Hormone-Dependent Prostate Cancer

Hormone-dependent prostate cancer is a type of prostate cancer that needs male hormones, particularly testosterone, to grow and survive. This characteristic makes it possible to treat the cancer by reducing or blocking these hormones in the body.

Table of contents

• What Is Hormone-Dependent Prostate Cancer?
• The Role of Male Hormones
• How Hormone Therapy Works
• Types of Hormone Therapy
• When Hormone Therapy Is Used
• When Cancer Becomes Resistant
• Side Effects of Hormone Therapy

What Is Hormone-Dependent Prostate Cancer?

Hormone-dependent prostate cancer, also called hormone-sensitive prostate cancer, is a cancer that depends on male sex hormones to grow^[1]. This type of cancer responds to treatments that lower or block these hormones. Other names for this condition include androgen-dependent, androgen-sensitive, castration-sensitive, or castrate-sensitive prostate cancer^[1].

hormone-sensitive prostate cancer, androgen-dependent prostate cancer, androgen-sensitive prostate cancer, castration-sensitive prostate cancer, castrate-sensitive prostate cancer

Hormone-receptor-positive prostate cancers make up a significant portion of prostate cancer cases^[3]. Along with breast cancer in women, prostate cancer in men represents one of the most common hormone-dependent cancers^[3].

• Prostate gland
• Testicles
• Adrenal glands

The Role of Male Hormones

Hormones are substances made by glands in the body that circulate in the bloodstream and control the actions of certain cells or organs^[1]. Androgens are male sex hormones that control the development and maintenance of male characteristics. The most abundant androgens in men are testosterone and dihydrotestosterone (DHT)^[1].

Androgens are required for normal growth and function of the prostate, a gland in the male reproductive system that helps make semen^[1]. These same hormones are also necessary for prostate cancers to grow. Androgens promote the growth of both normal and cancerous prostate cells by binding to and activating the androgen receptor, a protein that is found in prostate cells^[1].

Almost all testosterone is produced in the testicles, with a small amount produced by the adrenal glands^[1]. Although prostate cells do not normally make testosterone, some prostate cancer cells can acquire the ability to do so^[1]. Once the androgen receptor is activated, it stimulates the expression of specific genes that cause prostate cells to grow^[1].

How Hormone Therapy Works

Early in their development, prostate cancers need androgens to grow^[1]. Hormone therapy, also called androgen deprivation therapy (ADT), is a treatment that lowers or blocks testosterone^[2]. Most prostate cancer cells need testosterone to grow, so this treatment stops testosterone from being made or from reaching prostate cancer cells^[2].

Hormone therapies are treatments that decrease androgen levels or block androgen action. They can inhibit the growth of hormone-dependent prostate cancers^[1]. When hormone therapy works, it causes prostate cancer cells to die or to grow more slowly^[2].

Prostate cancer usually depends on the hormone testosterone to grow. Hormone therapy blocks or lowers the amount of testosterone in the body, which can lower the risk of prostate cancer coming back when used with other treatments^[4].

Types of Hormone Therapy

Hormone therapy can block the production or use of androgens in several ways^[1]. Currently available treatments include:

• Reducing androgen production by the testicles
• Blocking the action of androgens throughout the body
• Blocking androgen production throughout the body, including by prostate cancer cells^[1]

The most common types of hormone therapy include medicines that stop the body from making testosterone and medicines that block the action of testosterone in the body^[2]. Some medicines block signals that tell the testicles to make testosterone. These medicines are called luteinizing hormone-releasing hormone (LHRH) agonists and antagonists, also known as gonadotropin-releasing hormone (GnRH) agonists and antagonists^[2].

Other medicines are known as antiandrogens. These block the action of testosterone in the body. They are often used with LHRH agonists because LHRH agonists can cause a brief rise in testosterone levels before testosterone levels go down^[2].

In rare cases, surgery to remove the testicles may be used. This surgery is called an orchiectomy^[2]. It lowers testosterone levels in the body quickly. In some cases, only the part of the testicles that makes testosterone is removed. Both procedures are permanent^[2].

Hormone therapy in the form of medicine can be given all the time or off and on^[2].

When Hormone Therapy Is Used

Hormone therapy has long been an important treatment for men with advanced prostate cancer and is increasing in use before, during, and after other treatments^[7]. Hormone therapy may be used:

• Before radiation to try to shrink the tumor
• If prostate cancer returns after surgery or radiation
• If prostate cancer has spread (metastasized)^[7]

You might have hormone therapy with radiotherapy for prostate cancer that hasn’t spread to distant body parts^[4]. Clinical trials have shown that for patients with metastatic hormone-sensitive prostate cancer, adding newer types of medicines together with standard hormone therapy significantly extended the length of time before disease progression and improved survival^[12].

For many years, androgen deprivation therapy alone through surgical or chemical castration was the mainstay of treatment, yielding limited five-year survival rates^[13]. Today, hormone therapy is almost always combined with other therapies for better results^[12].

When Cancer Becomes Resistant

Most prostate cancers eventually stop responding to hormone therapy and become castration-resistant or castrate-resistant^[1]. This means they continue to grow even when androgen levels in the body are extremely low or undetectable. In the past, these tumors were also called hormone-resistant, androgen-independent, or hormone-refractory^[1].

However, these terms are rarely used now because the tumors are not truly independent of androgens for their growth^[1]. In fact, some newer hormone therapies have become available that can be used to treat tumors that have become castration-resistant^[1].

During the progression to androgen-independence, the signaling pathway has been found to be altered at many levels within prostate cancers^[5]. Understanding the molecular alterations that occur during this process will allow for improved therapeutic strategies^[5].

Side Effects of Hormone Therapy

Hormone therapy for prostate cancer can affect the levels of your hormones, which can cause different side effects^[4]. Treatment for prostate cancer can lower the amount of testosterone in your body, which leads to various symptoms^[15].

Common side effects include:

• Hot flushes
• Swollen breasts (called gynaecomastia)
• Sleep disturbances
• Weight changes and loss of muscle strength^[4][15]

Men who take these testosterone-blocking drugs may experience fatigue, loss of muscle mass, and a heightened risk of cardiovascular diseases^[22]. Low levels of sex hormones caused by hormone therapy can also lead to memory changes, difficulty thinking, and problems with concentration^[15].

Hormone therapy can also affect your risk of heart disease and diabetes^[15]. It can lead to bone thinning and weakness, a condition known as osteoporosis^[15]. Some treatments can damage the nerves or affect hormone levels needed to get an erection, affecting sex life and relationships^[15].

Support is available to help you cope with these hormone changes^[15]. It is important to discuss any side effects with your healthcare team so they can help you manage them effectively.