Androgens and antiandrogens
Content Reviewers:Yifan Xiao, MD
Contributors:Salma Ladhani, MD, Jake Ryan, Maria Emfietzoglou, MD, Elizabeth Nixon-Shapiro, MSMI, CMI
Androgens are a class of steroid hormones that act as agonists to androgen receptors.
Testosterone is the principal endogenous androgen, while synthetic androgens include testosterone derivatives and anabolic steroids.
They bind to and activate androgen receptors and are used in the treatment of conditions where testosterone levels in the body drop lower than normal, such as primary or secondary hypogonadism.
Now, antiandrogens or androgen antagonists include androgen receptor inhibitors, 5α-reductase inhibitors, and inhibitors of testosterone synthesis.
They prevent the biological effects of androgens like testosterone in the body and are used in the treatment of prostate cancer, benign prostatic hyperplasia, hair loss in males, and hirsutism in females.
Testosterone, the primary male hormone, is an androgen, andro meaning male and gen meaning “to produce,” which means testosterone helps generate the characteristics associated with male sexuality.
The effects of testosterone are first seen in the fetus, where it guides development of the male urogenital tract and external genitalia, as well as testicular descent through the inguinal canal.
Testosterone is primarily secreted by the fetal testicles.
The fetal ovaries also secrete testosterone but at much lower levels, and this largely explains the differences in fetal development between boys and girls.
In puberty, the hypothalamic-pituitary axis regulates testosterone levels and gonadal function.
The hypothalamus secretes gonadotropin-releasing hormone which causes the pituitary gland to secrete luteinizing hormone or LH and follicle-stimulating hormone or FSH.
These hormones travel to the testes and cause leydig cells to convert cholesterol into testosterone through a number of steps.
Two important intermediate molecules in that process are dehydroepiandrosterone, also called DHEA, and the molecule that it gets converted into - androstenedione.
The last step is to have the testicular enzyme 17β-hydroxysteroid dehydrogenase convert androstenedione into testosterone.
Alright, now testosterone is responsible for primary sexual development, which are the changes necessary for reproduction like enlargement of the penis and testes, as well as increasing libido.
Testosterone also helps with secondary sexual characteristics which aren’t required for reproduction but are associated with masculinity, like a male pattern of hair growth on the face, chest, axillary, and genital areas.
The hair itself changes from thin soft hair of childhood to thick and coarse hair of adulthood, and the voice eventually deepens.
Testosterone also has tissue-building effects, sometimes called anabolic effects.
It contributes to the growth spurt in puberty by making the bones longer, while it is also responsible for the closure of the epiphyseal plate in late puberty.
Other anabolic effects include development of broad shoulders and muscular arms and legs.
Last but not least, testosterone stimulates erythropoiesis, giving men a higher red blood cell count than women.
In some tissues, like the prostate gland and hair follicles, the enzyme 5ɑ-reductase converts testosterone into dihydrotestosterone or DHT which is like a more potent version of testosterone.
Now, in some pathological conditions, testosterone levels in the body drop lower than normal which can lead to a variety of problems ranging from delayed puberty in children to decreased libido in adults.
Low testosterone levels can also suspend normal growth, and affect secondary sexual characteristics during puberty, while it may cause anemia and decreased muscle mass in adults ultimately leading to limited physical ability.
On the other hand, too much androgen, especially testosterone, play an important role in both benign and malignant prostate diseases, hair loss, and hirsutism.
Okay, androgens, as a class of medication, are steroid hormones.
Testosterone itself can be given by subcutaneous implantation, by a transdermal patch, or via buccal administration.
Synthetic androgens are agonists that activate androgen receptors on the cell surface just like endogenous testosterone.
There are two types of synthetic androgens: the testosterone derivatives and the anabolic steroids.
Testosterone derivatives include fluoxymesterone and methyltestosterone, which are given orally, and testosterone esters like testosterone cypionate which are long-acting androgens given by intramuscular depot injection.
Now, testosterone and testosterone derivatives are mainly used for testosterone replacement therapy in hypogonadism in biological males, where low levels of testosterone in the body result in delayed puberty, or delayed sexual maturation.
They are used both in primary hypogonadism meaning testicular disease, and in secondary hypogonadism or hypopituitarism meaning pituitary disease, in order to stimulate the development of secondary sexual characteristics and accelerate growth.
They are also used in order to stimulate anabolism as a means of promoting recovery after a burn or injury, and in order to promote weight gain in patients with wasting syndromes, like those with cancer or AIDS.
Now, both testosterone and testosterone derivatives can cause masculinization in females, which includes enlargement of the clitoris, acne, and hirsutism, which is the growth of facial and chest hair, as well as menstrual irregularity.
In males, excessive doses inhibit LH release via a negative feedback mechanism which leads to a decrease in intratesticular testosterone and gonadal atrophy.
This inhibition of the pituitary can cause paradoxical feminization, including gynecomastia and infertility.
Other side effects include premature closure of epiphyseal plates, which impairs growth in children.
Finally, they cause an increase of low density lipoprotein, or LDL, and a decrease of high density lipoprotein, or HDL, which leads to obesity.
Alright, moving on to anabolic steroids now, which are androgens that have been modified chemically to increase their anabolic action.
They include medications like nandrolone and oxandrolone.
They tend to increase muscle size and strength, and promote erythropoiesis, meaning they increase red blood cell production.
However, their clinical use is limited.
Anabolic steroids are used only in the treatment of aplastic anemia, a condition where your bone marrow stops producing enough new blood cells.
They have also been abused illegally by athletes to increase athletic performance.
Now, side effects are similar to those caused by testosterone derivatives, however high doses of anabolic steroids can also cause cholestatic jaundice, a reduction in bile flow from the liver into the small intestine that eventually leads to bile salts depositing in the skin, giving it a yellowish color, increasing liver enzyme levels, and hepatocellular carcinoma, which is a liver tumor.
Androgens are hormones that are important in the development of male characteristics and reproduction. Common examples of androgens include testosterone and its metabolite dihydrotestosterone (DHT). Antiandrogens are drugs that block the effects of androgens. They are often used to treat conditions such as prostate cancer, benign prostatic hyperplasia (BPH), and hirsutism (excessive hair growth).
Androgens are produced by the testes, ovaries, adrenal glands, and fat tissue. Examples of antiandrogens include drugs like apalutamide, bicalutamide, and darolutamide.
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