By Medifit Biologicals.
This section describes how Anabolic steroids are used medically for Onco – Cancer patients and other diseases of wasting conditions.
Anabolic steroids were first made in the 1930s, and are now used therapeutically in medicine to stimulate muscle growth and appetite, induce male puberty and treat chronic wasting conditions, such as cancer and AIDS. The American College of Sports Medicine acknowledges that AAS, in the presence of adequate diet, can contribute to increases in body weight, often as lean mass increases and that the gains in muscular strength achieved through high-intensity exercise and proper diet can be additionally increased by the use of AAS in some individuals.
Androgenic anabolic steroids (AAS) are widely prescribed for the treatment of male hypogonadism; however, they may play a significant role in the treatment of other conditions as well, such as cachexia associated with human immunodeficiency virus, cancer, burns, renal and hepatic failure, and anemia associated with leukemia or kidney failure. A review of the anabolic effects of androgens and their efficacy in the treatment of these conditions is provided. Although the threat of various side effects is present, AAS therapy appears to have a favourable anabolic effect on patients with chronic diseases and muscle catabolism. We recommend that AAS can be used for the treatment of patients with acquired immunodeficiency syndrome wasting and in severely catabolic patients with severe burns. Preliminary data in renal failure-associated wasting are also positive. Advantages and disadvantages should be weighed carefully when comparing AAS therapy to other weight-gaining measures.
Oxandrolone for cancer‐related cachexia
Oxandrolone is now being studied in cancer‐related cachexia, says Dr Jamie Von Roenn, professor of medicine at the Feinberg School of Medicine of Northwestern University and the Robert H Lurie Comprehensive Cancer Center.
‘Oxandrolone has been used for many years to treat weight loss for a catchall of conditions, but until recently it hadn’t been studied in cancer patients,’ she says. ‘Now several manuscripts of studies in cancer patients are under preparation.’
A Phase II study, with Dr Von Roenn as lead investigator, found that oxandrolone at 10 mg bid achieved weight gain and improved energy in patients with advanced cancer and weight loss of at least 5%. Moreover, a correlation was observed between improvement in lean body mass and improved quality of life, she says.
‘Patients who gained weight on oxandrolone gained lean mass preferentially over fat, and those who remained weight stable [±2% of their baseline weight] gained lean mass and lost fat, while those who lost weight lost fat disproportionately.’
In contrast, cancer patients treated with megestrol acetate ‐ ‘the most potent appetite stimulator studied’, she says ‐ gain fat mass preferentially, not muscle mass.
‘Patients with cachexia lose muscle disproportionately, and we assume that is why they become so frail and have a cluster of symptoms that includes fatigue, weakness, and loss of appetite’, Dr Von Roenn says.
‘If a drug can maintain muscle mass, it should help patients have more energy. Megestrol acetate may be a good drug for palliative care, but for patients who are treated [for weight loss] early, a drug that preserves muscle mass would be more desirable. I am excited that people who took oxandrolone preserved lean body mass.’
‘In certain non‐cancer disease states, such as neurological disease with muscle atrophy, some very preliminary studies suggest an improvement in function with creatine treatment’
Based on the encouraging results of the Phase II trial, a Phase III placebo controlled study enrolled cancer patients with significant weight loss (ie, more than 3% in one month or at least 5% in six months) and a life expectancy of more than six months. The results are not yet available, but Dr Von Roenn says she and her colleagues are hopeful that the Phase II findings will be confirmed.
‘If that is the case, it would make sense to study oxandrolone in an earlier population’, she points out.
‘If changing weight is going to have an impact on survival, we have to be able to change the underlying metabolic abnormalities. Some of these effects are clearly related to lean tissue, so it would be advisable to study this drug upstream ‐ as soon as patients lose 5% of their body weight.’
Another question is whether oxandrolone will improve fatigue, weakness, and other symptoms associated with weight loss. The Eastern Cooperative Oncology Group is currently planning a Phase II study to look at the effect of oxandrolone on fatigue.
‘Improvement in muscle mass should correlate with improved energy and less fatigue’, Dr Von Roenn says.
