Non-hormonal prevention and treatment of genitourinary syndrome of menopause

Literature review

Authors

DOI:

https://doi.org/10.18370/2309-4117.2026.83.18-28

Keywords:

genitourinary syndrome of menopause, vulvovaginal atrophy, non-hormonal therapy, hyaluronic acid, polycarbophil

Abstract

Objective of the review: to evaluate the clinical efficacy of hyaluronic acid and polycarbophil in the treatment of genitourinary syndrome of menopause (GSM).

Materials and methods. A structured literature review was conducted in accordance with the PRISMA 2020 guidelines. The search was performed in MEDLINE (PubMed), EMBASE, and Cochrane Library databases for the period 2000–2025.

Analysis of the literature. The analysis demonstrated that both hyaluronic acid and polycarbophil showed statistically significant improvement in GSM symptoms. Most studies reported a reduction in vaginal dryness and dyspareunia intensity (p < 0.001), improvement in quality of life and sexual function scores (p < 0.001), and an increase in vaginal health index values. Comparative studies did not reveal statistically significant differences between hyaluronic acid and polycarbophil, indicating their clinical equivalence in symptomatic management. At the same time, vaginal estrogen therapy demonstrates a more pronounced and sustained effect.

A key finding was the high placebo effect observed in studies of vaginal moisturizers, which complicates data interpretation and highlights the need for larger and more standardized studies. Non-hormonal therapies (hyaluronic acid and polycarbophil) provide clinically meaningful relief of GSM symptoms; however, their effect is predominantly symptomatic and is not associated with restoration of the morphological structure of the vaginal epithelium. A major limitation of current research is the discrepancy between subjective and objective outcome measures, which restricts comprehensive evaluation of therapeutic efficacy.

Conclusions. Hyaluronic acid and polycarbophil are effective non-hormonal options for the treatment of mild to moderate GSM, improving symptoms and quality of life. Although vaginal estrogen therapy remains the most effective treatment due to its impact on both symptoms and morphological changes, hyaluronic acid and polycarbophil may be considered first-line therapy in mild to moderate cases, in patients with contraindications to hormones, and in combination regimens to enhance treatment efficacy and adherence.

