Prostate Surgery

Understanding Hormone Therapy for Prostate Cancer

Hormone therapy is a treatment that uses medicines to block or lower the amount of hormones in the body, as to slow down or prevent the growth of prostate cancer.

Unfortunately, hormone therapy has multiple potential side effects.

Patients who experience these side effects of hormone therapy have a reduced quality of life.

Your doctor will help you determine the best approach to treat your disease.

What is Hormone Therapy?

Hormone therapy (also known as androgen suppression therapy), is a treatment used to reduce the amount of male sex hormones in prostate cancer patients.

The main androgens in the body are testosterone and dihydrotestosterone (DHT). Lowering androgen levels or stopping them from getting into prostate cancer cells often makes prostate cancers shrink or grow more slowly.

However, it is important to note that hormone therapy alone does not cure prostate cancer.

Types of Hormone Treatment For Prostate Cancer

Inhibiting the brain control of testosterone levels.

The brain produces Luteinising hormone-releasing hormone (LHRH). LHRH controls the amount of testosterone in your body. Thus, chemical agents that activate LHRH can trick the brain into stopping the production of LHRH.

This response stops the stimulus to the testicles to produce testosterone. There are several ways to deliver LHRH antagonists, including injections, small implants, and oral medication. But they all reduce testosterone through similar mechanisms. LHRH antagonist includes Eligard and Zoladex.

Blocking the pituitary gland stimulation of the testicles to produce testosterone.

The pituitary gland is a small gland located below the brain. It uses the gonadotrophin-releasing hormone (GnRH) to make the testicles to produce testosterone. GnRH antagonist to block the communication between the pituitary gland and the testes. Degarelix marketed under Firmagon is a GnRH antagonist used in the USA and Europe.

Blocking the activity of testosterone.

Anti-androgens can target testosterone, inhibiting its pro-growth effects. Blocking testosterone activity in the sex organs makes it unusable by prostate cancer cells. Anti-androgen tablets are either used on their own or with other methods.

Surgical removal of the testicles (Orchidectomy).

The testes produce the majority (90 – 95%) of the testosterone in a man’s body. The adrenal glands produce the rest. Thus, removing the testes is the most effective way to stop testosterone production. Orchidectomy is permanent and can result in several long term side effects. These include infertility, depression and erectile dysfunction. Your doctor will help you determine if this method is suitable for you.

Combination androgen blockade.

Your doctor will use two or more ways to achieve the desired clinical outcome. Combining LHRH agonists with anti-androgen can control an increase in testosterone activity. Further, combination therapy useful if tumor growth continues in prostate cancer patients.

Intermittent hormone therapy.

Your doctor may give you hormone therapy in cycles to reduce side effects. Here, treatment is stopped and restarted at set intervals. Or, levels of prostate-specific antigen (PSA) is used to determine treatment cycles.

When is Hormone Therapy Used for Prostate Cancer?

Your suitability for hormone therapy depends on the stage of your cancer. You and your doctor will decide the best treatment option depending on your general health.

  • Metastatic prostate cancer: Prostate cancer may spread to other body parts, especially to the bone. It is common to treat metastatic prostate cancer with hormone therapy. Here, the aim is to control prostate cancer anywhere in the body.

  • Locally advanced prostate cancer: It is common for prostate cancer to reach the surrounding organs. This local spread usually affects seminal vesicles and the bladder. Hormone therapy alone or with radiation therapy may be used in locally advanced prostate cancer. Your doctor will help you decide the best type of hormone therapy for your case.

  • Localized prostate cancer: The majority of prostate cancer is contained in the prostate gland. Surgical treatment is the most effective way to treat localized prostate cancer. Hormone therapy is rarely offered to patients with localized prostate cancer undergoing surgery. Your surgeon may provide you with hormone therapy to support your primary treatment. Hormone therapy before or after radiation therapy, improves treatment outcome.

How is Hormone Therapy Used for Prostate Cancer?

Hormone therapy reduces the levels of androgen.