Another supplement that may hold promise for improving muscle mass in cancer patients with cachexia, she said, is called Juven ‐ the brand name of a combination of arginine, glutamine, and HMB (beta‐hydroxy‐beta‐methylbu‐tyrate).
‘If a drug can maintain muscle mass, it should help patients have more energy. I am excited that people who took oxandrolone preserved lean body mass’
Juven is used by body builders, and some intriguing early leads suggest that it may be useful in cancer patients as well, Dr Von Roenn says, adding that although as far as she knows there have not yet been any studies of the product in cancer patients, presumably there will be studies in the future.
Oral Anabolic Steroid Effective for Cancer Cachexia
The oral anabolic steroid oxandrolone can help cancer patients with involuntary weight loss to gain lean body mass, while improving their quality of life and performance status, a preliminary prospective study suggests.
“Oxandrolone appears not simply to increase weight in patients who often have severe disease-related cachexia, but also to help reverse the underlying pathology, improving metabolically active tissue compartments across the board,” said Jamie H. Von Roenn, MD, Professor of Medicine in the Division of Hematology/Oncology and Director of the Palliative Care & Home Hospice Program at Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center there. “This, in turn, may result in improved function and quality of life.”
In the four-month study of 131 patients with cancer-related involuntary weight loss, all of whom took 10 milligrams of oxandrolone twice a day, 81% of patients either gained or maintained weight, Dr. Von Roenn reported. Of note, she added, was that lean tissue weight increased by an average of 7.5% at four months.
Dr. Von Roenn reported data on the first 37 patients at the 2002 ASCO annual meeting, and a poster study about the final toxicity data on all 131 patients was presented at this year’s meeting.
Steroids are chemicals that are produced by glands in our bodies. They regulate many of our natural functions, from our body temperature and blood pressure to our emotions.
Pharmaceutically produced, synthetic steroids are used for a number of reasons in medicine. Steroids are a key component in the treatment of leukemia, lymphoma and myeloma.
What Steroids are Used in Cancer Therapy?:
When we think of someone “taking steroids,” we often think of muscle-bound pro athletes or weight lifters in skimpy garments, flexing for the camera. These types of steroids are called anabolic-androgenic steroids, and are not typically used in cancer care.
Most often, the steroids used in cancer patients are called corticosteroids. Examples of these types of steroids are:
Although well-documented reports linking steroids to liver cancer are rare, as more athletes use drugs to improve their performance or build their bodies, many types of dangerous side effects from the abuse of anabolic steroids are becoming known — and events are becoming more frequent.
Recently, there have been many instances in the news about famous athletes and performance-enhancing drugs, sometimes referred to as “doping.” In most cases, the drugs that are being used are anabolic steroids. These drugs are manufactured steroids that behave like the male hormone testosterone. In the United States, it is illegal to use anabolic steroids without a prescription.
“Anabolic steroids are male-related hormones that can be used to increase muscle mass. When these drugs are abused they can have many side effects, including liver damage,” notes George Y. Wu, MD, PhD, a professor of medicine, chief of the hepatology section, and Herman Lopata chair in hepatitis research at the University of Connecticut Medical Center in Farmington.
LIVER CANCER: WHAT ANABOLIC STEROIDS CAN TREAT
Anabolic steroids, under a doctor’s prescription, will treat certain conditions in which increasing bone strength and muscle mass are required for health reasons. These medications can be helpful in the following types of cases:
Liver Cancer: Anabolic Steroid-Related Liver Damage
Liver damage from anabolic steroids can cause a condition called cholestasis. With this condition, bile, a digestive fluid made in your liver, cannot get to where it needs to go and leaks out into your blood. Symptoms include:
Loss of appetite
Jaundice — the yellow discoloration of your eyes and skin
Damage to the liver is evident when enzymes called aminotransferases leak out of damaged liver cells into your bloodstream.
Another important point about anabolic steroids: They can be addictive. These steroids can cause steroid craving that leads to the need for more frequent and higher drug doses. Liver damage has been shown to be related to the cumulative effects of higher and more frequent use.
LIVER CANCER: CAN ANABOLIC STEROIDS CAUSE IT?
