NEW YORK (Reuters Health) – For men with hot flushes from androgen suppression for prostate cancer, medroxyprogesterone appears to be the best option for relief, according to a French research team.

Up to 80% of men treated with gonadotropin-releasing hormone (GnRH) analogues for prostate cancer report hot flushes, according to lead author Dr. Jacques Irani, from University Hospital in Poitiers, and his colleagues. Not surprisingly, however, most treatments for hot flushes have been studied in postmenopausal women.

In an online publication in The Lancet Oncology on December 7, the investigators describe a prospective, head-to-head trial comparing medroxyprogesterone with venlafaxine — a selective serotonin-reuptake inhibitor antidepressant — and with cyproterone – a steroidal anti-androgen.

Subjects were receiving quarterly subcutaneous injections of the GnRH analogue leuprorelin, 11-25 mg. At 6 months, patients who requested treatment for hot flushes or who experienced 14 or more hot flushes in the previous week were randomly assigned to venlafaxine 75 mg/day (n = 102), medroxyprogesterone 20 mg/day (n = 107), or cyproterone 100 mg/day (n = 100).

After 4 weeks, the median weekly number of hot flashes was 21.0 for the venlafaxine group, 4.0 for the cyproterone group, and 7.5 for the medroxyprogesterone group. Throughout the 12-week study, decreases in hot-flush scores were significantly larger for cyproterone and medroxyprogesterone than for venlafaxine, with no significant difference between cyproterone and medroxyprogesterone.

In the cyproterone and medroxyprogesterone groups, 60% to 84% of patients rated treatment efficacy as good, compared with 28% to 34% in the venlafaxine group (p < 0.001).

Rates of drop-out because of adverse events were comparable in the three groups. Two serious adverse events were related to the study drugs: one case of dyspnea due to cyproterone and one case of urticaria due to medroxyprogesterone.

Because cyproterone at higher doses is also a treatment for prostate cancer, and its use could interfere with therapy, the researchers recommend that medroxyprogesterone be considered the standard treatment for hot flushes caused by androgen-suppression therapy.

They caution, however: “Patients treated with a combination of GnRH analogues and cyproterone acetate or medroxyprogesterone acetate should be aware of the potential for withdrawal syndrome.”

Also, they add, if prostate-specific antigen levels begin to rise, discontinuation of cyproterone or medroxyprogesterone should be the first stop to consider.

Reference:
Lancet Oncol 2009.