Author Biographies

D.H. Konkov, P.L. Shupyk National Healthcare University of Ukraine, Kyiv

DSc, professor, Department of Reproductology and Clinical Embryology

V.O. Tykholaz, P.L. Shupyk National Healthcare University of Ukraine, Kyiv

DSc, professor, Department of Morphology and Physiology

V.O. Rud, National Pirogov Memorial Medical University, Vinnytsia

DSc, professor, Department of Obstetrics and Gynecology No. 2

O.V. Bulavenko, National Pirogov Memorial Medical University, Vinnytsia

DSc, professor, Department of Obstetrics and Gynecology No. 2

References

  1. Angelou K, Grigoriadis T, Diakosavvas M, Zacharakis D, Athanasiou S. The Genitourinary Syndrome of Menopause: An Overview of the Recent Data. Cureus. 2020;12(4):e7586. DOI: 10.7759/cureus.7586
  2. Cox S, Nasseri R, Rubin RS, Santiago-Lastra Y. Genitourinary Syndrome of Menopause. Med Clin North Am. 2023;107(2):357–69. DOI: 10.1016/j.mcna.2022.10.017
  3. Gandhi J, Chen A, Dagur G, Suh Y, Smith N, Cali B, et al. Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol. 2016;215(6):704–11. DOI: 10.1016/j.ajog.2016.07.045
  4. Moral E, Delgado JL, Carmona F, Caballero B, Guillán C, González PM, et al. Genitourinary syndrome of menopause: Prevalence and quality of life in Spanish postmenopausal women. The GENISSE study. Climacteric. 2018;21:167–73. DOI: 10.1080/13697137.2017.1421921
  5. Briggs P. BMS consensus statement: Genitourinary Syndrome of Menopause (GSM). Post Reprod Health. 2026;32(1):8–13. DOI: 10.1080/20533691.2026.2629181
  6. Pérez López FR, Vieira Baptista P, Phillips N, Cohen Sacher B, Fialho SC, Stockdale CK. Clinical manifestations and evaluation of postmenopausal vulvovaginal atrophy. Gynecol Endocrinol. 2021;37(8):740–5. DOI: 10.1080/09513590.2021.1931100
  7. Siusiuka VH, Avramenko NV, Pavliuchenko MI, Serhiienko MYu, Kniazeva AO. Vulvovaginal atrophy: modern approaches to diagnostics and management. Zaporozhye Medical Journal. 2024;26(6):506–11. DOI: 10.14739/2310-1210.2024.6.311942
  8. Am EF. Genitourinary syndrome of menopause. Aust Fam Physician. 2017;46(7):481–4.
  9. Calleja Agius J, Brincat MP. The urogenital system and the menopause. Climacteric. 2015;18 Suppl 1:18–22. DOI: 10.3109/13697137.2015.1078206
  10. Cahill EP. The new toolbox for reducing painful sex in menopause. Curr Opin Obstet Gynecol. 2026;38(2):109–16. DOI: 10.1097/GCO.0000000000001091
  11. Cucinella L, Cassani C, Martini E, Parrotta GE, Monne G, Colombo GM, et al. Sexual function after menopause: the role of vaginal estrogens. Maturitas. 2025;200:108681. DOI: 10.1016/j.maturitas.2025.108681
  12. Phillips NA, Bachmann GA. Genitourinary syndrome of menopause: Common problem, effective treatments. Cleve Clin J Med. 2018;85(5):390–8. DOI: 10.3949/ccjm.85a.15081
  13. Cyriac J, Sood R. Case-Based Perspectives on the Management of Genitourinary Syndrome of Menopause. Clin Pract. 2026;16(3):60. DOI: 10.3390/clinpract16030060
  14. Nappi RE, Cucinella L. Advances in pharmacotherapy for treating female sexual dysfunction. Expert Opin Pharm. 2015;16:(6):875–7. DOI: 10.1517/14656566.2015.1020791
  15. Konkov DH, Tykholaz VO, Dan N, Markevych B. L-arginine in the management of menopausal symptoms: vascular, metabolic and quality-of-life effects (systematic review). Reproductive health of woman. 2025;(8):122–8.
  16. Taran O, Konkov D, Bulavenko O, Lobastova T, Malinina O, Homon N, et al. Alternative therapy of menopausal vegetative disorders in women taking the metabolic status into account. Reprod Endocrinol. 2023;(69):80–8.
  17. Gabes M, KnГјttel H, Stute P, Apfelbacher CJ. Measurement properties of patient-reported outcome measures (PROMs) for women with genitourinary syndrome of menopause: a systematic review. Menopause. 2019;26(11):1342–53. DOI: 10.1097/GME.0000000000001390
  18. The NAMS 2020 GSM Position Statement Editorial Panel. The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020;27(9):976–92. DOI: 10.1097/GME.0000000000001609
  19. Fallacara A, Baldini E, Manfredini S, Vertuani S. Hyaluronic Acid in the Third Millennium. Polymers. 2018;10(7):701. DOI: 10.3390/polym10070701
