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Jen Landa, M.D. Ob/Gyn; Hormone Specialist; Chief Medical Officer of BodyLogicMD
This week the headlines have been all about a new study in the Journal of the American Medical Association that discusses the association of hormone therapy with the risks of death, heart attack and stroke in men with low testosterone levels. There are multiple problems with the current study that must be considered before men get scared off hormone therapy as women were scared off their potentially beneficial hormone replacement therapy. The current study misses so many important facets of hormone replacement therapy that the results are practically meaningless.
Multiple prior studies have shown that hormone therapy may protect against heart disease and decrease mortality. In a study published in June 2012 in the Journal of Clinical Endocrinology and Metabolism that also examined veterans, the authors concluded that hormone treatment resulted in a 39 percent decreased mortality risk vs. men not treated with testosterone. Importantly, many studies have shown that men with lower hormone levels are at a higher risk of mortality. A 2007 study also in the Journal of Clinical Endocrinology and Metabolism studied 794 men aged 50-91 years old for over 11 years and showed that men with hormone levels in the lowest quartile were 40 percent more likely to die than those with higher levels. In this study, low hormone also predicted increased risk of cardiovascular disease.
So, the important question here is why hormone therapy was associated with increased risks in this study when lower testosterone levels are clearly associated with increased risks of death and disease whereas higher levels of hormone are associated with protection against cardiovascular disease and mortality. There are multiple reasons for this outcome. In this study, the authors mention that only 60 percent of the patients had an additional hormone level checked after starting treatment. Without follow up testing it would be impossible to know if therapeutic increases in testosterone were achieved with the hormone treatment. The men who did have follow up testing did not have optimal increases in their levels of testosterone.
There are several risk factors of hormone replacement therapy that were not addressed in this study and do not tend to be addressed by doctors who prescribe hormone hormone therapy in general, unfortunately. Hormone therapy may cause increased concentration of red blood cells (erythrocytosis). A study published in the journal Therapeutics and Clinical Risk Management regarding risks and benefits of testosterone replacement therapy states that elevations in hemoglobin (concentration of red blood cells) may have bad outcomes because the blood can become thick, which could exacerbate vascular disease. The study authors state that the treatment for this increase in concentration of red blood cells is either dose adjustment of the hormone and/or periodic phlebotomy (drawing off blood as in blood or blood donation). This monitoring wasn’t done in the JAMA study.
There are other levels that must be followed when one is placed on testosterone therapy. One of the most important is estradiol (estrogen). Testosterone is known to convert to estrogen readily in men through a process called aromatization. A study in the Journal of Clinical Endocrinology and Metabolism in 2009 showed that testosterone treated men readily convert testosterone to estrogen in a dose dependent manner which means the higher the dose of testosterone, the higher the level of estrogen. A study in the Journal of the American Medical Association also in 2009 showed that men with heart disease with both low levels of estrogen and high levels of estrogen had increased mortality. Since estrogen levels were not assessed in the men in the current JAMA study, it is impossible to know whether subjects had high or low estrogen levels. The prior research states that estrogen levels must be kept in a middle range for optimal survival. Studies show that optimal estrogen levels also protect men from osteoporosis and protect their cognitive function as well. For testosterone therapy to produce optimal results, levels of estrogens must be assessed on an ongoing basis to assure that levels are not too high, which may increase risk of cardiovascular disease and mortality and cause other issues like gynecomastia or development of increased male breast tissue.
Testosterone converts to another hormone known as dihydrotestosterone (DHT). DHT was also studied in the previously mentioned Journal of Clinical Endocrinology and Metabolism study. The more testosterone a man receives, the more his DHT level will rise. Researchers in 2004 published in the journal Endocrinology that the hormone DHT enhances some of the early stages in atherosclerosis. With testosterone therapy it is possible for excess levels of DHT to be produced. Again, in this study, men given testosterone therapy were not monitored for high DHT levels which may have put them at additional, unnecessary risk for cardiovascular disease. High DHT levels can also be associated with symptoms of benign prostatic hypertrophy (benign growth of the prostate) and male pattern baldness as well.
In conclusion, testosterone therapy should not be taken lightly but when managed properly can improve low testosterone levels, which is associated with a lower risk of cardiovascular disease and a lower mortality risk. This elevation of testosterone can be accomplished safely only when proper additional monitoring is undertaken. Consider consulting a hormone specialist who is knowledgeable in this area to experience optimal results from testosterone therapy.