This creates an unfavorable environment (androgen deprivation) for prostate cancer cells. Hormone therapy affects prostate cancer cells anywhere in the body to, helping;

  1. Contain cancer cells in the prostate.

  2. Reduce the size of the prostate gland.

  3. Kill any prostate cancer cells that have moved to other organs.

Common Side Effects of Hormone Therapy

Hormone therapy blocks the production of testosterone, causing prostate cancer to shrink. However, testosterone controls sexual function, effects your mood and male characteristics. Therefore, reducing testosterone may change these normal functions.

Erectile dysfunction and lower sex drive are the most common side effect of androgen deprivation. Most men will experience some decline in sex drive due to hormone therapy.

More than half of men taking LHRH agonists or who had orchidectomy will sexual interest. Further, there is an increased difficulty having and maintaining an erection.

  • Changes in your physical appearance.

  • Sexual complications.

  • Reduced bone strength: lower testosterone can thin your bones. This increases the risk of breakage.

  • Low testosterone mediated loss of muscle mass and hair.

  • Smaller testes and penis.

  • Changes in behavior.

  • Increase in body fat caused by hormone-related changes in metabolisms.

  • Fatigue

Testosterone regulates the development of male reproductive organs and secondary male characteristics. Consequently, reduced testosterone due to hormone therapy alters essential physiological functions. You may experience impairment of skeletal muscle growth and the production of red blood cells.

Men treated with hormone therapy may also develop anemia. You may require interventions to manage the negative impact on libido, bone density, muscle mass, and blood cell production.

The extent of your symptoms will depend on your overall health and the method of hormone therapy you get. But your doctor will help you decide the best way to treat your prostate cancer.

How To Reduce The Side Effects Of Hormone Therapy For Prostate Cancer?

Following hormone therapy, you may become anxious about your sexual functions. Discuss your feelings with your partner and healthcare team.

Lower levels of testosterone will have a negative on your bone density and muscle mass.

Lifestyle changes such as supplementation, exercise, and diet can help you manage this side effect.

You may consider taking calcium and vitamin D supplements. There is a negative relationship between smoking and bone density. Thus, stop smoking after hormone therapy.

Natural ways to help you manage the symptoms of hormone therapy include:

  • A healthy diet and appropriate fluid intake to help you maintain a healthy body and mental state.

  • Regular exercise help build muscle and bone strength as well as reduce obesity.

  • Regular sleeping to help deal with potential fatigue and mental health problems.

Effectiveness of Hormone Therapy for Prostate Cancer

The reduction in testosterone levels after hormone therapy depends on the disease stage.

Bilateral orchiectomy is a surgical procedure in which both testicles are removed. For some patients, this is the most effective way to achieve an immediate reduction in testosterone levels.

However, it can have long-lasting side effects, including infertility, depression and sexual dysfunction.

Continuous introduction of LHRH agonists achieves suppression of testosterone by three weeks. But this reduction occurs after an initial surge in testosterone levels depending on its initial level. GnRH antagonists can reduce testosterone levels with 6 hours (Crawford et al., 2019).

Generally, using anti-androgens is the slowest way to reduce serum testosterone. They require several weeks to reduce serum testosterone. Doctors can modify the speed of their testosterone reduction by combining them with other methods.

What is the remission rate for patients who use hormone therapy to treat prostate cancer?

Primary hormone therapy (localized prostate):

The choice of hormone therapy as first-line therapy for prostate cancer is controversial. There is no improvement in overall survival. Consequently, the American Urological Association recommends against the use of hormone therapy for localized prostate cancer.

Akaza and colleagues found 43% – 62% 2-year progression-free survival rates depending on tumor stage. Another study investigated the long-term disease-free survival rates post androgen deprivation.

The study found that 75% and 45% were disease-free at 5 and 10 years, respectively. A more extensive study reviewed 993 patients with clinically localized disease. The researchers reported slightly higher disease-free survival rates (78%). Five years after primary androgen deprivation, 17.7% received definitive secondary therapy, and 4.1% died from prostate cancer.

