Clinical Evidence Regarding Spermidine-Hyaluronate Gel As a Novel Therapeutic Strategy in Vestibulodynia Management

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2024 Nov 27

PMID 39598571

Authors

Filippo Murina

Alessandra Graziottin

Nicla Toni

Maria Teresa Schettino

Luca Bello

Alessandra Marchi

Barbara Del Bravo

Dania Gambini

Lara Tiranini

Rossella Elena Nappi

Affiliations

Soon will be listed here.

Abstract

Vestibulodynia (VBD) represents a summation and overlapping of trigger factors (infections, hormonal disturbances, allergies, genetic aspects, psychological vulnerability, and others) with broad individual variability. As there are no standard treatment options for VBD, the disease is still in need of appropriate therapeutic tools. : A prospective observational trial was performed to confirm the efficacy of a topical gel containing a spermidine-hyaluronate complex (UBIGEL donna™) as either a stand-alone or companion treatment through a multicenter study on a large sample population. : For women with VBD (n = 154), the treatment consisted of approximately two months (4 + 4 weeks) of applications according to the posology of UBIGEL. Evaluation of symptoms was performed on relevant clinical endpoints: dyspareunia and vulvovaginal pain/burning by a visual scale (VAS); vestibular trophism by a vestibular trophic health (VeTH) score; vulvoscopy through a cotton swab test; and the level of hypertonic pelvic floor by a physical graded assessment of levator ani hypertonus. : A total of 154 patients treated with UBIGEL donna™ showed significant improvements across all five evaluated parameters, including pain, dyspareunia, swab test results, muscle hypertonicity, and vestibular trophism. Pain and dyspareunia scores decreased by 46.5% and 33.5%, respectively, while significant improvements were also observed in the other parameters ( < 0.0001). These improvements were consistent across various stratifications, including age and disease duration. : The findings of the present study suggest that UBIGEL donna™ is effective in alleviating pain and dyspareunia, as well as reducing vestibular hypersensitivity in women with VBD. Although UBIGEL donna™ alone cannot serve as a comprehensive substitute for all recommended therapies, we suggest that multimodal therapy strategies may be crucial for attaining substantial improvement in any aspect of the condition.

References

Schlaeger J, Glayzer J, Villegas-Downs M, Li H, Glayzer E, He Y . Evaluation and Treatment of Vulvodynia: State of the Science. J Midwifery Womens Health. 2022; 68(1):9-34. PMC: 10107324. DOI: 10.1111/jmwh.13456. View

Rains A, Bajzak K, Miller M, Swab M, Logan G, Jackman V . Multimodal and Interdisciplinary Interventions for the Treatment of Localized Provoked Vulvodynia: A Scoping Review of the Literature from 2010 to 2023. Int J Womens Health. 2024; 16:55-94. PMC: 10798054. DOI: 10.2147/IJWH.S436222. View

Falsetta M, Foster D, Bonham A, Phipps R . A review of the available clinical therapies for vulvodynia management and new data implicating proinflammatory mediators in pain elicitation. BJOG. 2016; 124(2):210-218. PMC: 5164873. DOI: 10.1111/1471-0528.14157. View

Choi Y, Park H . Anti-inflammatory effects of spermidine in lipopolysaccharide-stimulated BV2 microglial cells. J Biomed Sci. 2012; 19:31. PMC: 3320531. DOI: 10.1186/1423-0127-19-31. View

Bohm-Starke N, Hilliges M, Falconer C, Rylander E . Neurochemical characterization of the vestibular nerves in women with vulvar vestibulitis syndrome. Gynecol Obstet Invest. 1999; 48(4):270-5. DOI: 10.1159/000010198. View

Schibalski R, Shulha A, Tsao B, Palygin O, Ilatovskaya D . The role of polyamine metabolism in cellular function and physiology. Am J Physiol Cell Physiol. 2024; 327(2):C341-C356. PMC: 11427016. DOI: 10.1152/ajpcell.00074.2024. View

