Researchers Review BPH Risk Factors with View to New Therapeutic Approaches

Researchers Review BPH Risk Factors with View to New Therapeutic Approaches

A recent literature review concluded there are different hormonal pathways leading to the pathogenesis of benign prostatic hyperplasia (BPH), primarily androgens and their receptors, growth factors, and estrogen. Researchers believe such knowledge will manifest itself in the clinic through the development of new diagnostic tools and therapeutic approaches to BPH.

The review paper, “Endocrine control of benign prostatic hyperplasia,” was published in Andrology by University of Catania researchers.

BPH, the most common benign proliferative disease in aging men, is a condition that leads to the non-malignant enlargement of the prostate gland and is associated with the onset of bladder outflow obstruction and a series of lower urinary tract symptoms (LUTS), all of which can greatly affect a patient’s quality of life. The precise mechanisms of its pathogenesis are still not completely understood, and research has focused on the role of a series of factors, such as changes in epithelial cells and stromal cell interactions, along with changes in the local endocrine system. Androgens, the male sex hormones, have been thoroughly investigated, but their role remains controversial.

Clinical data suggests that a combination of therapies might be more beneficial than the monotherapies currently used, namely α-blockers — drugs frequently prescribed for hypertension and relief of BPH symptoms — and 5-α-reductase inhibitors, which prevent conversion of testosterone into its active metabolite dihydrotestosterone (DHT) by inhibiting the 5-α-reductase enzymes.

Evidence has suggested that androgen/androgen receptor (AR) interaction is a valuable target to effectively improve BPH symptoms. However, BPH incidence increases with age, accompanying the reduction of testicular testosterone production. This contradiction has led researchers to theorize there are other molecular players in the pathogenesis of BPH, namely growth factors, estrogen, inflammation, vitamin D metabolism, and metabolic syndrome.

Growth factors, mainly secreted by stromal cells, have a crucial role in the maintenance of prostate cellular equilibrium. Moreover, several studies report an interdependence between certain growth factors, such as insulin-like growth factor (IGF), fibroblast growth factor (FGF), transforming growth factor (TGF), and prostatic steroid hormone content. When alterations in the interactions between these factors occur, it may lead to modification of the balance between cell proliferation and death, resulting in BPH.

The role of estrogen in BPH was first based on observations that treatment of dogs with estrogen, in conjugation with androgens, led to the development of BPH and BPH-related LUTS. Moreover, while androgens decrease with age, estrogen levels remain constant, tipping the ratio between the sex hormones toward estrogen, which is associated with the development of BPH.

Additional research has also found a correlation between serum estrogen levels and prostate volume. However, contradicting results indicate that further research is needed to clarify definitively the role of estrogen and its receptor in the development of BPH.

The review further discusses studies pointing to inflammation, metabolic syndrome, and vitamin D metabolism as risk factors for BPH, although research is not fully conclusive.

“Overall, the data of the literature suggest that the pathogenesis of BPH is influenced by different hormonal mechanisms, in particular: the androgens and the activity of their receptor, the role of growth factors, and the importance of the estrogen metabolism. Moreover, other aspects must be considered such as the chronic inflammation, the effects of the metabolic syndrome, and the modulation exerted by vitamin D,” the authors conclude in their report.

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