Side effects of testosterone suppression in men with prostate cancer

This article was translated from the original Portuguese. Português

Introduction

• Why the side effects of testosterone suppression in men with prostate cancer matter (testosterone suppression)

The role of testosterone

• Biological functions of testosterone in the human body (testosterone suppression)
• Stimulation of prostate cancer cell growth

Testosterone in the body

• Production in the testicles and adrenal glands
• Role of the pituitary gland in stimulating testosterone production

Testosterone suppression

• Situations in which testosterone needs to be suppressed
• Traditionally used in cases of metastasis
• Exception: men who choose radiotherapy and have aggressive disease

Methods of testosterone suppression

• Surgical castration versus chemical blockers
• Agonist and antagonist drugs that act on testosterone production
• New drugs: Degarelix and Relugolix

Side effects of testosterone suppression

• Osteoporosis
• Memory changes and dementia
• Loss of muscle mass
• Decreased libido

Contact and questions

• Physician contact information
• Invitation to leave questions in the comments

Below is the transcript of the video:

The side effects of testosterone suppression in men with prostate cancer have become a highly relevant topic in medicine. Questions about this subject are frequent and concern the role testosterone plays in this disease, how it stimulates the cancer, the consequences of suppressing it and the situations in which this hormone needs to be blocked.

Testosterone has many biological functions besides acting as a fuel that can stimulate the growth of cancer cells. The goal of this video is to explain the biological roles of testosterone and why it should be blocked only in specific situations, not in every man with prostate cancer.

I am Bruno Benigno, a urologist and uro-oncologist, director of Clínica Uro Onco in São Paulo and one of the physicians at Hospital Alemão Oswaldo Cruz. It is a pleasure to interact with you through our social media, especially on Instagram (@dr_benigno), or through our website, www.clinicauroonco.com.br

Please consider subscribing to our channel and sharing this content if you found it useful. Now, let's move on. We are going to talk about the famous testosterone.

Testosterone is a high-molecular-weight molecule produced in the testicles and the adrenal glands. It is a hormone, which means it acts at a distance, on organs far from where it is produced. That is the definition of a hormone.

It is worth noting that testosterone is not exclusive to men: women also produce it, although in much smaller amounts.

Testosterone plays an important role at different stages of a man's life, especially during the embryonic phase, when the fetus needs this hormone for the development of the external genitalia, such as the penis and testicles. Testosterone is also essential during male puberty, when rapid growth occurs and secondary sexual characteristics develop, such as beard growth and voice change. In adulthood, testosterone continues to have effects, such as stimulating sperm production, although it can also have side effects such as baldness.

Testosterone, known as the main male sex hormone, plays a crucial role in our body. However, it does not act directly on every tissue. It is important to understand the action of a specific enzyme, referred to as DHT (dihydrotestosterone), which converts testosterone into its more potent form. The presence of this enzyme partly explains why the prostate is highly susceptible to the effects of testosterone, since the prostate is rich in DHT.

Let's look at this question in a little more depth.

As I mentioned earlier, testosterone is produced in the adrenal glands, located above the kidneys. These small glands, roughly the size of a matchbox, are responsible for only 5% of the body's total testosterone production. The other 95% comes from the testicles in men and from the ovaries in women.

However, the signal to produce this hormone comes from the brain, more precisely from a gland called the hypophysis or pituitary gland, which produces two essential hormones: LH (luteinizing hormone) and FSH (follicle-stimulating hormone). These hormones stimulate the testicles to produce testosterone and play a crucial role in this process.

Therefore, for everything to work properly, there must be balance in the production and function of the adrenal gland. Now let's look at the effects of testosterone on the human body. As mentioned earlier, it plays a fundamental role in several organs, such as muscles and bones, and in male sexual characteristics, such as the growth of the beard and facial hair in general.

It is thanks to testosterone that men are generally physically stronger than women. It also influences the skin, stimulates the development of the sexual organs and affects the production of blood cells.

Another important point is that testosterone acts by contact. This means that prostate cancer cells compete with the normal cells of the same gland. Because these cells are more avid for the hormone, they grow faster than normal tissue cells, which explains why testosterone acts as a stimulus for prostate cancer growth.

Now the question arises: how can testosterone production be reduced? The answer depends on the situation. Traditionally, testosterone production is blocked only when prostate cancer reaches the metastatic stage, that is, when the disease has spread to other organs.

In these cases, it is necessary to control most of the cells, and this can be done with a procedure known as hormone therapy (androgen deprivation), which can be achieved by surgical or chemical castration. In the past, castration was performed surgically, by removing the testicles.

Today, however, there are medications that perform this function without the need for surgery.

