Oxandrolone Troches

Oxandrolone is a synthetic testosterone derivative administered orally. Due to the removal of the methyl group from the C-19 position, it has anabolic effects that are stronger than androgenic effects. Oxandrolone has anabolic potential that is between three and thirteen times more than that of testosterone and methyltestosterone. Oxandrolone is helpful for increasing weight gain after burns or trauma as well as in some disease states including COPD and AIDS when combined with enough calories. The increase in weight is mostly the result of elevated lean body mass as opposed to increased body fat, which is frequently seen with nutritional supplements. When a medicine is stopped, the positive effects on lean body mass are lost. In order to counteract the protein catabolism brought on by extended corticosteroid treatment, oxandrolone is employed. Supportive data also exist for the treatment of patients with Duchenne’s muscular dystrophy, constitutional delay of growth and puberty, HIV wasting syndrome and associated muscle weakness, and short stature associated with Turner’s syndrome. Conflicting evidence exists as to whether or not anabolic steroids significantly increase athletic performance by increasing muscle strength, but the NCAA and IOC currently prohibit their use by athletes. Oxandrolone is not ergogenic at labeled doses but athletes often use higher doses; athletic use should be discouraged due to the risk for dyslipidemia, potential hepatotoxicity, and other serious side effects. Oxandrolone was approved by the FDA in July 1964 and became a controlled substance in 1991.

Through a direct stimulant impact on testosterone or dihydrotestosterone receptors, enhanced androgen receptor expression in skeletal muscle, and intracellular amino acid reutilization, oxandrolone stimulates skeletal muscle protein synthesis. The same intracellular receptors that testosterone and dihydrotestosterone bind to are found in the reproductive system, bone, skeletal muscle, brain, liver, kidney, and adipocytes. Gene expression is regulated by receptor binding.

Oxandrolone works directly as an androgen, as it cannot be aromatized to estrogen. In addition to myotrophic effects from androgen receptor interaction in skeletal muscle, it appears that testosterone and oxandrolone have myotrophic effects caused by decreased protein catabolism through interaction with glucocorticoid receptors. It is hypothesized that anabolic-androgenic steroids displace glucocorticoids bound to the glucocorticoid receptor. Another hypothesis is that anabolic-androgenic steroids interfere with the glucocorticoid response element (DNA binding region). Improvement in lean body mass is a result of the drug’s myotrophic effect. Unlike growth hormone, which causes irreversible hyperplasia, anabolic steroids cause hypertrophy, a reversible event.

In addition to protein synthesis in muscle, increases in serum albumin, prealbumin, and transferrin concentrations have been noted with oxandrolone. Increased erythrocyte production is apparently due to enhanced production of erythropoietic stimulating factors.

Oxandrolone also causes osteolytic bone resorption stimulation, osteoblast proliferation, bone matrix protein production, and synthesis of growth factors and cytokines, which are mediated by androgen receptors on osteoblasts. These effects on bone are responsible for the growth-promoting effects of oxandrolone.

Oxandrolone causes suppression of pituitary gonadotrophins through negative feedback. Thus, endogenous testosterone production is inhibited with oxandrolone due to inhibition of luteinizing hormone. Oxandrolone can also suppress follicle-stimulating hormone release via negative feedback inhibition. Furthermore, oxandrolone may exert a direct effect on the testes. Oxandrolone lowers HDL by induction of hepatic triglyceride lipase, an enzyme that catabolizes HDL.

Oxandrolone is categorized in FDA pregnancy risk category X and is not advised during pregnancy. When oxandrolone was administered in doses nine times greater than those used for humans, female animal offspring have shown signs of masculinization, infertility, and teratogenic consequences, including embryotoxicity and fetotoxicity. These outcomes are in line with the effects of other androgenic and anabolic hormones that are already known. Utilizing oxandrolone in females with the potential to become pregnant requires caution. The patient should be informed of the potential risk to the fetus if oxandrolone is used during pregnancy or if the patient becomes pregnant while taking this medication.^[1]

It is unknown if oxandrolone is excreted into breast milk. Nursing discontinuation or oxandrolone cessation is recommended for mothers who are breast-feeding.^[1] Oxandrolone is a synthetic testosterone derivative. Significant exposure to this androgen via breast-feeding may have adverse androgenic effects on the infant and the drug may also interfere with proper establishment of lactation in the mother.^[2] Historically, testosterone/androgens have been used adjunctively for lactation suppression.^[2] Alternative methods to breastfeeding are recommended in lactating women receiving anabolic/androgenic therapy.

Androgen therapy can result in hypoglycemia in patients with diabetes mellitus. Oxandrolone can inhibit the metabolism of oral antidiabetic agents and some androgens can lower blood glucose in patients with diabetes. Close monitoring of blood glucose concentrations in patients with diabetes mellitus taking oxandrolone is recommended.

