Androgen Replacement Therapy/Hypogonadism
The most widely used medical application for anabolic/androgenic steroids in the world is that of androgen replacement therapy. Also referred to as Hormone Replacement Therapy (HRT) or Testosterone Replacement Therapy (TRT), this therapy involves the supplementation of the primary male hormone testosterone to alleviate symptoms of low hormone levels (clinically referred to as hypogonadism). Patients may be adolescent males suffering from childhood hypogonadism or a specific disorder that causes androgenic hormone disruption, although most of the treated population consists of adult men over the age of 30. In most cases hormone levels have declined in these men as a result of the normal aging process.
The most common complaints associated with low testosterone in adult men include reduced libido, erectile dysfunction, loss of energy, decreased strength and/or endurance, reduced ability to play sports, mood fluctuations, reduced height (bone loss), reduced work performance, memory loss, and muscle loss. When associated with aging, these symptoms are collectively placed under the label of “andropause”. In a clinical setting this disorder is referred to as late-onset hypogonadism. Blood testosterone levels below 350ng/dL are usually regarded as clinically significant, although some physicians will use a level as low as 200ng/dL as the threshold for normal. Hypogonadism is, unfortunately, still widely underdiagnosed. Most physicians will also not recommend treatment for low testosterone unless a patient is complaining about symptoms (symptomatic androgen deficiency).
Androgen replacement therapy effectively alleviates most symptoms of low testosterone levels. To begin with, raising testosterone levels above 350ng/dL (the very low end of the normal range) will often restore normal sexual function and libido in men with dysfunctions related to hormone insufficiency. With regard to bone mineral density, hormone replacement therapy is also documented to have a significant positive effect. For example, studies administering 250 mg of testosterone enanthate every 21 days showed a 5% increase in bone mineral density after six months. Over time this may prevent some loss of height and bone strength with aging, and may also reduce the risk of fracture. Hormone replacement therapy also increases red blood cell concentrations (oxygen carrying capacity), improving energy and sense of well-being.Therapy also supports the retention of lean body mass, and improves muscle strength and endurance.
Unlike steroid abuse, hormone replacement therapy may have benefits with regard to cardiovascular disease risk. For example, studies tend to show hormone replacement as having a positive effect on serum lipids. This includes a reduction in LDL and total cholesterol levels, combined with no significant change in HDL (good) cholesterol levels. testosterone supplementation also reduces midsection obesity, and improves Insulin sensitivity and glycemic control. These are important factors in metabolic syndrome, which may also be involved in the progression of atherosclerosis. Additionally, testosterone replacement therapy has been shown to improve the profile of inflammatory markers TNF·, IL-1‚ and IL-10. The reduced inflammation may help protect arterial walls from degeneration by plaque and scar tissue. The medical consensus today appears to be that replacement therapy in otherwise healthy men generally does not have a negative effect on cardiovascular disease risk, and may actually decrease certain risk factors for the disease in some patients.
There are some concerns with initiating testosterone replacement therapy when the individual is in poor health. One study examined the safety of HRT in men aged 65 and older with limited mobility and various health conditions such as obesity, hypertension, diabetes, or hyperlipidemia. Each subject took a transdermal testosterone gel (10g/100mg) or placebo gel daily for six months. During the course of treatment, a total of 23 men in the testosterone group had cardiovascular-related adverse events. This was compared to only 9 in the placebo group. Another study with middle-aged hypogonadal men found that testosterone replacement therapy (testosterone enanthate 250mg/2 weeks) reduced vascular reactivity, an important factor in atherosclerosis. These studies suggest that care should be taken when considering HRT in men with heart disease, strong contributing factors to heart disease, or other chronic health conditions.
