Possible side effects of hormone therapy


Orchiectomy and LHRH agonists and antagonists can all cause similar side effects from lower levels of hormones such as testosterone. These side effects can include:


  • Reduced or absent sexual desire

  • Erectile dysfunction (impotence)

  • Shrinkage of testicles and penis

  • Hot flashes, which may get better or go away with time

  • Breast tenderness and growth of breast tissue

  • Osteoporosis (bone thinning), which can lead to broken bones

  • Anemia (low red blood cell counts)

  • Decreased mental sharpness

  • Loss of muscle mass

  • Weight gain

  • Fatigue

  • Increased cholesterol levels

  • Depression


Some research has suggested that the risk of high blood pressure, diabetes, strokes, heart attacks, and even death from heart disease is higher in men treated with hormone therapy, although not all studies have found this.


Anti-androgens have similar side effects. The major difference from LHRH agonists and antagonists and orchiectomy is that anti-androgens may have fewer sexual side effects. When these drugs are used alone, sexual desire and erections can often be maintained. When these drugs are given to men already being treated with LHRH agonists, diarrhea is the major side effect. Nausea, liver problems, and tiredness can also occur.


Abiraterone can cause joint or muscle pain, high blood pressure, fluid buildup in the body, hot flashes, upset stomach, and diarrhea.


Enzalutamide can cause diarrhea, fatigue, and worsening of hot flashes. This drug can also cause some nervous system side effects, including dizziness and, rarely, seizures. Men taking this drug are more likely to fall, which may lead to injuries.


Many side effects of hormone therapy can be prevented or treated. For example:


  • Hot flashes can often be helped by treatment with certain antidepressants or other drugs.

  • Brief radiation treatment to the breasts can help prevent their enlargement, but this is not effective once breast enlargement has occurred.

  • Several drugs can help prevent and treat osteoporosis.

  • Depression can be treated with antidepressants and/or counseling.

  • Exercise can help reduce many side effects, including fatigue, weight gain, and the loss of bone and muscle mass.


There is growing concern that hormone therapy for prostate cancer may lead to problems thinking, concentrating, and/or with memory, but this has not been studied thoroughly. Still, hormone therapy does seem to lead to memory problems in some men. These problems are rarely severe, and most often affect only some types of memory. More studies are being done to look at this issue.


Current issues in hormone therapy


There are many issues around hormone therapy that not all doctors agree on, such as the best time to start and stop it and the best way to give it. Studies are now looking at these issues. A few of them are discussed here.


Treating early-stage cancer: Some doctors have used hormone therapy instead of watchful waiting or active surveillance in men with early stage prostate cancer who do not want surgery or radiation. Studies have not found that these men live any longer than those who don’t get any treatment until the cancer progresses or symptoms develop. Because of this, hormone treatment is not usually advised for early-stage prostate cancer.


Early versus delayed treatment: For men who need (or will eventually need) hormone therapy, such as men whose PSA levels are rising after surgery or radiation or men with advanced prostate cancer who don’t yet have symptoms, it’s not always clear when it is best to start hormone treatment. Some doctors think that hormone therapy works better if it’s started as soon as possible, even if a man feels well and is not having any symptoms. Some studies have shown that hormone treatment may slow the disease down and perhaps even help men live longer.


But not all doctors agree with this approach. Some are waiting for more evidence of benefit. They feel that because of the side effects of hormone therapy and the chance that the cancer could become resistant to therapy sooner, treatment shouldn’t be started until a man has symptoms from the cancer. This issue is being studied.


Intermittent versus continuous hormone therapy: Most prostate cancers treated with hormone therapy become resistant to this treatment over a period of months or years. Some doctors believe that constant androgen suppression might not be needed, so they advise intermittent (on-again, off-again) treatment. The hope is that giving men a break from androgen suppression will also give them a break from side effects like decreased energy, sexual problems, and hot flashes.


In one form of intermittent hormone therapy, treatment is stopped once the PSA drops to a very low level. If the PSA level begins to rise, the drugs are started again. Another form of intermittent therapy uses hormone therapy for fixed periods of time – for example, 6 months on followed by 6 months off.


At this time, it isn’t clear how this approach compares to continuous hormone therapy Some studies have found that continuous therapy might help men live longer, but other studies have not found such a difference.


Combined androgen blockade (CAB): Some doctors treat patients with both androgen deprivation (orchiectomy or an LHRH agonist or antagonist) plus an anti-androgen. Some studies have suggested this may be more helpful than androgen deprivation alone, but others have not. Most doctors are not convinced there’s enough evidence that this combined therapy is better than starting with one drug alone when treating metastatic prostate cancer.


Triple androgen blockade (TAB): Some doctors have suggested taking combined therapy one step further, by adding a drug called a 5-alpha reductase inhibitor – either finasteride (Proscar) or dutasteride (Avodart) – to the combined androgen blockade. There is very little evidence to support the use of this triple androgen blockade at this time.


Castrate-resistant versus hormone-refractory prostate cancer: Both these terms are sometimes used to describe prostate cancers that are no longer responding to hormones, although there is a difference between the two.


  • Castrate-resistant means the cancer is still growing even when the testosterone levels are as low as what would be expected if the testicles were removed (called castrate levels). Levels this low could be from an orchiectomy, an LHRH agonist, or an LHRH antagonist. Some men might be uncomfortable with this term, but it’s specifically meant to refer to these cancers, some of which might still be helped by other forms of hormone therapy, such as the drugs abiraterone and enzalutamide. Cancers that still respond to some type of hormone therapy are not completely hormone-refractory.

  • Hormone-refractory refers to prostate cancer that is no longer helped by any type of hormone therapy, including the newer medicines.

Last Medical Review: 02/16/2016
Last Revised: 03/11/2016