透明质酸在阴道内的应用研究

冯旸子, 范琳媛, 白文佩, 刘朝晖

中国实用妇科与产科杂志 ›› 2025, Vol. 41 ›› Issue (11) : 1146-1148.

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中国实用妇科与产科杂志 ›› 2025, Vol. 41 ›› Issue (11) : 1146-1148. DOI: 10.19538/j.fk2025110117
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透明质酸在阴道内的应用研究

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冯旸子, 范琳媛, 白文佩, . 透明质酸在阴道内的应用研究[J]. 中国实用妇科与产科杂志. 2025, 41(11): 1146-1148 https://doi.org/10.19538/j.fk2025110117
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参考文献

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Genitourinary syndrome of menopause (GSM) refers to a collection of symptoms resulting from diminished hormonal, primarily estrogenic stimulation to the vulvovaginal or lower urinary tract and may affect up to 50% of postmenopausal women. Symptoms, which are typically progressive and unlikely to resolve spontaneously, may include, but are not limited to, vulvovaginal dryness, burning or irritation, dyspareunia, or urinary symptoms of urgency, dysuria or recurrent urinary tract infection. These symptoms are typically progressive and unlikely to resolve spontaneously. Diagnosis is clinical. Telemedicine may play a role in diagnosis, initiation of treatment, and follow-up of women with GSM. Effective treatments include moisturizers and lubricants, local hormonal therapy with estrogen or dehydroepiandrosterone, and oral selective estrogen receptor agonists. Laser or radiofrequency procedures, although currently utilized, are being studied to comprehensively understand their overall effectiveness and safety. Additionally, the influence and effect of the vaginal microbiome, as well as potential of treatment via its manipulation, is being studied. We performed a literature search of PubMed, Google Scholar, and Ovid with search terms of vulvovaginal atrophy and GSM and reviewed major US Society Guidelines to create this narrative review of this topic. The literature suggests that healthcare providers can make a significant impact of the health and quality of life of women by being proactive about discussing and providing interventions for GSM. A systematic approach with consideration of current guidelines and attention to developing protocols for interventions should be employed.Copyright © 2021 by The North American Menopause Society.
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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[J]. Cureus, 2023, 15(8):e44191. DOI:10.7759/cureus.44191.eCollection2023Aug.
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Jafarzade A, Mungan T, Aghayeva S, et al. A comparison of hyaluronic acid and estradiol treatment in vulvovaginal atrophy[J]. Eur Rev Med Pharmacol Sci, 2024, 28(2):571-576. DOI:10.26355/eurrev_202401_35054.
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Angelucci M, Frascani F, Franceschelli A, et al. Efficacy of intradermal hyaluronic acid plus polynucleotides in vulvovaginal atrophy:a pilot study[J]. Climacteric, 2022, 25(5):490-496. DOI:10.1080/13697137.2022.2052840.
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Barbero M, Villasco A, Villa M, et al. Conjugate treatment with high concentration normobaric oxygen and hyaluronic acid for vaginal atrophy:a prospective study[J]. Eur Rev Med Pharmacol Sci, 2023, 27(5):2011-2017. DOI:10.26355/eurrev_202303_31567.
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国家卫生健康委员会医政医管局. 乳腺癌诊疗指南(2022年版)[J]. 中华肿瘤杂志, 2023, 45(10):803-833. DOI:10.3760/cma.j.cn112152-20230706-00281-1
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Ekinci E, Nathoo S, Korattyil T, et al. Interventions to improve endocrine therapy adherence in breast cancer survivors:what is the evidence?[J]. J Cancer Surviv, 2018, 12(3):348-356.DOI:10.1007/s11764-017-0674-4.
Endocrine therapy reduces the risk of breast cancer recurrences and mortality in hormone receptor-positive (HR+) breast cancer survivors. However, non-adherence to treatment remains a significant problem. The aim of this study was to review current literature and ongoing trials to identify interventions employed to improve adherence to adjuvant endocrine therapy (AET) in breast cancer survivors.We searched PubMed and the National Library of Medicine registry of clinical trials using the terms "breast cancer" and "adherence" or "compliance" and "intervention" and "medication" or "endocrine therapy" or "hormone therapy" to identify published studies as well as ongoing clinical trials.Three hundred and sixty-three studies were identified; five studies met the inclusion criteria. Most studies enrolled postmenopausal women diagnosed with early stage HR+ breast cancer. Providing educational materials was the most common intervention implemented to improve adherence to one or more aromatase inhibitors. None of the studies found a significant improvement in adherence with the intervention evaluated. Twelve clinical trials investigating various interventions, mostly based on technology, to improve AET adherence were also identified.Improving adherence to AET in HR+ breast cancer survivors is an urgent medical need. While newer clinical trials are overcoming some of the limitations seen with published studies, tailored interventions led by clinicians need further investigation.Our study highlights the unmet clinical need to develop and test feasible interventions to improve AET adherence in HR+ breast cancer survivors to extend their long-term survival.
