Estrogens and Male Lower Urinary Tract Dysfunction

Abstract

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology and affect the majority of men at some time during their lives. The development of BPH/LUTS is associated with an increased ratio of estrogen to androgen levels, and this ratio, when mimicked in a variety of animals, induces BPH and lower urinary tract dysfunction (LUTD). While the precise molecular etiology remains unclear, estrogens have been implicated in the development and maintenance of BPH. Numerous endogenous and exogenous estrogens exist in humans. These estrogens act via multiple estrogen receptors to promote or inhibit prostatic hyperplasia and other BPH-associated processes. The prostate is an estrogen target tissue, and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of estrogen action directly affecting prostate growth and differentiation in the context of BPH is an understudied area and remains to be elucidated. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation illustrating their potential roles in the development of BPH as therapy. More work will be required to identify estrogen signaling pathways associated with LUTD in order to develop more efficacious drugs for BPH treatment and prevention.

Androgenic to oestrogenic switch in the human adult prostate gland is regulated by epigenetic silencing of steroid 5α-reductase 2

“…Here, we found that pERα was activated in human prostatic samples that lack SRD5A2 protein expression, although protein levels of ERα, ERβ and pERβ were not affected (Figure A). As the balance between ERα and ERβ plays a major role in modulating prostatic growth , our findings suggest that, in the absence of SRD5A2, alternative oestrogenic pathways are activated that may affect prostatic proliferative capacity , and that may serve as alternative targets for the treatment of BPH in selected patients who lack SRD5A2 expression .…”

“…Androgens and oestrogens exert similar, but distinct, effects on the prostate, and it is becoming clear that a finely tuned balance between the effects mediated by androgen receptor, by oestrogen receptor‐α (ERα) and by oestrogen receptor‐β (ERβ) is required for the maintenance of prostatic health . Oestrogens directly and indirectly affect the growth and differentiation of the prostate . Testosterone can be metabolized via CYP19/aromatase into the potent oestrogen, i.e.…”

CD8+ T cells promote proliferation of benign prostatic hyperplasia epithelial cells under low androgen level via modulation of CCL5/STAT5/CCND1 signaling pathway

“…To date, there has been no consensus on the etiology of BPH. Theories of BPH pathogenesis, including altered oestrogen/androgen balance 40 41 42 , increased oxidative stress 43 44 , metabolic syndromes 45 46 , chronic inflammation 3 , epithelial-mesenchymal transition 47 , and altered activity of autonomic nerves 48 , have been postulated. Consistent with the role of androgen in promoting human prostatic epithelial cells growth 49 , Finasteride, an inhibitor of androgen synthesis, can alleviate BPH symptoms through the significant prostatic epithelial cells atrophy and apoptosis thus reduction of prostate volume 50 51 52 53 and relieve LUTS secondary to BPH 54 55 .…”

Estrogen in the male: a historical perspective†

“…Estrogen has been shown to be involved in the most common human prostatic disease, benign prostatic hyperplasia [ 205 ]. The ability of early estrogen exposure to alter prostatic stem and progenitor cells and the involvement of estrogens in the etiology of benign prostatic hyperplasia suggest the possibility that developmental exposure to estrogens could induce changes that alter aging susceptibility to this hyperplastic growth and potentially other diseases such as prostatic cancer.…”