Hypertension is a common chronic disease in the elderly and a risk factor for benign prostatic hyperplasia. However, the effects of aging and hypertension on the prostate tissue are not well understood. Spontaneously hypertensive rats (SHRs) are genetically hypertensive, with reduced prostatic blood flow and glandular epithelial prostatic hyperplasia at 15 weeks of age [1]. In this study, we investigated the effects of aging and hypertension on prostate tissue using SHRs.

Male SHRs and Wistar Kyoto rats (WKYs) aged 36 or 72 weeks were used (n = 8). WKYs were used as normotensive controls. At each age, prostate weight, blood pressure, and prostatic blood flow were measured. Serum testosterone levels were also measured using ELISA. Morphological changes in the ventral prostate and left testis were evaluated using hematoxylin and eosin staining. The glandular epithelial area was calculated as an indicator of prostate growth and prostatic hyperplasia using ImageJ software. The outer diameter of the gland was calculated as an indicator of prostate gland size.

SHRs at 36 weeks had significantly greater prostate weight and prostate weight/body weight ratio than those of WKYs at each age. SHRs at 72 weeks showed significantly lower prostate weight than those of WKYs at 72 weeks.  
SHRs at 36 and 72 weeks had significantly higher mean blood pressure and lower prostatic blood flow than those of WKYs at each age. SHRs at 72 weeks showed significant decreases in prostate weight and prostate weight/body weight ratio and an increase in blood pressure compared to those in SHRs at 36 weeks. 
SHRs at 36 and 72 weeks had an increased glandular epithelial area in the ventral prostate than those in WKYs at each age. In contrast, SHRs at 72 weeks, but not at 36 weeks, showed a significant decrease in the outer diameter of the prostate gland compared to that in WKYs at each age (Fig. 1). SHRs at 72 weeks, but not at 36 weeks, had lower serum testosterone levels than those of WKYs at each age. SHRs at 72 weeks of age showed significant increases in sloughing of the seminiferous epithelium, neutrophil infiltration, and atherosclerosis compared to those in WKYs at the same age.

SHRs at 36 weeks showed increased prostate weight/body weight ratio and glandular epithelial area compared to those in WKYs at the same age. In contrast, SHRs at 72 weeks showed decreased prostate weight and outside diameter of the gland in the ventral prostate and increased glandular epithelial area compared to those of WKYs at the same age. These data suggest that middle age is associated with glandular epithelial prostatic hyperplasia and aging causes glandular epithelial prostatic hyperplasia and atrophy of the prostate gland in SHRs. Prostatic atrophy occurs in most elderly men [2], and its causes include age, inflammation, radiation, and anti-androgens [2]. After the development of the prostate gland in adults, a reduction in testosterone levels causes regression of benign prostatic hyperplasia [3]. Testosterone is primarily produced in the testes. Current data show that aged SHRs had decreased serum testosterone levels and testicular damage. Aging and hypertension can decrease serum testosterone levels via testicular damage, suggesting that aging causes prostate gland atrophy via decreased serum testosterone levels and testicular damage in SHRs.

This is the first study to show that aging causes not only glandular epithelial prostatic hyperplasia but also atrophy of the prostate gland in SHRs. Aging and hypertension can cause prostate atrophy and decrease the prostate weight via decreased testosterone levels and testicular damage.

Saito M et al. Prostatic ischemia induces ventral prostatic hyperplasia in the SHR; possible mechanism of development of BPH. Sci Rep 2014;4:3822.
Egevad L et al. Benign mimics of prostate cancer. Pathology 2021;53:26-35.
Marks LS et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA 2006;296:2351-61.

Continence 15S (2025) 102087
DOI: 10.1016/j.cont.2025.102087