In general, the use of androgens in children should be undertaken only with extreme caution; growth suppression as a result of accelerated bone maturation may occur. The risk of compromised adult growth is greater with oxandrolone use in younger aged patients. X-ray examination of bone age every six months is recommended while on oxandrolone. Of note, anabolic-androgenic steroids can increase height without significantly affecting bone age. Completion of epiphyseal fusion leading to growth cessation does not occur with oxandrolone since it is not aromatized into substances with estrogenic properties.

Oxandrolone can stimulate the growth of cancerous tissue and is contraindicated in male patients with known prostate cancer or breast cancer. Patients with prostatic hypertrophy should be treated with caution because of the possible development of malignancy. Periodic assessment of prostate-specific antigen is recommended for older patients.

Oxandrolone is contraindicated in patients with primary or secondary hypercalcemia due to osteolytic bone resorption stimulation. The risk of androgen-induced hypercalcemia is higher in immobile patients and in those with metastatic breast cancer. Frequent determination of serum and urine calcium concentrations is recommended in immobile patients and in females with breast cancer. Oxandrolone is contraindicated in females with breast cancer who have hypercalcemia.

Alterations in the serum lipid profile consisting of decreased HDL and increased LDL occur with oxandrolone. The drug should be used cautiously in patients with hypercholesterolemia and in those with cardiac disease, especially in those with arteriosclerosis, coronary artery disease, and myocardial infarction. Monitoring of lipoprotein concentrations is recommended during oxandrolone therapy. During treatment with androgens, edema can occur because of sodium retention. Thus, this is another reason to use oxandrolone cautiously in patients with heart failure, peripheral edema, or severe cardiac disease.

Oxandrolone should be used cautiously, if at all, in patients with pre-existing hepatic disease or cholestasis. Androgenic-anabolic steroids have been associated with the development of certain types of hepatic disease including peliosis hepatis (blood-filled cysts in the liver and sometimes splenic tissue), benign and malignant liver tumors (e.g., hepatocellular cancer), cholestatic hepatitis, and jaundice. Rarely, hepatic failure has occurred. Baseline liver function tests and exclusion of preexisting liver disease are recommended prior to oxandrolone initiation, and periodic liver function test assessment is suggested while on therapy, particularly for adult patients 65 years of age and older. During treatment with androgens, edema can occur because of sodium retention. This is another reason to use oxandrolone cautiously in patients with severe hepatic disease.^[1]

During treatment with androgens, edema can occur because of sodium retention. Due to the possible fluid retention, oxandrolone is contraindicated in patients with severe renal disease. Patients with heart failure, nephrosis, nephrotic phase of nephritis, or peripheral edema should be treated with caution.

Oxandrolone at doses of 5 or 10 mg twice daily has been studied in 4 clinical trials involving a total of 339 patients with 172 of these patients 65 years of age or older. Mean weight gain was similar between geriatric and younger adults, with no differences in efficacy found between the 2 dosages; however, elderly patients (particularly elderly women), were more likely to experience fluid retention and elevations in hepatic transaminases (LFTs). Based on these data and because the half-life of oxandrolone is prolonged in this patient population, the manufacturer recommends using a lower dose when treating geriatric patients.^[1] The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of medications in residents of long-term care facilities. According to the OBRA guidelines, the use of appetite stimulants should be reserved for situations where assessment and management of underlying correctable causes of anorexia and weight loss are not feasible or successful, and after evaluating the potential benefits versus risks. Appetite and weight should be monitored at least monthly and the appetite stimulant should be discontinued if there is no improvement. Possible adverse effects of oxandrolone include fluid retention, excessive sexual stimulation, virilization of females, and feminization of males.^[3]

Oxandrolone should generally be avoided in patients with polycythemia, as oxandrolone, especially in high doses, can cause further increases in the red cell mass. Periodic assessment of hemoglobin and hematocrit is recommended.

Hepatotoxicity caused by oxandrolone may arise from peliosis hepatis, hepatoma formation that causes cholestasis and jaundice, or direct hepatic necrosis. With the exception of peliosis hepatis, which has also been observed with testosterone, the 17a-alkylation appears to be the cause of the hepatic consequences. There does not seem to be a link between dose or duration and the development of peliosis hepatis. Cholestasis-related jaundice is infrequent when used as directed and is dose- and duration-related. Jaundice and peliosis hepatis are typically cleared up with the termination of oxandrolone. Since most tumors are benign and androgen-dependent, hepatoma regression or growth cessation typically happens with oxandrolone withdrawal. However, hepatomas associated with androgens or anabolic steroids are much more vascular than other hepatic tumors and may be undetected until life-threatening intra-abdominal hemorrhage develops. Hepatocellular carcinoma has been associated rarely with long-term, high-dose anabolic steroid therapy and may regress with drug cessation. Baseline liver function tests and exclusion of preexisting liver disease are recommended prior to therapy initiation. Underlying liver disease and concomitant use of other hepatotoxic drugs may potentiate or increase the severity of liver toxicity. Elderly patients may experience elevated hepatic enzymes more commonly than younger adults; a lower dose is recommended in elderly patients. Periodic assessment of liver function tests in all patients while on oxandrolone with drug discontinuation upon hepatic disease development is recommended. Other manifestations of hepatotoxicity can include elevated hepatic enzymes, hepatitis, or hepatic failure.^[1]

