Objective: To evaluate the effect of iatrogenic menopause on the physiology of the vagina of the ewe, and to evaluate if vaginal changes in ewes can be translated to women with the genitourinary syndrome of menopause (GSM). Design: Animal study, randomised design for ovariectomy or control, blinded for allocation and outcome assessment. Setting: University of Cape Town, South Africa. Population or Sample: Twenty-five Dohne Merino ewes. Methods: Iatrogenic menopause was induced in 20 animals by bilateral ovariectomy. Five animals served as a control group (no intervention). Differences between groups were determined by linear regression analyses (adjusted for baseline scores) at 5 months after ovariectomy. Main Outcome Measures: Vaginal epithelial thickness, pH, vaginal maturation value, vaginal maturation index, epithelial glycogen accumulation, content of elastin fibres, collagen, and vascularity. Results: Ovariectomised ewes showed epithelial thinning of the vaginal wall from 146 µm to 47 µm (mean, p <0.001 ). In addition, epithelial glycogen accumulation (43%) and the vascularity (23%) of the vaginal wall significantly decreased as compared to the control group. No differences were found for vaginal pH, vaginal cytology outcomes, elastin fibres and collagen content. Conclusions: This study established the ewe as a suitable large animal model for GSM. Furthermore, the similar relevant outcomes in humans and ewes hold great value for future translational research for the evaluation and optimisation of different treatment modalities for GSM. Funding: None. Keywords: Atrophy, ewe, genitourinary syndrome of menopause, model, ovariectomy.

Objective: To compare the host and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold to the response to PP mesh in an animal model of vaginal POP surgery. Design: A study employing a sheep model Setting: KU Leuven Center for Surgical Technologies Population: 14 parous female Mule sheep Methods: P4HB scaffolds were surgically implanted in the posterior vaginal wall of sheep. The comparative PP mesh data were obtained from an identical protocol. Main outcome measures: Gross necropsy, histological and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Results: Gross necropsy revealed no implant related adverse events using P4HB scaffolds. The tensile stiffness of the P4HB explants increased at 180-days (12.498 ± 2.66 N/mm (P=0.019)) as compared to 60-days (4.585 ± 1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB scaffolds exhibited excellent tissue integration with dense connective tissue and a moderate initial host response. P4HB scaffolds induced a significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as compared to PP mesh (0.99 ± 0.78 SEM, score 0-4) at 180-days. Conclusions: P4HB scaffold facilitated a gradual load transfer to vaginal tissue over time. The fully absorbable P4HB scaffold, in comparison to PP mesh, has a favorable host response with comparable load bearing capacity. If these results are also observed at longer follow-up, a clinical study for vaginal POP surgery may be warranted to demonstrate efficacy. Key words: Pelvic organ prolapse, vaginal surgery, Poly-4-hydroxybutyrate, degradable scaffold, host response, biomechanics.