Key takeaways

  • Hormone blockade therapy, which includes both oral and injectable options, aims to slow or stop the growth of prostate cancer cells by reducing androgen levels.
  • Injectable hormone blockade therapies, such as LHRH agonists and antagonists, are administered by healthcare professionals and can be given from once a month to every 6 months.
  • Oral hormone blockade therapies offer the convenience of daily pills that can be taken at home. LHRH antagonists, androgen synthesis inhibitors, and anti-androgens are available in oral form.

Prostate cancer is considered advanced once it has spread beyond the tissues of the prostate. It may be classified in one of two ways:

  • Locally advanced: if it remains confined to local tissues of the prostate and nearby lymph nodes
  • Metastatic: once it has spread to more distant parts of the body

Because hormones play an important role in the growth of prostate cancer cells, hormone therapy is often an essential part of treatment for this type of cancer. Several types of hormone therapy are available to treat prostate cancer, including oral and injectable forms of treatment.

In this article, we explore the differences between oral and injectable hormone therapies, including how they are used and what to expect during treatment.

Hormone therapy is a type of treatment that aims to decrease the levels or activity of sex hormones called androgens. It is also sometimes called androgen deprivation therapy (ADT).

Androgens, such as testosterone, act as fuel for prostate cancer cells. Decreasing androgen levels in people with prostate cancer can disrupt cancer cell growth, resulting in slowed tumor growth or even tumor shrinkage.

Hormone therapy can be used at several points throughout prostate cancer treatment and is typically used in combination with other treatment approaches such as surgery, chemotherapy, or radiation therapy.

Some tumors eventually stop responding to hormone therapy, even when testosterone levels are lowered. This type of cancer is referred to as castration-resistant.

Hormone therapy may be performed surgically by removing the testicles, which are the major source of androgens in the body. It can also be done medically by using injectable or oral medications.

Injectable hormone therapies for advanced prostate cancer work by disrupting the activity of luteinizing hormone-releasing hormone (LHRH). LHRH stimulates the pituitary gland to produce luteinizing hormone, which, in turn, tells the testicles to produce androgens.

LHRH agonists are a type of injectable hormone therapy that works by desensitizing the pituitary gland to LHRH. It works in the same way as the body’s natural LHRH, essentially flooding the system with signals to produce luteinizing hormone.

At first, the high levels of LHRH cause a surge in testosterone production. But after 1 to 2 weeks, the continually high levels of LHRH agonists lead the pituitary gland to “ignore” the signal, resulting in decreased production of luteinizing hormone and, in turn, decreased androgen production.

There are several types of LHRH agonists used to treat prostate cancer in the United States:

  • leuprolide (sold under the brand names Lupron and Eligard)
  • leuprolide mesylate (Camcevi)
  • goserelin (Zoladex)
  • triptorelin (Trelstar)

Another type of injectable hormone therapy used to treat advanced prostate cancer is known as an LHRH antagonist. Like LHRH agonists, this medication works to stop the production of luteinizing hormone.

Instead of turning up the production signal, though, LHRH antagonists work by immediately blocking the binding of LHRH to the pituitary gland, thereby disrupting the signals that trigger the production of luteinizing hormone.

Unlike other therapies that cause a temporary 1- to 2-week surge in testosterone before levels fall, LHRH antagonists lead directly to a rapid drop in testosterone production.

Degarelix (Firmagon) is an LHRH antagonist that is given as an injection to treat prostate cancer.

Injectable therapies are administered by a healthcare professional under the skin. They may also be given as a small implant (Histrelin). They are given anywhere from once per month to once every 6 months, depending on a person’s treatment needs.

Relugolix (Orgovyx) is an LHRH antagonist that can be taken as a daily pill to treat advanced prostate cancer. It works in a similar way to the injectable LHRH antagonist — by immediately blocking pituitary signaling to reduce androgen production in the testicles.