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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]. J Cancer Surviv, 2017, 11(4):477-485. DOI:10.1007/s11764-017-0606-3.
A randomized pilot trial evaluated the hypothesis that early intervention lessens sexual dysfunction in the first year on aromatase inhibitors. A secondary aim was comparing the efficacy of two vaginal moisturizers.Fifty-seven postmenopausal women with early stage breast cancer starting aromatase inhibitors were randomized to three treatment groups. All received a handout on managing sexual and other side effects. The Usual Care group received no additional therapy. The Active Treatment groups received a 6-month supply of a vaginal moisturizer (hyaluronic acid-based in Active Group-H and prebiotic in Active Group-P) and a vaginal lubricant and dilator, plus access to an educational website and phone coaching. Questionnaires completed at baseline, 6, and 12 months included the Female Sexual Function Index (FSFI), Menopausal Sexual Interest Questionnaire (MSIQ), Female Sexual Distress Scale-Revised (FSDS-R), and a menopausal symptom scale.Forty-nine women (86%) provided follow-up data. Mean age was 59 and 77% were non-Hispanic Caucasian. Sexual function was impaired at baseline, but remained stable over 12 months for all groups. The combined active treatment group had less dyspareunia (P = 0.07) and sexual distress (P = 0.02) at 6 months than the Usual Care group. At 6 months, the Active-H group improved significantly more than the Active-P group on FSFI total score (P = 0.04).Sexual counseling helped women maintain stable sexual function on aromatase inhibitors. Active intervention resulted in better outcomes at 6 months.This promising pilot trial suggests a need for more research on preventive counseling to maintain sexual function during aromatase inhibitor treatment.
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Gold D, Nicolay L, Avian A, et al. Vaginal laser therapy versus hyaluronic acid suppositories for women with symptoms of urogenital atrophy after treatment for breast cancer:A randomized controlled trial[J]. Maturitas, 2023, 167:1-7. DOI:10.1016/j.maturitas.2022.08.013.
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Carter J, Goldfarb S, Baser RE, et al. A single-arm clinical trial investigating the effectiveness of a non-hormonal,hyaluronic acid-based vaginal moisturizer in endometrial cancer survivors[J]. Gynecol Oncol, 2020, 158(2):366-374. DOI:10.1016/j.ygyno.2020.05.025.
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Dinicola S, Pasta V, Costantino D, et al. Hyaluronic acid and vitamins are effective in reducing vaginal atrophy in women receiving radiotherapy[J]. Minerva Ginecol. 2015, 67(6):523-531.
During the last decades, therapies targeting cervical cancer have been considerably improved. Surgery and radiotherapy (RT) represent the main common therapeutic approach in cervical cancer. In order to minimize the side effects of radiotherapy approach, several protocols have been developed such as brachytherapy (BRT). Among the side effects associated with RT, the vaginal atrophy is the most important and common one. Vaginal atrophy, in turn, leads to additional alterations like inflammation, associated to relevant symptoms such as itching, burning and dyspareunia. All these alterations heavily affect the quality of women's life. The aim of our study was to evaluate the toxicity induced by RT on vaginal mucosa, and the adjuvant action of a product containing LMWHA, vitamin A, and Vitamin E (Santes®, Lo.Li. Pharma, Rome, Italy). The introduction of adjuvant therapies may have likely had a relevant place in providing that result.A prospective randomized study was designed. From October 2006 to October 2008, 45 women with a mean age 38 ± 6 years were enrolled. After surgery, all patients were treated with 4 weeks of RT and 4 weeks of BRT, concomitantly with chemiotherapy. They were randomly assigned in two groups: 23 women were treated with two suppositories (Santes®) per day for 4 months. For the first two months the preventive treatment was simultaneous to RT and BRT. Instead the control groups for composed by 22 patients and they did not undergo any treatment during RT. To evaluate the efficacy of Santes® treatment three biopsies were performed.At the second biopsy, after the BRT therapy, the treated group showed a statistically significant improvement (P<0.05 vs. control) on inflammation, cell atypia, fibrosis, mucositis and bleeding. At the third biopsy, two months after BRT, further statistically improvement were observed for all RT/BRT associated side effects. The treatment showed an efficacy also in terms of pain severity.Our data suggest that low molecular weight HA shows good performances in treating RT-damaged tissue and plays a key role in all steps of the healing process. Indeed the results shows that women exposed to RT treatments and simultaneously treated with Santes®, had an optimal resolution of vaginal atrophy and related symptoms.
