A Laser and Topical Treatment Combination in the Vulvo-vaginal Atrophy Management in Breast Cancer Patients.

NCT05585476 | Not Yet Recruiting

• 1 other identifier: FJD-LCO2-19-01
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

The genito-urinary syndrome of menopause severely affects patients with a history of gynecological cancer, especially those diagnosed with breast cancer. At the present time, we do not have solid scientific evidence on treatments that can be effective and safe to address this pathology. Based on the above, we have developed our working hypothesis where it is postulated that the microfractionated laser treatment of C02, in conjunction with topical regenerative treatment, constitute an effective alternative in the management of vulvo-vaginal atrophy in oncological patients who have contraindicated hormonal treatments.

Conditions

Female Urogenital Diseases; Breast Cancer Female

Keywords

Vulvovaginal atrophy; Breast cancer; Hormone therapy; Regenerative topical treatment; C02 microfractionated laser

Outcome Measures

Primary Outcomes (16)

• Presence of symptoms at the vulvovaginal level and their intensity

  This group will include the following items: * Pain with sexual intercourse (dyspareunia). * Feeling of vaginal stiffness. * Dryness. * Vulvar itching. * Vulvar and/or vaginal burning. * Urinary frequency (more than 8 times a day). * Burning when urinating (dysuria). The way to measure the intensity of these symptoms will be through Visual Analog Scale Of Symptom Intensity, with absolute values ranging from 0 to 10. We will consider improvement a reduction of 2 or more points in at least 50% of the items. Meeting only this item is already considered an efficacy criterion.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Impact in the quality of life of vulvo-vaginal symptoms.

  The tool used will be the Sexual Function-Vaginal Changes Questionnaire. Scores equal to or less than 24 points will result in an impact on quality of life. A rise of 3 or more points is considered a significant improvement. The severity levels of quality of life impairment will be as follows: * Mild (scores between 24 and 17) * Moderate (scores between 16 and 8) * Severe (scores between 7 and 1)

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Changes in vulvar physical examination

  We will use the following measurement system: Vulvar Health Index Score. It is based on the macroscopic inspection of the vulva performed through a colposcope. The scores range from 0 to 24, being higher to greater atrophy. It is considered a diagnosis of atrophy scores greater than 8 or having obtained 3 points in any of the items. The degrees of gravity are set as follows: 1. Between 9 and 14 points, mild 2. Between 15 and 20 points, moderate 3. Between 21 and 24 points, severe. A reduction of 3 or more points in the overall score or at least one point will be considered a favorable response if there has been an item with a score of 3.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Changes in vaginal physical examination

  We will use the following measurement systems: Vaginal Health Index Score. It is based on the macroscopic inspection of the vagina performed through a colposcope. Scores range from 5 to 25 points (scores equal to or less than 15 are considered diagnostic of atrophy). It is carried out by assessing different items related to exploratory findings. We can categorize the scores into different degrees of severity of vulvo-vaginal atrophy objectified to the examination: 1. \>from 15 points, absence of atrophy 2. Between 15 and 13 points, mild 3. Between 12 and 9 points, moderate 4. Between 8 and 5 points, severe An increase of 2 or more points in the overall score will be considered a favourable response.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Thickness of the vaginal epithelium

  The collection of the sample will consist of taking biopsy of vaginal mucosa using a 4 mm punch as an instrument. Once obtained, the sample will be stained with hematoxylin-eosin and subjected to microscopic assessment. The unit of measurement shall be in nanometers.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Quantification of cellular glycogen

  The collection of the samples will consist of taking biopsies of vaginal mucosa using a 4 mm punch as an instrument. The sample will undergo the Schiff technique (PAS) and the number of stained cells will be determined.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Number of capillaries in vaginal mucosa

  The collection of samples will consist of taking biopsies of vaginal mucosa using a 4 mm punch as an instrument. The immunohistochemical technique will be applied with antibodies against CD31 and a quantitative assessment of the number of capillaries / field of 40 increases will be carried out.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Amount of Lactobacillus in vaginal microbiota

  It will be measured through microbiological study. Samples shall be obtained by vaginal exudate. The measurements will be made by WERFEN system and PCR technique.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Amount of Candida spp in vaginal microbiota

  It will be measured through microbiological study. Samples shall be obtained by vaginal exudate. The measurements will be made by WERFEN system and PCR technique.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Amount of Gardnerella vaginalis in vaginal microbiota

  It will be measured through microbiological study. Samples shall be obtained by vaginal exudate. The measurements will be made by WERFEN system and PCR technique.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Free glycogen detection in vaginal discharge

  It will be measured through microbiological study. Samples shall be obtained by vaginal exudate. Free glycogen detection will be performed using a commercial kit.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Vaginal pH

  It will be measured through microbiological study. Samples shall be obtained by vaginal exudate.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Skin elasticity

  It will be performed with the Dual cutometer MPA 580 ® and will determine different characteristics of the vulvar skin. The value will be given in the unit of measurement N / m².

