for these risk factors for cardiovascular disease. If a patient has a high red blood cell count, the dose of the testosterone can be decreased or the patient can be sent for blood donation to reduce the high red blood cell count and thus any increased risks of clots or heart attacks. Additionally, high estrogen levels may increase the risk of heart attack and stroke. There are medications that can be prescribed to control high estrogen levels and keep estrogen in the proper, low risk range. These precautions need to be used when prescribing testosterone therapy and studies need to be done reflecting results of testosterone use when these precautions are followed.
Additional concerns abound with the quality of the results of this newest study. The most glaring has been totally ignored by the authors. They compared the groups of men started on testosterone therapy to men who were started on PDE5 inhibitors and found a lower risk of heart disease in the PDE5 inhibitor group. PDE5 inhibitors are drugs used to treat men with erectile dysfunction -- Viagra and others are in this class. The authors state they used this group so there would theoretically be an increase in sexual activity in both groups. They ignored one very important point, though. PDE5 inhibitors work in many tissues throughout the body, including having significant positive effects on the cardiovascular system. Two of the PDE5 inhibitors have recently been approved for treatment of idiopathic pulmonary hypertension because of the ability of PDE5 inhibitors to relax blood vessels. A new study out this month in the Journal of Cardiovascular Pharmacology and Therapeutics states that PDE5 inhibitors have potential as cardiovascular drugs in patients with coronary artery disease and even possible improvement in heart failure patients. With the data that PDE5 inhibitors can decrease the risk of heart disease and help to relax blood vessels in men with heart disease, how can the authors of the testosterone therapy study possibly think that men on PDE5 inhibitors would be a good control group against the men placed on testosterone therapy?
The results of the Plos One study run counter to a large body of literature of the last 20 years that supports testosterone treatment as an important therapy that can improve cholesterol levels, decrease blood sugar levels, reduce body fat and increase lean muscle mass, all factors that would reduce the risk of heart disease. A new review article was published in December 2013 in the esteemed Journal of the American Heart Association with the goal of providing a comprehensive review of the clinical literature that has examined the associations between testosterone and cardiovascular disease. Well over 100 studies were reviewed, and the authors concluded that low levels of testosterone are associated with higher rates of mortality and cardiovascular- related mortality, higher rates of obesity and diabetes. Additionally, the severity of disease correlated with the degree of testosterone deficiency. Testosterone therapy has been shown to relax coronary arteries and improve ability of patients with congestive heart failure to exercise. Testosterone therapy has been shown to lower blood sugar in diabetics and to lower body mass index in obese patients. Finally, studies have associated lower testosterone levels with thicker walls of some of the major blood vessels. This thickening increases the risk of atherosclerosis thus leading researchers to conclude that low levels of testosterone increase the risk for atherosclerosis. All of these factors point to the conclusion that optimal testosterone levels decrease the risk of cardiovascular disease.
The results of the current study, despite all the news media coverage, are essentially meaningless. Testosterone therapy can be an excellent way to help men to enhance their quality of life and decrease their risk of multiple diseases, as shown in many studies. Importantly though, the therapy should not be undertaken lightly and should be properly monitored by a hormone specialist that is well versed in the risks of therapy and the treatment of possible side effects for patients to have optimal benefits from the therapy.