Testosterone is the primary sex hormone (androgen or steroid hormone) produced by the testes and it plays an essential role in the health men. Beyond determining the male sex characteristics, testosterone is a determinant of muscle strength, bone mass, libido, potency, and sperm production, or spermatogenesis.
As men grow older, testosterone levels fall, with a steeper decline in unbound or free testosterone; the biologically active portion. The decline in testosterone levels associated with aging is attributable to a number of factors. There is a decline in the absolute number of Leydig cells, which produce testosterone in the testes, and each remaining cell shows a reduced testosterone production. Furthermore, those aging cells respond less robustly to their signal to produce testosterone. Another factor affecting the functional availability of testosterone is the age-related increase in sex hormone binding globulin (SHBG). Up to 50% of circulating testosterone is bound to SHBG, so increased SHBG reduces the available amount of free testosterone. The net result is gradually declining testosterone levels and less available free testosterone. The condition of testosterone, or androgen, deficiency in aging is known as andropause. Its prevalence in healthy males over the age of 40 has been demonstrated in observational studies, but there is no agreed upon blood level that defines andropause. The risk of having low testosterone levels is significantly higher in men with hypertension, hyperlipidemia, diabetes, obesity and asthma or chronic obstructive pulmonary disease than in men without these conditions, and has been noted to be as high as 40% in some studies.
Lower testosterone levels have been associated with poorer cognitive function, higher body mass index, increased body fat, declining muscle mass and strength and impaired general and sexual health in aging men. Recently, lower testosterone levels have also been linked to a number of chronic diseases including, metabolic syndrome, type II diabetes, cardiovascular disease, and prostate cancer, and has been shown to predict higher overall mortality.
EARLY SIGNS
The first signs of declining testosterone levels are generally vague: diminished subjective perception of energy levels, feeling like you’ve lost your edge, increased irritability, decline in mood, decline in memory and concentration, and loss of early morning erections. Interestingly, the decline in sex drive and frequency of sexual thoughts usually precedes the decline in actual performance. More often than not, these symptoms are dismissed as “just getting older”. If not addressed, testosterone levels continue to fall and patients notice difficulty with maintaining muscle mass and strength, difficulty controlling body fat, reduced stamina and poorer athletic performance; despite a maintained activity level or exercise regime. Increased erectile dysfunction, decreased sense of well being and decreased bone mass are other identifiable signs or symptoms of andropause.
Whenever testosterone is discussed, most people think first of male sexual potency and the reproductive organs. The heart, in fact, is one of the organs with the greatest number of testosterone receptors. Testosterone is associated with several effects on cardiac health. It has been linked with reducing coronary artery disease and hypertension risks as well as improving cardiac function in patients with preexisting heart disease. In Circulation, the journal of the American Heart Association, a study in 2000 demonstrated that low-dose testosterone reduced angina symptoms in men with stable angina. Reported in the same Journal in 2007, low testosterone concentrations were associated with increased mortality due to cardiovascular disease, cancer and all causes. Several other studies in the Journal of the American College of Cardiology and Circulation documented the association of low testosterone with increased intima medial thickness; a surrogate marker for heart disease. A 2009 review article in the International Journal of Impotence Research noted that “erectile dysfunction is a marker for underlying vascular disease and its presence predicts increased incidence of subsequent cardiovascular disease.”
ERECTILE DYSFUNCTION MAY PREDICT HEART DISEASE
Erectile dysfunction affects up to 10% of men in their 40’s and more than half of all men by age 70. Reported in JAMA, the Journal of the American Medical Association in 2005, nearly 9500 men aged 55 and older were evaluated every three months over a nine year period for cardiovascular disease and erectile dysfunction (ED). At the start of the study, 85% had no cardiovascular (CV) disease and 47% had ED. The authors found over the course of the study that the risk of incident cardiovascular events was nearly double for men with ED; an association in a similar range to that for current smokers or individuals with family history of CV disease.
More evidence of this frightening association comes from a ten-year Mayo Clinic study. In that study, the strong association between ED and coronary artery disease (CAD) suggested they could be “differing manifestations of a common underlying vascular pathology.” Study participants were divided by ten-year intervals and the youngest men (age 40-49) had the lowest incidence of ED. In each age group, the incidence of CAD increased dramatically in those with ED. Surprisingly, “the risk was highest in the youngest men with ED”. That is, those 40-49 year olds with ED were found to have the highest incidence density of CAD per 1000 person-years. This data suggests all men with ED, and particularly young men with ED, are ideal candidates for cardiovascular risk factor screening. Other factors that can contribute to ED include: diabetes, hypertension, high cholesterol, obesity, cigarette smoking, anxiety, depression and certain pharmaceutical medications. (See the April newsletter: https://alternityhealthcare.com/newsletters/vol2_iss4.html)
Interestingly, average male testosterone levels have dropped over the last 15 years, according to a 2007 population study published in the Journal of Endocrinology and Metabolism. During this same time period, in an effort to reduce the incidence of atherosclerotic heart disease, there has been a push to reduce cholesterol to ever lower and lower levels. Despite that effort, cardiovascular disease incidence has exploded: it is the leading cause of death in the United States. And, the idea that cholesterol is the main cause of atherosclerotic cardiovascular disease is becoming increasingly tenuous; since more than 60% of those having a heart attack have a normal cholesterol profile. Cholesterol, though vilified as the cause of cardiovascular disease, is the precursor molecule for testosterone and all other steroid hormones. Reducing cholesterol too much can interfere with adequate testosterone production. Has the zeal to reduce cholesterol inadvertently affected testosterone levels, ED incidence and, by extension actually increased the risk for cardiovascular disease?
