Efficacy and safety of prolonged-release hyaluronic acid derivative vaginal application in the postpartum period: a prospective randomised clinical trial

Claudio Gustavino, Paolo Sala, Nadia Cusini, Brunella Gravina, Cecilia Ronzini, Diletta Marcolin, Valerio Gaetano Vellone, Michele Paudice, Rossella Nappi, Sergio Costantini, Simone Ferrero, Fabio Barra, Claudio Gustavino, Paolo Sala, Nadia Cusini, Brunella Gravina, Cecilia Ronzini, Diletta Marcolin, Valerio Gaetano Vellone, Michele Paudice, Rossella Nappi, Sergio Costantini, Simone Ferrero, Fabio Barra

Abstract

Introduction: In puerperium, the hypoestrogenic state induced by delivery and subsequently sustained by lactation may lead to vaginal dryness, burning, and itching sensation, contributing to the onset of sexual dysfunction.

Material and methods: This was a prospective, randomized, controlled, open-label study (NCT04560283) for evaluating the effects of application of a prolonged-release hyaluronic acid derivative vaginal gel in restoring sexual function during the postpartum period. Eighty-five patients were randomized to apply prolonged-release Hydeal-D 0.2% vaginal gel (Fidia Farmaceutici, Abano Terme, Italy; n = 43) every three days for 12 consecutive weeks or expectant management (n = 42).

Results: Women undergoing treatment had a more elevate increase in Female Sexual Function Index (FSFI) total score (+15.1 ± 11.9 vs +6.5 ± 8.9, p < 0.001) and a higher decrease in vaginal pH (-1.2 ± 0.7 vs -0.2 ± 1.1; p < 0.001). Moreover, the proportion of vaginal smears with maturation index (VMI) >65 was significantly higher in patients treated (80.6% vs 35.3%; p = 0.004). Edinburgh Postnatal Depression Scale (EPDS) decreased significantly in both groups with no inter-group difference (p = 0.459). Only two cases (4.8%) of moderate vaginal burning sensation were reported in patients undergoing local vaginal therapy.

Conclusions: The results of our study demonstrated that hyaluronic acid derivative vaginal gel (Hydeal-D) was able to improve sexual function of puerperal women in the short-term treatment.KEY MESSAGEIn the puerperium, the hypoestrogenic state induced by delivery and subsequently sustained by lactation may lead to vaginal dryness, burning, and itching sensation, contributing to the onset of sexual dysfunction.Hydeal-D is a prolonged-release hyaluronic acid derivative characterised by elevated resistance to enzymatic breakdown. During puerperium, its local application may improve the vaginal microenvironment by ensuring a better migration and proliferation of cells involved in local tissue repair.Among puerperal women, Hydeal-D vaginal gel causes a significant improvement of sexual function, including desire, arousal, and lubrification, compared to expectant management. Furthermore, it leads to a decrease in vaginal pH and an increase of the trophic status of vaginal epithelium.

Keywords: Prolonged-release hyaluronic acid derivative vaginal gel; hydeal-D; postnatal depression; randomised trial; sexual function; vaginal dryness; vaginal lubrification; vaginal maturation index; vaginal pH.

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Cytological appearance of vaginal smear. Low vaginal maturation index (A); 50–64 moderate vaginal maturation index (B); high vaginal maturation index (C).
Figure 2.
Figure 2.
Flow-chart of the study.
Figure 3.
Figure 3.
Vaginal maturation index at V1 and V2.

