Table 9. Treatment Options by Stage for Prostate Cancer continued...
Hormonal Therapy and Its Complications
Several different hormonal approaches are used in the management of various stages of prostate cancer.
These approaches include the following:
- Bilateral orchiectomy.
- Estrogen therapy.
- LH-RH agonist therapy.
- Antiandrogen therapy.
- Androgen deprivation therapy.
- Antiadrenal therapy.
Benefits of bilateral orchiectomy include the following:
- Ease of the procedure.
- Immediacy in lowering testosterone levels.
- Low cost relative to the other forms of androgen deprivation therapy.
Disadvantages of bilateral orchiectomy include the following:[34,73]
Bilateral orchiectomy has also been associated with an elevated risk of coronary heart disease and myocardial infarction.[74,75,76]
(Refer to the PDQ summary on Sexuality and Reproductive Issues for more information on loss of libido and impotence; refer to the PDQ summary on Fever, Sweats, and Hot Flashes.)
Estrogens at a dose of 3 mg per day of diethylstilbestrol (DES) will achieve castrate levels of testosterone. Like orchiectomy, estrogens may cause loss of libido and impotence. Estrogens also cause gynecomastia, and prophylactic low-dose radiation therapy to the breasts is given to prevent this complication.
DES is no longer manufactured or marketed in the United States and is seldom used today because of the risk of serious side effects, including myocardial infarction, cerebrovascular accidents, and pulmonary embolism.
Luteinizing hormone-releasing hormone (LH-RH) agonist therapy
LH-RH agonists, such as leuprolide, goserelin, and buserelin lower testosterone to castrate levels. Like orchiectomy and estrogens, LH-RH agonists cause impotence, hot flashes, and loss of libido. Tumor flare reactions may occur transiently but can be prevented by antiandrogens or short-term estrogens at a low dose for several weeks.
There is some evidence that LH-RH agonists are associated with increased risk of cardiovascular morbidity or mortality, although the results are conflicting.[74,75,76,77]
Evidence (LH-RH agonists and cardiovascular disease):
- In a population-based study within the Department of Veterans Affairs' system, LH-RH agonists were associated with an increased risk of diabetes as well as cardiovascular disease, including coronary heart disease, myocardial infarction, sudden death, and stroke.[74,75,76]
- A systematic evidence review and meta-analysis of eight trials (4,141 patients) of men with nonmetastatic prostate cancer who were randomly assigned to receive or not receive LH-RH agonists found no difference in cardiovascular death rates (11.0% vs. 11.2%; RRdeath of 0.93; 95% CI, 0.79–1.10; P = .41). Median follow-up in those studies was 7.6 to 13.2 years. No excess risk of LH-RH agonists was found regardless of treatment duration or patient age (median age of <70 or ≥70 years).
Antiandrogen agents used in the treatment of prostate cancer include flutamide and bicalutamide. The pure antiandrogen, flutamide, may cause diarrhea, breast tenderness, and nausea. Case reports show fatal and nonfatal liver toxic effects.