Dr. Wu says that reports exist showing a slightly increased risk of developing liver cancer with long-term use of high-dose anabolic steroids. However, he says, “the scientific evidence supporting a cause-and-effect relationship is weak.”
But these steroids are known to cause tumors that form in your liver. Called hepatic adenomas, these tumors are not cancerous. However, they are dangerous because they can rupture and cause serious bleeding in the liver. There have been several reported deaths caused by bleeding from ruptured hepatic adenomas. The link between hepatic adenomas and anabolic steroid use in athletes is increasing. Recently, a case of a hepatic adenoma turning into liver cancer was reported.
Liver Cancer: Anabolic Side Effects
While there is not a strong link between liver cancer and anabolic steroids, there is strong evidence for serious liver damage. Other side effects of anabolic steroids include:
High blood pressure
Increased levels of bad cholesterol
Infertility in men
Menstrual abnormalities in women
If you are an athlete or a body-builder and you are tempted to use anabolic steroids, consider that besides the legal and social risks involved, these drugs can and do cause life-theatening medical complications.
The severity of liver injury due to anabolic steroids ranges from minor, transient serum enzyme elevations to profound and prolonged cholestasis, as well as hepatic peliosis and benign and malignant liver tumors. The first priority in management should be stopping the androgenic steroid. Unfortunately, athletes and body builders may resist this recommendation. Merely decreasing the dose of androgenic steroid or switching to another formulation is not appropriate and should be specifically discouraged. Patients being treated for hypogonadism may be switched to an unmodified form of testosterone, given by injection or cutaneous patch. Patients with marked cholestasis may be benefitted by symptomatic therapy of pruritus and fat soluble vitamin supplementation. Ursodiol is often used in drug induced cholestasis, but is efficacy has never been shown in a controlled prospective manner. Use of corticosteroids is usually ineffective and should be avoided. The syndrome is usually reversible with stopping therapy, but full recovery is often delayed. In addition, fatalities have been reported; usually due to marked cholestasis complicated by malnutrition, renal failure and associated opportunistic infections.
Representative androgenic steroids include the following: danazol, fluoxymesterone, methandienone, methenolone, methyltestosterone, nandrolone, norethandrolone, oxandrolone, oxymetholone, stanozolol, testosterone (cypionate, enanthate, propionate).
Corticosteroids (Glucocorticoids) for Cancer
How It Works
Corticosteroids are strong anti-inflammatory drugs. They are used to reduce swelling that causes cancer pain.
Corticosteroids are available as pills, syrups, injections, and intravenous (IV) solutions. The type and extent of a disease determines the exact dose and schedule of administering these drugs.
Why It Is Used?
Corticosteroids reduce swelling and inflammation that may cause cancer pain. They are used with other drugs, such as ondansetron and aprepitant, to control and prevent nausea and vomiting caused by chemotherapy.
How Well It Works?
Corticosteroids work well to reduce swelling and pain caused by cancer. When they are used with other drugs, such as ondansetron and aprepitant, they may control and prevent nausea and vomiting caused by chemotherapy.
Side effects are common with steroids and can include:
Nausea, vomiting, stomach upset, or ulcers. To reduce these side effects, take your pills with a full glass of fluid and a small snack.
Fluid retention, causing swelling of the hands and feet.
Increased risk of infection.
Preexisting diabetes getting worse.
Menstrual period changes.
Changes in behavior, such as symptoms of paranoia or psychosis.
Muscle wasting. You may notice that it is difficult to climb stairs or rise from sitting to standing without assistance.
Some problems may occur with long-term use. These include:
High blood pressure.
Development of diabetes.
What To Think About?
During treatment with corticosteroids, do not take any other prescription or nonprescription medicines, including herbal products, without first talking to your doctor. Many other drugs can interact with corticosteroids, resulting in side effects or changes in how well the drugs work.
Do not stop taking corticosteroids suddenly. Withdrawal effects can occur. So it is very important to take the prescribed dose at the times recommended by your doctor. You will be given instructions on how to reduce (taper) your dose gradually at the end of your treatment. Have your doctor write these instructions out for you. If you have any questions about how to taper your dose, call your doctor. Tapering is usually only needed if you use corticosteroids for a long time. It may not be needed if you use the steroids only for short periods.
Dexamethasone, if given too rapidly by IV, may cause temporary itching or burning in the vaginal or rectal area. This goes away after a few minutes.
To minimize side effects of oral corticosteroids, take your pills with a full glass of liquid and a small snack.
Corticosteroids should be used during pregnancy only if the benefits to the mother outweigh the risks to the fetus. If you are or may be pregnant, talk to your doctor before using corticosteroids. This drug can pass through your body into breast milk and should not be used while you are breast-feeding.
Avoid sources of infection. Wash your hands frequently, and keep them away from your mouth and eyes. Your immune system may be weakened while you are taking corticosteroids.
Steroids used to treat cancer and cancer pain is not the same as steroids used by body builders (anabolic steroids).
Do not use alcohol or street drugs while you are taking corticosteroids. Tell your doctor if you need more pain relief.
Most policies specifically exclude coverage of steroids for performance enhancement. For plans without this exclusion, androgens and anabolic steroids as well as other medical interventions for performance enhancement are not covered because performance enhancement of non-diseased individuals is not considered treatment of disease or injury. Please check benefit plan descriptions for details.
Aetna considers anabolic steroids medically necessary for any of the following indications:
AIDS wasting syndrome; or
Anemia accompanying renal failure; or
Bone marrow failure anemias; or
Breast cancer; or
Conditions associated with decreased fibrinolytic activity due to anti-thrombin III deficiency or fibrinogen excess (including cutaneous vasculitis, scleroderma of Raynaud’s disease, vasculitis of Behcet’s disease, complications of deep vein thrombosis such as venous lipodermatosclerosis, other vascular disorders associated with these forms of reduced fibrinolytic activity, and prevention of recurrent venous thrombosis associated with anti-thrombin III deficiency); or
Constitutional delay in growth (androgenic anabolic steroids); or
Delayed male puberty (androgenic anabolic steroids); or
Endometriosis (danazol) or
Female to male gender reassignment; or
Fibrocystic breast disease or mastalgia (danazol) or
Growth failure in children with growth hormone deficiency (treatment adjunct); or
Hereditary angioedema; or
Hypospadias (testosterone injection as pre-surgical adjuvant hormonal therapy); or
Klinefelter’s syndrome with hypogonadism (androgenic anabolic steroids) or
Microphallus (androgenic anabolic steroids); or
Refractory red cell production anemias (including aplastic anemia, myelofibrosis, myelosclerosis, agnogenic myeloid metaplasia, hypoplastic anemias caused by malignancy or myelotoxic drugs); or
Severe burn injury; or
Symptomatic androgen deficiency in men (androgenic anabolic steroids) (androgen deficiency is indicated by either a low total testosterone level (below 200 ng/dL), or a low normal total testosterone levels (above 200 ng/dL but below 500 ng/dL) plus elevated sex hormone binding globulin or
Weight loss from cancer chemotherapy.
Two total testosterone levels are required to determine medical necessity of testosterone replacement. Two morning samples drawn between 8:00 a.m. and 10:00 a.m. obtained on different days are required.
Injectable androgens are considered experimental and investigational for treatment of female menopause because of insufficient evidence in the peer-reviewed literature.
Aetna considers androgen therapy experimental and investigational to improve live birth outcome in poor responders undergoing in-vitro fertilization/intra-cytoplasmic sperm injection treatment because of insufficient evidence.
Aetna considers androgens and anabolic steroids experimental and investigational as a treatment for chronic obstructive pulmonary disease, chronic pressure ulcers and for other indications because of insufficient evidence in the peer-reviewed literature.
Aetna considers testosterone injections experimental and investigational for the treatment of amyotrophic lateral sclerosis, female sexual dysfunction/hypoactive sexual desire disorder, and heart failure because of insufficient evidence in the peer-reviewed literature.
Androgens and anabolic steroids include:
Depot forms of testosterone include testosterone cypionate and testosterone undecanoate.
