Combined Androgen Blockade: Pro And Con
Crawford ED, Eisenberger MA, McLeod DG, et al. A Controlled Trial of Leuprolide With and Without Flutamide in Prostatic Carcinoma. New England Journal of Medicine 1989 321:41924. PMID: 2503724.
Eisenberger MA, Blumenstein BA, Crawford ED, et al. Bilateral Orchiectomy With or Without Flutamide for Metastatic Prostate Cancer. New England Journal of Medicine 1998 339:103642. PMID: 9761805.
Two large meta-analyses that reviewed many studies comparing combined androgen blockade to monotherapy concluded that the combination offered only a small survival advantage and even that finding was inconsistent between the two analyses. One analysis, which reviewed 27 randomized studies involving 8,275 men, estimated that combined androgen blockade improved five-year survival by only 2% to 3%, at most. However, an advantage of only 2% to 3%, when applied to thousands of men undergoing treatment, translates into hundreds of lives extended obviously an important benefit to the men who gain months and even years of life as a result. That is why I use combined therapy for all of my patients who undergo hormone treatments.
How Might Hormone Therapy Make Me Feel
Hormone therapy itself can affect your mood. You may find that you feel more emotional than usual or just different to how you felt before. Some men find that they cry a lot. You may also get mood swings, such as getting tearful and then angry. Just knowing that these feelings are caused by hormone therapy can help.
Everyones different some men are surprised by the side effects and how upsetting they find them. Others have fewer symptoms or are not as worried by them.
Some of the other side effects of hormone therapy are hard to come to terms with. Physical changes, such as putting on weight, or changes to your sex life, might make you feel very different about yourself. Some men say they feel less masculine because of their diagnosis and treatment.
If youre starting hormone therapy very soon after being diagnosed with prostate cancer, you might still feel upset, shocked, frightened or angry about having cancer. These feelings are normal, and it’s okay to feel this way.
Things in your day-to-day life can change because of the hormone therapy. Your relationships with your partner, family and friends might change. Or you might be too tired to do some of the things you used to do.
Some men experience low moods, anxiety or depression. This could be directly caused by the hormone therapy itself, or because you’ve been diagnosed with prostate cancer. It could also be due to the impact that treatment is having on you and your family.
What can help?
Talking about it
Types Of Hormonal Therapies
There are 3 types of hormonal therapies for the treatment of prostate cancer. They may be used alone or together.
- Luteinizing hormone-releasing hormone agonists block the signal from your pituitary gland that tells your testicles to make testosterone. Leuprolide and goserelin are LHRH agonists. Theyre given by injection either once a month or every 3, 4, or 6 months.
- Anti-androgens are medications that block testosterone from attaching to cancer cells. This keeps it from helping cancer cells grow. One example of an anti-androgen is bicalutamide . This is a pill you take once a day.
- If youre taking bicalutamide, make sure you take it at the same time every day, with or without food.
- Your healthcare team will tell you when to start taking this medication.
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What Are The Side Effects Of Hormone Therapy For Prostate Cancer
Because androgens affect many other organs besides the prostate, ADT can have a wide range of side effects , including:
- loss of interest in sex
Studer UE, Whelan P, Albrecht W, et al. Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer Trial 30891. Journal of Clinical Oncology 2006 24:18681876.
Zelefsky MJ, Eastham JA, Sartor AO. Castration-Resistant Prostate Cancer. In: Vincent T. DeVita J, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology, 9e. Philadelphia, PA: Lippincott Williams & Wilkins 2011.
Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. European Urology 2021 79:150158.
How Does Hormone Therapy Work Against Prostate Cancer
Early in their development, prostate cancers need androgens to grow. Hormone therapies, which are treatments that decrease androgen levels or block androgen action, can inhibit the growth of such prostate cancers, which are therefore called castration sensitive, androgen dependent, or androgen sensitive.
Most prostate cancers eventually stop responding to hormone therapy and become castration resistant. That is, 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 however, these terms are rarely used now because the tumors are not truly independent of androgens for their growth. In fact, some newer hormone therapies have become available that can be used to treat tumors that have become castration resistant.
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What Have I Learned By Reading This
You learned about:
If you have any questions, please talk to your doctor or healthcare team. It is important that you understand what is going on with your treatment. This knowledge will help you take better care of yourself and feel more in control so that you can get the most from your treatment..
- The results of any tests you have taken such as your Prostate-Specific Antigen test.
- When you found out you had prostate cancer.
- Information on the kinds of treatment you have had for your prostate cancer including:
- The places and dates where you had your treatment.
- What type of treatment you had. And,
- Any medicines you took before, during, and after your prostate cancer treatment.
- What hormone therapy is
How Should I Use Eligard
Take Eligard exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.
Different brands or strengths of leuprolide are used to treat different conditions. It is very important that you receive exactly the brand and strength your doctor has prescribed. Always check your medication to make sure you have received the correct brand and type prescribed by your doctor.
