Endogenous androgens are responsible for the normal growth and development
of the male sex organs and for maintenance of secondary sex characteristics.
These effects include the growth and maturation of prostate, seminal vesicles,
penis, and scrotum. The development of male hair distribution, such as beard,
pubic, chest, and axillary hair; laryngeal enlargement, vocal chord thickening,
alterations in body musculature, and fat distribution. Drugs in this class also
cause retention of nitrogen, sodium, potassium, phosphorus, and decreased urinary
excretion of calcium. Androgens have been reported to increase protein anabolism
and decrease protein catabolism. Nitrogen balance is improved only when there
is sufficient intake of calories and protein.
Androgens are responsible for the growth spurt of adolescence and for the eventual
termination of linear growth which is brought about by fusion of the epiphyseal
growth centers. In children, exogenous androgens accelerate linear growth rates,
but may cause a disproportionate advancement in bone maturation. Use over long
periods may result in fusion of the epiphyseal growth centers and termination
of growth process. Androgens have been reported to stimulate the production
of red blood cells by enhancing the production of erythropoietic stimulating
During exogenous administration of androgens, endogenous testosterone release
is inhibited through feedback inhibition of pituitary luteinizing hormone (LH).
At large doses of exogenous androgens, spermatogenesis may also be suppressed
through feedback inhibition of pituitary follicle stimulating hormone (FSH).
There is a lack of substantial evidence that androgens are effective in fractures,
surgery, convalescence and functional uterine bleeding.
Testosterone given orally is metabolized by the gut and 44 percent is cleared
by the liver of the first pass. Oral doses as high as 400 mg per day are needed
to achieve clinically effective blood levels for full replacement therapy. The
synthetic androgen, Methyltestosterone, is less extensively metabolized by the
liver and has a longer half-life. It is more suitable than testosterone for
Testosterone in plasma is 98 percent bound to a specific testosterone-estradiol
binding globulin, and about 2 percent is free. Generally, the amount of this
sex-hormone binding globulin in the plasma will determine the distribution of
testosterone between free and bound forms, and the free testosterone concentration
will determine its half-life.
About 90 percent of a dose of testosterone is excreted in the urine as glucuronic
and sulfuric acid conjugates of testosterone and its metabolites; and 6 percent
of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation
of testosterone occurs primarily in the liver. Testosterone is metabolized to
various 17-keto steroids through two different pathways. There are considerable
variations of the half-life of testosterone as reported in the literature, ranging
from 10 to 100 minutes.
In many tissues the activity of testosterone appears to depend on reduction
to dihydrotestosterone, which binds to cytosol receptor proteins. The steroid-receptor
complex is transported to the nucleus where it initiates transcription events
and cellular changes related to androgen action.