Either chemical debulking or surgical debulking (orchiectomy) can significantly reduce the amount of androgens produced in the body, which in turn can have an impact on other organ functions and inevitably produce side effects.
The main side effects include:
- Decreased sex drive;
- Erectile dysfunction;
- Hot flashes;
- osteoporosis;
- Fractures;
- Muscle weakness;
- Lipid changes;
- insulin resistance;
- weight gain;
- Mood swings;
- Fatigue;
- Male breast enlargement.
Lower androgens can cause side effects such as diarrhea, breast enlargement, nausea, hot flashes, decreased libido and erectile dysfunction, and the anti-androgen drug flutamide may also cause impaired liver function.
Medications that inhibit the production of androgens by the adrenal glands, such as ketoconazole, amiloride, and abiraterone acetate, may cause diarrhea, itching and rash, fatigue, erectile dysfunction (with long-term use), and liver damage.
Estrogens are used to treat bone loss from anti-androgen therapy, but also increase the risk of cardiovascular disease, including heart attacks and strokes. Because of these side effects, estrogen is now rarely used in the treatment of prostate cancer.
Endocrine therapy can exacerbate some of the adverse effects of radiation therapy, particularly erectile dysfunction and fatigue. In addition, the side effects of endocrine therapy are enhanced with longer dosing.
How to reduce the side effects of endocrine therapy?
- Diphosphonates (such as zoledronic acid and alendronate) can be used to slow osteoporosis and increase bone density caused by endocrine therapy. A new drug, denosumab, which increases bone density through other mechanisms, was approved in the United States in 2011. However, some studies have reported a strong association between zoledronic acid and denosumab and a rare complication, osteonecrosis of the jaw.
- Exercise may help reduce side effects from endocrine therapy, including bone loss, muscle loss, weight gain, fatigue, and insulin resistance. Several clinical trials are already evaluating whether exercise is effective in reversing or preventing the side effects of endocrine therapy for prostate cancer.
- The side effects of endocrine therapy for prostate cancer on sexual function are one of the most problematic issues. Drugs used to treat erectile dysfunction, such as sildenafil, are often ineffective for sexual dysfunction caused by endocrine therapy for prostate cancer because these drugs do not restore lost libido.
After most men stop receiving endocrine therapy, the sexual dysfunction caused by low levels of androgens and the emotional side effects fade away. However, if patients receive endocrine therapy for years, these side effects may not go away completely. Over time, side effects like osteoporosis will persist even after stopping the medication.
Patients should inform their clinicians of all medications they are taking, including over-the-counter herbal medications. This is because some herbal medications can interact with drug metabolizing enzymes in the body, which can be detrimental to endocrine therapy.
Related articles: