indication

To be used as hormone replacement or substitution of diminished or absent endogenous testosterone. Use in males: For management of congenital or acquired hypogonadism, hypogonadism associated with HIV infection, and male climacteric (andopause). Use in females: For palliative treatment of androgen-responsive, advanced, inoperable, metastatis (skeletal) carcinoma of the breast in women who are 1-5 years postmenopausal; testosterone esters may be used in combination with estrogens in the management of moderate to severe vasomotor symptoms associated with menopause in women who do not respond to adequately to estrogen therapy alone.

pharmacology

Testosterone is a steroid hormone from the androgen group. Testosterone is primarily secreted from the testes of males. In females, it is produced in the ovaries, adrenal glands and by conversion of adrostenedione in the periphery. It is the principal male sex hormone and an anabolic steroid. In both males and females, it plays key roles in health and well-being. Examples include enhanced libido, energy, immune function, and protection against osteoporosis. On average, the adult male body produces about twenty times the amount of testosterone than an adult female's body does.

mechanism of action

The effects of testosterone in humans and other vertebrates occur by way of two main mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Free testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly than T, so that its androgenic potency is about 2.5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.

toxicity

Side effects include amnesia, anxiety, discolored hair, dizziness, dry skin, hirsutism, hostility, impaired urination, paresthesia, penis disorder, peripheral edema, sweating, and vasodilation.

biotransformation

Testosterone is metabolized to 17-keto steroids through two different pathways. The major active metabolites are estradiol and dihydrotestosterone (DHT).

absorption

Approximately 10% of the testosterone dose applied on the skin surface is absorbed into systemic circulation

half life

10-100 minutes

route of elimination

About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form.

drug interactions

Acenocoumarol: The androgen, Testosterone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testosterone is initiated, discontinued or dose changed.

Anisindione: The androgen may increase the anticoagulant effect of anisindione.

Cyclosporine: The androgen, Testosterone, may increase the hepatotoxicity of Cyclosporine. Testosterone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.

Dicumarol: The androgen may increase the anticoagulant effect of dicumarol.

Docetaxel: Testosterone may increase the serum levels and toxicity of docetaxel.

Warfarin: Testosterone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if testosterone is initiated, discontinued or dose changed.