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Amount of transdermal water in the skin

  It will be performed with the Dual cutometer MPA 580 ® and will determine different characteristics of the vulvar skin. The value will be given in the unit of measurement g/h/m².

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Skin pigmentation

  It will be performed with the Dual cutometer MPA 580 ® and will determine different characteristics of the vulvar skin. The degree of pigmentation of the skin will be determined based on the concentration of melanin.

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Degree of vascularization of the skin

  It will be performed with the Dual cutometer MPA 580 ® and will determine different characteristics of the vulvar skin. To determine the degree of vascularization of the skin, specific wavelengths will be used, corresponding to the maximum level of spectral absorption of hemoglobin and avoiding other color influences (for example, bilirubin). The result corresponding will be immediately displayed in the form of index figures, on a scale of 0 - 999.

  From prior consultation at the beginning of treatment to 24 months after it ends.

Secondary Outcomes (3)

• Presence of bladder hyperactivity clinic

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Presence of urge urinary incontinence

  From prior consultation at the beginning of treatment to 24 months after it ends.

• Impact of urinary incontinence on quality of life

  From prior consultation at the beginning of treatment to 24 months after it ends.

Study Arms (3)

Laser + Regenerative topical treatment

EXPERIMENTAL

The treatments used in this arm are the following: 1. º Microfractionated laser treatment of C02, through the AcupulseDuo generator of the company Lumenis®. The treatment regimen would consist of three sessions in total with periodicity of 4 weeks, between the first and the second, and 6 weeks between the second and third. The application of laser energy will be carried out by vaginal and vulvar terminals. The dose applied will consist of monopulse shots distributed throughout the vaginal mucosa and vulvar skin of 10 mJ of energy and at a density of 10%. 2. nd Topical treatment: It consists of the application of XCM® intim of the company Mucosa Innovations. The route of administration would be vulvo-vaginal. The dose applied would be 2 ml of total product every 12 hours during 36 months.

Device: C02 microablative laser; Combination Product: Regenerative topical treatment

Regenerative topical treatment

EXPERIMENTAL

In this arm, only the regenerative treatment of XCM® intim of the company Mucosa Innovations will be used. The route of administration would be vulvo-vaginal. The dose applied would be 2 ml of total product every 12 hours. The total duration of treatment would be 36 months.

Combination Product: Regenerative topical treatment

Laser treatment

EXPERIMENTAL

The treatments used in this arm are the following: 1. º Microfractionated laser treatment of C02, through the AcupulseDuo generator of the company Lumenis®. The treatment regimen would consist of three sessions in total with periodicity of 4 weeks, between the first and the second, and 6 weeks between the second and third. The application of laser energy will be carried out by vaginal and vulvar terminals. The dose applied will consist of monopulse shots distributed throughout the vaginal mucosa and vulvar skin of 10 mJ of energy and at a density of 10%. 2. ºPlacebo vulvo-vaginal topical gel, consisting of a watery base.

Device: C02 microablative laser

Interventions

C02 microablative laser DEVICE

The C02 microablative laser was the first to be used in the treatment of menopausal genitourinary syndrome. Its mechanism of action is based on the emission of light at a wavelength of 10600nm that is absorbed by the water molecules contained in the vaginal mucosa, leading to local remodeling of connective tissue and neoformation of collagen, elastic fibers and other components of the extracellular matrix.

Laser + Regenerative topical treatment; Laser treatment

Regenerative topical treatment COMBINATION_PRODUCT

It is a moisturizing and regenerating gel whose active ingredients are olive oil, trimethylglycine and xylitol.

Laser + Regenerative topical treatment; Regenerative topical treatment

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet ALL of the following criteria to be included in the study:
• Patients over 18 years of age
• Who have a history of breast malignancy, and are on adjuvant or neoadjuvant treatment with hormone therapy.
• That they suffer symptoms related to vulvo-vaginal atrophy and thus become evident to the gynecological examination (Vaginal Health Index\<ó=15).
• That this clinic significantly affects your quality of life ( score in Sexual Function-Vaginal Changes Questionnaire less than or equal to 24 points).
• Who have not received any treatment for vulvo-vaginal atrophy in at least the previous 6 months. Purely moisturizing or emollient treatments that do not contain any regenerating substance (hyaluronic acid, gotu kola, vitamin E or rosehip oil) are not considered exclusive.
• That they agree to participate and give their written I consent.