Eligard is injected under the skin or into a muscle, once every month or once every 3 to 6 months. A healthcare provider can teach you how to properly use the medication by yourself.
Read and carefully follow any Instructions for Use provided with your medicine. Do not use Eligard if you don’t understand all instructions for proper use. Ask your doctor or pharmacist if you have questions.
Your symptoms may become temporarily worse as your hormones adjust to leuprolide.
Keep using the medicine as directed, and tell your doctor if your condition is still worse after 2 months of using Eligard.
You may need frequent medical tests while using leuprolide.
Store Eligard in the refrigerator. Do not freeze. You may take the medicine out and allow it to reach room temperature before mixing and injecting your dose. Mixed medicine must be used within 30 minutes.
You may also store Eligard in its original packaging at room temperature for up to 8 weeks.
Initial Versus Delayed Hormone Therapy
Since the introduction of androgen withdrawal therapy, controversy has existed over its optimal timing. Many have advocated beginning treatment at the time of diagnosis in hopes of delaying disease progression and possibly prolonging survival. Others have argued that survival is not prolonged and the treatment may be deferred until symptoms develop.
Early studies by Nesbit and Baum provide evidence to support the immediate treatment of advanced prostate cancer.27 They compared patients who were treated with orchiectomy, DES, or both and then compared them with untreated historical controls. The treated group showed a 5-year survival rate of 34% versus 10% in the untreated group.27 These and other similar studies provided the basis for the early treatment of advanced prostate cancer.
While Youre Taking Hormonal Therapy
- Tell your doctor or nurse if youre taking any medications, including patches and creams, or if youve changed medications. Some medications may change the way hormonal therapy works. Tell your doctor if youre taking:
- Medications that require a prescription
- Medications that dont require a prescription
- Any herbal remedies, vitamins, or dietary supplements
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What Kinds Of Medical Information Should I Keep
It is important for you to keep a copy of your prostate cancer treatment records. You may not always see the same doctor for your follow-up care, so having this information to share with another doctor can be very helpful. The following is a list of medical information you may want to keep.
Remember, you have the right to copies of all your medical paperwork and the actual slides, x-rays and any other information about your health care and treatment. A good idea would be to create two copies of your medical information and keep them in folders. Keep one folder at home and take the other one with you to your doctors appointments. Whenever you see a new doctor, it is important for you to let them know about your prostate cancer and any treatment that you have had.
Kinds Of Hormone Therapy
Hormone therapy is a category encompassing a number of treatments. In some conditions or diseases, certain hormones are prescribed in order to increase their levels. This is frequently referred to as hormone replacement therapy . Hormones can be natural or synthetic, meaning produced commercially . Patients who do not have prostate cancer but have symptoms from low testosterone levels, such as fatigue, may be prescribed testosterone as a type of HRT. In certain cases, patients with prostate cancer under control may receive this type of hormone therapy however, because of the risk of activating the cancer, some doctors advise against it. Male children or adults with hypogonadism are prescribed testosterone as HRT.
As mentioned previously, HT in prostate cancer aims to reduce production of the hormone testosterone, rather than increase it, thereby interfering with cancer cells’ ability to use it to grow.
The hormone therapies that have become standard prostate cancer treatments are the ones we discuss in detail in this guide. All decisions regarding these treatments should be carefully made by the patient and doctor together.
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How Hormone Therapy Is Given
Hormone therapy may be given in many ways. Some common ways include:
- Oral. Hormone therapy comes in pills that you swallow.
- Injection. The hormone therapy is given by a shot in a muscle in your arm, thigh, or hip, or right under the skin in the fatty part of your arm, leg, or belly.
- Surgery. You may have surgery to remove organs that produce hormones. In women, the ovaries are removed. In men, the testicles are removed.
Hormone Therapies For Breast Cancer Treatment
Several treatment options are available for treating hormone-sensitive breast cancers. Some drugs block the effects of estrogen on the cancer cells in the breast, while others prevent estrogen production altogether.
Common hormone therapy drugs include Tamoxifen , Arimidex® , and Femara® , along with Faslodex® for recurrent breast cancer.
Breast cancer in males may also be treated with tamoxifen. Tamoxifen is currently being studied as hormone therapy for the treatment of other types of cancer.
Also Check: Can You Test For Hormone Imbalance
A New Option In Hormonal Therapy For Advanced Prostate Cancer
The Food and Drug Administration approved a new type of hormonal therapy for men with advanced prostate cancer in December 2020. Instead of traveling to a medical office to obtain an injection of a medication to suppress testosterone, men could swallow a tablet.
The medication, relugolix, has been a significant improvement, especially during the COVID-19 pandemic era, says Upstate urologic oncologist Hanan Goldberg, MD. We tried to limit patients coming to the hospital or the clinic because cancer patients are more at risk of COVID-19.
Androgen deprivation therapy to suppress male hormones may be prescribed to slow the growth of prostate cancer cells, and it has been shown to extend the lives of men with advanced prostate cancer. The oral and injectable medications are likely to produce the same side effects: hot flashes, fatigue, mood swings and others. Goldberg tells his patients its similar to menopause.
