INVESTIGATIVE UROLOGY

The potential of hormones and selective oestrogen receptor modulators in preventing voiding dysfunction in rats
Tantiwongse K, Fandel TM, Wang G, Breyer BN, Walsh TJ, Bella AJ, Lue TF
Knuppe Molecular Urology Laboratory, Department of Urology, University of California-San Francisco, San Francisco, CA, USA
BJU Int. 2008; 102: 242-6

• Objective: To investigate whether oestrogen, selective oestrogen receptor modulators (SERMs), and growth hormone (GH) can prevent the development of voiding dysfunction in a postpartum postmenopausal rat model of voiding dysfunction.
• Materials and Methods: Immediately after spontaneous delivery, nine primiparous Sprague-Dawley rats served as uninjured controls (sham group) and 54 underwent intravaginal balloon dilation. On day 7, the 54 subject rats underwent bilateral ovariectomy. A week later, six treatment groups of nine rats were randomized to receive: normal saline (injured control group), 17beta-oestradiol (E(2)), raloxifene, levormeloxifene, GH, or GH + E(2). The treatment groups received daily subcutaneous injections for 3 weeks. The effects of hormone treatment were examined by conscious cystometry at the end of the study. Voiding dysfunction was defined to include overactive bladder and sphincter deficiency.
• Results: The sham rats had a mean (sd) voiding frequency of 3 (0.87) times in 10 min and a bladder capacity of 0.43 (0.13) mL with smooth cystometry curves. The number of rats in each treatment group (each group contained nine rats) that had voiding dysfunction was as follows: E(2), three; raloxifene, six; levormeloxifene, four; and controls, four (P > 0.05 among the groups). Only one rat in the GH-treated group and no rats in the GH + E(2)-treated group had voiding dysfunction, which was significantly less in the GH + E(2)-treated group than in the controls (P = 0.041).
• Conclusion: This functional data suggest that the development of voiding dysfunction can be prevented by short-term administration of GH and GH + E(2) in our rat model. SERMs and E(2) alone seem to have no therapeutic effect.
  
  
• Editorial Comment
  This is a wished study by Dr. Lue and collaborators that have been working on this topic for the last years. They analyzed if short-term therapy with ultra-low dose of estrogen, selective estrogen receptor modulators (SERMs), and growth hormone (GH) can prevent the development of voiding dysfunction in a postpartum, postmenopausal voiding dysfunction rat model. By using conscious cistometry, developed in its own laboratory, the authors found that short-term therapy with E2, SERMs and GH suggest that, in the dosage and duration used, GH and GH + E2 seem to prevent the development of voiding dysfunction while E2 alone and SERMs do not have significant effects. With this paper, we are able to better understand the effect of these hormones on voiding, with the consequent clinical implications for treating and preventing post-partum and postmenopausal voiding dysfunction.

Dr. Francisco J. B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, RJ, Brazil
E-mail: sampaio@urogenitalresearch.org