You may not qualify if:

• Patients who present ANY of the following criteria may not be selected to participate in this study:
• Medical or surgical history that at the discretion of the researcher does not allow participation in the study.
• Refusal to participate in the study and to sign consent.
• Have completely completed the adjuvant hormonal treatment.
• Have a history of vulvar, vaginal and/or cervical malignancy.
• Have received radiation therapy to the pelvic and/or genital region.
• Sjögren's syndrome and other pathologies that occur with mucosal involvement.
• Present any type of disease that occurs with alteration of collagenogenesis.
• Intake of other cytotoxic drugs that lead to mucositis and alterations of tissue regeneration in the last 6 months.
• Have previously received laser and/or radiofrequency treatment for the treatment of genital atrophy or other pelvic floor dysfunctions.
• Active urinary and/or genital tract infection.
• Diagnosis of gestation at the time of recruitment.
• History of malignant neoplasm of the urinary tract.
• Have severe stress urinary incontinence (Sandvik test with a score equal to or greater than 8)
• Diagnosis of pelvic organ prolapse grade III or higher according to the POP-Q classification.

Sponsors & Collaborators

• Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz: lead
• Lumenis Be Ltd.: collaborator
• Mucosa Innovations, S.L.: collaborator

Related Publications (67)

• Nappi RE, Particco M, Biglia N, Cagnacci A, Di Carlo C, Luisi S, Paoletti AM. Attitudes and perceptions towards vulvar and vaginal atrophy in Italian post-menopausal women: Evidence from the European REVIVE survey. Maturitas. 2016 Sep;91:74-80. doi: 10.1016/j.maturitas.2016.06.009. Epub 2016 Jun 11.

  PMID: 27451324 BACKGROUND

• Amori P, Di Nardo V, Vitiello G, Franca K, Hercogova J, Wollina U, Daaboul F, Tchernev G, Lotti T. Primavera: A new therapeutical approach to vulvo-vaginal atrophy. Dermatol Ther. 2018 Nov;31(6):e12678. doi: 10.1111/dth.12678. Epub 2018 Nov 8.

  PMID: 30411455 BACKGROUND

• Palma F, Xholli A, Cagnacci A; as the writing group of the AGATA study. The most bothersome symptom of vaginal atrophy: Evidence from the observational AGATA study. Maturitas. 2018 Feb;108:18-23. doi: 10.1016/j.maturitas.2017.11.007. Epub 2017 Nov 10.

  PMID: 29290210 BACKGROUND

• Gandhi J, Chen A, Dagur G, Suh Y, Smith N, Cali B, Khan SA. Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol. 2016 Dec;215(6):704-711. doi: 10.1016/j.ajog.2016.07.045. Epub 2016 Jul 26.

  PMID: 27472999 BACKGROUND

• Mocan-Hognogi RF, Costin N, Malutan A, Ciortea R, Trif IA, Nagy AL, Bogdan ML, Mihu D. Histological changes in the vulva and vagina from ovariectomised rats undergoing oestrogen treatment. Folia Morphol (Warsz). 2016;75(4):467-473. doi: 10.5603/FM.a2016.0026. Epub 2016 Nov 10.

  PMID: 27830882 BACKGROUND

• Rozenberg S, Joris A, Albert V, Antoine C, Vandromme J. [La menopause et le traitement hormonal de la menopause : une actualisation]. Rev Med Brux. 2018;39(4):259-263. French.

  PMID: 30320986 BACKGROUND

• Sadovsky R, Basson R, Krychman M, Morales AM, Schover L, Wang R, Incrocci L. Cancer and sexual problems. J Sex Med. 2010 Jan;7(1 Pt 2):349-73. doi: 10.1111/j.1743-6109.2009.01620.x.

  PMID: 20092444 BACKGROUND

• Trinkaus M, Chin S, Wolfman W, Simmons C, Clemons M. Should urogenital atrophy in breast cancer survivors be treated with topical estrogens? Oncologist. 2008 Mar;13(3):222-31. doi: 10.1634/theoncologist.2007-0234.

  PMID: 18378532 BACKGROUND

• Sturdee DW, Panay N; International Menopause Society Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric. 2010 Dec;13(6):509-22. doi: 10.3109/13697137.2010.522875. Epub 2010 Sep 30.