Androgens are mostly produced in the testicles, but they are also made in small amounts in the adrenal glands. In someone with prostate cancer, they can also be made in small amounts in the prostate gland or prostate cancer cells.

Other types of oral hormone therapies work to block the production of androgens from other tissues. These types of medications are sometimes referred to as androgen synthesis inhibitors. They include:

  • abiraterone (Zytiga), which blocks the CYP17 enzyme that is required for androgen production
  • ketoconazole (Nizoral), an antifungal that blocks androgen production in the adrenal glands

The largest group of oral hormone therapies used to treat advanced prostate cancer are anti-androgens, or androgen receptor antagonists.

These medications work by blocking interactions between androgens and the proteins they interact with in prostate cancer cells. This blocks the activity of androgens in these cells so that they can no longer drive cancer cell growth.

There are two groups of anti-androgens: first-generation and second-generation. Second-generation anti-androgens bind more tightly to the androgen receptor than first-generation anti-androgens do, resulting in stronger blockage of androgen activity.

First-generation anti-androgens include:

  • flutamide (Eulexin)
  • bicalutamide (Casodex)
  • nilutamide (Nilandron)

Second-generation anti-androgens include:

  • apalutamide (Erleada)
  • darolutamide (Nubeqa)
  • enzalutamide (Xtandi)

Anti-androgens are taken as daily pills.

Androgens have many effects throughout your body. Any type of hormone therapy that affects androgen levels can cause side effects related to lower testosterone levels, such as:

  • fatigue
  • reduced sexual energy or drive
  • erectile dysfunction
  • hot flashes
  • gynecomastia (enlarged or tender breast tissue)
  • loss of muscle mass
  • weight gain
  • mood swings
  • osteoporosis (loss of bone density), which can increase the likelihood of bone fractures

Different medications may also have unique side effects based on how they work in your body.

LHRH agonists, for example, may cause an initial increase in tumor size or number shortly after starting treatment because of the flood of androgens, but this effect is usually temporary.

LHRH agonists may also cause other side effects, depending on where the prostate cancer is located, such as:

  • neuropathy or spinal cord compression
  • blood in the urine or urinary blockages
  • bone pain
  • changes in blood chemistry (e.g., elevated blood glucose, increased cholesterol) that can increase the likelihood of diabetes or heart disease

Sexual side effects may be less common with anti-androgens when they are used alone. Alone or in combination with other drugs, anti-androgens may cause:

  • nausea or diarrhea
  • liver problems
  • rash
  • dizziness or, in rare cases, seizures
  • worsening of fatigue or hot flashes

In most cases, side effects from hormone therapy can be managed with medication or lifestyle changes, such as diet changes and exercise.

When weighing hormone treatment options for advanced prostate cancer, your healthcare team will consider a variety of factors, including:

  • which treatments you’ve tried so far
  • whether the tumor is known to be hormone-sensitive
  • how far the tumor has spread beyond the prostate
  • how likely the tumor is to continue spreading

In most cases, oral therapies (anti-androgens) are used in combination with injectable options, especially if the cancer has metastasized (traveled outside of the prostate beyond the pelvis). This line of treatment may also be used if injectable treatment is no longer working on its own.

Injectable therapies may also be combined with other medications, such as chemotherapy.

Oncologists will also consider your personal preferences when recommending a treatment. Some people may prefer the convenience of an oral medication that they can take at home over an injectable medication that must be given at a clinic. Others may prefer a treatment that they need to take only every few months, rather than every day.

The cost of anti-androgen therapy or ADT in the oral formulation may be high, which is another consideration for many people.

Different types of hormone therapy, including injectable and oral options, may be used alone or in combination to treat advanced prostate cancer. The right treatment option for you will depend on your treatment history and how the cancer responds to hormone therapy.

The effectiveness of treatment depends not only on how well the tumor may respond but also on how the side effects of treatment and logistics of care affect your life. An open discussion can help ensure that your healthcare team makes the best decision for you.