The brain is another organ with an abundance of testosterone receptors. Testosterone was found to be associated with maintained cognitive function in the aging brain, lowered dementia risk and improvements in the neurophysiology of patients with preexisting dementia. A study published in the journal Neurology in 2004 demonstrated an association between low testosterone levels and subsequent development of Alzheimer’s disease. Another small study in the Archives of Neurology, 2006, evaluated the effects of testosterone therapy on cognition, neuropsychiatric symptoms, and quality of life in male patients with Alzheimer’s disease and healthy elderly men. It found that patients receiving testosterone had significant improvement in quality-of-life scores, improved numerical scores and less decline in visuospatial functions. The Health in Men Study published in the Clinical Endocrinology Journal 2008 concluded that “higher serum free testosterone is associated with better cognitive function in aging men.” In this same journal, an observational study of 3453 men aged 65-83 years suggested that healthy lifestyle choices may slow the decline in testosterone. These interventions included:
- no smoking
- moderate physical activity
- avoiding excessive alcohol
- eating fish > 3 times per week
- eating red meat a < 6 times per week
- maintaining a BMI < 25
- using reduced fat milk
- avoiding added salt in food
Numerous population studies have demonstrated the inverse relationship between both retention of lean mass and gain in fat mass associated with declining testosterone levels. In addition to correlating testosterone decline with loss of lean mass, studies have been done looking at the relationship between testosterone replacement and a return to a more favorable body composition. The consensus in the literature is that testosterone supplementation is accompanied by gains in lean mass across all age groups, reduced body fat with some preferential fat loss on the trunk (central or visceral fat). Visceral fat accumulation and waist circumference have been shown to be independent risk factors for the development of coronary artery disease (CAD). Like the relationship between lean mass, there is a similar correlation between testosterone levels and bone mineral density (BMD) noted in multiple studies over the last 20 years. Retained lean mass is associated with increased strength and coordination, maintained physical function and less injury from falls. Body fat reduction is associated with reduced risk for the development of CAD, type II diabetes and metabolic syndrome. Maintained BMD reduces the risk for the development of osteoporosis and subsequent fractures.
CONTROVERSY
Many physicians hesitate to offer testosterone replacement to aging men with the misguided belief that testosterone causes or fuels prostate cancer. A review of the medical literature, however, reveals no such causal association. A retrospective analysis published in the New England Journal of Medicine in 2004 found no causal relationship between testosterone replacement and prostate cancer or heart disease. A 2007 review out of Harvard concluded that: “Although there is yet to be a large, long term, controlled study on the effect of [testosterone replacement therapy] on [prostate cancer] risk, it should be abundantly clear that raising [testosterone] in hypogonadal men has little, if any, impact on prostate cancer risk or growth in the short to medium term. The withholding of testosterone replacement therapy in men because of fear of prostate cancer risk or progression is no longer tenable in an age of evidence-based medicine, because neither evidence nor theory supports this position.” Perceived risks associated with testosterone treatments and its abuse in the areas of athletic enhancement has caused much apprehension and confusion without scientific basis.
TESTING
Before making the decision to supplement with testosterone, appropriate lab testing should be undertaken. Two tests, total testosterone and free testosterone are essential.
Additional information can be gained from measuring dihydrotestosterone (DHT) and estrogen; two substances to which testosterone can be metabolized. These can affect the amount of testosterone available and can cause unwanted side effects, such as breast enlargement, hair loss and prostate enlargement. A baseline PSA must be obtained to screen for preexisting prostate disease. Monitoring growth hormone, thyroid hormone, leutinizing hormone (LH), DHEA, lipid profile and blood count are also clinically prudent in a comprehensive hormone optimization program.
TESTOSTERONE SUPPLEMENTATION
There are a variety of formulations and routes of administration of testosterone available. The best method and formulation should be determined individually between patient and physician. Optimally, the delivery method and formulation should be clinically effective in alleviating the signs and symptoms of testosterone decline and produce predictable, reproducible physiologic levels of testosterone. Currently, there are no recommended oral testosterone formulations. Topical placement with creams or patches – the route of choice for testosterone replacement in women – has limited application in men. Although convenient, there are several distinct disadvantages: low obtainable maximum serum testosterone levels, a large percentage converted to DHT, troublesome local skin reactions and a very large skin area needed to achieve therapeutic levels. The current standard bearer for direct testosterone supplementation is weekly intramuscular injections of a depot formulation (suspended in oil). This route gives predictable results, adequate therapeutic levels and avoids excess conversion to DHT. Subcutaneous testosterone pellets or implants are available but require a small surgical procedure to insert them. They also produce predictable therapeutic levels.
Another alternative is to stimulate your own testicular function to produce more testosterone, using human chorionic gonadotropin (HCG). This method mimics your natural pituitary physiology but responsiveness declines with advancing age; greater than 90% response rate at age 40 to under 50% at age 65. A simple blood test can help predict the likelihood of success.
If you, or someone you love, is experiencing symptoms of andropause, or have concerns about your hormone balance, I recommend seeking out a physician that specializes in bioidentical hormone replacement therapy. It is equally important to address other lifestyle issues such as: (1) eating a balanced diet that includes colorful fruits and vegetables, quality proteins and fish, healthy fats and a moderate amount of whole grains, (2) engaging in regular physical activity or exercise, (3) avoid smoking or excessive alcohol consumption, (4) getting 7-9 restful hours of sleep per night. Rather than narrowly focusing on just your hormone levels, a comprehensive program will expose your total health picture and help you move toward achieving optimal health.