  PMID: 20883118 BACKGROUND

• Pfeiler G, Glatz C, Konigsberg R, Geisendorfer T, Fink-Retter A, Kubista E, Singer CF, Seifert M. Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients. Climacteric. 2011 Jun;14(3):339-44. doi: 10.3109/13697137.2010.529967. Epub 2011 Jan 13.

  PMID: 21226657 BACKGROUND

• Nappi RE, Palacios S, Particco M, Panay N. The REVIVE (REal Women's VIews of Treatment Options for Menopausal Vaginal ChangEs) survey in Europe: Country-specific comparisons of postmenopausal women's perceptions, experiences and needs. Maturitas. 2016 Sep;91:81-90. doi: 10.1016/j.maturitas.2016.06.010. Epub 2016 Jun 15.

  PMID: 27451325 BACKGROUND

• Palacios S, Castelo-Branco C, Currie H, Mijatovic V, Nappi RE, Simon J, Rees M. Update on management of genitourinary syndrome of menopause: A practical guide. Maturitas. 2015 Nov;82(3):308-13. doi: 10.1016/j.maturitas.2015.07.020. Epub 2015 Jul 26.

  PMID: 26261035 BACKGROUND

• Tadir Y, Gaspar A, Lev-Sagie A, Alexiades M, Alinsod R, Bader A, Calligaro A, Elias JA, Gambaciani M, Gaviria JE, Iglesia CB, Selih-Martinec K, Mwesigwa PL, Ogrinc UB, Salvatore S, Scollo P, Zerbinati N, Nelson JS. Light and energy based therapeutics for genitourinary syndrome of menopause: Consensus and controversies. Lasers Surg Med. 2017 Feb;49(2):137-159. doi: 10.1002/lsm.22637. Epub 2017 Feb 21.

  PMID: 28220946 BACKGROUND

• Gambacciani M, Cervigni M. Erbium laser in gynecology: aims, aspirations and action points. Climacteric. 2015;18 Suppl 1:2-3. doi: 10.3109/13697137.2015.1082258. No abstract available.

  PMID: 26366792 BACKGROUND

• Vizintin Z, Lukac M, Kazic M, Tettamanti M. Erbium laser in gynecology. Climacteric. 2015;18 Suppl 1:4-8. doi: 10.3109/13697137.2015.1078668.

  PMID: 26366793 BACKGROUND

• Salvatore S, Nappi RE, Zerbinati N, Calligaro A, Ferrero S, Origoni M, Candiani M, Leone Roberti Maggiore U. A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study. Climacteric. 2014 Aug;17(4):363-9. doi: 10.3109/13697137.2014.899347. Epub 2014 Jun 5.

  PMID: 24605832 BACKGROUND

• Sokol ER, Karram MM. Use of a novel fractional CO2 laser for the treatment of genitourinary syndrome of menopause: 1-year outcomes. Menopause. 2017 Jul;24(7):810-814. doi: 10.1097/GME.0000000000000839.

  PMID: 28169913 BACKGROUND

• Siliquini GP, Tuninetti V, Bounous VE, Bert F, Biglia N. Fractional CO2 laser therapy: a new challenge for vulvovaginal atrophy in postmenopausal women. Climacteric. 2017 Aug;20(4):379-384. doi: 10.1080/13697137.2017.1319815. Epub 2017 May 15.

  PMID: 28503946 BACKGROUND

• Gaspar A, Brandi H, Gomez V, Luque D. Efficacy of Erbium:YAG laser treatment compared to topical estriol treatment for symptoms of genitourinary syndrome of menopause. Lasers Surg Med. 2017 Feb;49(2):160-168. doi: 10.1002/lsm.22569. Epub 2016 Aug 22.

  PMID: 27546524 BACKGROUND

• Antonino P, Gloria C. A new approach to treatment of vulvo-vaginal atrophy. Maturitas. 2015 Aug;81(4):499. doi: 10.1016/j.maturitas.2015.03.003. Epub 2015 Mar 11. No abstract available.

  PMID: 25835752 BACKGROUND

• Filippini M, Del Duca E, Negosanti F, Bonciani D, Negosanti L, Sannino M, Cannarozzo G, Nistico SP. Fractional CO2 Laser: From Skin Rejuvenation to Vulvo-Vaginal Reshaping. Photomed Laser Surg. 2017 Mar;35(3):171-175. doi: 10.1089/pho.2016.4173. Epub 2016 Dec 30.

