Objectives. Urinary and fecal control deteriorates after menopause, but it is not clear whether this is age or hormone related. This study investigates whether administration of estrogen and/or the anti-aging growth hormone-releasing peptide, ghrelin, improves the adverse effects of menopause/aging on urethral and anal canal submucosal blood vessel counts in middle-age rats. Methods. Female Wistar rats (13 months old) underwent ovariectomy, followed 1 month later by intraperitoneal once-daily administration of 17-β estradiol (10 μg/kg), ghrelin (2 μg/kg), both hormones, or vehicle (n = 6 in each of four groups) for 42 days. An age-matched sham group (n = 6) received no intervention. Submucosal blood vessels were counted by light microscopy in five randomly selected fields from five nonconsecutive sections (5 μm thick) per rat of formalin-fixed and paraffin-embedded tissue blocks of the urethra and anal canal stained with hematoxylin-eosin. The results are expressed as the mean vessel number per high power field (×400). Results. Ovariectomy significantly reduced submucosal urethral and anal vascular counts below the sham values (7.41 ± 0.98 versus 5.46 ± 0.82, P = 0.003 and 7.16 ± 1.11 versus 4.92 ± 0.65, P = 0.0009, respectively). Estrogen restored the urethral counts (7.76 ± 0.88, P = 0.5) and ghrelin or combined estrogen and ghrelin administration significantly increased the counts to greater than the sham counts (8.68 ± 0.99, P = 0.04 and 9.72 ± 1.21, P = 0.004, respectively). Estrogen, ghrelin, and combined estrogen and ghrelin administration also restored the anal counts to sham levels (7.26 ± 0.97, P = 0.8; 6.56 ± 0.78, P = 0.3; and 7.76 ± 0.88, P = 0.3, respectively). Conclusions. Combined or individual replacement of estrogen and ghrelin produces a beneficial effect by reversing the ovariectomy-induced decrease in urethral and anal canal submucosal vessel numbers in middle-age rats.
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