  20. Shifren JL. Genitourinary Syndrome of Menopause. Clin Obstet Gynecol. 2018;61(3):508–16. DOI: 10.1097/GRF.0000000000000380
  21. Harten IA, Evanko SP, Choe CH, Lee EW, Patel BN, Bogdani M, et al. The extracellular matrix molecules versican and hyaluronan in urethral and vaginal tissues in stress urinary incontinence. Neurourol Urodyn. 2021;40:771–82. DOI: 10.1002/nau.24635
  22. Nappi RE, Cucinella L, Martini E, Cassani C. The role of hormone therapy in urogenital health after menopause. Best Pract Res Clin Endocrinol Metab. 2021;35:101595. DOI: 10.1016/j.beem.2021.101595
  23. Nappi RE, Martella S, Albani F, Cassani C, Martini E, Landoni F. Hyaluronic Acid: A Valid Therapeutic Option for Early Management of Genitourinary Syndrome of Menopause in Cancer Survivors? Healthcare (Basel). 2022;10(8):1528. DOI: 10.3390/healthcare10081528
  24. Thapa R, Pandey P, Parat MO, Gurung S, Parekh HS. Phase transforming in situ gels for sustained and controlled transmucosal drug delivery via the intravaginal route. Int J Pharm. 2024;655:124054. DOI: 10.1016/j.ijpharm.2024.124054
  25. Okur NГњ, YaДџcД±lar AP, Siafaka PI. Promising Polymeric Drug Carriers for Local Delivery: The Case of in situ Gels. Curr Drug Deliv. 2020;17(8):675–93. DOI: 10.2174/1567201817666200608145748
  26. Ferreira SBDS, Silva JBD, Borghi Pangoni FB, Junqueira MV, Bruschi ML. Linear correlation between rheological, mechanical and mucoadhesive properties of polycarbophil polymer blends for biomedical applications. J Mech Behav Biomed Mater. 2017;68:265–75. DOI: 10.1016/j.jmbbm.2017.02.016
  27. Leyva Gómez G, Piñón Segundo E, Mendoza Muñoz N, Zambrano-Zaragoza ML, Mendoza-Elvira S, Quintanar-Guerrero D. Approaches in Polymeric Nanoparticles for Vaginal Drug Delivery: A Review of the State of the Art. Int J Mol Sci. 2018;19(6):1549. DOI: 10.3390/ijms19061549
  28. Ostróżka Cieślik A, Michalak M, Bryś T, Kudła M. The Potential of Hydrogel Preparations Containing Plant Materials in Supporting the Treatment of Vaginal and Vulvar Infections—Current State of Knowledge. Polymers. 2025;17(4):470. DOI: 10.3390/polym17040470
  29. Caviglioli G, Baldassari S, Cirrincione P, Russo E, Parodi B, Gatti P, et al. An innovative matrix controlling drug delivery produced by thermal treatment of DC tablets containing polycarbophil and ethylcellulose. Int J Pharm. 2013;458(1):74–82. DOI: 10.1016/j.ijpharm.2013.10.014
  30. Thapa R, Gurung S, Parat M O, Parekh HS, Pandey P. Application of Sol–Gels for Treatment of Gynaecological Conditions - Physiological Perspectives and Emerging Concepts in Intravaginal Drug Delivery. Gels. 2022;8:99. DOI: 10.3390/gels802009
  31. Polycarbophil item page [Internet]. Available from: https://www.formulationbio.com/polycarbophil-item-3334.html
  32. Baldassari S, Cirrincione P, Ailuno G, Drava G, Arpicco S, Caviglioli G. Towards a better understanding of thermally treated polycarbophil matrix tablets for controlled release. Int J Pharm X. 2021;3:100098 DOI: 10.1016/j.ijpx.2021.100098
  33. Arana Linares AC, Caicedo PA, Villegas Torres MF, González-Barrios AF, Cortes N, Osorio EH, et al. Preformulation Study of Controlled Release Galantamine Matrix Tablets Containing Polyethylene Oxide, Hydroxypropyl Methylcellulose, and Ethylcellulose. Pharmaceutics. 2025;17(9):1139. DOI: 10.3390/pharmaceutics17091139
  34. Ailuno G, Iacobazzi RM, Lopalco A, Baldassari S, Arduino I, Azzariti A, et al. The Pharmaceutical Technology Approach on Imaging Innovations from Italian Research. Pharmaceutics. 2021;13(8):1214. DOI: 10.3390/pharmaceutics13081214
  35. Donders GGG, Ruban K, Bellen G, Grinceviciene S. Pharmacotherapy for the treatment of vaginal atrophy. Expert Opin Pharm. 2019;20:821–35. DOI: 10.1080/14656566.2019.1574752
  36. Lev Sagie A. Vulvar and Vaginal Atrophy: Physiology, Clinical Presentation, and Treatment Considerations. Clin Obs Gynecol. 2015;58:476–91. DOI: 10.1097/GRF.0000000000000126