  PMID: 28056209 BACKGROUND

• Murina F, Karram M, Salvatore S, Felice R. Fractional CO2 Laser Treatment of the Vestibule for Patients with Vestibulodynia and Genitourinary Syndrome of Menopause: A Pilot Study. J Sex Med. 2016 Dec;13(12):1915-1917. doi: 10.1016/j.jsxm.2016.10.006. Epub 2016 Nov 15.

  PMID: 27864031 BACKGROUND

• Hutchinson-Colas J, Segal S. Genitourinary syndrome of menopause and the use of laser therapy. Maturitas. 2015 Dec;82(4):342-5. doi: 10.1016/j.maturitas.2015.08.001. Epub 2015 Aug 12.

  PMID: 26323234 BACKGROUND

• Rabley A, O'Shea T, Terry R, Byun S, Louis Moy M. Laser Therapy for Genitourinary Syndrome of Menopause. Curr Urol Rep. 2018 Aug 17;19(10):83. doi: 10.1007/s11934-018-0831-y.

  PMID: 30117032 BACKGROUND

• Salvatore S, Nappi RE, Parma M, Chionna R, Lagona F, Zerbinati N, Ferrero S, Origoni M, Candiani M, Leone Roberti Maggiore U. Sexual function after fractional microablative CO(2) laser in women with vulvovaginal atrophy. Climacteric. 2015 Apr;18(2):219-25. doi: 10.3109/13697137.2014.975197. Epub 2014 Dec 16.

  PMID: 25333211 BACKGROUND

• Sokol ER, Karram MM. An assessment of the safety and efficacy of a fractional CO2 laser system for the treatment of vulvovaginal atrophy. Menopause. 2016 Oct;23(10):1102-7. doi: 10.1097/GME.0000000000000700.

  PMID: 27404032 BACKGROUND

• Behnia-Willison F, Sarraf S, Miller J, Mohamadi B, Care AS, Lam A, Willison N, Behnia L, Salvatore S. Safety and long-term efficacy of fractional CO2 laser treatment in women suffering from genitourinary syndrome of menopause. Eur J Obstet Gynecol Reprod Biol. 2017 Jun;213:39-44. doi: 10.1016/j.ejogrb.2017.03.036. Epub 2017 Apr 2.

  PMID: 28419911 BACKGROUND

• Perino A, Calligaro A, Forlani F, Tiberio C, Cucinella G, Svelato A, Saitta S, Calagna G. Vulvo-vaginal atrophy: a new treatment modality using thermo-ablative fractional CO2 laser. Maturitas. 2015 Mar;80(3):296-301. doi: 10.1016/j.maturitas.2014.12.006. Epub 2014 Dec 25.

  PMID: 25596815 BACKGROUND

• Perino A, Cucinella G, Gugliotta G, Saitta S, Polito S, Adile B, Marci R, Calagna G. Is vaginal fractional CO2 laser treatment effective in improving overactive bladder symptoms in post-menopausal patients? Preliminary results. Eur Rev Med Pharmacol Sci. 2016 Jun;20(12):2491-7.

  PMID: 27383297 BACKGROUND

• Pitsouni E, Grigoriadis T, Tsiveleka A, Zacharakis D, Salvatore S, Athanasiou S. Microablative fractional CO2-laser therapy and the genitourinary syndrome of menopause: An observational study. Maturitas. 2016 Dec;94:131-136. doi: 10.1016/j.maturitas.2016.09.012. Epub 2016 Sep 16.

  PMID: 27823733 BACKGROUND

• Gonzalez Isaza P, Jaguszewska K, Cardona JL, Lukaszuk M. Long-term effect of thermoablative fractional CO2 laser treatment as a novel approach to urinary incontinence management in women with genitourinary syndrome of menopause. Int Urogynecol J. 2018 Feb;29(2):211-215. doi: 10.1007/s00192-017-3352-1. Epub 2017 May 18.

  PMID: 28523400 BACKGROUND

• Athanasiou S, Pitsouni E, Antonopoulou S, Zacharakis D, Salvatore S, Falagas ME, Grigoriadis T. The effect of microablative fractional CO2 laser on vaginal flora of postmenopausal women. Climacteric. 2016 Oct;19(5):512-8. doi: 10.1080/13697137.2016.1212006. Epub 2016 Aug 24.

  PMID: 27558459 BACKGROUND

• Pitsouni E, Grigoriadis T, Falagas ME, Salvatore S, Athanasiou S. Laser therapy for the genitourinary syndrome of menopause. A systematic review and meta-analysis. Maturitas. 2017 Sep;103:78-88. doi: 10.1016/j.maturitas.2017.06.029. Epub 2017 Jun 27.

