Guide to Hormone Replacement Therapy for Men
Hormones and Aging
For decades, women have been choosing estrogen replacement therapy to alleviate the dramatic decline of hormone production known as menopause. Less widely known, however, is the fact that men also undergo a similar decline in the production of hormones, including testosterone, as they age. This ‘male menopause’ is called andropause. In the next few sections we will discuss these hormones, their effects, and the rationale behind their use as anti-aging therapies.
Testosterone and Men
Over the past few years, a number of reports have appeared in the mainstream press about testosterone replacement therapy (TRT) in healthy aging men. News stories often exalt the muscle-boosting, fat-busting effects of TRT in both athletes and in sedentary but healthy older men. At the same time, naysayers warn of the dangers of manipulating our hormones in the absence of term studies proving the safety and effectiveness of TRT.
So how do we separate the myths from the magic?
The decision to start TRT is a complex and personal decision. The benefits of maintaining a youthful level of testosterone are well documented, and we at Youth Diagnostics™ believe that the preponderance of evidence supports its use in many men as they age. However, our knowledge is incomplete, as it often is in clinical medicine. As with any other clinical treatment, it is optimal for men considering TRT to understand the many variables that factor into their decision to start the therapy. Below we will discuss the various aspects of hormone replacement to help you decide, along with the guidance of your physician, whether TRT is right for you.
What is Testosterone?
Testosterone is a member of the steroid family of hormones derived from cholesterols. Ninety-five percent of circulating testosterone is produced in the testicles and is regulated by another hormone released from the pituitary gland, called luteinizing hormone (LH). Throughout the day, LH is released in spurts that stimulate the release of testosterone from the testicles. The signals are particularly strong in the early morning which accounts for higher testosterone levels and typical morning erections. By late evening, the levels of testosterone can fall by 50 percent, which then signals the pituitary gland to rev up its production of LH and begin the cycle all over again.
When discussing testosterone levels, we must be sure to distinguish between the total and free levels found in the blood. The vast majority (between 97 and 99 percent) of testosterone secreted is bound to a protein called ‘sex hormone binding globulin’ (SHBG). This serves to keep the testosterone from being removed by our body’s natural filtration system, the kidneys. The free testosterone is able to enter the body’s cells and perform its natural biological functions.
In addition to testicular production, a small amount of testosterone is produced through the conversion of precursor steroid hormones such as androstenedione and androstenediol. Unfortunately, a greater portion of the androstenedione gets converted into estrogens rather than testosterone, minimizing the muscle-sustaining effects and maximizing other feminizing side effects, such as breast enlargement, in its users.
While testosterone is a member of the group of compounds known as ‘anabolic steroids,’ which are muscle- and bone-building molecules, it is actually different from the kind that is widely known for its abuse by body builders and professional athletes. Such drugs include decadurabolin, oxandrolone, and methyltestosterone, which are different in structure from testosterone and also have different side effect profiles. As potent anabolic hormones, these steroids, when abused, can have adverse effects on other organ systems, such as the brain and liver. Because of the abuse of these unnatural anabolic steroids, this group of steroids, of which testosterone is a member, has been regulated on the same level as morphine, narcotics and other schedule III substances. The resulting effect has been to tarnish the general perception of testosterone among doctors and the public, to the detriment of many who could benefit from the responsible use of testosterone through TRT.
What are the effects of a low testosterone level?
Low levels of testosterone can lead to a disease state called ‘hypogonadism,’ which is an extremely well-documented and treatable condition.
Hypogonadism affects many organ systems and leads to an overall decrease in lean muscle mass, strength, and bone density. The counter-effect is an increase in body fat, both subcutaneously around the waist and also around the organs, which is the unhealthiest kind of fat accumulation. The excess abdominal fat begins a dangerous cycle in which the fat instigates a decline in testosterone levels, which in turn perpetuates a continued accumulation of abdominal fat. The increase in visceral fat (the fat around your organs) is more than an aesthetic concern. An increase of this kind of fat raises your risk of diabetes and cardiovascular disease.
Testosterone also has significant neurological effects, as the brain has numerous receptors for testosterone. Thus, low testosterone levels are associated with depression, low libido, decreases in memory, and a lower sense of well-being.
While impotence is not primarily caused by low testosterone, erectile dysfunction is a symptom of low testosterone. Many men who undergo TRT report that these mild symptoms improve with the therapy.
What is a low testosterone level?
