A new study out of Australia looked at whether the use of transdermal (i.e., applied to the skin) estradiol improved cognitive function for men on ADT. The study was inspired by some evidence suggesting that estradiol is cognitively protective for women before menopause. One may suppose that estradiol may cognitively benefit men on ADT, if it protects them from hot flashes that disrupt their sleep. Indeed, a good night’s sleep helps keep one mentally alert during the day. So that sounds reasonable.
Men in the study were randomly assigned to receive either transdermal estradiol as a topical gel or a placebo while on ADT. All the men were administered a huge battery of cognitive tests at baseline and again at one, three and six months. As such, this was a rigorous, well-designed study.
However, the paper had a negative result. Adding estradiol showed no major effect on cognition for prostate cancer patients with castrate levels of testosterone from ADT.
A big problem was that there were only 39 men in each group. With sample sizes so small, it is not surprising that no major differences were found between the two groups.
This study is a testament to how the COVID-19 pandemic has disrupted quality-of-life research in prostate cancer. Sadly, this study was under powered because the pandemic forced the researchers to prematurely close the study.
This research is too interesting and too important to be abandoned completely. One hopes that the researchers will either be able to extend the study once the pandemic is under control or that others will follow up on the research.
With small sample sizes, it’s particularly important to match participants as closely as possible on each arm of a study…and as closely as possible on as many criteria as possible. Indeed, the men in both groups had a mean age of 72 years and were very similar in most other ways. However, one might wonder whether patients who are much younger might see some benefit from the add-back estradiol not detected in this study. That is based on the fact that hot flash intensity and bother is greater for younger men.
We hope this research will not be abandoned completely. Indeed, we would like to see it revisited in future studies involving larger sample sizes and a more diverse patient population.
To read the study abstract, see: https://pubmed.ncbi.nlm.nih.gov/35150156/
Reference:
Russell N, Allebone J, Dandash O, Hoermann R, Cheung AS, Zajac JD, Handelsman DJ, Kanaan RA, Grossmann M. Effect of estradiol on cognition in men undergoing androgen deprivation therapy: A randomized placebo-controlled trial. Clin Endocrinol (Oxf). 2022 Feb 12. doi: 10.1111/cen.14689. Epub ahead of print. PMID: 35150156.