  PMID: 28778337 BACKGROUND

• Flint R, Cardozo L, Grigoriadis T, Rantell A, Pitsouni E, Athanasiou S. Rationale and design for fractional microablative CO2 laser versus photothermal non-ablative erbium:YAG laser for the management of genitourinary syndrome of menopause: a non-inferiority, single-blind randomized controlled trial. Climacteric. 2019 Jun;22(3):307-311. doi: 10.1080/13697137.2018.1559806. Epub 2019 Jan 24.

  PMID: 30676818 BACKGROUND

• Escribano JJ, Gonzalez-Isaza P, Tserotas K, Athanasiou S, Zerbinati N, Leibaschoff G, Salvatore S, Sanchez-Borrego R. In response to the FDA warning about the use of photomedicine in gynecology. Lasers Med Sci. 2019 Sep;34(7):1509-1511. doi: 10.1007/s10103-019-02744-1. Epub 2019 Mar 4.

  PMID: 30830556 BACKGROUND

• Lester J, Pahouja G, Andersen B, Lustberg M. Atrophic vaginitis in breast cancer survivors: a difficult survivorship issue. J Pers Med. 2015 Mar 25;5(2):50-66. doi: 10.3390/jpm5020050.

  PMID: 25815692 BACKGROUND

• Crandall C, Petersen L, Ganz PA, Greendale GA. Association of breast cancer and its therapy with menopause-related symptoms. Menopause. 2004 Sep-Oct;11(5):519-30. doi: 10.1097/01.gme.0000117061.40493.ab.

  PMID: 15356404 BACKGROUND

• Fiorica J. Association of breast cancer and its therapy with menopause-related symptoms. Menopause. 2004 Sep-Oct;11(5):502-4. doi: 10.1097/01.gme.0000131667.98625.42. No abstract available.

  PMID: 15356401 BACKGROUND

• 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 Mar;14(3):413-424. doi: 10.1016/j.jsxm.2017.01.010. Epub 2017 Feb 12.

  PMID: 28202320 BACKGROUND

• Kingsberg SA, Larkin L, Krychman M, Parish SJ, Bernick B, Mirkin S. WISDOM survey: attitudes and behaviors of physicians toward vulvar and vaginal atrophy (VVA) treatment in women including those with breast cancer history. Menopause. 2019 Feb;26(2):124-131. doi: 10.1097/GME.0000000000001194.

  PMID: 30130293 BACKGROUND

• Kingsberg SA, Krychman ML. Resistance and barriers to local estrogen therapy in women with atrophic vaginitis. J Sex Med. 2013 Jun;10(6):1567-74. doi: 10.1111/jsm.12120. Epub 2013 Mar 27.

  PMID: 23534861 BACKGROUND

• Santen RJ, Stuenkel CA, Davis SR, Pinkerton JV, Gompel A, Lumsden MA. Managing Menopausal Symptoms and Associated Clinical Issues in Breast Cancer Survivors. J Clin Endocrinol Metab. 2017 Oct 1;102(10):3647-3661. doi: 10.1210/jc.2017-01138.

  PMID: 28934376 BACKGROUND

• Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas. 1996 Apr;23(3):259-63. doi: 10.1016/0378-5122(95)00955-8.

  PMID: 8794418 BACKGROUND

• Sinha A, Ewies AA. Non-hormonal topical treatment of vulvovaginal atrophy: an up-to-date overview. Climacteric. 2013 Jun;16(3):305-12. doi: 10.3109/13697137.2012.756466. Epub 2013 Jan 8.

  PMID: 23215675 BACKGROUND

• Dezzutti CS, Brown ER, Moncla B, Russo J, Cost M, Wang L, Uranker K, Kunjara Na Ayudhya RP, Pryke K, Pickett J, Leblanc MA, Rohan LC. Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity. PLoS One. 2012;7(11):e48328. doi: 10.1371/journal.pone.0048328. Epub 2012 Nov 7.

  PMID: 23144863 BACKGROUND

• Ship JA, McCutcheon JA, Spivakovsky S, Kerr AR. Safety and effectiveness of topical dry mouth products containing olive oil, betaine, and xylitol in reducing xerostomia for polypharmacy-induced dry mouth. J Oral Rehabil. 2007 Oct;34(10):724-32. doi: 10.1111/j.1365-2842.2006.01718.x.

  PMID: 17824884 BACKGROUND

• Lopez-Pintor RM, Ramirez L, Serrano J, de Pedro M, Fernandez-Castro M, Casanas E, Hernandez G. Effects of Xerostom(R) products on xerostomia in primary Sjogren's syndrome: A randomized clinical trial. Oral Dis. 2019 Apr;25(3):772-780. doi: 10.1111/odi.13019. Epub 2019 Jan 8.

