Selective Estrogen Receptor Modulators for BPH

New Factors on the Ground

M Garg; D Dalela; D Dalela; A Goel; M Kumar; G Gupta; S N Sankhwar


Prostate Cancer Prostatic Dis. 2013;16(3):226-232. 

In This Article

Future Prospects

Recent progress in the experimental studies for the use of SERMs in treating prostatic diseases is highly encouraging. Tamoxifen can induce apoptosis in human prostate stromal cells.[82] A selective ERβ agonist 8b-VE2 induces apoptosis in different prostatic cells in aromatase knockout mice independent of androgens.[54] There are myriads of in vivo and in vitro studies, which confirm the potentials of ER modulators such as toremifene, raloxifene and tamoxifene in inhibiting the proliferation of prostatic epithelial cells and stromal cells, and inhibiting ER activity.[82]

Although limited clinical trials of the SERMS in human BPH have been carried till now, its potential for use in prostate diseases can be evident from the animal studies.[83] Tamoxifen resulted in decreased prostate volume in seven beagles with spontaneous BPH.[84] Gonzalez[85] did a randomized trial study in dogs with BPH and showed that there was a 28.5% decrease in prostate volume in the tamoxifen group compared with placebo.

Negative concerns about the use of these drugs in prostate diseases are further negated by ongoing trials and clinical studies on prostate cancer. In a double-blind, phase III study, toremifene in 80 mg doses significantly reduced the incidence of vertebral fractures in men with prostate cancer on androgen-deprivation therapy compared with the placebo group. Although thromboembolic events were more frequent, there was a significant improvement in bone mineral density and serum lipid profile in toremifene group.[86] Although in an another phase III randomized double-blind study of 3 years, in which 1590 patients with high-grade prostatic intraepithelial neoplasia were randomized to receive 20 mg toremifene or placebo, the toremifene was not found to decrease the incidence of prostate cancer compared with that of placebo.[87] These preliminary studies indicate that SERMs are well tolerated in men, and have been shown to even ameliorate the side effects of androgen ablation therapy in men with prostate cancer.[86,88]

Because of the continuous increment in our understanding of behavior of ER in a tissue-selective manner and with the developments of newer more specific SERMs and other β-slective ligands, in future, these drugs may become integral part of treatment regime of BPH therapy.