Those of us with advanced prostate cancer who have used hormone therapy (ADT) often find that we are plagued with hot flashes that are detrimental to our quality of life (QOL). I believe that hot flashes are the most common side effect complained about by men who are on ADT, in the scheme of seriousness they are low down, but in their effect on our QOL they are way up on the top of most of our lists.

It’s often been thought that treatments that can help women who have hot flashes because of their hormone therapy to treat their cancer or due to menopause to deal with hot flashes can have a similar, positive effect on men on ADT. In a clinical trial that was supported by the National Cancer Institute, National Center for Complementary and Alternative Medicine, this theory was disproved.

The trial found that the commonly used treatments for hot flashes in women with cancer or who are in menopause, the antidepressant venlafaxine or soy protein — alone or in combination did not reduce the frequency or severity of hot flashes in men having ADT.

The trial did find that certain measures of QOL improved with soy protein but not with venlafaxine or the combination. These results were reported in the Journal of Clinical Oncology by Mara Z. Vitolins, DrPH, RD of Wake Forest University in Winston-Salem, N.C. According to Dr. Vitolins, “In this randomized, placebo-controlled trial testing venlafaxine and soy in men experiencing hot flashes, there was improvement in the number and severity of vasomotor symptoms in all treatment group…This could be regression to the mean…This could also be due to a placebo effect related to participating in a double-blind trial… Both illustrate the necessity of including a control condition when testing therapies for hot flashes.”

As we survivors know and can verify hot flashes and other vasomotor symptoms occur in about 80% of men with prostate cancer treated with ADT. The symptoms may persist for years, and hot flashes, in particular, have been shown to have a negative effect on our QOL. Complicating the problem is a lack of effective therapies.

Not surprising to us men there have been few studies evaluating SSRIs or SNRIs in men with prostate cancer as opposed to the many studies in women. A small case-report series suggested the SSRI sertraline relieved hot flashes in men over a 1- to 2-month period. Studies of venlafaxine have demonstrated positive effects on postmenopausal symptoms in women. However, two clinical trials involving men with prostate cancer yielded conflicting results.

In women there have been several studies evaluating soy protein and cross-cultural comparisons have shown lower rates of menopausal symptoms in women where soy is regularly consumed versus those where it is not. Isoflavones, soy constituents that have estrogenic and antiestrogenic properties, have produced mixed results in women.

“Because venlafaxine and soy have an impact on different physiologic mechanisms proposed to play a role in hot flashes, these treatments could potentially provide more relief when taken together,” the authors noted.

In this trial to evaluate that potential men who had four or more moderate-to-severe hot flashes daily and a life expectancy ?9 months with advanced prostate cancer treated with ADT were enrolled.

The men were randomized to one of four groups: milk protein and placebo, venlafaxine and milk protein, soy protein and placebo, or venlafaxine and soy protein. Their treatment continued for 12 weeks, and the primary endpoint was the change in hot flash severity symptom score (HFSSS), defined as the number of hot flashes times severity. All subjects kept a daily diary of medication adherence and the number and severity of hot flashes (1=mild, 2=moderate, and 3=severe).

The subject pool consisted of 120 men, ages 46 to 91, about 80% of who were white and were overweight or obese. The mean number of hot flashes ranged from 9 to 10 at baseline across the four treatment groups. Frequency declined in all groups and averaged about 5 across the four groups.

Severity averaged about 2.5 at baseline, declining to about 1.7 after 12 weeks.

The four treatment groups had a mean HFSSS of 21 to 22 at baseline, declining to about 9 in the milk protein/placebo and venlafaxine/milk protein groups by week 12, 11 in the venlafaxine/soy protein group, and 13.6 in the soy protein/placebo group.

The change in HFSSS from baseline to 12 weeks achieved statistical significance in all four groups (P<0.001), but the authors found no significant differences between treatment groups.Evaluation of QOL scores showed no significant effect of venlafaxine on total score or scores for any subscales. Men assigned to soy had significantly higher scores on emotional and functional subscales (P=0.025, P=0.041, respectively). No other significant differences were found.All of the therapies were well tolerated, as a total of 19 adverse events were reported, none of which was definitely associated with treatment.Joel T Nowak, M.A., M.S.W.