Secondary hormone therapy (Advanced prostate cancer):

Androgen-deprivation therapy is the standard treatment for patients with advanced prostate cancer. More than 70% of metastatic prostate cancers respond to hormone therapy.

Metastatic prostate cancer responds to androgen deprivation therapy within 18 months. Reduction in prostate-specific antigen and clinical benefits are achieved in 90% and 80%, respectively (Maru et al., 2018). However, only 50% experience remission over 2-years follow-up (Maru et al., 2018).

The high rate of recurrence is attributed to continuous androgen-deprivation, which can drive androgen-independent growth. Intermittent hormone therapy improves remission rates post hormone therapy for advanced prostate cancer.

For instance, Maru and colleagues showed that intermittent hormone therapy has higher disease-free survival rates (93%) compared to continuous hormone therapy (57%).

Alternatives to hormone therapy for prostate cancer

The best treatment depends on your disease stage, symptoms, and general health. Your doctor will help you determine the best treatment for your case.

Conclusion

Hormone therapy benefits both symptomatic patients and those with advanced disease. But it is not necessarily useful for patients with the non-symptomatic hormone-sensitive disease. The side-effects and cost of hormone therapy are essential factors to consider.

Many patients (45%) regard their quality of life as most important compared to 29% who prefer prolonged survival. Therefore you should discuss with your doctor the benefits and risks of hormone therapy. This will help you to make an informed decision.

Sources

  1. Akaza, H., Homma, Y., Okada, K., Yokoyama, M., Moriyama, N., Usami, M., Hirao, Y., Tsushima, T., Ohashi, Y., Aso, Y., 2000. Early results of LH-RH agonist treatment with or without chlormadinone acetate for hormone therapy of naive localized or locally advanced prostate cancer: a prospective and randomized study. Jpn. J. Clin.Oncol. 30, 131–136.
  2. Bolla, M., Gonzalez, D., Warde, P., Dubois, J.B., Mirimanoff, R.-O., Storme, G., Bernier, J., Kuten, A., Sternberg, C., Gil, T., 1997. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N. Engl. J. Med. 337, 295–300.
  3. Crawford, E.D., Heidenreich, A., Lawrentschuk, N., Tombal, B., Pompeo, A.C., Mendoza-Valdes, A., Miller, K., Debruyne, F.M., Klotz, L., 2019. Androgen-targeted therapy in men with prostate cancer: Evolving practice and future considerations. Prostate Cancer Prostatic Dis. 22, 24–38.
  4. Kawakami, J., Cowan, J.E., Elkin, E.P., Latini, D.M., DuChane, J., Carroll, P.R., 2006. Androgen‐deprivation therapy as primary treatment for localized prostate cancer: data from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE).
  5. Cancer Interdiscip. Int. J. Am. Cancer Soc. 106, 1708–1714. Klotz, L., Toren, P., 2012. Androgen deprivation therapy in advanced prostate cancer: is intermittent therapy the new standard of care? Curr. Oncol. 19, S13.
  6. Labrie, F., Candas, B., Gomez, J.-L., Cusan, L., 2002. Can combined androgen blockade provide long-term control or possible cure of localized prostate cancer? Urology 60,
    115–119.
  7. Maru, S., Uchino, H., Osawa, T., Chiba, S., Mouri, G., Sazawa, A., 2018. Long-term treatment outcomes of intermittent androgen deprivation therapy for relapsed prostate cancer after radical prostatectomy. PloS One 13, e0197252.
  8. Roach, M., Bae, K., Speight, J., Wolkov, H.B., Rubin, P., Lee, R.J., Lawton, C., Valicenti, R., Grignon, D., Pilepich, M.V., 2008. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J. Clin. Oncol. 26, 585–591.
  9. Small, E.J., Vogelzang, N.J., 1997. Second-line hormonal therapy for advanced prostate cancer: a shifting paradigm. J. Clin. Oncol. 15, 382–388.

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