There are other areas of concern with elderly patients. To begin with, testosterone administration may increase prostate volume and PSA values. While this does not appear to be of clinical significance with normal healthy patients, benign prostate hypertrophy and prostate cancer can be stimulated by testosterone. Men with prostate cancer, high PSA values, or breast cancer are generally not prescribed testosterone. Androgen supplementation has also been linked to sleep apnea, which can interfere with the most restful (REM) phase of sleep. The studies have produced conflicting data, however, and the potential relationship remains the subject of much debate. Lastly, testosterone replacement therapy has demonstrated negative, positive, and neutral effects on cognitive functioning in elderly men. Studies do suggest that the dose can dictate the level of response, with the most positive effects noted when the androgen level reaches the mid-to upper-range of normal, not supraphysiological. Elderly patients with preexisting deficits in cognitive function should have their cognitive performance and blood hormone levels monitored closely during hormone replacement therapy.
Common Treatment Protocols
Transdermal application is the most commonly prescribed method for supplementing testosterone in the United States and Canada, and is generally the first course of therapy initiated with androgen replacement therapy patients. This method of drug delivery offers a number of advantages to the patient when compared to injection. Since the transdermal application is painless, patient compliance and comfort is increased in comparison. Transdermal application also provides stable day-to-day hormone levels, and does not produce the broad fluctuations usually noticed with injectable testosterone esters. The most common protocol among hormone replacement doctors is to prescribe a dosage of 2.5-10 mg of testosterone per day (approximate absorbed dose). This is applied as a rub-on gel or adhesive transdermal patch that is replaced daily. Note that due to metabolism in the skin, transdermal application of testosterone tends to increase serum dihydrotestosterone (DHT) levels more profoundly than testosterone injection. This may exacerbate androgenic side effects during therapy in some patients, causing some to seek out injectable forms of testosterone as an alternative.
Testosterone enanthate and testosterone cypionate are the most widely prescribed injectable testosterone drugs in the United States and Canada. In many other markets the blended ester products Sustanon 100 and Sustanon 250 are also commonly prescribed. Injection of one of these testosterone ester products will provide the patient supplemental androgen levels for approximately 2 to 3 weeks after each application. The most common protocol among hormone replacement doctors is to administer 200 mg of testosterone enanthate or cypionate once every 2 to 3 weeks. It is important to remember that testosterone esters will deliver varying levels of testosterone to the body on a day-to-day basis throughout each application window. Levels will be highest the first several days after injection, and will slowly decline to baseline over the following weeks. Physicians are usually encouraged to monitor their patients closely to ensure androgen supplementation is sustaining hormone levels within the normal range (and alleviating symptoms of hypogonadism) throughout the entire therapeutic period. The longer acting injectable testosterone preparation Nebido (testosterone undecanoate) is undergoing review in the U.S., and has already been approved in other markets. This drug requires only 4 to 5 injections per year for most patients.
Testosterone undecanoate (Andriol) is the only prescription medication that delivers testosterone via an oral capsule. This medication is not approved for sale in the United States, but is a prescription drug in Canada and many other markets around the world. Patient compliance and comfort are high with this form of therapy, as there are no special routines or requirements aside from taking a few capsules each day with meals. Oral testosterone undecanoate is usually given at an initial dosage of 120 to 160 mg per day, which equates to three to four 40 mg capsules. This dosage may be reduced in subsequent weeks to 120 mg per day. The capsules are given in two divided doses per day, which are usually taken with breakfast and dinner. While this form of therapy is highly convenient, serum hormone levels can fluctuate greatly on a day-to-day basis. The amount of fat consumption has a particularly strong impact on hormone bioavailability, and meals providing at least 20 grams of fat are recommended when taking the capsules for maximum absorption. Note that as with transdermal testosterone, oral testosterone undecanoate tends to increase serum dihydrotestosterone (DHT) levels more profoundly than testosterone injections.