[19]
Murakami N, Nakamura S, Kashihara T, et al. Hyaluronic acid gel injection in rectovaginal septum reduced incidence of rectal bleeding in brachytherapy for gynecological malignancies[J]. Brachytherapy, 2020, 19(2):154-161. DOI:10.1016/j.brachy.2019.11.004.
The purpose of this study was to report our initial clinical results of hyaluronic acid gel injection (HGI) in the rectovaginal septum (RVS) to reduce the incidence of rectal bleeding in vaginal brachytherapy for gynecologic malignancies.Since 2008, CT based image-guided adaptive brachytherapy (IGABT) was initiated, and since 2015, HGI in the RVS was introduced in our institution. Vaginal cylinder with or without tandem or additional interstitial needles were applied for patients with gynecologic malignancies. Rectum dosimetric parameters and incidence of late rectum bleeding were compared between patients with and without HGI in the RVS.Between May 2008 and October 2017, 83 patients with gynecologic malignancies were treated with IGABT involving vaginal cylinder. Eleven patients who were treated for palliative intention were excluded, and 72 patients were subjected to the analysis. Of the total 72 patients 46 were with uterine cervical cancer, 19 uterine corpus cancer, five vaginal cancer, one vulvar cancer, and one ovarian cancer. Fifteen and 57 patients were irradiated with and without HGI in the RVS, respectively. With a median follow-up period of 57.7 (4.7-123.1) months, 30 (41.7%) patients suffered from radiation-related rectal bleeding. Patients with HGI in the RVS had a statistically significant lower incidence of rectal bleeding compared with those without it (13.3% vs. 49.1%, p = 0.01).HGI in the RVS reduced the incidence of late rectal bleeding for patients with gynecologic malignancies treated by vaginal cylinder and was not associated with HGI-procedure-related adverse events.Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
[20]
牛小溪, 李婷, 刘朝晖. 复方沙棘籽油栓对体外白假丝酵母菌感染受损阴道上皮细胞保护作用的研究[J]. 中国实用妇科与产科杂志, 2017, 33(2):195-199.DOI:10.19538/j.fk2017020116.
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Wei G, Liu Q, Wang X, et al. A probiotic nanozyme hydrogel regulates vaginal microenvironment for Candida vaginitis therapy[J]. Sci Adv, 2023, 9(20):eadg0949. DOI:10.1126/sciadv.adg0949.
\n Molecular therapeutics are limited for\n Candida\n vaginitis because they damage normal cells and tissues of vagina, aggravating the imbalance of vaginal microbiota and increasing the recurrence. To tackle this limitation, through the combination of peroxidase-like rGO@FeS\n 2\n nanozymes [reduced graphene oxide (rGO)] with\n Lactobacillus\n -produced lactic acid and H\n 2\n O\n 2\n, a responsive hyaluronic acid (HA) hydrogel rGO@FeS\n 2\n /\n Lactobacillus\n @HA (FeLab) is developed. FeLab has simultaneous anti–\n Candida albicans\n and vaginal microbiota–modulating activities. In particular, the hydroxyl radical produced from rGO@FeS\n 2\n nanozymes and\n Lactobacillus\n kills\n C. albicans\n isolated from clinical specimens without affecting\n Lactobacillus\n. In mice with\n Candida\n vaginitis, FeLab has obvious anti–\n C. albicans\n activity but hardly damages vaginal mucosa cells, which is beneficial to vaginal mucosa repair. Moreover, a higher proportion of\n Firmicutes\n (especially\n Lactobacillus\n ) and a decrease in\n Proteobacteria\n reshape a healthy vaginal microbiota to reduce the recurrence. These results provide a combined therapeutic of nanozymes and probiotics with translational promise for\n Candida\n vaginitis therapy.\n
[22]
Berreni N, Salerno J, Chevalier T, et al. Evaluation of the effect of multipoint intra-mucosal vaginal injection of a specific cross-linked hyaluronic acid for vulvovaginal atrophy:a prospective bi-centric pilot study[J]. BMC Womens Health, 2021, 21(1):322. DOI: 10.1186/s12905-021-01435-w.
Vulvo-vaginal atrophy (VVA) is one of the common consequences of estrogen deficiency especially after the menopause. Several studies have assessed the effects of Hyaluronic acid (HA) on physical and sexual symptoms associated with VVA with promising results. However, most of these studies have focused on subjective assessment of symptom response to topically administered preparations. Nonetheless, HA is an endogenous molecule and it is logical that its effects are best realized if injected in the superficial epithelial layers. Desirial® is the first crosslinked HA that is administered by injection in the vaginal mucosa. The aim of this study was to explore the effect of multipoint vaginal intra-mucosal injections of specific cross-linked hyaluronic acid (DESIRIAL®, Laboratoires VIVACY) on several clinical and patient reported core outcomes.
[23]
González-Isaza P, Sánchez-Prieto M, Sánchez-Borrego R. Chronic vulvar fissure:approach with cross-linked hyaluronic acid. Int Urogynecol J, 2023, 34(7):1495-1499. DOI:10.1007/s00192-022-05401-4.

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国家自然科学基金面上项目(81771530)

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