Estrogens and androgens have both been implicated as causes of benign prostatic hyperplasia (BPH). Although epidemiological data on an association between serum androgen concentrations and BPH are inconsistent, it is generally accepted that androgens play a permissive role in BPH pathogenesis. In clinical practice, inhibitors of 5α-reductase (which converts testosterone to the more potent androgen dihydrotestosterone) have proven effective in the management of BPH, confirming an essential role for androgens in BPH pathophysiology. To date, multiple lines of evidence support a role for estrogens in BPH pathogenesis. Studies of the two estrogen receptor (ER) subtypes have shed light on their differential functions in the human prostate; ERα and ERβ have proliferative and antiproliferative effects on prostate cells, respectively. Effects of estrogens on the prostate are associated with multiple mechanisms including apoptosis, aromatase expression and paracrine regulation via prostaglandin E2. Selective estrogen receptor modulators or other agents that can influence intraprostatic estrogen levels might conceivably be potential therapeutic targets for the treatment of BPH.
Androgens play a permissive role in the pathogenesis of benign prostatic hyperplasia (BPH)
Inhibition of 5α-reductase activity is currently the mainstay of hormonal treatment of BPH
Increasing evidence from epidemiological, animal and in vitro studies supports a role for estrogens in the pathogenesis of BPH
Estrogen receptors ERα and ERβ mediate proliferative and antiproliferative effects of estrogens on prostate cells, respectively
Some androgens are weak ligands for ERs but might have potent agonistic effects on prostate cells because of high tissue concentrations
The prevalence of ERα and ERβ in hyperplastic prostate raises the potential of selective estrogen receptor modulators as potential therapeutic agents for BPH
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The authors declare no competing financial interests.
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Ho, C., Habib, F. Estrogen and androgen signaling in the pathogenesis of BPH. Nat Rev Urol 8, 29–41 (2011). https://doi.org/10.1038/nrurol.2010.207
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