Testosterone should be administered only to a man who is hypogonadal, as evidenced by clinical symptoms and signs consistent with androgen deficiency and a distinctly subnormal serum testosterone concentration. In comparison, increasing the serum testosterone concentration in a man who has symptoms suggestive of hypogonadism but whose testosterone concentration is already normal will not relieve those symptoms. The principal goal of testosterone therapy is to restore the serum testosterone concentration to the normal range. The role of testosterone replacement to treat the decline in serum testosterone concentration that occurs with increasing frequency above age 60 in the absence of identifiable pituitary or hypothalamic disease is uncertain.
Measurement of the serum testosterone concentration is usually the most important single diagnostic test for male hypogonadism because a low value usually indicates hypogonadism. Measurement of the serum total (free plus protein-bound) testosterone concentration is usually an accurate reflection of testosterone secretion. Interpretation of serum testosterone measurements should take into consideration its diurnal fluctuation, which reaches a maximum at about 8 AM and a minimum, approximately 70 percent of the maximum, at about 8 PM. It is easier to distinguish subnormal from normal when normal is higher, so the measurements should always be made at 8 AM. If a single 8 AM value is well within the normal range, testosterone production can be assumed to be normal. If a single 8 AM value is low or borderline low or does not fit with the clinical findings, the measurement should be repeated once or twice before making the diagnosis of hypogonadism.
In a prospective, double-blind, placebo-controlled, 16-week study, examined the benefits of anabolic steroids in patients with severe chronic obstructive pulmonary disease (COPD) who did not participate in a structured rehabilitation program. Biweekly intra-muscular injections of either the drug (nandrolone decanoate) or placebo were administered. A total of 16 patients with severe COPD were randomized to either placebo or nandrolone decanoate. The placebo group weighed 55.32 +/- 11.33 kg at baseline and 54.15 +/- 10.80 kg at 16 weeks; the treatment group weighed 68.80 +/- 6.58 kg at baseline and 67.92 +/- 6.73 kg at 16 weeks. Lean body mass remained unchanged, 71 +/- 6 kg versus 71 +/- 7 kg in placebo group and 67 +/- 7 kg versus 67 +/- 7 kg in treatment group, at baseline and 16 weeks respectively. The distance walked oin 6 mins was unchanged at baseline, 8 weeks, and 16 weeks in placebo (291.17 +/- 134.83 m, 282.42 +/- 115.39 m, 286.00 +/- 82.63 m) and treatment groups (336.13 +/- 127.59 m, 364.83 +/- 146.99 m, 327.00 +/- 173.73 m). No improvement occurred in forced expiratory volume in 1 second, forced vital capacity, maximal inspiratory pressure, maximal expiratory pressure, VO(2) max or 6-min walk distance or health related quality of life. The authors concluded that administration of anabolic steroids (nandrolone decanoate) outside a dedicated rehabilitation program did not lead to either weight gain, improvement in physiological function, or better quality of life in patients with severe COPD.
It is interesting to note that while testosterone treatment improved body composition and sexual function in men with COPD in a 6-month trial, no improvement in pulmonary function was found.
Miller and Btaiche (2009) stated that severe thermal injury is associated with hyper-metabolism and hyper-catabolism, leading to skeletal muscle breakdown, lean body mass loss, weight loss, and negative nitrogen balance. Muscle protein catabolism in patients with severe thermal injury is the result of stress-induced increased release of cytokines and counter-regulatory hormones. Coupled with decreased serum anabolic hormone concentrations such as testosterone and growth hormone along with the presence of insulin resistance, anabolism in patients with severe thermal injury is inefficient or impossible during the acute post-burn period. This causes difficulty in restoring lean body mass and regaining lost body weight, as well as poor healing of the burn wound and delayed patient recovery. Oxandrolone, a synthetic derivative of testosterone, has been used in adult patients with severe thermal injury to enhance lean body mass accretion, restore body weight, and accelerate wound healing. In clinical studies, oxandrolone 10 mg orally twice-daily improved wound healing, restored lean body mass, and accelerated body weight gain. During the rehabilitation period, oxandrolone therapy with adequate nutrition and exercise improved lean body mass, increased muscle strength, and restored body weight. However, most data on oxandrolone use in adult patients with severe thermal injury were derived from single-center studies, many of which enrolled a relatively small number of subjects and some of which had a poor design. The authors stated that multi-center, prospective, randomized studies are needed to better define the optimal oxandrolone dosage and to confirm the safety and effectiveness of this drug in adult patients with severe thermal injury.