Anabolic steroids are commonly prescribed for the treatment of hereditary angioedema, a rare and potentially life-threatening disorder of the immune system. Hereditary angioedema is caused by genetic mutations of blood clotting factors, characterized by a decrease in the level or functioning of the protein C1 esterase inhibitor. This protein controls C1, which is a “complement system” protein that plays an important role in the control of inflammation. Symptoms of hereditary angioedema include an intermittent but rapid swelling of the hands, arms, legs, lips, eyes, tongue, or throat. Swelling may also be noticed in the digestive tract, resulting in abdominal cramping, nausea, or vomiting. In the most serious cases, the patient may notice a swelling of the throat and a blockage of the airway passages, resulting in asphyxiation and sudden death. Many attacks occur without a specific trigger, although stress, trauma, surgery, and dental work are commonly associated with angioedema attacks.
Oral c-17 alpha alkylated anabolic/androgenic steroids have been shown to be a useful form of preventive therapy, stabilizing complement system protein levels and reducing the frequency and severity of angioedema attacks. They are usually administered in a low dose, which is to be taken for long-term support of this disorder. The anabolic steroids that have been most commonly used in the United States for this purpose are stanozolol and danocrine, although historically many other agents have also been prescribed including oxandrolone, methyltestosterone, oxymetholone, fluoxymesterone, and methandrostenolone. The amount of steroid needed can vary depending on the individual, and is usually maintained at the lowest therapeutically effective dosage in an effort to offset undesirable side effects. FDA approved prescribing guidelines for stanozolol recommended an initial dosage of 2 mg three times daily (6 mg per day). This would be slowly adjusted downward to a maintenance level after a positive response was noted, usually to 2 mg given once every 1 to 2 days.
As a class of drugs, anabolic/androgenic steroids stimulate the synthesis of erythropoietin in the kidneys, a hormone that supports the manufacture of new red blood cells. By doing this,the administration of steroids tends to increase the red cell count and hematocrit level, making them of tangible therapeutic value for treating certain forms of anemia (a disease characterized by insufficient red blood cell production). Forms of anemia likely to respond to steroid therapy include anemias caused by renal insufficiency, sickle cell anemia, refractory anemias including aplastic anemia, myelofibrosis, myelosclerosis, agnogenic myeloid metaplasia, and anemias caused by malignancy or myelotoxic drugs. The level of response will vary depending on the patient, type of therapy, and form of anemia, but in many cases the management of a normal hematocrit level can be achieved.
In the United States, both oxymetholone (Anadrol 50) and nandrolone decanoate (Deca- Durabolin) are approved by the FDA for the treatment of severe anemia. The guidelines for using oxymetholone with both male and female anemic patients (children and adults) recommend a dosage of 1-2 mg/kg/per day. This would equate to a daily dosage of 75-150 mg for an individual weighing about 160 lbs. Doses as high as 5 mg/kg/day are sometimes necessary to achieve the desired therapeutic response. The guidelines for nandrolone decanoate recommend a dosage of 50-100 mg per week for women and 100-200 mg per week for men. Children (2 to 13 years of age) are recommended a dosage of 25-50 mg every 3 to 4 weeks.
In recent years, the advent of recombinant erythropoietin as a prescription drug has changed the face of anemia treatment considerably. While anabolic/androgenic steroids still offer therapeutic value here, and are still marketed and sold to treat anemic patients, they are presently regarded as adjunct or fallback medications for use only when therapy with an erythropoietin alone has failed to achieve a desired response. The hematocrit increase from anabolic/androgenic steroids is generally less predictable and positive than the newer erythropoietins, and these drugs also tend to produce very noticeable side effects when given in the levels necessary to stimulate erythropoiesis, especially in women and children. In many instances the risks to therapy strongly outweigh the benefits of anabolic/androgenic steroids, given that there are newer and directly targeted medications available with much lower side effect potential.