He notes one important difference with the oral medication. A study published in the New England Journal of Medicine found a 54 percent lower risk of major cardiovascular side effects in men who took relugolix, compared with those who had injections. For patients who have prostate cancer but also have cardiovascular issues going on, this drug is probably preferable.
This article appears in the spring 2022 issue of Cancer Care magazine.
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Good Prostate Cancer Care
Your MDT will be able to recommend what they feel are the best treatment options, but ultimately the decision is yours.
You should be able to talk with a named specialist nurse about treatment options and possible side effects to help you make a decision.
You should also be told about any clinical trials you may be eligible for.
If you have side effects from treatment, you should be referred to specialist services to help stop or ease these side effects.
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Figure : How Hormone Therapy Affects The Androgen Cascade
The male sex hormones are known as androgens. Probably the best known hormone in this family is testosterone. Most androgens are produced in the testicles.
Androgens fuel the growth of prostate cells, including prostate cancer cells. Hormone therapy also known as androgen-deprivation therapy seeks to cut off the fuel supply. But different therapies work in different ways.
A. The hypothalamus releases pulses of LHRH, which signals the pituitary gland to release the hormones FSH and LH.
B. LH travels through the bloodstream. When it reaches the testicles, it binds to specialized cells that secrete testosterone into the bloodstream.
C. In the prostate, the enzyme 5-alpha-reductase converts testosterone and other types of androgens into dihydrotestosterone , which stimulates the growth of prostate cells and fuels the growth of cancer, if it is present.
Centrally acting agents
LHRH agonists flood the pituitary gland with messages to crank out LH. This causes a temporary surge of testosterone until receptors in the pituitary are overloaded. Then testosterone levels drop sharply.
The GnRH antagonist jams receptors in the pituitary gland so that it cannot respond to the pulses of LHRH sent by the hypothalamus. This prevents the LH signal from being sent and no testosterone is made in the testicles.
DES inhibits secretion of LHRH from the hypothalamus.
Peripherally acting therapies
Orchiectomy removes the testicles, preventing testosterone production.
Evidence For Combining Hormone Therapy And Radiation Treatment
Bolla M, Collette L, Blank L, et al. Long-Term Results with Immediate Androgen Suppression and External Irradiation in Patients with Locally Advanced Prostate Cancer : A Phase III Randomised Trial. Lancet 2002 360:1036. PMID: 12126818.
Bolla M, Gonzalez D, Warde P, et al. Improved Survival in Patients with Locally Advanced Prostate Cancer Treated with Radiotherapy and Goserelin. New England Journal of Medicine 1997 337:295300. PMID: 9233866.
DAmico AV, Schultz D, Loffredo M, et al. Biochemical Outcome Following External Beam Radiation Therapy With or Without Androgen Suppression Therapy for Clinically Localized Prostate Cancer. Journal of the American Medical Association 2000 284:12803. PMID: 10979115.
DAmico AV, Manola J, Loffredo M, et al. Six-Month Androgen Suppression Plus Radiation Therapy Versus Radiation Therapy Alone for Patients with Clinically Localized Prostate Cancer: A Randomized Controlled Trial. Journal of the American Medical Association 2004 292:8217. PMID: 15315996.
Denham JW, Steigler A, Lamb DS, et al. Short-Term Androgen Deprivation and Radiotherapy for Locally Advanced Prostate Cancer: Results from the Trans-Tasman Radiation Oncology Group 96.01 Randomised Controlled Trial. Lancet Oncology 2005 6:84150. PMID: 16257791.
Nesslinger NJ, Sahota RA, Stone B, et al. Standard Treatments Induce Antigen-Specific Immune Responses in Prostate Cancer. Clinical Cancer Research 2007 13:1493502. PMID: 17332294.
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Evidence About Hormone Therapy And Prostatectomy
Gleave ME, La Bianca S, Goldenberg SL. Neoadjuvant Hormonal Therapy Prior to Radical Prostatectomy: Promises and Pitfalls. Prostate Cancer and Prostatic Diseases 2000 3:13644. PMID: 12497089.
Hurtado-Coll A, Goldenberg SL, Klotz L, Gleave ME. Preoperative Neoadjuvant Androgen Withdrawal Therapy in Prostate Cancer: The Canadian Experience. Urology 2002 60:4551. PMID: 12231047.
Kumar S, Shelley M, Harrison C, et al. Neo-adjuvant and Adjuvant Hormone Therapy for Localized and Locally Advanced Prostate Cancer. Cochrane Database of Systematic Reviews 2006 CD006019. PMID: 17054269.
Soloway MS, Sharifi R, Wajsman Z, et al. Randomized Prospective Study Comparing Radical Prostatectomy Alone Versus Radical Prostatectomy Preceded by Androgen Blockade in Clinical Stage B2 Prostate Cancer. The Lupron Depot Neoadjuvant Prostate Cancer Study. Journal of Urology 1995 154:4248. PMID: 7541859.