LOW TESTOSTERONE LEVELS & FRACTURE RISK IN ELDERLY MEN
Following a recent column in which I discussed the risks versus benefits of testosterone supplementation in older men, a reader wrote to ask me if there were still any medically appropriate reasons for men to receive testosterone replacement therapy. Aside from its use to treat flagging libido in men with documented low levels of this primary male sex hormone in the blood, the indications for testosterone supplementation in older men have been rather controversial. The only other mainstream clinical indication for testosterone replacement therapy, to date, has been to treat—or prevent—osteoporosis (a weakening of the bones due to loss of mineral content), in an effort to prevent the skeletal fractures that become more common as we age. Unfortunately, there is far more clinical data to support the use of hormonal and non-hormonal therapies in elderly, postmenopausal women (who suffer from osteoporosis and osteoporosis-related fractures more commonly than older men do) than is the case for men.
Both testosterone in men and estrogen in women play an important role in maintaining strong, healthy bones (as does a calcium-rich diet and adequate Vitamin D levels throughout one’s adult life). Both of these sex hormones naturally decline as we age, however (it should be noted that women’s bodies naturally produce small amounts of testosterone, and men’s bodies also produce small amounts of estrogen). In women, the ovaries stop producing estrogen altogether after menopause, and only very low levels of estrogen are produced, mainly by the body’s fat cells, thereafter. This places older women at a considerably greater risk of osteoporosis, and fractures, than elderly men, as testosterone levels gradually decline with age in men, but the testes of most men continue to produce significant amounts of testosterone throughout life. Another significant factor is that the larger and more heavily mineralized skeletal system of men offers added protection against osteoporosis and fractures in later life, when compared to the thinner, smaller, and less heavily mineralized bones of women.
A new study, just published in the Archives of Internal Medicine, suggests that decreased levels of testosterone in the blood (and to a slightly lesser degree, decreased levels of estrogen in the blood as well) may indeed be linked to an increased risk of fractures in older men. In this study, more than 600 men, aged 60 years or greater, were monitored between 1989 and 2005, for an average observation period of about 6 years. Levels of testosterone and estradiol (the active form of estrogen) in the blood were measured in all study volunteers upon entry into the study. Additionally, clinical risk factors for osteoporosis and osteoporosis-related fractures were assessed, including bone mineral density, calcium intake history, age, weight, and smoking history.
During the period of observation, 113 of the study volunteers experienced an osteoporosis-related fracture. When the data collected in this study were analyzed, the men with the lowest testosterone levels in their blood were noted to have a 48% relative increase in the risk of osteoporosis-related fractures, and hip fractures in particular, for which the relative risk was almost double of that experienced by the men with the highest testosterone levels. At the same time, a 21% relative increase in the risk of fractures was also noted for men with the lowest levels of estradiol in their blood. While testosterone supplementation is not without risk, the results of this study certainly suggest that older men with very low testosterone levels in the blood should at least be considered for testosterone replacement (although only under the supervision of physicians who are knowledgeable and experienced in Endocrinology, a specialty that focuses of the body’s hormones and hormone-producing glands). Older men with a family history of osteoporosis and very low testosterone levels should particularly consider a consultation with an experienced Endocrinologist.
EXPOSURE TO AIR POLLUTION & GENETIC DAMAGE IN SPERM CELLS
In our increasingly urban, industrialized world, chronic exposure to environmental pollutants has become a major public health concern. Long-term exposure to particulate air pollution, and especially to diesel engine exhaust, has previously been linked to an increased risk of both chronic lung disease and cancer by previous studies. As a research and clinical fellow in Surgical Oncology, a few years back, I lived in an area of west Los Angeles that abutted I-405, an extremely busy interstate highway that was always jam-packed with big commercial trucks and their rattling, wheezing big diesel engines. No matter how often, or how thoroughly, we cleaned our home, the very next morning, every window sill that faced I-405 would again be covered with a thin layer of black soot, hurled into the air by thousands of passing diesel-powered vehicles. These particulate pollutants, which are capable of reaching the deepest recesses of our lungs, are considered to be carcinogenic, based upon previous animal and human research data.
A new research study, published in the journal Proceedings of the National Academy of Sciences, provides further scientific evidence that particulate air pollutants can directly cause mutations and other damage to our DNA which, in turn, may increase the risk for cancer development. What is especially unique about this study, and worrisome as well, was the finding that exposure to particulate air pollutants also appears to damage the DNA of sperm cells in male mice (more about the potential significance of this finding in a moment…).
Male mice were divided into two groups for this study. All mice were housed in a facility situated near a major highway and steel mill, where the ambient air was known to contain high levels of particulate air pollutants. One group of mice was housed in cages that were fully exposed to the polluted ambient air around them, while the second group of mice was housed in special cages outfitted with high-efficiency HEPA air filtration systems. At the end of the study, the animals were euthanized, and their testicles were then subjected to multiple standard tests for DNA mutations and damage known to be associated with an increased risk of cancer. Strikingly, the sperms cells in the mice that were exposed to high levels of particulate air pollutants revealed significant DNA mutations and other signs of “DNA injury” when compared to the animals that were housed in cages with HEPA filters.