By its general medical definition, hypogonadism is associated with a testosterone level below 300 ng/dl, largely because virtually all men who fall below this range exhibit the signs and symptoms discussed above. But how about men with testosterone levels of 350 or 450 ng/dl who also exhibit significant symptoms? And what about men with average levels of about 600 ng/dl? Is this an adequate level of testosterone or does a man with a level of 900 ng/dl necessarily feel better, have denser bones, stronger muscles, and greater sexual potency?
When we were teenagers, our natural testosterone levels ranged from 800 to 1500 ng/dl. We do not have to describe the vitality we felt then. More than enough studies show the improvements in strength, muscle, and libido when middle-aged men with “normal” testosterone levels opt to increase their testosterone levels to the upper end of normal. Why then should a man be denied treatment if his testosterone level is 500 ng/dl and he experiences symptoms, such as loss of muscle mass and decreased libido? This gets us to the heart of the issue when debating the use of testosterone as an anti-aging therapy.
Do testosterone levels decline with age?
The answer is yes! Certainly the changes in hormone levels as we age differ between genders. With menopause, women experience periods of dramatic drops in estrogen levels. Andropause, as it is popularly termed, however, is more gradual in its hormone changes.
One of the most comprehensive studies on testosterone levels in aging men has been the Massachusetts Male Aging Study. The study found that total testosterone levels declined by about five percent per decade starting in the thirties to the seventies, and more precipitously in ill or obese men. Some men did not have much of a decline at all. Because of the gradual nature of decline, most men assumed treatment was not necessary. What most did not realize, however, was that the level of free testosterone declined twice as fast, causing hypogonadism in about 50 percent of men over 55 years old. After several subsequent studies confirmed this fact, it is widely acknowledged that, much like menopause for women, men also experience declines in testosterone levels as they age.
To determine if the decline in free testosterone is correlated with some of the symptoms of aging, Dr. John Morley looked at 54 men between the ages of 20 and 84 years old to determine if their bioavailable testosterone levels could predict which of them had declining levels of cognitive and physical functions. As a result of the study, Morley confirmed a strong correlation between the two variables, as have many subsequent studies. It is now widely acknowledged that testosterone levels decline with age and that this decline plays an important role in many of the manifestations of aging. Other factors, such as obesity, smoking, chronic illness, and stress can be very important determinants as well.
When should I start TRT?
At some point in a man’s lifespan he will experience a significant drop in testosterone, though this drop may take place during different decades for different individuals. It is generally acknowledged that if testosterone levels drop below 300 ng/dl, treatment can be necessary and beneficial. But what about a 50-year-old healthy male with a total testosterone of 500 ng/dl who has always had 30 percent higher levels than the average male since he was 20? Should he wait until he reaches the “magic” number of 300 ng/dl before he begins TRT, even though he may be exhibiting typical symptoms such as decreased libido, excess weight gain, and mild depression? Herein lies the debate.
The questions that need to be answered are whether one can expect a benefit from raising his testosterone levels to those of an average young adult, and whether he can expect any detrimental effects in doing so.
Many studies have analyzed the effects of raising testosterone levels in young men to the high adolescent range - 1000 to 2000 ng/dl. In all of these studies, lean muscle mass increased and fat mass decreased.
Other studies with lower doses were conducted involving moderately obese men; again, lean mass increased and fat decreased even more. Additionally, insulin resistance (a pre-diabetic state) improved, triglycerides decreased, and energy levels increased. In none of the studies were there increases in aggressive behavior as seen at the abusive levels of those looking to achieve athleticism outside of the human bell curve.
Many more published studies have shown similar effects in older men (over 65) with mildly low testosterone levels. The NIA has published the results of TRT studies on body composition (lean muscle and fat ratios) in 108 men, in which subjects demonstrated a 6 lb fat loss and 5 lb lean muscle gain when their testosterone levels were raised from an average of 370 to 640 ng/dl for 36 months. The same men showed an increase in bone density if they started out with a low bone density. The accumulating evidence shows that whenever the testosterone level is raised — no matter the starting level — you see benefits in body composition.
Is TRT safe?
The short-term risks or side effects of TRT are few. Acne may occur in individuals with a genetic susceptibility to acne; however, acne medications are usually very effective in addressing this. Male pattern baldness can be exacerbated as well, though this too can be effectively treated with a medication that inhibits the conversion of testosterone to dihydrotestosterone, called finasteride or Propecia.