The androgenic effects of oxandrolone can affect both males and females. Manifestations include acne vulgaris, clitoromegaly, hirsutism, libido increase, penile enlargement, priapism, CNS depression, and CNS excitability including insomnia. Excessive sexual stimulation is more likely in geriatric males. Because irreversible virilization of women can occur, oxandrolone should be discontinued with the development of voice deepening or hoarseness, hirsutism, acne, or clitoromegaly. Estrogen supplementation does not prevent oxandrolone-induced virilizing changes and some changes may persist despite prompt drug discontinuation. Menstrual irregularity, amenorrhea, or oligomenorrhea can occur due to oxandrolone-induced suppression of gonadotropins.^[1]

Peripheral edema can occur with oxandrolone as the result of increased fluid retention (in association with sodium retention/ hypernatremia) and is manifested by weight gain. In the treatment of patients with impaired renal function or congestive heart failure, fluid retention is of greater clinical significance. Elderly patients may be more likely to experience fluid retention when compared to younger adult patients; a lower dose is recommended for elderly patients. Other serum electrolytes (i.e., calcium (hypercalcemia), phosphate (hyperphosphatemia), and potassium (hyperkalemia)) are also retained. Hypercalcemia can also be a result of the stimulatory effect of oxandrolone on osteolytic bone resorption.^[1]

Prostate cancer as a secondary malignancy or prostatic hypertrophy can develop during prolonged therapy with oxandrolone especially in elderly men. Periodic assessment of prostate-specific antigen is recommended especially for geriatric patients. Signs of acute epididymitis (e.g., fever, chills, pain in the inguinal region) or urinary urgency should prompt drug withdrawal and dosage reevaluation.^[1]

Male patients receiving oxandrolone may experience feminization due to gonadotrophin suppression. The feminizing effects are generally reversible with drug discontinuation. Impotence (erectile dysfunction), libido decrease, oligospermia, testicular atrophy, bladder irritation (bladder discomfort), gynecomastia, and epididymitis may occur.^[1]

Oxandrolone has the potential for teratogenesis (possible masculinization of the fetus) and, thus, is a pregnancy category X drug.^[1]

Periodic lipoprotein monitoring is recommended due to the possible development of hypercholesterolemia consisting of decreased high-density lipoproteins (HDL) and increased low-density lipoproteins. Alteration in the total cholesterol concentration may be minimal. The percentage decrease in HDL was 44% from one study of patients on 7.5 mg daily. There appears to be minimal to no dose relationship to the degree of HDL lowering. The nadir of HDL appears to occur in about seven days with reversal of these changes within one month of oxandrolone discontinuation. The magnitude of these changes can be significant, especially for patients with preexisting cardiac disease. Periodic assessment of serum lipoprotein concentrations is recommended especially for patients with cardiovascular disease.^[1]

Anabolic steroids may cause suppression of clotting factors II, V, VII, and X. A clotting factor deficiency or coagulopathy may occur with oxandrolone.^[1]

Periodic measurement of hemoglobin and hematocrit is warranted in patients receiving high doses of oxandrolone due to the potential development of polycythemia.^[1]

Oxandrolone is in FDA pregnancy risk category X because it should not be used during pregnancy. When oxandrolone was administered at levels nine times greater than what a human would get, the consequences on female animal progeny included masculinization of the fetus, infertility, and teratogenic effects, including embryotoxicity and fetotoxicity. These outcomes are consistent with the known outcomes of other androgenic and anabolic hormones. In females with the potential to get pregnant, oxandrolone should be used with caution. The potential risk to the fetus should be discussed with the patient if oxandrolone is used during pregnancy or if the patient gets pregnant while taking this medication.^[1]

If oxandrolone is secreted into breast milk is unknown. It is advised that nursing mothers stop breastfeeding or stop using oxandrolone.^[1] Oxandrolone is a synthetic testosterone derivative. Significant exposure to this androgen via breastfeeding may have adverse androgenic effects on the infant and the drug may also interfere with the proper establishment of lactation in the mother.^[2] Historically, testosterone/androgens have been used adjunctively for lactation suppression.^[2] Alternative methods to breastfeeding are recommended in lactating women receiving anabolic/androgenic therapy.

Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.

1. Oxandrin (oxandrolone) tablet package insert. East Brunswick, NJ: Savient Pharmaceuticals, Inc.; 2006 Jan.
2. Kochenour NK. Lactation suppression. Clin Obstet Gynecol. 1980;23:1045-1059.
3. Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.