Woerdeman and de Ronde (2010) stated that a variety of clinical conditions/diseases are complicated by loss of weight and skeletal muscle, which may contribute to morbidity and mortality. Anabolic androgenic steroids have been demonstrated to increase fat-free mass, muscle mass and strength in healthy men and women without major adverse events and therefore could be beneficial in these conditions. The authors provided an overview of clinical trials with anabolic androgenic steroids in the treatment of chronic diseases including HIV-wasting, chronic renal failure, COPD, muscular disease, alcoholic liver disease, burn injuries and post-operative recovery. Relevant studies were identified in PubMed (years 1950 to 2010), bibliographies of the identified studies and the Cochrane database. Although the beneficial effects of anabolic androgenic steroids in chronic disorders are promising, clinically relevant endpoints such as quality of life, improved physical functioning and survival were mainly missing or not significant, except for burn injuries. The authors concluded that more studies are needed to confirm their long-term safety and effectiveness.
Oxandrolone, an anabolic steroid used to treat muscle wasting in HIV patients, is associated with decreased loss of lean body mass, improved wound healing compared with placebo, and decreased hospital stay in severe burn injury. However, oxandrolone may prolong the need for mechanical ventilation in trauma patients and can elevate serum transaminase levels.
Sunkara and colleagues (2011) noted that many trials have evaluated the use of androgen supplements and androgen-modulating agents to improve outcome of poor responders undergoingin-vitro fertilization (IVF) treatment. These investigators performed a systematic review and meta-analysis of controlled trials of androgen adjuvants (testosterone, dehydroepiandrostereone) and the androgen-modulating agent (letrozole) in poor responders undergoing IVF treatment. Searches were conducted on MEDLINE, EMBASE, Cochrane Library, ISRCTN Register and ISI proceedings. All randomized and non-randomized controlled trials were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The main outcome measure was clinical pregnancy rate. The secondary outcome measures were dose and duration of gonadotrophin use, cycles cancelled before oocyte retrieval, oocytes retrieved and ongoing pregnancy rates. A total of 2,481 cycles in women considered as poor responders undergoing IVF/intra-cytoplasmic sperm injection (ICSI) treatment were included in 9 controlled trials. Meta-analyses of these studies did not show any significant difference in the number of oocytes retrieved and ongoing pregnancy/live-birth rates with androgen supplementation or modulation compared with the control groups. The authors concluded that there is currently insufficient evidence from the few randomized controlled trials to support the use of androgen supplementation or modulation to improve live birth outcome in poor responders undergoing IVF/ICSI treatment.
Makinen and Huhtaniemi (2011) stated that normal testicular function is essential for the maintenance of male physical strength and behavior irrespective of age. A new term of late-onset hypogonadism (LOH) has been coined for the condition of decreased testosterone and hypogonadal symptoms in aging men. The most important testicular hormone, testosterone, is responsible for the gender-specific androgenic-anabolic effects in men. Testicular production of testosterone remains stable until around the age of 40 years after which it declines by 1 to 2 % annually. Despite this age-related decline, serum testosterone levels in most older men remain within the reference range of younger men. The decreasing androgen levels are paralleled by well-defined objective biological and non-specific subjective signs and symptoms of aging. Because these symptoms are similar to those observed in young men with documented hypogonadism, androgen replacement therapy (ART) has been considered a logical way to treat them. These researchers conducted a thorough review of the existing literature to evaluate the current concepts and controversies related to aging men and ART. Although it is intuitively logical that the symptoms of LOH are due to the aging-related deficiency of testosterone, and that they can be reversed by ART, the evidence for this is still variable and often weak. In particular, evidence-based information about long-term benefits and risks of ART in aging men is largely missing. The authors concluded that despite widespread use, evidence-based proof for the objective benefits and side effects of ART of elderly men is still scanty, and such treatments should be considered experimental.
