Therapeutics

Androgen deprivation treatment in prostate cancer

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.e8555 (Published 9 January 2013)
Cite this as: BMJ 2013;346:e8555

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  1. Benjamin C Thomas, senior clinical fellow12,
  2. David E Neal, honorary consultant urological surgeon 1, professor of surgical oncology2
  1. 1Department of Urology, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
  2. 2Department of Oncology, University of Cambridge, Cambridge CB2 0QQ, UK
  1. Correspondence to: BC Thomas bct26{at}cam.ac.uk

A 65 year old man presents with lower back pain and acute urinary retention. He has tenderness over his lumbar spine, a palpable urinary bladder, and a firm, irregularly enlarged prostate on digital rectal examination. His prostate specific antigen (PSA) level was 75 ng/mL (75 µg/L) (normal range <4.0 ng/mL). A transrectal ultrasound guided biopsy of the prostate confirms prostate cancer. A bone scan shows increased uptake in the pelvis and lumbar spine suggestive of metastases. His urinary retention is treated. After discussion of the diagnosis and treatment options with the patient, a decision is made to start androgen deprivation treatment.

What is androgen deprivation treatment?

Androgen deprivation treatment refers to treatments that act by reducing the effects of testosterone and other androgens, thus inhibiting the progression of prostate cancer.1 Surgical castration was the first form of such treatment, but the main treatments now are luteinising hormone releasing hormone (LHRH) agonists and anti-androgens.

LHRH agonists

LHRH agonists such as goserelin, leuprorelin, and triptorelin induce castrate levels of testosterone by binding to their associated receptors in the anterior pituitary. This results in down regulation of the receptors, reducing luteinising hormone release from the pituitary and decreasing testosterone production by testicular Leydig cells. The initial stimulation of the receptors may lead to an initial flare-up of testosterone level, lasting up to 10 days. Castrate levels of testosterone (<1.74 nmol/L (< 50 ng/dL)) are reached within four weeks.

Anti-androgens

This is a broad category of drugs that act mainly by inhibiting signalling through the androgen receptor, sometimes by competing with testosterone and dihydrotestosterone for receptor binding. Diminished signalling through the androgen receptor leads to apoptosis and inhibition of prostate cancer growth. There are two classes of anti-androgens: steroidal (cyproterone acetate) and non-steroidal (bicalutamide, nilutamide, and flutamide).

Newer drugs

Other forms of androgen deprivation treatment include LHRH antagonists, such as degarelix, which binds …

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