  PMID: 30561129 BACKGROUND

• Martin M, Marin A, Lopez M, Linan O, Alvarenga F, Buchser D, Cerezo L. Products based on olive oil, betaine, and xylitol in the post-radiotherapy xerostomia. Rep Pract Oncol Radiother. 2017 Jan-Feb;22(1):71-76. doi: 10.1016/j.rpor.2016.09.008. Epub 2016 Nov 25.

  PMID: 27920611 BACKGROUND

• Villa A, Wolff A, Aframian D, Vissink A, Ekstrom J, Proctor G, McGowan R, Narayana N, Aliko A, Sia YW, Joshi RK, Jensen SB, Kerr AR, Dawes C, Pedersen AM. World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction: prevalence, diagnosis, and treatment. Clin Oral Investig. 2015 Sep;19(7):1563-80. doi: 10.1007/s00784-015-1488-2. Epub 2015 May 22.

  PMID: 25994331 BACKGROUND

• Gil-Montoya JA, Silvestre FJ, Barrios R, Silvestre-Rangil J. Treatment of xerostomia and hyposalivation in the elderly: A systematic review. Med Oral Patol Oral Cir Bucal. 2016 May 1;21(3):e355-66. doi: 10.4317/medoral.20969.

  PMID: 27031061 BACKGROUND

• Lopez-Lopez J, Jane Salas E, Chimenos Kustner E. [Prognosis and treatment of dry mouth. Systematic review]. Med Clin (Barc). 2014 Feb 4;142(3):119-24. doi: 10.1016/j.medcli.2013.02.036. Epub 2013 May 31. Spanish.

  PMID: 23726507 BACKGROUND

• Valimaa H, Savolainen S, Soukka T, Silvoniemi P, Makela S, Kujari H, Gustafsson JA, Laine M. Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands. J Endocrinol. 2004 Jan;180(1):55-62. doi: 10.1677/joe.0.1800055.

  PMID: 14709144 BACKGROUND

• Leimola-Virtanen R, Salo T, Toikkanen S, Pulkkinen J, Syrjanen S. Expression of estrogen receptor (ER) in oral mucosa and salivary glands. Maturitas. 2000 Aug 31;36(2):131-7. doi: 10.1016/s0378-5122(00)00138-9.

  PMID: 11006500 BACKGROUND

• ZISKIN DE, MOULTON R. A comparison of oral and vaginal epithelial smears. J Clin Endocrinol Metab. 1948 Feb;8(2):146-65. doi: 10.1210/jcem-8-2-146. No abstract available.

  PMID: 18907981 BACKGROUND

• van der Bijl P, van Eyk AD. Human vaginal mucosa as a model of buccal mucosa for in vitro permeability studies: an overview. Curr Drug Deliv. 2004 Apr;1(2):129-35. doi: 10.2174/1567201043479975.

  PMID: 16305378 BACKGROUND

• Morelli L, Zonenenschain D, Del Piano M, Cognein P. Utilization of the intestinal tract as a delivery system for urogenital probiotics. J Clin Gastroenterol. 2004 Jul;38(6 Suppl):S107-10. doi: 10.1097/01.mcg.0000128938.32835.98.

  PMID: 15220672 BACKGROUND

• Cribby S, Taylor M, Reid G. Vaginal microbiota and the use of probiotics. Interdiscip Perspect Infect Dis. 2008;2008:256490. doi: 10.1155/2008/256490. Epub 2009 Mar 29.

  PMID: 19343185 BACKGROUND

• Mothes AR, Runnebaum M, Runnebaum IB. Ablative dual-phase Erbium:YAG laser treatment of atrophy-related vaginal symptoms in post-menopausal breast cancer survivors omitting hormonal treatment. J Cancer Res Clin Oncol. 2018 May;144(5):955-960. doi: 10.1007/s00432-018-2614-8. Epub 2018 Feb 27.

  PMID: 29487993 BACKGROUND

• Becorpi A, Campisciano G, Zanotta N, Tredici Z, Guaschino S, Petraglia F, Pieralli A, Sisti G, De Seta F, Comar M. Fractional CO2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects. Lasers Med Sci. 2018 Jul;33(5):1047-1054. doi: 10.1007/s10103-018-2471-3. Epub 2018 Mar 1.