The main concern among men about the effects of TRT is the potential for long-term risks and whether or not TRT increases the risk of prostate cancer or cardiovascular disease. At physiologic replacement levels - the range we keep our patients within - there is no evidence of any increased risk of prostate cancer nor enlargement of the prostate to the point of exhibiting symptoms. While the longest prospective study on TRT has been the three-year NIA study, which didn’t indicate any prostate problems, the overwhelming majority of case-controlled, retrospective, epidemiological studies following men for several years show no increased risk in men whose testosterone levels are higher than average. It is a well-documented fact that prostate cancers shrink when testosterone is blocked; however, testosterone itself is not proven to have a causal role in prostate cancer. For those who have an occult cancer, excess testosterone may cause it to grow; however, we screen all of our patients with a PSA (prostate specific antigen) before starting TRT and we continue to monitor PSA twice a year.
The concern about the link between testosterone and heart disease is based on the fact that men have a higher incidence of heart disease than women and that men have higher testosterone levels than women; therefore, higher testosterone levels may cause a greater incidence of heart disease. This is faulty reasoning in regard to hormone replacement therapy. In fact, there are many studies that show just the opposite. The issue has been studied extensively, and there is a greater incidence of heart disease in men with low testosterone levels than those with high levels. Other studies have looked at the effect of TRT on cholesterol levels and universally found a decrease in total cholesterol, LDL, and triglycerides, and no change or only a slight decrease in HDL. Finally, restoring testosterone levels to youthful levels can reverse changes in body shape, which is a proven risk of cardiovascular disease.
How do I get started with TRT?
The first step is to prepare bloodwork to determine your various hormone levels, including total testosterone, free testosterone, SHBG, estradiol, and PSA. The next step is to perform our Youth Diagnostics™ workup to determine if TRT is necessary in the context of your individual health. If you are a candidate we place you on a bioidentical cream- or gel-based transdermal testosterone therapy. We use a cream so that the testosterone is absorbed slowly through the skin, thereby avoiding any large swings in testosterone levels and also avoiding injection. The following few months will be dedicated to monitoring and adjusting your dose, depending on how you feel, as well as your laboratory test results.
In addition to your regimen, we often add supplements such as saw palmetto and pygeum to avoid potential side effects in the prostate. An adequate level of zinc will also minimize conversion of testosterone to estradiol, an important hormone for men as well, but only at specific doses. With close monitoring, most of these adverse effects can be avoided.
DHEAS is an important hormone in the overall endrocrine system and is among the most critical hormones in any HRT program. DHEA is accessible over the counter, which has generated significant amounts of press coverage and has resulted in a glut of information that can be contradictory and confusing. Between adolescence and old age, the physiologic levels of DHEA in the human body gradually declines, a course that is correlated with numerous health hazards, including increased risk of heart disease among men, a hampered immune system for men and women, as well as reduced insulin sensitivity.
Scientific studies in which the level of DHEAS (the form found circulating in the blood) was restored to the levels of a 20-year-old have produced impressive results in older adults. It has also proven effective for people in various disease states where the DHEAS level is lower than expected for their age group. In a six-month study, Yen and Morales administered 50 mg of DHEA to a group of adults aged 40 to 70 years. The patients experienced a rise in lean muscle mass and a drop in fat mass, and had a notable increase in their perception of their psychological and physical well-being. Additional studies demonstrated positive changes in the body’s immune functions.
At Youth Diagnostics™, our physicians assess patients’ DHEA-S level and prescribe the necessary supplements to restore DHEA levels back to that of a 20-year-old individual. As with all treatments, we continuously monitor and evaluate DHEA levels once a patient is on therapy.
DHEAS is very safe and does not require a prescription. While no evidence suggests an increased risk of breast or prostate cancer, patients who have had either cancer should not take the hormone. Before starting DHEA therapy, our physicians screen patients for breast cancer. One side effect of DHEA includes increased hair growth and acne in patients who have had a tendency for acne as a teenager.
The thyroid gland produces thyroxine (T4) and triiodothyronine (T3)—hormones that help to regulate metabolism in the human body. The thyroid hormone that is most prominent in the blood is thyroxine (T4), which has a longer half-life than T3.
Thyroid hormones affect all cells in the body in a variety of important ways. These impacts include increasing the basal metabolic rate, affecting protein synthesis, regulating bone growth, improving neuronal maturation and affecting the body’s sensitivity to many other hormones. The body depends on thyroid hormones to ensure proper development and differentiation of all cells in the body. Many different physiological and pathological factors can influence the synthesis of thyroid hormones, which also regulate protein, fat, and carbohydrate metabolism, and stimulate vitamin metabolism.