Anabolic/androgenic steroids are sometimes prescribed to treat beast cancer in postmenopausal women or premenopausal women who have had their ovaries removed. These drugs are of value when the cancer is hormone responsive, which means that its growth can be affected (positively or negatively) by hormonal manipulation. Androgens and estrogens have opposing actions on hormone-responsive tumors, with estrogens supporting the growth of breast cancer tissue and androgens inhibiting it67. The supplementation of an anabolic/androgenic steroid can shift the androgen to estrogen balance in a direction that favors a reduction in tumor size, a therapy that has elicited a successful response in a fair number of patients. The masculinizing side effects of steroid therapy can be very pronounced in women, however, so therapy is usually initiated with great caution. An oral androgen such as fluoxymesterone is usually preferred to a slower acting injectable steroid such as nandrolone decanoate as well, as it can be abruptly halted if undesirable side effects become too apparent. Both primarily anabolic agents, however, have been widely prescribed for this purpose. In recent years the development of newer and more targeted anti-estrogenic drugs such as selective estrogen receptor modulators (SERMs) and aromatase inhibiting drugs have almost completely eliminated the use of anabolic/androgenic steroids for breast cancer treatment. Medicative treatment for breast cancer today usually consists of a SERM like Nolvadex (tamoxifen), which may be used with a strong aromatase inhibitor such as Arimidex (anastrozole) or Femara (exemestane). Anabolic/androgenic steroids are still made available in the United States and many other nations for treating breast cancer, and are sometimes still applied. They are very much regarded as adjunct or fallback medications, however, for use only when therapy with anti-estrogenic drugs alone has failed to achieve a desired response.
Decreased Fibrinolytic Activity
Anabolic steroids may be prescribed to treat conditions associated with decreased fibrinolytic activity. Fibrinolysis is the process in which a blood clot is broken down and metabolized by the body. It represents a counter to blood coagulation, with the two systems working together to maintain the hemostatic balance. Disorders of the fibrinolytic system are rare, although can be very serious in nature when they do occur. Decreased fibrinolytic activity can result in a shift in blood clotting factors that greatly favor coagulation (hypercoagulability), increasing the risk of a serious cardiovascular event such as thromboembolism, heart attack, or stroke. Oral C-17 alpha alkylated anabolic steroids are recognized to increase fibrinolytic activity, and as a result have been beneficial in many patients suffering from decreased fibrinolytic activity linked to Antithrombin III deficiency or fibrinogen excess. stanozolol has been most commonly used in the United States for this treatment, although similar therapeutic benefits can be seen with many other anabolic steroids. The maintenance dose is tailored to the individual, and is determined with close monitoring of both side effects and changes to blood coagulation parameters. Esterified injectables and oral non-alkylated steroids do not produce the same fibrinolytic response.
In a small percentage of cases, anabolic/androgenic steroids may be prescribed for the treatment of male infertility. When the cause of infertility is low sperm concentration due to Leydig-cell secretion deficiencies, an androgen might be able to alleviate the condition. In such cases the steroid may increase the sperm count, sperm quality and the fructose concentration, which can increase the chance of conception. The oral androgen mesterolone (Proviron) is most commonly prescribed for this purpose, although has not been granted FDA approval for sale in the United States. Note that anabolic/androgenic steroids usually reduce male fertility, so the potential for these agents to successfully treat male fertility is limited.
Anabolic steroids may be prescribed to treat growth failure in children, both with and without growth hormone deficiency. These agents have been shown to have positive effects on both muscle and bone mass. When they are administered before the ends of the long bones (epiphysis) have fused and further linear growth has been halted, their anabolic effects on bone may support an increase in height. This can occur both through direct anabolic action of the steroid on bone cells, and indirectly via the stimulation of growth hormone and IGF-1 release. An anabolic steroid that is non-aromatizable and non-estrogenic is typically used for this purpose, as estrogen is known to cause an acceleration of growth arrest. Anabolic steroid therapy must always be used with caution in pediatric patients, however. In addition to the possibility of common adverse effects, even non-aromatizable steroids may accelerate the rate of epiphysis closure.