Shelton and Rajfer (2012) noted that androgen deficiency in aging men is common, and the potential sequelae are numerous. In addition to low libido, erectile dysfunction, decreased bone density, depressed mood, and decline in cognition, studies suggest strong correlations between low testosterone, obesity, and the metabolic syndrome. Because causation and its directionality remain uncertain, the functional and cardiovascular risks associated with androgen deficiency have led to intense investigation of testosterone replacement therapy in older men. Although promising, evidence for definitive benefit or detriment is not conclusive, and treatment of LOH is complicated.
The British Committee for Standards in Haematology’s guideline on “The diagnosis and management of myelofibrosis” provided the following recommendations:
Danazol should be considered as a therapeutic option to improve the hemoglobin concentration of patients with myelofibrosis and transfusion-dependent anaemia (Evidence level 2, Grade B).
Recommended starting dose is 200 mg daily, with a gradual dose escalation, depending on tolerability and patient weight (to a maximum of 600 mg daily for patients less than80 kg and 800 mg for patients greater than 80 kg) (Evidence level 2, Grade B).
Patients should be treated for a minimum period of 6 months. Responding patients should be maintained for a further 6 months on 400 mg daily before titrating down the dose to the minimum required in order to maintain a response (Evidence level 2, Grade B).
Toma et al (2012) stated that low testosterone is an independent predictor of reduced exercise capacity and poor clinical outcomes in patients with heart failure (HF). These investigators examined if testosterone therapy improves exercise capacity in patients with stable chronic HF. They searched Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (1980 to 2010). Eligible studies included randomized controlled trials (RCTs) reporting the effects of testosterone on exercise capacity in patients with HF. Reviewers determined the methodological quality of studies and collected descriptive, quality, and outcome data. A total of 4 trials (n = 198; men, 84 %; mean age of 67 years) were identified that reported the 6-minute walk test (2 RCTs), incremental shuttle walk test (2 RCTs), or peak oxygen consumption (2 RCTs) to assess exercise capacity after up to 52 weeks of treatment. Testosterone therapy was associated with a significant improvement in exercise capacity compared with placebo. The mean increase in the 6-minute walk test, incremental shuttle walk test, and peak oxygen consumption between the testosterone and placebo groups was 54.0 m (95 % confidence interval [CI]: 43.0 to 65.0 m), 46.7 m (95 % CI: 12.6 to 80.9 m), and 2.70 ml/kg per min (95 % CI: 2.68 to 2.72 mL/kg per min), respectively. Testosterone therapy was associated with a significant increase in exercise capacity as measured by units of pooled SDs (net effect, 0.52 SD; 95 % CI: 0.10 to 0.94 SD). No significant adverse cardiovascular events were noted. The authors concluded that given the unmet clinical needs, testosterone appears to be a promising therapy to improve functional capacity in patients with HF. They stated that adequately powered RCTs are required to assess the benefits of testosterone in this high-risk population with regard to quality of life, clinical events, and safety.
On March 6, 2014, the Food and Drug Administration (FDA) approved testosterone undecanoate injectable (Aveed, Endo Pharmaceuticals) for the treatment of men with hypogonadism. Aveed is a long-acting depot formulation of testosterone in castor oil and benzyl benzoate. It offers a novel dosing schedule, with a single 3-ml (750 mg) intra-muscular injection given once at initiation of therapy, at 4 weeks, and then every 10 weeks thereafter. The approval follows 3 previous rejections of Aveed by the FDA for safety and risk/benefit concerns and comes just a month after the FDA announced that it is investigating cardiovascular safety data for all testosterone preparations. The FDA is requiring that Aveed’s label contain a boxed warning regarding the risks of serious pulmonary oil micro-embolism (POME) and anaphylaxis and is making the product available only through a restricted distribution scheme known as a risk evaluation and mitigation strategy (REMS) to ensure that it is used only in men for whom the benefits out-weigh the risks.
