Introduction
Testosterone is a steroid sex hormone indicated to treat primary hypogonadism and hypogonadotropic hypogonadism. Testosterone antagonizes the androgen receptor to induce gene expression that causes the growth and development of masculine sex organs and secondary sexual characteristics.
Testosterone was isolated from samples and also synthesized in 1935.
Uses
Testosterone is a hormone used to treat hypogonadism, breast carcinoma in women, or the vasomotor symptoms of menopause.
Testosterone is indicated to treat primary hypogonadism and hypogonadotropic hypogonadism.
Associated Conditions
Pharmacodynamics
Testosterone antagonizes the androgen receptor to induce gene expression that causes the growth and development of masculine sex organs and secondary sexual characteristics. The duration of action of testosterone is variable from patient to patient with a half life of 10-100 minutes. The therapeutic index is wide considering the normal testosterone levels in an adult man range from 300-1000ng/dL. Counsel patients regarding the risk of secondary exposure of testosterone topical products to children.
Mechanism of Action
The androgen receptor exists in the cytoplasm bound to the heat shock proteins HSP90, HSP70, and other chaperones. After binding to an androgen, the androgen receptor dissociates from HSP90 and undergoes a conformational change to slow the rate of dissociation from the androgen receptor. The androgen-receptor complex is transported into the nucleus where it binds to DNA and recruits other transcriptional regulators to form a pre-initiation complex and eventually induce expression of specific genes.
Testosterone and its active metabolite dihydrotestosterone (DHT) antagonize the androgen receptor to develop masculine sex organs including the prostate, seminal vesicles, penis, and scrotum.
Antagonism of the androgen receptor is also responsible for the development of secondary sexual characteristics including facial and body hair, enlargement of the larynx, thickening of the vocal cords, and changes in muscle and fat distribution.
Absorption
A single 100mg topical dose of testosterone has an AUC of 10425±5521ng*h/dL and a Cmax of 573±284ng/dL. Testosterone is approximately 10% bioavailable topically.
Volume of Distribution
The volume of distribution of testosterone in elderly men is 80.36±24.51L.
Protein Binding
Testosterone is 40% bound to sex hormone binding globulin, 2% unbound, and the remainder is bound to albumin and other proteins.
Route of Elimination
90% of an intramuscular dose is eliminated in urine, mainly as glucuronide and sulfate conjugates. 6% is eliminated in feces, mostly as unconjugated metabolites.
Half Life
The half life of testosterone is highly variable, ranging from 10-100 minutes.
Clearance
The mean metabolic clearance in middle aged men is 812±64L/day.
Toxicity
Data regarding an overdose with a topical testosterone product is not readily available. In the case of overdose with an injectable product, patients may present with a cerebrovascular event. Treat overdoses by stopping testosterone products, washing off any topical products with soap and water, and initiating symptomatic and supportive treatments.
Food Interactions
No interactions found.
Dosage
Starting dose of testosterone gel 1.62% is 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet), applied topically once daily in the morning.
Apply to clean, dry, intact skin of the shoulders and upper arms. Do not apply testosterone gel 1.62% to any other parts of the body including the abdomen, genitals, chest, armpits (axillae), or knees.
Dose adjustment: testosterone gel 1.62% can be dose adjusted between a minimum of 20.25 mg of testosterone (1 pump actuation or a single 20.25 mg packet) and a maximum of 81 mg of testosterone (4 pump actuations or two 40.5 mg packets). The dose should be titrated based on the pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment or following dose adjustment. Additionally, serum testosterone concentration should be assessed periodically thereafter.
Patients should wash hands immediately with soap and water after applying testosterone gel 1.62% and cover the application site(s) with clothing after the gel has dried. Wash the application site thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated.
