Presentation Authors: Lindsey Burleson*, Greenville, NC, Shelby Powers, Greenville , NC, Michael Odom, Dillon Ellis, Jae Won Jung, Greenville, NC, Bridget Koontz, Durham, NC, Johanna Hannan, Greenville , NC
Introduction: Women with cervical and endometrial cancers treated with radiation therapy (RT) can experience injury to surrounding normal tissues leading to genitourinary dysfunction. While radiation therapy is indicated in 53% of cervical cancer treatment regimens, little is known on the short or long-term effects of pelvic RT induced injury. This study characterizes the impact of pelvic RT on sexual and urinary function in female rats.
Methods: Female Sprague-Dawley rats (10 weeks) received a single dose (0 or 20 Gy) of x-ray radiation to the cervix (Sham: n=5, RT: n=16). At 4 or 9 weeks post-RT, sexual function was measured in vivo by pelvic nerve stimulated increases in vaginal blood flow (VBF) via laser Doppler. VBF was normalized to mean arterial pressure (MAP) measured by carotid cannulation. Ex vivo tissue bath experiments assessed vaginal adrenergic, cholinergic and electrical field stimulated (EFS) contractions. Bladder and urethral internal and external sphincters were also assessed for cholinergic, caffeine and EFS neurogenic contractility.
Results: Following RT, maximal VBF/MAP and the area under the curve (AUC) was markedly lower 4 weeks post-RT (Fig 1A; p < 0.05). Interestingly by 9 weeks, VBF and AUC had normalized. Cholinergic-mediated vaginal contraction was reduced at 4 weeks post-RT but recovered at 9 weeks post-RT (Fig.1B, p < 0.05). After 9-weeks RT, adrenergic-mediated vaginal contraction remained elevated (Fig. 1C, p < 0.05). Neurogenic EFS vaginal contractions were unchanged with RT. Cholinergic bladder contractions to carbachol were unchanged with RT but EFS-mediated contractions were reduced in both RT groups (p < 0.05). Internal urethral sphincter cholinergic contractility was unchanged with RT. In contrast, external urethral sphincter contractions to both caffeine and EFS were elevated at 4 and 9 weeks post-RT (p < 0.05).
Conclusions: Our model of pelvic RT demonstrates impaired sexual arousal and increased vaginal contractility. Acute decrease in VBF paired with chronic increase in vaginal contractility may contribute to vaginal dryness and dyspareunia experienced post-RT. Similar to previous RT studies, the bladder developed decreased neurogenic contractions. This model will allow us to understand the pathophysiology of RT-induced sexual and urinary dysfunction and discover radioprotective therapies.
Source of Funding: BSOM Summer Scholars Research Award, International Society for the Study of Women's Sexual Health