  37. Nappi RE, Martini E, Cucinella L, Martella S, Tiranini L, Inzoli A, et al. Addressing Vulvovaginal Atrophy/Genitourinary Syndrome of Menopause for Healthy Aging in Women. Front Endocrinol. 2019;10:561. DOI: 10.3389/fendo.2019.00561
  38. Godha K, Tucker KM, Biehl C, Archer DF, Mirkin S. Human vaginal pH and microbiota: An update. Gynecol Endocrinol. 2018;34:451–5. DOI: 10.1080/09513590.2017.1407753
  39. Wasnik VB, Acharya N, Mohammad S. Genitourinary Syndrome of Menopause: A Narrative Review Focusing on Its Effects on the Sexual Health and Quality of Life of Women. Cureus. 2023;15(11):e48143. DOI: 10.7759/cureus.48143
  40. Escobar C, Rosenblum N. Vaginal Estrogen—What a Urologist Should Know. Urology. 2021;151:37–43. DOI: 10.1016/j.urology.2020.05.034
  41. Faubion SS, Sood R, Kapoor E. Genitourinary Syndrome of Menopause: Management Strategies for the Clinician. Mayo Clin Proc. 2017;92:1842–9. DOI: 10.1016/j.mayocp.2017.08.019
  42. Kingsberg SA, Krychman M, Graham S, Bernick B, Mirkin S. The Women’s EMPOWER Survey: Identifying Women’s Perceptions on Vulvar and Vaginal Atrophy and Its Treatment. J Sex Med. 2017;14:413–24. DOI: 10.1016/j.jsxm.2017.01.010
  43. Da Silva AS, Baines G, Araklitis G, Robinson D, Cardozo L. Modern management of genitourinary syndrome of menopause. Fac Rev. 2021;10:25. DOI: 10.12703/r/10-25
  44. Cunha AR, Machado RM, Palmeira-de-Oliveira A, Martinez-de-Oliveira J, das Neves J, Palmeira-de-Oliveira R. et al. Characterization of commercially available vaginal lubricants: a safety perspective. Pharmaceutics. 2014;6(3):530–42. DOI:10.3390/pharmaceutics6030530
  45. Sarmento ACA, Kamilos MF, Costa APF, Vieira-Baptista P, Eleutério J Jr, Gonçalves AK. Use of moisturizers and lubricants for vulvovaginal atrophy. Front Reprod Health. 2021;3:781353 DOI: 10.3389/frph.2021.781353.
  46. Indarti J, Permatas RP, Hiksas R. Efficacy of polycarbophil moisturizing gel in women with genitourinary syndrome of menopause: a randomized controlled trial. J South Asian Feder Obstet Gynaecol. 2022;14(6):719–23. DOI: 10.5005/jp-journals-10006-2155
  47. Cagnacci A, Franco Barattini D, Casolati E, Mangrella M, Piccolo E, Piazza R, et al. Short and long-term effect of polycarbophil vaginal gel on vaginal atrophy of peri- and post-menopausal women: the TRIPLE study. Eur J Obstet Gynecol Reprod Biol. 2024;299:303–8. DOI: 10.1016/j.ejogrb.2024.06.033
  48. Albalawi NS, Almohammadi MA, Albalawi AR. Comparison of the Efficacy of Vaginal Hyaluronic Acid to Estrogen for the Treatment of Vaginal Atrophy in Postmenopausal Women: A Systematic Review. Cureus. 2023;15(8):e44191. DOI: 10.7759/cureus.44191
  49. Palacios S. Hyaluronic acid in the management of postmenopausal vaginal atrophy: from moisturizer to mucosal regenerator. Gynecol Endocrinol. 2025;41(1):2545368. DOI: 10.1080/09513590.2025.2545368
  50. Roehrs H, Stocco JG, Pott F, Blanc G, Meier MJ, Dias FA. Dressings and topical agents containing hyaluronic acid for chronic wound healing. Cochrane Database Syst Rev. 2023;7(7):CD012215. DOI: 10.1002/14651858
  51. Jokar A, Davari T, Asadi N, Ahmadi F, Foruhari S. Comparison of the hyaluronic acid vaginal cream and conjugated estrogen used in treatment of vaginal atrophy of menopause women: a randomized controlled clinical trial. Int J Community Based Nurs Midwifery. 2016;4(1):69–78.
  52. Hirschberg AL, Bitzer J, Cano A, Ceausu I, Chedraui P, Durmusoglu F, et al. Topical estrogens and non-hormonal preparations for postmenopausal vulvovaginal atrophy: An EMAS clinical guide. Maturitas. 2021;148:55 61. DOI: 10.1016/j.maturitas.2021.04.005
  53. Briggs P; British Menopause Society Medical Advisory Council. BMS Consensus Statement: Genitourinary Syndrome of Menopause (GSM) [Internet]. London: British Menopause Society; 2025 [cited 2026 Apr 30]. Available from: https://thebms.org.uk/wp-content/uploads/2025/11/09-NEW-BMS-ConsensusStatement-Genitourinary-Syndrome-of-Menopause-GSM-NOV2025-B.pdf
  54. American College of Obstetricians and Gynecologists’ Committee on Clinical Consensus—Gynecology. Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer: Clinical Consensus. Obstet Gynecol. 2021;138(6):950–60. DOI: 10.1097/AOG.0000000000004601
