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Editorials

Long term androgen deprivation therapy in prostate cancer

BMJ 2008; 337 doi: https://doi.org/10.1136/bmj.a1361 (Published 22 September 2008) Cite this as: BMJ 2008;337:a1361

Re: Osteoporosis in Patients with Prostate Cancer on Long-Term Androgen Deprivation

With the increasing indications for and duration of androgen
deprivation therapy (ADT) in men with prostate cancer using gonadotrophin-
releasing hormone (GnRH) agonists, the many side-effects of reduced levels
of serum sex-steroids are becoming apparent. Presumably the new GnRH
antagonists will have similar toxicity.

The rapid response from Sherriff et al that osteoporosis is another
potentially serious adverse event in men on ADT is therefore an important
reminder that the toxicity of this treatment is not limited to the
cardiovascular system, the topic specifically discussed in our editorial
and prompting their rapid response.

Testosterone deficiency is associated with muscle weakness, diabetes,
changes in body composition and erectile dysfunction. Oestrogen deficieny
is a consequence of testosterone deficiency because oestrogen is produced
through aromatisation of testosterone. Adverse effects of oestrogen
deficiency include increased fracture risk, lipid changes, memory loss,
gynaecomastia and hot flushes (1). It may well be that in future, a
battery of screening tests will precede the initiation of ADT with GnRH,
including for example, dual-energy X-ray absorptiometry scans as well as
serum lipids, cholesterol and glucose.

Some of these issues have been covered in a recent review of the
topic in which a rationale for the re-emergence of oestrogen as a
treatment for prostate cancer is offered (2). In addition to its role in
reducing testosterone to castrate levels, oestrogen should also diminish
the toxicity of GnRH ADT. This hypothesis has developed into the subject
of a multicenter randomised trial comparing the efficacy and toxicity of
transdermal oestrogen with GnRH in this group of men (3).

In the meantime, perhaps it is timely for guidelines for the use of
GnRH in prostate cancer to be produced as suggested by Sherriff et al?
Could this be a role for NICE?

1. Freedland SJ, Eastham J, Shore N. Androgen deprivation therapy
and oestrogen deficiency induced adverse effects in the treatment of
prostate cancer. Prostate Cancer and Prostatic Diseases 2009;12:333-338.

2. Ockrim JL, Lalani EN, Abel PD. Parenteral oestrogen treatment for
prostate cancer: a new dawn for an old therapy. Nature Clin Pract Oncol
2006;3:552-63.

3. Langley RE, Godsland IF, Clarke N, Dearnaley D, Knockelbergh R,
Kynaston H, et al. Early hormone data from a multi-centre randomized trial
using transdermal oestrogen patches as first-line hormone therapy in
patients with locally advanced or metastatic prostate cancer. Brit J Urol
Int 2008;102:442-5.

Competing interests:
1. Principal Investigator for Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) randomised controlled trial of LHRH vs transdermal estrogens in prostate cancer.
2. Consultant for Ascend Pharmacueticals

Competing interests: No competing interests

11 January 2010
Paul D Abel
Professor & Hon Consultant Urologist
'B' Block, Dept of Surgery, Imperial College, Hammersmith Campus, DuCane Road, LONDON, W12 0NN