LH-RH agonists can also cause PSA levels to rise temporarily. Administering flutamide, a drug known as an antiandrogen, for 2 weeks prior to LH-RH agonists may not only prevent PSA surge but also induce early declines in PSA levels.
Side Effects. Side effects include hot flashes and occasionally nipple and breast tenderness.
Antiandrogens
Antiandrogens are powerful drugs produced in the adrenal gland. They are used alone or in maximal androgen blockage (MAB), in which they are combined with LH-RH agonists or orchiectomy to completely block androgen hormones. Antiandrogens are either steroidal or nonsteroidal.
Nonsteroidal Antiandrogens. The nonsteroidal antiandrogen drugs include:
- Flutamide (Eulexin, Drogenil). Flutamide has produced extended response in some patients. Side effects may include diarrhea and liver damage, which has been fatal in rare cases; liver function must be monitored closely.
- Nilutamide (Nilandron). Nilutamide is associated with reversible interstitial pneumonitis, nausea, alcohol intolerance, and visual disturbances.
- Bicalutamide (Casodex). Bicalutamide is effective and appears to have fewer severe side effects than other antiandrogens, including loss of sexual interest, osteoporosis, visual disturbance, and interstitial pneumonia. This drug is proving to have survival rates equal to those of maximal androgen blockage.
An interesting 2002 study suggested that flutamide may actually trigger a pathway that causes cell proliferation, which could be the reason why complete androgen blockage ultimately fails to prevent cancer progression.
Steroidal Antiandrogens. The steroidal antiandrogens act like female hormones and include:
- Megestrol Acetate. Megestrol acetate suppresses androgen production, but incompletely, and is generally not used as initial therapy.
- Cyproterone Acetate. Cyproterone combined with estrogen may prevent the testosterone surge that occurs with LH-RH agonists.
Gonadotropin-Releasing Hormone (GnRH) Antagonists
Gonadotropin-releasing hormone (GnRH) stimulate the pituitary gland to release luteinizing hormone-releasing hormones (LH-RH). Drugs known as GnRH antagonists, such as abarelix (Plenaxis) and histrelin, block this action. They have two advantages over LH-RH agonists:
- They do not cause the same testosterone surge that can temporarily worsen cancer symptoms
- They seem to reduce testosterone levels more quickly
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