It is important to emphasize that removing the testicles or performing chemical castration is not always necessary. When prostate cancer is detected early, while the disease is localized and there is no metastasis, treatment often involves only surgery or radiotherapy, without the need for hormone therapy. There is, however, an exception to this rule.

In men who choose radiotherapy and have a more aggressive prostate cancer, even without metastasis, testosterone suppression may be recommended, usually for a period of six months to two years.

As for methods of hormone therapy, the surgical approach, although older, is no longer the only option. There has been a major revolution in drug development, with medications such as goserelin, triptorelin and the well-known Zoladex, which block testosterone production in the testicles. These medications can be given monthly, every three months or every six months, depending on the formulation supplied by the manufacturer.

In addition, in some situations where testosterone levels need to be lowered immediately, direct antagonists of hormone production can be used. A recent example is Degarelix, marketed as Firmagon, which virtually shuts down testosterone production in less than 48 hours.

Chemical castration, a procedure commonly used to inhibit the production of testosterone — the hormone associated with tumor growth — has gained momentum with Relugolix, an oral testosterone blocker. This new drug has proven particularly beneficial for patients with a high volume of metastases, those at risk of spinal cord compression, or those who experience a mild increase in pain before the medication takes effect. Because it is taken by mouth, it eliminates the need for monthly or quarterly injections, offering patients greater convenience.

Other drugs have also played an important role in fighting advanced prostate cancer. These are the so-called peripheral antiandrogens, which do not interfere with testosterone production but act as antagonists of this hormone. Among them, cyproterone acetate has been widely used in Brazil because of its low cost, despite bothersome side effects such as breast enlargement (gynecomastia) and a higher risk of heart attack and cardiovascular events. In the private sector, however, a more advantageous alternative is already available: bicalutamide, marketed as Casodex, which has fewer side effects than cyproterone acetate.

In recent years, third-generation testosterone blockers have been the big breakthrough in the treatment of metastatic prostate cancer. By combining peripheral and central blockade, these drugs have proven highly effective, especially in advanced stages of the disease, where they are used after chemotherapy. However, recent studies have shown that these medications are also effective in men newly diagnosed with metastases, significantly increasing their life expectancy. This finding has been considered revolutionary, bringing hope to patients with advanced prostate cancer.

Although these advances are promising, it is important to be aware of the possible side effects of testosterone suppression. The most feared is osteoporosis, because testosterone plays a crucial role in bone health. However, there are medications available to reverse this condition, and patients should be monitored regularly with bone densitometry (DEXA) scans. Other side effects, such as memory changes and dementia, affect about 5 to 10% of patients undergoing testosterone suppression. Loss of muscle mass and decreased libido are also unwanted side effects associated with testosterone suppression.

As levels of this hormone fall, patients may experience loss of muscle mass, gain in fat mass and changes in sexual desire, such as decreased libido, erectile difficulties and reduced sexual interest. These side effects are significant challenges, because it is essential to balance disease control with keeping adverse effects to a minimum.

It is important to stress that, despite the potential side effects, the benefits of these treatments have been remarkable. Men with metastatic prostate cancer have seen a significant increase in life expectancy thanks to these testosterone blockers. These drugs represent a true revolution in medicine, offering hope and prolonging these patients' survival.

For those consulting with their physicians, it is essential to understand the reason a testosterone blocker is being prescribed and to be aware of both the benefits and the risks of treatment. Patients are encouraged to discuss their questions and concerns with their healthcare providers, who are prepared to offer appropriate guidance and personalized care.

To conclude this explanation, we would like to thank everyone for their attention, and we are happy to answer any questions in the comments. It will be a pleasure to interact and provide additional information.

We hope this material helps patients come to their medical appointments with in-depth knowledge about the use of testosterone blockers, understanding both their significant benefit in increasing life expectancy in metastatic prostate cancer and the risks and side effects associated with treatment. Thank you again for your attention, and see you next time.

🔸contact: ☎(11) 2769-3929 📱(11) 99590-1506 | whatsapp: 📲 https://bit.ly/2HCRkgt 💻 https://www.clinicauroonco.com.br/ Appointments: http://bit.ly/2WMMiCI R. Borges Lagoa 1070, Cj 52 V. Mariana - São Paulo - SP Dr. Bruno Benigno CRM SP 126265 Urologist at H. Alemão Oswaldo Cruz Uro-oncology and Robotic Surgery Instagram: @dr_benigno

Dr. Bruno Benigno
Urologist and uro-oncologic surgeon (CRM-SP 126.265 · RQE 60022). More than 1,500 robotic surgeries. Member of the AUA, EAU and SBU. Meet Dr. Bruno · In the Media

This content is educational and does not replace a medical consultation. Each case must be assessed individually, based on AUA, EAU and NCCN guidelines.