The most striking aspect of this study is that it revealed that exposure to particulate air pollutants not only increases mutations in the DNA of our bodies’ cells, but also in our reproductive cells as well. This raises at least the possibility that high levels of air pollution may not only have an adverse potential impact on the health of individual human beings, but that these adverse health effects might also be passed along to our offspring as a result of DNA damage occurring in sperm cells as well (this study did not evaluate the effects of exposure to particulate air pollutants on the ova of female mice, so the effects, if any, of such exposure on the ovaries of mice is unknown at this time).
A couple of major caveats must be raised before applying the worrisome findings of this study to humans, however. First of all, this was an animal study that involved the use of mice, and not men (undoubtedly, very few men would have volunteered for such a study...). As we have learned from many other previous studies, mice and men are similar in many ways, but not in every way. Unfortunately, what is observed to happen in mice in the laboratory does not always prove to also happen in humans. Secondly, because the ambient air in urban areas contains a very complex stew of chemical and particulate contaminants, and because this study did not specifically identify the individual pollutants that caused the observed damage to sperm cells, we cannot be certain which substances in the polluted air actually caused the DNA damage. These caveats aside, however, this is a very important public health study, and it should compel further study in humans in an effort to learn whether or not chronic exposure to polluted air might be exposing our unborn children and grandchildren to diseases (both benign and malignant) transmitted through sperm and, possibly, ova, damaged by such exposure.
STATINS & TRAUMA SURVIVAL IN THE ELDERLY
Despite recent reports calling into question the degree of cardiovascular protections offered by statins in patients who are not already at very high risk of coronary artery disease or stroke, the preponderance of clinical data regarding these extremely popular drugs continues to show a marked reduction in the risk of heart attack and stroke in most patients who take statins for the appropriate indications. Although still the subject of debate by experts, there is also a growing body of evidence that certain statins might be associated with at least a mild reduction in the incidence of some types of cancer as well (I have summarized several of these studies in previous columns, which are archived and still available for online review). Although the mechanism behind the anti-cancer effect of statins, if any, is not clearly understood, many experts believe that the anti-inflammatory effects of statins drugs may play an important role in both the prevention of heart disease and in cancer risk reduction. Now, a new study takes a rather novel look at the protective effects of statins on an unusual group of patients, and once again, the anti-inflammatory heart-protective effects of statin drugs may have an important role to play.
A new research paper in the Journal of Trauma, Injury, Infection & Critical Care looked at the impact of chronic statin use on the survival of elderly patients admitted to 69 different hospitals following moderate-to-severe traumatic injuries. More than 1,200 patients, 65 years of age and older, were included in this study. Multiple clinical factors were analyzed, and then correlated with mortality in this large group of elderly trauma patients. Among the factors evaluated were ongoing statin use prior to injury, gender, age, and associated health conditions (e.g., a history of cardiovascular disease, heart attack, stroke, diabetes, high blood pressure, emphysema, kidney disease, and smoking). The severity of these patients’ traumatic injuries was then graded using the previously validated Abbreviated Injury Scale. All of the resulting data was statistically analyzed and correlated to the risk of death following admission to the hospital.
Overall, the pre-injury use of statin drugs among these seriously injured elderly patients was associated with a whopping 67% reduction in the risk of death while in the hospital! When the researchers further analyzed the data, they found that this apparent life-saving effect of statin drugs only applied to those patients with a previous history of cardiovascular disease. In this group of patients, pre-injury use of statins was associated with a 70% reduction in the risk of death while hospitalized. Among the elderly patients taking statins, but without any significant history of cardiovascular disease, the death rate was actually somewhat greater, by 40%, when compared to patients with a similar health history and who were note taking statin drugs at the time of injury. This intriguing study dovetails nicely with existing data showing that the initiation of statin drugs immediately after a heart attack appears to reduce mortality, as well as the risk of subsequent heart attacks. Based upon this trauma research study, it would appear that long-term statin use may also protect the cardiovascular system of patients with heart and vascular disease when these body systems are under the tremendous physiological stress that results from serious injury.
Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity.
Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center
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Copyright 2008. Robert A. Wascher, MD, FACS. All rights reserved.
Dr. Wascher's Archives:1-12-2008: Statins, Diabetes & Stroke and Obesity; GERD & Esophageal Cancer
12-16-2007: Honey vs. Dextromethorphan vs. No Treatment for Kids with Night-Time Cough, Acupuncture & Hot Flashes in Women with Breast Cancer, Physical Activity & the Risk of Death, Mediterranean Diet & Mortality