  PMID: 29492713 BACKGROUND

• Pieralli A, Fallani MG, Becorpi A, Bianchi C, Corioni S, Longinotti M, Tredici Z, Guaschino S. Fractional CO2 laser for vulvovaginal atrophy (VVA) dyspareunia relief in breast cancer survivors. Arch Gynecol Obstet. 2016 Oct;294(4):841-6. doi: 10.1007/s00404-016-4118-6. Epub 2016 May 12.

  PMID: 27170261 BACKGROUND

• Pagano T, De Rosa P, Vallone R, Schettini F, Arpino G, Giuliano M, Lauria R, De Santo I, Conforti A, Gallo A, Nazzaro G, De Placido S, Locci M, De Placido G. Fractional microablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of nonestrogenic local treatments: a retrospective study. Menopause. 2018 Jun;25(6):657-662. doi: 10.1097/GME.0000000000001053.

  PMID: 29286986 BACKGROUND

• Leone Roberti Maggiore U, Parma M, Candiani M, Salvatore S. Microablative Fractional CO2 Laser for Vulvovaginal Atrophy in Women With a History of Breast Cancer. J Minim Invasive Gynecol. 2015 Nov-Dec;22(6S):S100. doi: 10.1016/j.jmig.2015.08.269. Epub 2015 Oct 15. No abstract available.

  PMID: 27678561 BACKGROUND

• Jha S, Wyld L, Krishnaswamy PH. The Impact of Vaginal Laser Treatment for Genitourinary Syndrome of Menopause in Breast Cancer Survivors: A Systematic Review and Meta-analysis. Clin Breast Cancer. 2019 Aug;19(4):e556-e562. doi: 10.1016/j.clbc.2019.04.007. Epub 2019 Apr 19.

  PMID: 31227415 BACKGROUND

• Gambacciani M, Levancini M, Cervigni M. Vaginal erbium laser: the second-generation thermotherapy for the genitourinary syndrome of menopause. Climacteric. 2015 Oct;18(5):757-63. doi: 10.3109/13697137.2015.1045485.

  PMID: 26029987 BACKGROUND

• Robinson D, Flint R, Veit-Rubin N, Araklitis G, Cardozo L. Is there enough evidence to justify the use of laser and other thermal therapies in female lower urinary tract dysfunction? Report from the ICI-RS 2019. Neurourol Urodyn. 2020 Jul;39 Suppl 3:S140-S147. doi: 10.1002/nau.24298. Epub 2020 Feb 10.

  PMID: 32040871 BACKGROUND

• Alvisi S, Baldassarre M, Martelli V, Gava G, Seracchioli R, Meriggiola MC. Effects of ospemifene on vaginal epithelium of post-menopausal women. Gynecol Endocrinol. 2017 Dec;33(12):946-950. doi: 10.1080/09513590.2017.1332589. Epub 2017 May 31.

  PMID: 28562130 BACKGROUND

• Alvisi S, Baldassarre M, Gava G, Mancini I, Gagliardi M, Seracchioli R, Meriggiola MC. Structure of Epithelial and Stromal Compartments of Vulvar and Vaginal Tissue From Women With Vulvo-Vaginal Atrophy Taking Ospemifene. J Sex Med. 2018 Dec;15(12):1776-1784. doi: 10.1016/j.jsxm.2018.10.009. Epub 2018 Nov 13.

  PMID: 30446472 BACKGROUND

Related Links

• Spanish Agency for Medicines and Health Products. SmPC Blissel 50 micrograms/gram vaginal gel
• EUROPEAN MEDICINES AGENCY. Data sheet Prasterone 6.5 milligrams
• EUROPEAN MEDICINES AGENCY. Technical Sheet Ospemifene 60 mg

MeSH Terms

Conditions

Female Urogenital Diseases; Breast Neoplasms

Condition Hierarchy (Ancestors)

Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Amalia Cañadas Molina

  Employee

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amalia Cañadas Molina

CONTACT

+34 653422973; amalia.canadas@fjd.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: In order to mask the patients from the treatment group to which they have been assigned, a simulated laser treatment session will be carried out in the case of patients belonging to the topical regenerative treatment group, which will consist of keeping the device turned off during it but faithfully reproducing both the duration as the sounds emitted by the device through recording previously made. In the case of patients assigned to laser treatment exclusively, they will be provided with a topical placebo (water-based), which must be applied with the same regimen as the emollient treatment under study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A single-blind, randomized, controlled clinical trial is proposed, in which the patients included will be assigned to one of the three treatment arms.

Study Record Dates

• First Submitted: September 21, 2022
• First Posted: October 18, 2022
• Study Start: October 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share