Salminen et al.1 present evidence that LHRH analogs, by lowering endogenous estradiol levels, impair certain cognitive processes in prostate cancer (PCa) patients. Others have shown that estradiol cognitively protects spatial memory in older men.2
Currently, estrogens are used as secondary, rather than primary, hormonal therapies for PCa patients. We propose that estradiol is likely to be more protective of cognition if it is used before patients start on an LHRH agonist.
Salminen et al. do not cite data that has shown no cognitive benefits of estradiol treatment in PCa patients.3 To reconcile those differences, we suggest that estradiol's cognitive benefits are likely to be greatest in patients who have not already experienced cognitive decline—either from LHRH agonists or aging. We base this suggestion on data from menopausal women, which reveal a critical window of time at menopause when estrogenic compounds are protective of cognition.4 After cognitive decline has set in, exogenous estrogens may actually play a negative role. Extending these results to men, we should expect that estradiol will be most beneficial to PCa patients if used earlier rather than later.
Estradiol lowers patients' risk of osteoporosis and incidences of hot flashes, while costing less than LHRH agonists. So, then, why not use estradiol as primary hormonal therapy for PCa?
The risk of thromboembolism is real, but it can be greatly reduced if estradiol is applied transdermally. Supposedly, gynecomastia can be reduced with prophylactic radiotherapy; however, its effectiveness has not been proven in prospective studies, nor does it significantly reduce the incidence of breast complaints from patients on estradiol.
Again, extrapolating from postmenopausal women, physicians should be aware that estrogens may increase urinary incontinence in patients already experiencing incontinence secondary to a prostatectomy and radiotherapy for localized PCa.5