Rationale for using aromatase inhibitors to manage benign prostatic hyperplasia. Experimental studies

Area of Science:

• Urology
• Endocrinology
• Pathology

Background:

• Benign prostatic hyperplasia (BPH) is increasingly viewed as a stromal disease.
• Estrogens are implicated in the causative or permissive role of BPH development.
• The androgen:estrogen ratio shifts towards estrogens with age, both systemically and within the prostate.

Purpose of the Study:

• To investigate the role of estrogens in the pathogenesis of benign prostatic hyperplasia (BPH).
• To explore the potential of estrogen deprivation as a therapeutic strategy for BPH.

Main Methods:

• Analysis of human prostate tissue to assess estrogen accumulation and estrogen receptor presence.
• Animal studies using beagles and cynomolgus monkeys, involving administration of aromatizable substrates (androstenedione) and aromatase inhibitors (atamestane).
• Measurement of intraprostatic estrogen concentrations and estrogen receptor levels in experimental models.

Main Results:

• Estrogens preferentially accumulate in the stroma of hyperplastic human prostate tissue.
• Estrogen receptors are present in the prostate, meeting classical binding criteria.
• In animal models, androstenedione stimulated stromal and smooth muscle growth, effects reversed by aromatase inhibitors.
• Androstenedione increased intraprostatic estrogen and estrogen receptor levels, which were normalized by atamestane.

Conclusions:

• Both clinical and animal data strongly support a significant role for estrogens in the development of BPH.
• Estrogen deprivation emerges as a potential therapeutic approach for managing human BPH.