Androgens

Published on 08/04/2017 by admin

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Last modified 08/04/2017

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50–400 mg every 2–4 wk Transdermal patch Testosterone Androderm One patch/day (delivers 2 or 4 mg/24 hr) III Applied to the arm, back, abdomen, or thigh, but not the scrotum. Causes local irritation. Transdermal gel Testosterone AndroGel, Testim 5–10 g of 1% gel once daily (delivers 50–100 mg/day) III

Apply AndroGel to upper arm, shoulder, or abdomen, but not the scrotum. Apply Testim only to upper arm or shoulder.

Apply Fortesta to the front and inner thigh.

Easier to use and better tolerated than testosterone patches. Can transfer to others via intimate contact.

Fortesta 40–70 mg of 2% gel once daily Transdermal topical solution Testosterone Axiron 60–180 mg once daily III Apply to one or both armpits at the same time each morning. Easier to use and better tolerated than testosterone patches. Can transfer to others via skin-to-skin contact. Nasal Gel Testosterone Natesto 11 mg (2 pump actuations) per nostril 3 times a day III Natesto nasal gel is delivered by a metered-dose pump. Each actuation of the pump delivers 5.5 mg of testosterone. Implantable pellets Testosterone Testopel 150–450 mg (2–6 pellets) subQ every 3–6 months III Implanted subQ. Long lasting. Produce steady blood levels. Buccal system Testosterone Striant One buccal system (30 mg) every 12 hr III Provides fairly steady testosterone levels but may cause mouth or gum irritation.

CSA, Controlled Substances Act; subQ, subcutaneously.

Delayed Puberty

In some boys, puberty fails to occur at the usual age (i.e., before age 15 years). Most often, this failure reflects a familial pattern of delayed puberty and does not indicate pathology. Puberty can be expected to occur spontaneously, but later than usual. Hence, although androgen therapy can be employed, treatment is not an absolute necessity. However, the psychological pressures of delayed sexual maturation are sometimes greater than a boy can tolerate. In these cases, a limited course of androgen therapy is indicated. Both fluoxymesterone [Androxy] and methyltestosterone [Android, Methitest, Testred] are approved for this purpose.

If delayed puberty is the result of true hypogonadism, long-term replacement therapy is indicated (see later section “Androgen Preparations for Male Hypogonadism”).

Replacement Therapy in Menopausal Women

Testosterone replacement therapy can alleviate some menopausal symptoms, especially fatigue, reduced libido, and reduced genital sensitivity. Testosterone is not approved for replacement in women in the United States, although it is approved in the United Kingdom.

Treatment of Transsexualism

Testosterone is used as masculinizing therapy for patients who are born with a female body but self-identify as male. Anticipated effects are increased hair growth over the face and body, a deepening of the voice, breast tissue atrophy, and cessation of menses. An increase in muscle tissue relative to adipose tissue also occurs. Therapy is highly individualized by specialists in transgender health.

Cachexia

Cachexia is a wasting of the body associated with severe illnesses such as AIDS, severe trauma, and chronic systemic infections. Testosterone levels often decline in these patients, putting them at risk for wasting and loss of muscle mass. Testosterone therapy decreases this risk. Oxandrolone [Oxandrin] is FDA approved for this purpose. Oxandrolone is an anabolic steroid that is a synthetic derivative of testosterone.

 

imageBlack Box Warning: Oxandrolone [Oxandrin]

Oxandrolone can cause peliosis hepatitis, a condition in which blood-filled cysts form in the liver leading to liver failure or intraabdominal hemorrhage. It can also contribute to the development of highly vascular liver tumors.

An increased risk for atherosclerosis can occur secondary to marked elevations in LDL and decreases in HDL.

Anemias

Androgens are sometimes used in men and women to treat anemias that have been refractory to other therapy. Anemias most likely to respond include aplastic anemia, anemia associated with renal failure, Fanconi anemia, and anemia caused by cancer chemotherapy. Androgens help relieve anemia by promoting synthesis of erythropoietin, the renal hormone that stimulates production of red blood cells and, possibly, white blood cells and platelets. With the emergence of other therapies such as erythropoietin stimulating agents, however, androgens have fallen out of failure for off-label treatment of anemia.

