The Effects of Oestrogen on Vaginal Wound Healing: A Systematic Review and Meta-analysis

Overview

Journal Neurourol Urodyn

Date 2021 Oct 13

PMID 34643282

Citations 7

Authors

Eva V Vodegel

Arnoud W Kastelein

Charlotte H J R Jansen

Jacqueline Limpens

Sandra E Zwolsman

Jan-Paul W R Roovers

Carlijn R Hooijmans

Zeliha Guler

Affiliations

Soon will be listed here.

Abstract

Aims: To determine the effects of oestrogen or oestrogen deprivation on vaginal wound healing. Impaired wound healing following prolapse surgery may increase the risk of recurrent prolapse in the future. Vaginal oestrogen therapy may improve wound healing, hereby possibly improving surgical outcomes.

Methods: A systematic search of OVID MEDLINE, OVID Embase, and Web of Science was conducted up to January 28, 2020. We included original studies comparing wound healing-related outcomes of oestrogen exposed subjects (female animals and women) to hypo-oestrogenic subjects after vaginal surgery. Data on wound healing-related outcome measures were extracted. For each individual comparison, the standardised mean difference (Hedges' g; SMD) and 95% confidence interval (CI) were calculated.

Results: Of the 1474 studies reviewed, 14 studies were included for review, and 11 provided data for meta-analysis. Oestrogen improves neovascularisation (SMD: 1.13, 95% CI: 0.67-1.60), microscopic wound closure (SMD: 0.98, 95% CI: 0.66-1.29), collagen synthesis (SMD: 1.08, 95% CI: 0.42-1.74), and tissue strength (SMD: 1.26, 95% CI: 0.53-1.99) in animals. Oestrogen increases granulation (SMD: 1.67, 95% CI: 0.54-2.79) and accelerates macroscopic wound closure (SMD: 1.82, 95% CI: 1.22-2.42) in women and animals. Oestrogen decreases the inflammatory response (SMD: -0.58, 95% CI: -1.14 to -0.02) in women and animals and reduces levels of transforming growth factor (TGF)-β1 (SMD: -1.68, 95% CI: -2.52 to -0.83) in animals. All results were statistically significant.

Conclusions: Oestrogen therapy has a positive effect on vaginal wound healing. Future studies should determine whether oestrogen therapy has the potential to improve surgical outcomes.

Citing Articles

Long-term effects of vaginal surgery and endogenous ovarian hormones on the vagina and bladder.

Ho T, Zhang J, Wen Y, Guo S, Dobberfuhl A, Chen B Sex Med. 2023; 11(6):qfad063.

PMID: 38074491 PMC: 10710297. DOI: 10.1093/sexmed/qfad063.

The Microcirculation of Vaginal Tissue in Women with Obstetric Vesicovaginal Fistula and Short-Term Effects of Surgical Repair on Microvascular Parameters.

Maljaars L, Kastelein A, Latul Y, Nakoma G, Chipungu E, Roovers J Gynecol Obstet Invest. 2023; 88(5):302-309.

PMID: 37734334 PMC: 10658999. DOI: 10.1159/000534066.

Supramolecular Fibrous Hydrogel Augmentation of Uterosacral Ligament Suspension for Treatment of Pelvic Organ Prolapse.

Miller B, Wolfe W, Gentry J, Grewal M, Highley C, De Vita R Adv Healthc Mater. 2023; 12(22):e2300086.

PMID: 37220996 PMC: 11468651. DOI: 10.1002/adhm.202300086.

The Effect of Growth Factors on Vaginal Wound Healing: A Systematic Review and Meta-analysis.

van Velthoven M, Gudde A, Struijs F, Oosterwijk E, Roovers J, Guler Z Tissue Eng Part B Rev. 2023; 29(4):429-440.

PMID: 37051705 PMC: 10701546. DOI: 10.1089/ten.TEB.2022.0225.

Absorbable Electrospun Poly-4-hydroxybutyrate Scaffolds as a Potential Solution for Pelvic Organ Prolapse Surgery.

Verhorstert K, Gudde A, Weitsz C, Bezuidenhout D, Roovers J, Guler Z ACS Appl Bio Mater. 2022; 5(11):5270-5280.

PMID: 36315937 PMC: 9682484. DOI: 10.1021/acsabm.2c00691.