References

    1. Leeman LM, Rogers RG.. Sex after childbirth: postpartum sexual function. Obstet Gynecol. 2012;119(3):647–655.
    1. Banaei M, Azizi M, Moridi A, et al. . Sexual dysfunction and related factors in pregnancy and postpartum: a systematic review and Meta-analysis protocol. Syst Rev. 2019;8(1):161.
    1. Agarwal SK, Kim J, Korst LM, et al. . Application of the estrogen threshold hypothesis to the physiologic hypoestrogenemia of lactation. Breastfeed Med. 2015;10(2):77–83.
    1. Gutzeit O, Levy G, Lowenstein L.. Postpartum female sexual function: risk factors for postpartum sexual dysfunction. Sex Med. 2020;8(1):8–13.
    1. Garantziotis S, Savani RC.. Hyaluronan biology: a complex balancing act of structure, function, location and context. Matrix Biol. 2019;78–79:1–10.
    1. Neuman MG, Nanau RM, Oruna-Sanchez L, et al. . Hyaluronic acid and wound healing. J Pharm Pharm Sci. 2015;18(1):53–60.
    1. Litwiniuk M, Krejner A, Speyrer MS, et al. . Hyaluronic acid in inflammation and tissue regeneration. Wounds. 2016;28(3):78–88.
    1. Ruscheinsky M, De la Motte C, Mahendroo M.. Hyaluronan and its binding proteins during cervical ripening and parturition: dynamic changes in size, distribution and temporal sequence. Matrix Biol. 2008;27(5):487–497.
    1. Dos Santos CCM, Uggioni MLR, Colonetti T, et al. . Hyaluronic acid in postmenopause vaginal atrophy: a systematic review. J Sex Med. 2021;18(1):156–166.
    1. Campoccia D, Doherty P, Radice M, et al. . Semisynthetic resorbable materials from hyaluronan esterification. Biomaterials. 1998;19(23):2101–2127.
    1. Chen J, Geng L, Song X, et al. . Evaluation of the efficacy and safety of hyaluronic acid vaginal gel to ease vaginal dryness: a multicenter, randomized, controlled, open-label, parallel-group, clinical trial. J Sex Med. 2013;10(6):1575–1584.
    1. Andreucci CB, WHO Maternal Morbidity Working Group, Bussadori JC, Pacagnella RC, Chou D, Filippi V, Say L, et al. . Sexual life and dysfunction after maternal morbidity: a systematic review. BMC Pregnancy Childbirth. 2015;15:307.
    1. Hess R, Austin RM, Dillon S, et al. . Vaginal maturation index self-sample collection in mid-life women: acceptability and correlation with physician-collected samples. Menopause. 2008;15(4):726–729.
    1. Cruz VL, Steiner ML, Pompei LM, et al. . Randomized, double-blind, placebo-controlled clinical trial for evaluating the efficacy of fractional CO2 laser compared with topical estriol in the treatment of vaginal atrophy in postmenopausal women. Menopause. 2018;25(1):21–28.
    1. Paraiso MFR, Ferrando CA, Sokol ER, et al. . A randomized clinical trial comparing vaginal laser therapy to vaginal estrogen therapy in women with genitourinary syndrome of menopause: the VeLVET trial. Menopause. 2020;27(1):50–56.
    1. Cox JL, Holden JM, Sagovsky R.. Detection of postnatal depression. Development of the 10-item edinburgh postnatal depression scale. Br J Psychiatry. 1987;150:782–786.
    1. Gibson J, McKenzie-McHarg K, Shakespeare J, et al. . A systematic review of studies validating the edinburgh postnatal depression scale in antepartum and postpartum women. Acta Psychiatr Scand. 2009;119(5):350–364.
    1. Advani P, Brewster AM, Baum GP, et al. . A pilot randomized trial to prevent sexual dysfunction in postmenopausal breast cancer survivors starting adjuvant aromatase inhibitor therapy. J Cancer Surviv. 2017;11(4):477–485.
    1. Tachedjian G, Aldunate M, Bradshaw CS, et al. . The role of lactic acid production by probiotic lactobacillus species in vaginal health. Res Microbiol. 2017;168(9–10):782–792.
    1. Anderson DJ, Marathe J, Pudney J.. The structure of the human vaginal stratum corneum and its role in immune defense. Am J Reprod Immunol. 2014;71(6):618–623.
    1. Roy EJ, Mackay R.. The concentration of oestrogens in blood during pregnancy. J Obstet Gynaecol Br Emp. 1962;69:13–17.
    1. MacIntyre DA, Chandiramani M, Lee YS, et al. . The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci Rep. 2015;5:8988.
    1. Wisniewski PM, Wilkinson EJ.. Postpartum vaginal atrophy. Am J Obstet Gynecol. 1991;165(4 Pt 2):1249–1254.
    1. Barbara G, Pifarotti P, Facchin F, et al. . Impact of mode of delivery on female postpartum sexual functioning: spontaneous vaginal delivery and operative vaginal delivery vs. cesarean section. J Sex Med. 2016;13(3):393–401.
    1. F Carbonel AA, Azevedo Lima PD, Lim JJ, et al. . Effects of soy isoflavones on the concentration of hyaluronic acid in the vagina of type 1 diabetic rats. Climacteric. 2017;20(6):564–570.
    1. Liu SB, Liu SL, Gan XL, et al. . The effects of hyaluronic acid vaginal gel on the vaginal epithelium of ovariectomized rats. Gynecol Endocrinol. 2015;31(3):208–213.
    1. Lavitola G, Della Corte L, De Rosa N, et al. . Effects on vaginal microbiota restoration and cervical epithelialization in positive HPV patients undergoing vaginal treatment with carboxy-methyl-beta-glucan. Biomed Res Int. 2020;2020:5476389.
    1. Torcia MG.Interplay among vaginal microbiome, immune response and sexually transmitted viral infections. Int J Mol Sci. 2019;20(2): 266
    1. Gariboldi S, Palazzo M, Zanobbio L, et al. . Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of beta-defensin 2 via TLR2 and TLR4. J Immunol. 2008;181(3):2103–2110.
    1. Dusio GF, Cardani D, Zanobbio L, et al. . Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal epithelium. Immunol Cell Biol. 2011;89(5):630–639.

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