An article published Online First and in The Lancet Oncology reports that the hormonal treatments cyproterone acetate and medroxyprogesterone acetate are the most efficient at reducing hot flushes. This is a common side-effect in men being treated with hormone therapy for prostate cancer. But in general, medroxyprogesterone should become the standard treatment for preventing hot flushes in these patients.

The main standard treatment for advanced prostate cancer is androgen suppression therapy or hormone therapy. It uses surgery or gonadotrophin-releasing hormone (GnRH) analogues such as leuprorelin to block the production of male producing sex hormones (androgens) that stimulate prostate cancer cells to grow. Up to 80 percent of patients undergoing treatment with GnRH analogues experience hot flushes. They are a common and unpleasant side effect.

Previous research has shown that the following treatments are all effective at preventing hot flushes:

• hormonal treatments (such as cyproterone acetate)
• progestagens (such as medroxyprogesterone)
• non-hormonal treatments such as selective serotonin-re-uptake inhibitor antidepressants (for example, venlafaxine)

However, direct comparisons between these drugs have not been made in men being treated with androgen-suppression therapy for prostate cancer.

Jacques Irani and colleagues from France examine in this randomised trial the efficacy of three drugs at preventing hot flushes in order to establish clear treatment recommendations for these patients. The drugs are: cyproterone acetate, medroxyprogesterone acetate, and venlafaxine.

A total of 919 men with prostate cancer were recruited from 106 urology centres in France between 2004 and 2007. For six months, all patients were initially treated with leuprorelin. After six months, patients who had fourteen or more hot flushes in the week before evaluation or those who spontaneously requested treatment were randomly assigned to further treatment with either venlafaxine (n=102), medroxyprogesterone (n=108), or cyproterone acetate (n=101). Patients were assessed at weeks 4, 8, and 12 after randomization. They were asked to complete a self-evaluation questionnaire to analyse the frequency and severity of hot flushes for a week before each assessment.

In general, results indicated that all three drugs produced did reduce the occurrence of hot flushes. There was little difference in tolerance. However, the hormonal treatments cyproterone acetate and medroxyprogesterone acetate were considerably more effective at reducing hot flushes than venlafaxine in all assessments.

Following four weeks of treatment, 219 patients (70.9 percent) had an improvement of at least 50 percent in their hot flush scores. In addition, 70 patients (22.7 percent) reported an absolute absence of hot flushes.

The median daily hot-flush score relative change between randomisation and week 4 was:

• -47•2% for venlafaxine
• -94•5% for cyproterone
• -83•7% for medroxyprogesterone

Serious side-effects occurred in 16 patients:

• Four cases in the venlafaxine group
• Seven in the cyproterone group
• Five in the medroxyprogesterone group

Only two cases were considered to be related to the drugs.

The authors write in conclusion: “Cyproterone acetate and medroxprogesterone acetate are more effective at 12 weeks for treating hot flushes in men treated with GnRH analogues for prostate cancer…[however] as cyproterone is a recognised treatment in prostate cancer, and its use could interfere with hormone therapy, medroxprogesterone should be the standard treatment.”

“Efficacy of venlafaxine, medroxyprogesterone acetate, and cyproterone acetate for the treatment of vasomotor hot flushes in men taking gonadotropin-releasing hormone analogues for prostate cancer: a double-blind, randomised trial”
Jacques Irani, Laurent Salomon, Rostand Oba, Philippe Bouchard, Nicolas Mottet
DOI: 10.1016/S1470-2045(09)70338-9

Written by Stephanie Brunner (B.A.)