According to the Prescribing Information, Aveed (testosterone undecanoate) injection is indicated for testosterone replacement therapy in adult males (18 years and older) for primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired). The most common side effects of Aveed include acne, difficulty sleeping, feeling tired, increased estradiol level, increased prostate specific antigen, increased red blood cell count, irritability, low testosterone level, mood swings, and pain at the injection.
Reis and Abdo (2014) evaluated the use of androgens in the treatment of a lack of libido in women, comparing 2 periods, i.e., before and after the advent of the phosphodiesterase type 5 inhibitors. These researchers also analyzed the risks and benefits of androgen administration. They searched the Latin-American and Caribbean Health Sciences Literature, Cochrane Library, Excerpta Medica, Scientific Electronic Library Online, and Medline (PubMed) databases using the search terms disfunção sexual feminina/female sexual dysfunction, desejo sexual hipoativo/female hypoactive sexual desire disorder, testosterona/testosterone, terapia androgênica em mulheres/androgen therapy in women, and sexualidade/sexuality as well as combinations thereof. They selected articles written in English, Portuguese, or Spanish. After the advent of phosphodiesterase type 5 inhibitors, there was a significant increase in the number of studies aimed at evaluating the use of testosterone in women with hypoactive sexual desire disorder. However, the risks and benefits of testosterone administration have yet to be clarified.
The European Federation of Neurological Societies’ guidelines on the clinical management of amyotrophic lateral sclerosis (Andersen et al, 2012) did not recommend testosterone for the treatment of amyotrophic lateral sclerosis because of insufficient evidence of its effectiveness.
In a parallel-group, placebo-controlled, randomized trial, Bauman et al (2013) examined if oxandrolone increases the percentage of target pressure ulcers (TPUs) that heal compared with placebo and whether healed ulcers remain closed 8 weeks after treatment. A total of 1,900 patients were prescreened, 779 screened, and 212 randomly assigned inpatients with spinal cord injury (SCI) and stage III or IV TPUs. Oxandrolone, 20 mg/d (n = 108), or placebo (n = 104) until the TPU healed or 24 weeks. The primary outcome was healed TPUs. The secondary outcome was the percentage of TPUs that remained healed at 8-week follow-up. A total of 24.1 % (95 % CI: 16.0 % to 32.1 %) of TPUs in oxandrolone recipients and 29.8 % (CI: 21.0 % to 38.6 %) in placebo recipients healed (difference, -5.7 percentage points [CI: -17.5 to 6.8 percentage points]; p = 0.40). At 8-week follow-up, 16.7 % (CI: 9.6 % to 23.7 %) of oxandrolone recipients and 15.4 % (CI: 8.5 % to 22.3 %) of placebo recipients retained a healed TPU (difference, 1.3 percentage points [CI: -8.8 to 11.2 percentage points]; p = 0.70). No serious adverse events were related to oxandrolone. Liver enzyme levels were elevated in 32.4 % (CI: 23.6 % to 41.2 %) of oxandrolone recipients and 2.9 % (CI: 0.0 % to 6.1 %) of placebo recipients (p < 0.001). The authors concluded that oxandrolone showed no benefit over placebo for improving healing or the percentage of TPUs that remained closed after 8 weeks of treatment.
Androgen deficiency is indicated by either a low total (free plus protein-bound) serum testosterone level (below 200 ng/dL), or a low normal total testosterone levels (above 200 ng/dL but below 500 ng/dL) plus elevated sex hormone binding globulin (above the normal reference range indicated in the table below or above the testing laboratory’s normal reference range). Two total testosterone levels are required to determine medical necessity of testosterone replacement. Two morning samples drawn between 8:00 a.m. and 10:00 a.m. obtained on different days are required.
Note: The Endocrine Society’s clinical practice guideline on “Testosterone therapy in adult men with androgen deficiency syndromes” stated that reference laboratories ranges should be used for reporting testosterone levels.
0-1 mo 11-71
1-12 mo 60-209
1-3 yr 42-156
4-6 yr 39-146
7-9 yr 38-114
10-12 yr 32-93
13-15 yr 13-93
16-18 yr 11-54
>18 yr 13-71
By Medifit Biologicals.