Having too much or too little of thyroxine can result in hyperthyroidism or hypothyroidism. Hyperthyroidism occurs when too much free thyroxine and/or free triiodothyronine is circulating in the blood. The condition is fairly common and is found in about 2 percent of women and 0.2 percent of men. Hypothyroidism affects 10 percent of older adults and involves a deficiency of thyroid hormones. Clinical depression can sometimes be caused by hypothyroidism, an example of which is Hashimoto's thyroiditis.
Our patients on thyroid treatment plans are regularly monitored for healthy thyroid function and control of appropriate thyroid levels.
Melatonin is a compound that occurs naturally in the human body. Its levels in the human body rise and fall over the course of the day, in accordance with circadian rhythms and other biological processes within the body. In the evenings, melatonin levels increase and often help people fall asleep, which is why the hormone is commonly used to overcome insomnia or recover from jet-lag.
Melatonin exerts its power by activating melatonin receptors. It also acts as a potent antioxidant that protects cell DNA. Melatonin secretions are regulated by light rhythms and occur in the pineal gland of the brain. Other cells in the body also produce melatonin, including bone marrow cells, lymphocytes and epithelial cells. The melatonin in these cells is not regulated by daylight cycles and is more highly concentrated among these cells than in the blood.
In the United States, melatonin is sold over the counter as a dietary supplement, to address falling levels of melatonin production, which happens as the body ages. We frequently prescribe melatonin supplements for patients starting at age 40, with increasing dosages as one grows older. Melatonin supplements should be taken once daily at bedtime.
Products containing melatonin have been available over-the-counter as a dietary supplement in the United States. It is well documented that humans produce less and less melatonin as they age. Because of this we often recommend melatonin regularly at bedtime starting at age 40 and increasing the dose as they get older.
Growth hormones (GH) stimulate growth, cell reproduction and regeneration, both in humans and other animals. There are two types of GH - somatotropin, which is produced naturally in animals, and somatropin, which is created through recombinant DNA technology. Replacement therapy uses the latter.
Produced by the somatotroph cells in the pituitary gland, human growth hormones (hGH) are released into the blood in spurts during deep sleep. When it reaches the bloodstream, hGH stimulates the liver to produce “insulin-like growth factor I” (IGF-I). Because hGH is released in spurts, it is difficult to measure accurately at any given time. Instead, IGF-I levels, which are more constant, are used as a gauge for hGH production.
An interesting historical fact behind hGH is that its application for anti-aging treatment began when the hormone was being studied for dwarfism and pituitary trauma. These are diseases or conditions in which hGH production is greatly reduced or non-existent. To treat these disease states, the human growth hormone was replaced in the patients, but only until growth was achieved.
At the time of the research, replacement hormones for hGH were obtained from human cadavers until 1986, when new advances in recombinant DNA enabled the mass production of pure, uncontaminated hGH using bacteria. The availability of large amounts of hormone for research led to further study into hGH beyond just its growth roles, to include physiologic functions.
Many patients who were treated with hGH for dwarfism or pituitary trauma experienced several medical problems once they stopped taking hGH treatment. In essence, they found themselves aging prematurely, with twice the risk of heart disease, increased abdominal fat, lower muscle mass, depression, social isolation and poor professional performance. A Swedish study on these patients, however, discovered that a single year of hGH treatment successfully reversed all of the effects of premature aging. The results eventually caused the FDA to approve hGH replacement therapy in August 1996 to treat growth hormone-deficient adults (GHDA).
Concurrently in Wisconsin, another scientist was also exploring the biologic effects of hGH. He documented the continuous decline in growth hormone secretions starting around 30 years of age and sought to correlate this decline with changes in body composition. By 1990, the scientist had published his findings in the New England Journal of Medicine - hGH replacement showed enormous age-reversing effects in 21 men, age 61 to 81. Following six months of therapy, study subjects acquired an average of 8.8% lean body mass and lost 14% fat mass; increased their skin thickness by 7% (skin becomes thinner and less elastic with age); increased their bone density by 1.4%; and reported an enhanced sense of overall well-being. Rudman characterized these impacts as “equivalent in magnitude to the changes incurred during 10 to 20 years of aging.”
The landmark study sparked substantial interest in hGH as an anti-aging therapy, inspiring nine new clinical trials by the National Institutes of Health to test the effect of hGH replacement therapy on healthy adults above age 65. These trials had substantial implications, recognizing that some 40% of adults over 60 have the same IGF-I levels as children with stunted growth or people with pituitary damage.
As with all aspects of science, however, debates continue today about the practice of physiological manipulation. Some opportunistic groups and individuals have also misused and falsely advertised their products, particularly when they stand to profit financially. However, leading experts in the field of anti-aging therapy continue to consider hGH a vital part of adult hormonal therapy and one of the most valuable tools we have to help people live longer, healthier lives.