Jiang D, Guo Y, Niu C, Long S, Jiang Y, Wang Z . Exploration of the Antioxidant Effect of Spermidine on the Ovary and Screening and Identification of Differentially Expressed Proteins. Int J Mol Sci. 2023; 24(6). PMC: 10051986. DOI: 10.3390/ijms24065793. View

Goldstein A, Belkin Z, Krapf J, Song W, Khera M, Jutrzonka S . Polymorphisms of the androgen receptor gene and hormonal contraceptive induced provoked vestibulodynia. J Sex Med. 2014; 11(11):2764-71. DOI: 10.1111/jsm.12668. View

Igarashi K, Kashiwagi K . Modulation of cellular function by polyamines. Int J Biochem Cell Biol. 2009; 42(1):39-51. DOI: 10.1016/j.biocel.2009.07.009. View

10.

Kang H, Lee K, Kim S, Choi H, Park S . Autophagy impairment induces premature senescence in primary human fibroblasts. PLoS One. 2011; 6(8):e23367. PMC: 3152578. DOI: 10.1371/journal.pone.0023367. View

11.

Zou D, Zhao Z, Li L, Min Y, Zhang D, Ji A . A comprehensive review of spermidine: Safety, health effects, absorption and metabolism, food materials evaluation, physical and chemical processing, and bioprocessing. Compr Rev Food Sci Food Saf. 2022; 21(3):2820-2842. DOI: 10.1111/1541-4337.12963. View

12.

Rider J, Hacker A, Mackintosh C, Pegg A, Woster P, Casero Jr R . Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide. Amino Acids. 2007; 33(2):231-40. DOI: 10.1007/s00726-007-0513-4. View

13.

Dharan R, Shemesh A, Millgram A, Zalk R, Frank G, Levi-Kalisman Y . Hierarchical Assembly Pathways of Spermine-Induced Tubulin Conical-Spiral Architectures. ACS Nano. 2021; 15(5):8836-8847. DOI: 10.1021/acsnano.1c01374. View

14.

Eva L, MacLean A, Reid W, Rolfe K, Perrett C . Estrogen receptor expression in vulvar vestibulitis syndrome. Am J Obstet Gynecol. 2003; 189(2):458-61. DOI: 10.1067/s0002-9378(03)00365-x. View

15.

Ghisalberti C, Morisetti A, Bestetti A, Cairo G . Potent trophic activity of spermidine supramolecular complexes in in vitro models. World J Biol Chem. 2013; 4(3):71-8. PMC: 3746280. DOI: 10.4331/wjbc.v4.i3.71. View

16.

Paul S, Kang S . Natural polyamine inhibits mouse skin inflammation and macrophage activation. Inflamm Res. 2013; 62(7):681-8. DOI: 10.1007/s00011-013-0620-5. View

17.

Pukall C, Strigo I, Binik Y, Amsel R, Khalife S, Bushnell M . Neural correlates of painful genital touch in women with vulvar vestibulitis syndrome. Pain. 2005; 115(1-2):118-27. DOI: 10.1016/j.pain.2005.02.020. View

18.

Watanabe S, Kusama-Eguchi K, Kobayashi H, Igarashi K . Estimation of polyamine binding to macromolecules and ATP in bovine lymphocytes and rat liver. J Biol Chem. 1991; 266(31):20803-9. View

19.

Bergeron S, Reed B, Wesselmann U, Bohm-Starke N . Vulvodynia. Nat Rev Dis Primers. 2020; 6(1):36. DOI: 10.1038/s41572-020-0164-2. View

20.

Murina F, Torraca M, Graziottin A, Nappi R, Villa P, Cetin I . Validation of a clinical tool for vestibular trophism in postmenopausal women. Climacteric. 2023; 26(2):149-153. DOI: 10.1080/13697137.2023.2171287. View