In the United States, oxandrolone is the anabolic steroid most widely prescribed for the treatment of growth failure. It is usually given as a supportive medication, used to augment the anabolic effects of Human Growth Hormone therapy. The drug is typically taken for periods of 6-12 months at a time, in an effort to accelerate the growth rate without substantially affecting the rate of epiphysis fusion. A dosage of 2.5 mg per day is often used for this purpose, although this may be adjusted upwards or downwards depending on the patient’s sex, age, bodyweight, and sensitivity to adverse effects. When used under optimal conditions, the result may be an enhancement of the growth rate and an increase in total height compared to not initiating therapy. This benefit has been difficult to achieve consistently in clinical studies, however. A number of trials with oxandrolone have failed to produce a statistically significant effect on total height, questioning its ultimate value. The short-term benefits of anabolic steroids on the growth rate, however, remain well supported.
The steroid methyltestosterone is approved for prescription sale in the United States and many other markets to improve libido in female menopause patients. Small doses of the drug are typically included in products that also supplement estrogens, the combination aimed at treating the full spectrum of menopause symptoms, including reduced female libido. The dosage used is low compared to those of other clinical applications for methyltestosterone, and will usually amount to no more than 2mg per day.
In the United States, however, the use of an anabolic steroid such as nandrolone decanoate for the direct treatment of osteoporosis is presently viewed as controversial. In spite of substantial clinical data and history supporting the use of steroids for this purpose in the United States, many medical organizations hold the opinion that the potential side effects of steroid therapy are too substantial to justify their benefits with osteoporosis. No agent is presently FDA approved for this purpose. oxandrolone does remain FDA approved for osteoporosis patients, but for the specific purpose of alleviating bone pain associated with the disease, not for augmenting bone mineral density. Anabolic steroids remain in use for osteoporosis in many other nations, however, and are still prescribed to varying patient populations including men, women, and the elderly.
Anabolic steroids increase bone mineral density, and may be prescribed for the treatment of osteoporosis. Benefits of therapy include the stimulation of new bone formation, inhibition of bone resorption (breakdown), and enhancement of calcium absorption. These drugs have additionally been shown to reduce bone pain associated with osteoporosis79, a frequent complication with elderly patients suffering from the condition. Osteoporosis is most common in postmenopausal women, and is usually linked to the changes in hormonal chemistry that are noted later in life. This disorder does occur to a high degree in the elderly of both sexes, however. Osteoporosis can also be caused by the prolonged administration of corticosteroids, which can directly stimulate bone resorption and inhibit new bone growth. This is identified as steroid- or glucocorticoid-induced osteoporosis. nandrolone decanoate is the anabolic steroid most commonly prescribed for the treatment of osteoporosis. The drug tends to offer measurable benefits with regard to bone density, and may reduce the likelihood of bone fracture in patients. The dosage used to treat postmenopausal women is usually 50 mg once every 3 to 4 weeks. Adverse reactions are common with therapy, however, including virilization symptoms (hoarseness and body/facial hair growth) and unfavorable alterations in serum cholesterol. Therapy appears to be better tolerated in patients above the age of 65, who as a group seem to notice lower adverse effects. Male patients are given a nandrolone decanoate dosage of 50 mg once every 1 to 2 weeks. Therapy for both sexes is usually conducted for at least six months, and may last for one year or longer if necessary. The long therapeutic window is usually required in order to give the drug enough time to measurably effect bone strength.
Turner’s and Klinefelter's Syndrome
Anabolic/androgenic steroids may be used to treat certain genetic conditions, most commonly Turner’s syndrome in females and Klinefelter’s syndrome in males. Both are chromosomal disorders characterized by deviations from the normal XX/XY pairing. They result in (among other health issues) abnormalities in growth, sexual development, and ongoing sexual functioning. Males with Klinefelter’s syndrome are sterile, and typically have a rounder (less muscular) physique. They also develop small testicles (microorchidism), and may suffer with gynecomastia. In these patients the supplementation of testosterone (in a similar fashion to that used for androgen replacement therapy) is common, and can help alleviate some of the issues with sexual functioning and body composition. Females with Turner’s syndrome will be of short stature, and develop other physical abnormalities including a broad chest, low hairline, low-set ears, and webbed neck. Low doses of a primarily anabolic steroid may be used in adolescent patients as an adjunct to growth hormone therapy to support the linear growth rate. oxandrolone is the steroid most commonly used in the United States for this purpose, and has been clinically successful at increasing final height when used in dosage of .05-.1 mg/kg per day.