Adverse Effects

PATIENT-CENTERED CARE ACROSS THE LIFESPAN

Androgens

Life Stage Considerations or Concerns
Children Androgens can cause virilization in children. They can also accelerate epiphyseal closure, thereby decreasing adult height.
Pregnant women Androgens are Pregnancy Risk Category X: the ability to cause fetal harm outweighs any possible therapeutic benefit. Potential fetal changes include vaginal malformation, clitoral enlargement, and formation of a structure resembling the male scrotum. Virilization is most likely when androgens are taken during the first trimester. Women who become pregnant while using androgens should be informed about the possible effect on the fetus.
Breastfeeding women Testosterone is excreted in breast milk. Breastfeeding is contraindicated.
Older adults Older patients are at an increased risk for thromboembolic conditions such as myocardial infarction or stroke. Beers Criteria identify testosterone and methyltestosterone as potentially inappropriate for patients 65 years and older.

Virilization in Women, Girls, and Boys

Virilization is the most common complication of androgen therapy. When taken in high doses by women, androgens can cause acne, deepening of the voice, proliferation of facial and body hair, male-pattern baldness, increased libido, clitoral enlargement, and menstrual irregularities. Clitoral growth, hair loss, and lowering of the voice may be irreversible. Masculinization can also occur in children. Boys may experience growth of pubic hair, penile enlargement, increased frequency of erections, and even priapism (persistent erection). In girls, growth of pubic hair and clitoral enlargement may occur. To prevent irreversible masculinization, androgens must be discontinued when virilizing effects first appear.

Premature Epiphyseal Closure

When given to children, androgens can accelerate epiphyseal closure, thereby decreasing adult height. To evaluate androgen effects on the epiphyses, radiographic examination of the hand and wrist should be performed every 6 months.

Hepatotoxicity

Androgens can cause cholestatic hepatitis and other disorders of the liver. Clinical jaundice may occur but is rare. Patients receiving androgens should undergo periodic tests of liver function. If jaundice develops, it will reverse after discontinuation of androgen use. Androgens may also be carcinogenic: hepatocellular carcinoma has developed in some patients after prolonged use of these drugs.

It must be emphasized that not all androgens are hepatotoxic: liver damage is associated primarily with the 17-alpha-alkylated androgens. These androgens all share a structural feature in common: an alkyl group substituted on carbon 17 of the steroid nucleus. Because of their capacity to cause liver damage, the 17-alpha-alkylated compounds should not be used long term. In contrast to the 17-alpha-alkylated androgens, testosterone and the testosterone esters (testosterone cypionate, testosterone enanthate) are not associated with liver disease.

Effects on Cholesterol Levels

Androgens can lower plasma levels of high-density lipoprotein (HDL) cholesterol (“good cholesterol”) and elevate plasma levels of low-density lipoprotein (LDL) cholesterol (“bad cholesterol”). These actions may increase the risk for atherosclerosis and related cardiovascular events.

Prostate Cancer

Androgens do not cause prostate cancer, but they can promote the growth of this cancer after it occurs. Accordingly, androgens are contraindicated for men with diagnosed prostate cancer. Men without diagnosed prostate cancer should be monitored for emergence of covert cancer.

Edema

Edema can result from androgen-induced retention of salt and water. This complication is a concern for patients with heart failure and for those with a predisposition to developing edema from other causes. Treatment consists of discontinuing the androgen and giving a diuretic, if needed.

Abuse Potential

As discussed later, androgens are frequently misused (abused) to enhance athletic performance. Because of their abuse potential, nearly all androgens are regulated as Schedule III controlled substances.

Risk for Thromboembolic Events

There have been post-marketing reports of thromboembolic events, including stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism. These events are believed to be the result of testosterone’s erythropoietic effects. While long-term clinical trials are not available and randomized control trials have been inconclusive, the concern was sufficient to prompt the U.S. Food and Drug Administration (FDA) to issue a Testosterone Product Safety Alert in 2014 to address this potential life-threatening concern. (See www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm384225.htm)

Androgen Preparations for Male Hypogonadism

Treatment options for androgen replacement therapy have expanded in recent years. In the past, intramuscular (IM) therapy with a long-acting testosterone ester was the major treatment mode. Today, we have six attractive alternatives: a nasal gel, transdermal patch, transdermal gel, topical solution, buccal tablet, and implantable subcutaneous pellets. All of these formulations are regulated as Schedule III controlled substances.

Oral Androgens

Only two androgens are approved for oral therapy of male hypogonadism. Both drugs—fluoxymesterone and methyltestosterone—are 17-alpha-alkylated androgens and therefore pose a risk for hepatotoxicity. Accordingly, they should not be used long term and hence are not first-line agents.

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