Endocrine Therapy in Prostate Cancer

What Is Prostate and Prostate Cancer?

Uncontrollable and out-of-control growth of cells (that can invade surrounding tissues) is known as cancer, and prostate cancer occurs when the cells in the prostate gland start to grow abnormally. The prostate is an organ in the male body that makes some of the fluid found in the semen. It is located below the bladder and in front of the rectum. Some of the vital structures surrounding the prostate are seminal vesicles, urethra, etc. The urethra carries urine as well as semen out of the body through the penis and passes through the center of the prostate. The size of the prostate changes with age, in a young man, it is the size of a walnut, but in older men, it grows larger than that.

Prostate cancer is one of the most common types of cancer. There are multiple types of prostate cancer, including:

• Adenocarcinoma: Almost all prostate cancers are adenocarcinomas. These develop from the prostate gland cells.

• Small cell carcinoma.

• Neuroendocrine tumors.

• Transitional cell carcinomas.

• Sarcomas.

Many prostate cancers grow slowly and stay confined in the prostate gland, and these types of prostate cancer cause no serious harm. At the same time, some types grow aggressively and spread quickly. The symptoms of prostate cancer include trouble in urination, blood in urine or semen, erectile dysfunction, unusual weight loss, pain in bones, etc.

What Are Male Sex Hormones?

Hormones are signaling molecules produced by several glands that flow in the bloodstream and influence the growth and development of cells and organs. Androgen is a male sex hormone that controls the development and regulation of male characteristics. The androgens that are most abundantly found in males are testosterone and dihydrotestosterone (DHT). Androgens are crucial for the normal growth and functioning of the prostate gland.

On the other hand, androgens also play a vital role in the growth of prostate cancer. Androgens promote the growth and development of both normal and cancerous cells without any discrimination. They do so by binding and activating the androgen receptors (a protein that is expressed in prostate cells). Once these androgen receptors are activated, they stimulate the expression of genes that promotes the growth of prostate gland cells.

How Does Hormone Therapy Work Against Prostate Cancer?

Prostate cancer grows with the help of androgens. Hormone therapies used for the treatment of prostate cancer work by either blocking the action of androgens or by decreasing the level of androgens in the body, which are therefore called castration sensitive, androgen-dependent, or androgen sensitive.

When Is Hormone Therapy Used?

Hormone therapy may be used:

• In cases where cancer has spread aggressively, surgery or radiation cannot treat it.

• In cases where surgery cannot be done for some other reason like; patients over seventy years of age have a higher risk of developing complications, presence of other systemic conditions, bleeding disorders, etc.

• In cases when cancer recurs after surgery and radiation therapy.

• Hormone therapy is used in conjunction with radiation therapy.

• Hormone therapy is used before radiation therapy to shrink cancer and make the treatment more effective.

What Are the Types of Hormone Therapy?

The hormone therapies used to treat prostate cancer either block the production of androgens or limit the use of androgens. The treatment is done in the following ways:

1. Reduction of androgen production by testicles.

2. Blocking the action of androgens throughout the body.

3. Block synthesis of androgen throughout the body.

What Are the Treatments Available For Lowering Testicular Androgen Levels?

Androgen deprivation therapy (ADT) is the most commonly used hormonal therapy used for the treatment of prostate cancer.

• Orchiectomy (Surgical Castration): Removal of testicles, also known as surgical castration, can result in the reduction of testosterone in the body by up to 90%. In this procedure, the surgeon removes the testicles where most of the androgens are made. This causes most prostate cancers to stop growing or shrink. A type of orchiectomy known as subcapsular orchiectomy removes only the tissues in the testicles that produce androgens (instead of the entire testicle). Unlike some other treatment modalities, orchiectomy is permanent and irreversible.

• Luteinizing Hormone-Releasing Hormone Antagonist: Drugs called Luteinizing hormone-releasing hormone (LHRH) antagonists prevent the pituitary gland from secreting a hormone known as the luteinizing hormone. These are synthetic proteins that structurally mimic LHRH and bind to the LHRH receptors present in the pituitary gland. Normally when the androgen levels are low in the body, the pituitary gland produces a luteinizing hormone which subsequently stimulates testicles to produce androgens. LHRH antagonist prevents the pituitary gland from producing luteinizing hormone. Eventually, testicles stop producing the androgens, and treatment with these drugs is called medical castration. The LHRH antagonists used are Leuprolide, Goserelin, Triptorelin, etc.

• Drugs Called Luteinizing Hormone-Releasing Hormone (LHRH) Antagonists: Drugs called LHRH (luteinizing hormone-releasing hormone) antagonists are another form of medical castration. The LHRH antagonist, also known as GnRH antagonist, prevents LHRH from binding with LHRH receptors in the pituitary gland.

• Estrogens: Estrogens can also inhibit androgen production in the testicles, but they are rarely used because of their multiple side effects.

What Are Treatments That Block Action of Androgen in the Body?

Hormone therapy that blocks the action of androgen in the body is also known as antiandrogen therapy. These are usually used in cases where androgen deprivation therapy does not work. Antiandrogen therapies include:

• Androgen Receptor Blockers: These are drugs that compete with the androgens in binding with the androgen receptors. Because androgen receptor blockers do not prevent the production of androgens in the body, they are used in conjunction with ADT (this is called combined androgen blockade).

• Androgen Synthesis Inhibitors: These are drugs that inhibit the synthesis of androgens from all tissues that produce them.

What Are the Possible Side Effects of Therapy?

Androgens, as hormones, affect many other organs apart from the prostate. Therefore, they cause several side effects, including:

• Reduced sex drive.

• Erectile dysfunction.

• Loss of bone density.

• Easy bone fractures.

• Loss of muscle mass.

• Changes in blood lipids.

• Unusual weight gain.

• Insulin resistance.

• Fatigue and tiredness.

• Growth of breasts in men (gynecomastia)

• Mood swings.

• Hot flashes.

• Depression.

• Anemia.

• Elevated cholesterol levels.

Conclusion:

Prostate cancer is a commonly occurring cancer in men, and the prostate is a vital organ responsible for the production of androgen (male sex hormones). Androgens are responsible for the growth and development of normal as well as cancerous cells in the prostate gland. Therefore, hormonal therapy works by either blocking the action of androgens or by decreasing the level of androgen in the body. Although hormone therapy for prostate cancer is not a definitive treatment, it helps in improving the condition. However, the result of the therapy varies in different individuals.