Androgen deprivation therapy (ADT) lowers testosterone and estradiol to castrate concentrations in men. It is a common treatment for prostate cancer, which is androgen-dependent, and the most prevalent contemporary cause of severe hypogonadism in older men. Men receiving ADT experience accelerated osteoporosis leading to fractures, accumulation of fat mass, loss of muscle mass, sexual dysfunction, hot flushes, and, reportedly, adverse neuropsychological effects.
Accumulating evidence suggests that many of the biological actions of testosterone in men are dependent on endogenous aromatisation of testosterone to estradiol. This raises the prospect of whether adverse effects of ADT in men with prostate cancer could be mitigated by replacing estradiol (‘estradiol add-back’).
Two randomised controlled trials of transdermal estradiol add-back (over 4 weeks, and 6 months, respectively), were conducted in men undergoing ADT for prostate cancer. These trials were designed to test the hypotheses that transdermal estradiol would reduce the ADT-associated unbalanced and accelerated bone remodelling, leading to better maintenance of volumetric bone mineral density; reduce the ADT-associated increase in fat mass; reduce ADT-associated changes in cognition; and reduce hot flushes and thereby improve quality of life.
The results of the trials will be presented in detail. They provide high quality evidence for this intervention to be used clinically. They also offer new insights into the biological actions of estradiol in men by providing direct observations of estradiol effects, in the absence of testosterone.