  55. Hocké C, Diaz M, Bernard V, Frantz S, Lambert M, Mathieu C, et al. Genitourinary syndrome of menopause: CNGOF and GEMVi clinical practice guidelines. Gynecol Obstet Fertil Senol. 2021;49(5):394–413.
  56. Chen J, Geng L, Song X, Li H, Giordan N, Liao Q. Evaluation of the efficacy and safety of hyaluronic acid vaginal gel. Arch Gynecol Obstet. 2013;288:593–9. DOI: 10.1016/j.gofs.2021.03.025
  57. Ekin M, Yaşar L, Savan K, Temur M, Uhri M, Gencer I, Kıvanç E. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Arch Gynecol Obstet. 2011 Mar;283(3):539–43. DOI: 10.1007/s00404-010-1382-8
  58. Casiano Evans EA, Hobson DTG, Aschkenazi SO, Alas AN, et al. Nonestrogen Therapies for Treatment of Genitourinary Syndrome of Menopause: A Systematic Review. Obstet Gynecol. 2023;142(3):555–70. DOI: 10.1097/AOG.0000000000005288
  59. Ribeiro LDS, Silveira RCCP, Vasques CI, de Menêses AG, Dos Reis PED, Ferreira EB. Hyaluronic acid to manage radiotoxicities in gynecological cancer patients: a scoping review. Support Care Cancer. 2024;32(7):439. DOI: 10.1007/s00520-024-08614-z
  60. Iliescu DG, Petrita R, Teodorescu C, et al. Real world performance and safety of vaginal ovules in reducing the vaginal symptoms associated with vulvovaginal atrophy and postmenopausal sexual dysfunction. Biomed Rep. 2024;20(3):35. DOI: 10.3892/br.2024.1723
  61. Cuccu I, Golia D’Augè T, Firulli I, De Angelis E, Buzzaccarini G, D’Oria O, et al. Update on Genitourinary Syndrome of Menopause: A Scoping Review of a Tailored Treatment-Based Approach. Life (Basel). 2024;14(11):1504. DOI:10.3390/life14111504
  62. Fidecicchi T, Gambacciani M. Hyaluronic acid and erbium laser for the treatment of genitourinary syndrome of menopause. Climacteric. 2025;28(1):87–92. DOI: 10.1080/13697137.2024.2418492
  63. Yoshikata R, Yamaguchi M, Mase Y, Tatsuyuki A, Myint KZY, Ohta H. Evaluation of the efficacy of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women: A pilot randomized controlled trial. PLoS One. 2022;17(12):e0270242. DOI: 10.1371/journal.pone.0270242
  64. Lester J, Pahouja G, Andersen B, Lustberg M. Atrophic Vaginitis in Breast Cancer Survivors: A Difficult Survivorship Issue. J Pers Med. 2015;5(2):50–66. DOI: 10.3390/jpm5020050
  65. Della Corte L, Palumbo M, Pollio A, Nobile I, Cuomo L, Bifulco G. Non-hormonal vaginal gel improves vaginal and sexual health in menopausal women: results from a 6-month prospective study. Eur J Obstet Gynecol Reprod Biol. 2026;318:114902. DOI: 10.1016/j.ejogrb.2025.114902
  66. Cagnacci A, Barattini DF, Casolati E, Pecoroni A, Mangrella M, Patrascu LC. Polycarbophil vaginal moisturizing gel versus hyaluronic acid gel in women affected by vaginal dryness in late menopausal transition: A prospective randomized trial. Eur J Obstet Gynecol Reprod Biol. 2022;270:239 245. DOI: 10.1016/j. ejogrb.2022.01.021
  67. Yodplob T, Sirisopana K, Jongwannasiri M, Sirisreetreerux P, Viseshsindh W, Kochakarn W. Local treatment with a polycarbophil-based cream in postmenopausal women with genitourinary syndrome of menopause. Int Urogynecol J. 2021;32(2):317–22. DOI: 10.1007/s00192-020-04282-9
  68. Vale F, Rezende C, Raciclan A, Bretas T, Geber S. Efficacy and safety of a non-hormonal intravaginal moisturizer for the treatment of vaginal dryness in postmenopausal women with sexual dysfunction. Eur J Obstet Gynecol Reprod Biol. 2019;234:92–95. DOI: 10.1016/j.ejogrb.2018.12.040
  69. Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2016 Aug 31;2016(8):CD001500. DOI: 10.1002/14651858.CD001500.pub3

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2026-05-14

How to Cite

Konkov, D., Tykholaz, V., Rud, V., & Bulavenko, O. (2026). Non-hormonal prevention and treatment of genitourinary syndrome of menopause: Literature review. REPRODUCTIVE ENDOCRINOLOGY, (83), 18–28. https://doi.org/10.18370/2309-4117.2026.83.18-28

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No. 83 (2026)

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Menopause management

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