BPH Therapy That Stabilizes Estrogen Receptor β May Work Best, Study Suggests

BPH Therapy That Stabilizes Estrogen Receptor β May Work Best, Study Suggests

Researchers recently studied the biochemical pathways involved in the mechanism of action of BOH combination therapy with 5α- reductase (5AR) inhibitors, such as dutasteride, and nonsteroidal anti-inflammatory drugs (NSAIDs). Their findings suggest the contradictory effects of certain molecules may reduce the anti-inflammatory effects of the therapy and, as such, it may be important to include compounds that stabilize estrogen receptor β (ERβ) signaling.

The study, “Opposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor β (ERβ) Response to 5α- reductase Inhibition in Prostate Epithelial Cells,” was published in The Journal of Cell Biology.

Benign prostatic hyperplasia (BPH) and consequent lower urinary tract symptoms result from extended proliferation of smooth muscle and epithelial cells due to the effect of an androgen hormone (dihydrotestosterone, or DHT). This hormone is synthesized from testosterone through the action of enzymes called 5-α-reductases, which are active in the prostate and also contribute to tissue vascularization. BPH pharmacotherapies include 5α- reductase (5AR) inhibitors, including drugs such as dutasteride that block these specific enzymes. Dutasteride has been shown to reduce prostatic volume, inhibit DHT, and elevate serum testosterone levels to some extent. Importantly, as DHT is the precursor for estrogen receptor β (ERβ) ligands, these drugs can potentially limit ERβ activation, which maintains prostate tissue homeostasis. But many patients are resistant to the therapy, and ultimately require surgical intervention.

Chronic inflammation has been implicated in the pathologies of BOH and prostate cancer. Such observations have led to the hypothesis that a combination treatment using nonsteroidal anti-inflammatory drugs (NSAIDs), which reduce inflammatory molecules such as cyclooxygenase (COX), and 5AR inhibitors may improve BPH and associated symptoms. For this reason, researchers focused on the influence of one inflammatory mediator, COX-2, on ERβ function in BPH-derived epithelial cells. The results suggest that COX-2 both positively and negatively impacts ERβ action, which can lead to the reduction of the positive effects of anti-inflammatory benefits of NSAIDs.

“Future therapies designed to limit proliferation and chronic inflammation while maintaining ERβ activation may provide more rational treatment strategies and thus serve to provide better clinical outcomes for patients with symptomatic BPH,” the researchers concluded.

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