References

Brufani M, Rizzi N, Meda C, Filocamo L, Ceccacci F, DAiuto V . Novel Locally Active Estrogens Accelerate Cutaneous Wound Healing-Part 2. Sci Rep. 2017; 7(1):2510. PMC: 5451472. DOI: 10.1038/s41598-017-02820-y. View

Kilkenny C, Parsons N, Kadyszewski E, Festing M, Cuthill I, Fry D . Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PLoS One. 2009; 4(11):e7824. PMC: 2779358. DOI: 10.1371/journal.pone.0007824. View

Florian-Rodriguez M, Chin K, Hamner J, Acevedo J, Keller P, Word R . Effect of Protease Inhibitors in Healing of the Vaginal Wall. Sci Rep. 2019; 9(1):12354. PMC: 6710245. DOI: 10.1038/s41598-019-48527-0. View

Cody J, Jacobs M, Richardson K, Moehrer B, Hextall A . Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database Syst Rev. 2012; 10:CD001405. PMC: 7086391. DOI: 10.1002/14651858.CD001405.pub3. View

Mukai K, Nakajima Y, Urai T, Komatsu E, Nasruddin , Sugama J . 17β-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice. Int Wound J. 2014; 13(5):636-44. PMC: 7949953. DOI: 10.1111/iwj.12336. View

Gantwerker E, Hom D . Skin: histology and physiology of wound healing. Facial Plast Surg Clin North Am. 2011; 19(3):441-53. DOI: 10.1016/j.fsc.2011.06.009. View

Ripperda C, Maldonado P, Acevedo J, Keller P, Akgul Y, Shelton J . Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall. Menopause. 2017; 24(7):838-849. PMC: 5484719. DOI: 10.1097/GME.0000000000000840. View

Guo S, DiPietro L . Factors affecting wound healing. J Dent Res. 2010; 89(3):219-29. PMC: 2903966. DOI: 10.1177/0022034509359125. View

Balgobin S, Montoya T, Shi H, Acevedo J, Keller P, Riegel M . Estrogen alters remodeling of the vaginal wall after surgical injury in guinea pigs. Biol Reprod. 2013; 89(6):138. PMC: 4076355. DOI: 10.1095/biolreprod.113.112367. View

10.

Zwetsloot P, van der Naald M, Sena E, Howells D, IntHout J, de Groot J . Standardized mean differences cause funnel plot distortion in publication bias assessments. Elife. 2017; 6. PMC: 5621838. DOI: 10.7554/eLife.24260. View

11.

Ashcroft G, Greenwell-Wild T, Horan M, Wahl S, Ferguson M . Topical estrogen accelerates cutaneous wound healing in aged humans associated with an altered inflammatory response. Am J Pathol. 1999; 155(4):1137-46. PMC: 1867002. DOI: 10.1016/S0002-9440(10)65217-0. View

12.

Trenti A, Tedesco S, Boscaro C, Trevisi L, Bolego C, Cignarella A . Estrogen, Angiogenesis, Immunity and Cell Metabolism: Solving the Puzzle. Int J Mol Sci. 2018; 19(3). PMC: 5877720. DOI: 10.3390/ijms19030859. View

13.

Denman M, Gregory W, Boyles S, Smith V, Edwards S, Clark A . Reoperation 10 years after surgically managed pelvic organ prolapse and urinary incontinence. Am J Obstet Gynecol. 2008; 198(5):555.e1-5. DOI: 10.1016/j.ajog.2008.01.051. View

14.

Mukai K, Urai T, Asano K, Nakajima Y, Nakatani T . Evaluation of Effects of Topical Estradiol Benzoate Application on Cutaneous Wound Healing in Ovariectomized Female Mice. PLoS One. 2016; 11(9):e0163560. PMC: 5033238. DOI: 10.1371/journal.pone.0163560. View

15.

Sjovall A . The influence of oestrogens upon the healing of vaginal wounds in rats. Acta Endocrinol (Copenh). 1953; 12(3):249-59. DOI: 10.1530/acta.0.0120249. View

16.

Thornton M . Estrogens and aging skin. Dermatoendocrinol. 2013; 5(2):264-70. PMC: 3772914. DOI: 10.4161/derm.23872. View

17.

Hardman M, Emmerson E, Campbell L, Ashcroft G . Selective estrogen receptor modulators accelerate cutaneous wound healing in ovariectomized female mice. Endocrinology. 2007; 149(2):551-7. DOI: 10.1210/en.2007-1042. View

18.

Cretti A . [The influence of oestradiol and progesterone on wound healing]. Rocz Akad Med Im Juliana Marchlewskiego Bialymst Suppl. 1966; 14:1-60. View

19.

Sjovall A . The influence of oestrogen upon the healing of vaginal wounds in rats. Acta Obstet Gynecol Scand. 2010; 27(1):1-10. DOI: 10.3109/00016344709159873. View

20.

Reinke J, Sorg H . Wound repair and regeneration. Eur Surg Res. 2012; 49(1):35-43. DOI: 10.1159/000339613. View