What to Expect from hGH Therapy
Every patient may have different levels of IGF-I, which is the primary indicator for hGH secretion in your body. Depending on your starting level of IGF-I, our physicians will prescribe the appropriate dosages needed to achieve optimal levels in your body (350 to 400 ng/ml). Most people above age 35 will have reduced levels of IGF-I and may benefit from supplementation.
While every patient’s experience will vary, the benefits you can expect from hGH therapy include:
- Decreased fat mass by 10 to 14 percent after approximately 6 months (predominantly around the waist) without any change in diet and exercise
- Increased lean muscle mass of approximately 7 to 10 percent in the first six months of therapy
- Improved bone density after one year of therapy. Percentage increase depends on starting levels of hormone
- Improved cardiac and lung function, lowered blood pressure
- Increased physical and mental energy
- Increased skin hydration and less propensity for developing wrinkles
- Accelerated wound healing
- Increased immune system functioning, including thymus regrowth (critical to the function of T-cells)
- Decreased total and LDL cholesterol levels, and increased HDL levels
- Improved sleep
- improved vision
- Improved mood
The more severe your starting deficiency of growth hormones (below 100 ng/ml, for example), the more significant changes you will see in your body composition in the first six months of treatment. If you have a mild deficiency of growth hormones to start with, the treatment will serve to prevent the onset of age-related changes.
Safety of hGH Replacement Therapy
A great deal of evidence exists today affirming the safety of growth hormone replacement therapy in adults with deficiencies in growth hormones, which led the FDA to approve hGH for treatment. As normal healthy adults share similar body compositions as GHDA, we believe hGH treatment, with careful and appropriate dosages, are safely applicable for non-GHDA as well. Without a doubt, hGH use has been abused by many, which unfortunately has generated unfounded fear and misinformation about the therapy program. However, not one of the long-term growth hormone replacement studies by the NIH was halted due to adverse effects. Data suggests no adverse effects in GHDA who have used the therapy for a decade, nor does any evidence suggest that long-term use of hGH can increase the risk of cancer.
“When one does not abuse or overdose human growth hormone, there is simply no evidence suggesting that human growth hormone replacement therapy causes any long term side effects,” according to Dr. Bengtsson, a leading expert in the field, (Hormone Research, 43, p 93-99, 1995). Still, cancer patients should not take growth hormones, as they may worsen the disease. At Youth Diagnostics™, we screen patients for cancer regularly.
The Problem of Dose
Many different sources may offer conflicting and contradictory evidence about the benefits or negative effects of hGH. One study involving older men documented a high incidence of side effects. However, these men were taking hGH doses that exceeded the amounts needed to achieve positive changes. The study subjects also took the dosages only three times a week, whereas new research indicates that hGH injections should be administered 1-2 times daily, using lower dosages than those used in the study. At this rate and dosage level, no significant side effects occur. Patients may experience swelling or aching in the joints for a few days during the early period of therapy.
No other hormone has demonstrated the ability to achieve the kinds of positive changes that hGH can generate. But growth hormones may not be for everybody. hGH therapy can be expensive (approximately $400 to $800 per month). Others may be uncomfortable with injections, which are the only safe and effective method for administering the hormone, and must be done in small doses each day. We encourage our patients to avoid any offers of non-injectable or hGH stimulators that are available online and over the counter.
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8. Johannsson G, Rosen T, Bosaeus I, Sjostrom L, Bengtsson BA. Two years of growth hormone (GH) treatment increases bone mineral content and density in hypopituitary patients with adult-onset GH deficiency [see comments]. J Clin Endocrinol Metab. 1996;81:2865-73.
9. Klatz R, Kahn C. Grow Young With HGH. . First ed. New York: HarperCollins; 1997:368.
10. Morales AJ, Nolan JJ, Nelson JC, Yen SSC. Effects of Replacement Dose of Dehydroepiandrosterone in Men and Women of Advancing Age. Journal of Clinical Endocrinology and Metabolism. 1994;78:1360-1367.
11. Rosen T, Johannsson G, Johansson J-O, Bengtsson B-A. Consequences of Growth Hormone Deficiency in Adults and the Benefits and Risks of Recombinant Human Growth Hormone Treatment. Hormone Research. 1995;43:93-99.
12. Sears, Barry. The Anti-Aging Zone. New York : ReganBooks. 1998. 13. Somers, Suzanne. The Sexy Years. Crown Publishing Group. 2004.e encourage our patients to exercise regularly.