Weight Loss/Muscle Wasting
Anabolic steroids may be administered for the treatment of clinically significant weight loss. Common causes include prolonged corticosteroid therapy, extensive surgery, chronic infections or severe trauma. In a general sense, these agents can be highly useful when a patient is subject to a long hospital stay or period of bed rest, when normal daily muscle stimulation is not present and a significant loss of muscle mass is noticed. Severe burn injuries may also call for the supportive application of anabolic steroids, as this is a type of injury also associated with secondary muscle loss. Anabolic steroids may additionally be prescribed to individuals with weight loss not associated with any known cause. The failure to maintain a healthy (normal) level of body weight for ones’ height, and an inability of diet and exercise alone to correct weight loss, are usually the determining factors in recommending such treatment.
The significant loss of lean body mass can present its own set of health issues. Individuals that are chronically underweight may suffer from low energy and a reduced sense of wellness, and are at greater risk of mortality. Severe weight loss during recovery from surgery or illness may also measurably delay or complicate the recovery phase. In the most severe cases, an ability of the patient to maintain acceptable lean body mass can be the key determining factor in recovery. The ability of anabolic steroids to increase protein synthesis makes them among the most accepted agents for the treatment of clinically significant weight loss, provided the patient does not have a health condition or is taking any other medicine that would exclude them from using these drugs. They can positively affect both muscle and bone as well, making them very versatile anabolic agents.
In the United States, oxandrolone is the agent most frequently prescribed for most kinds of clinically significant weight loss. The dosage used for this purpose is typically 10 mg given twice per day (20 mg total), although lower doses may be given in some female, elderly, or younger patients in an effort to avoid undesirable androgenic side effects. The drug is commonly administered for a period of 3 to 4 weeks during the early stages of recovery, although may be given for a longer duration if necessary. Given that the support of constructive protein metabolism is a trait shared by virtually all anabolic steroids, many agents other then oxandrolone are clinically useful for this purpose. In many other regions, agents with a high anabolic-to-androgenic activity ratio are predominantly used for this purpose including stanozolol, nandrolone, methenolone, and methandrostenolone.
Anabolic steroids may also be prescribed to treat more severe cases of muscle wasting. This is a condition characterized by strong ongoing protein catabolism, which means that muscle protein is being predominantly broken down (as opposed to synthesized) in the body, and a progressive loss of weight, strength, and energy is noticed. In a medical setting, severe muscle wasting is referred to as cachexia. Cachexia is not associated with insufficient food intake (dietary malnutrition), but has a metabolic cause than cannot be alleviated with changes in diet. This cause is also usually identified when discussing the condition (ie, cancer cachexia, HIV related cachexia). HIV related muscle wasting is the most common form of cachexia treated with anabolic steroids. The use of these drugs as supportive therapy for cancer cachexia has not been well established, however, and currently the subject of ongoing investigation.
Nandrolone decanoate, oxandrolone, and oxymetholone have been the anabolic steroids most commonly used in the U.S. to treat muscle wasting specifically associated with HIV infection. Although no specific FDA recommendations have been adopted, studies with nandrolone decanoate have shown a dosage of 150 mg every 14 days to have a similar anabolic benefit, and a significantly lower incidence of side effects, as 6 mg (18 IU) of Human Growth Hormone per day. In 2003, oxymetholone was the subject of successful Phase III clinical trials for HIV wasting. The dosage of this study (100-150 mg per day) mirrors those that are most commonly prescribed by physicians. In recent years, however, the discontinuance of nandrolone decanoate on the pharmaceutical market and a perceived higher patient comfort profile in oxandrolone has made oxandrolone the preferred agent for HIV cachexia. The dosage of oxandrolone used may range from 20 mg to 80 mg per day. The most consistent clinical benefits have been seen with a 40 mg and 80 mg daily dose.
Wlliam Llewellyn (2011) - Anabolics