Efficacy and safety of promestriene in the treatment of genitourinary syndrome of menopause in women with breast cancer
Publicado
feb 16, 2024
Almetrics
Dimensions
Google Scholar
##plugins.themes.bootstrap3.article.details##
Resumen
Objective: To evaluate the efficacy and safety of vaginal promestriene in women with triple-negative breast cancer who experience vulvovaginal symptoms and signs related to genitourinary syndrome of menopause (GUMS).
Materials and methods: prospective, multicenter regional, randomized, triple-blind, placebo-controlled study in women ≥ 45 years of age, survivors of breast cancer with triple-negative hormone receptors, symptomatic of SGUM, who consulted in three private clinics in the Coffee Region (Caldas, Risaralda and Quindío), Colombia; between 2019 and 2023. They were randomized into two groups to receive promestriene (n=77) and placebo (n=75). Follow-up was 12 months, recording satisfaction with therapy, adverse effects, vaginal health index score, and Female Sexual Function Index (IFSF). The levels of estradiol, androgens and gonadotropins were analyzed. Descriptive statistics were applied.
Results: Treatment with promestriene improved all variables of the vaginal health index, as well as the domains and total score of the IFSF. Hormone concentrations remained within the postmenopausal range. Estradiol throughout the treatment presented minimal oscillations without statistical significance. Adverse effects were mild and tolerable. Satisfaction with therapy was close to 90 %.
Conclusions: Promestriene was shown to be effective and safe for the treatment of symptoms and signs of GUM, without relevant changes in serum estradiol levels. The results support the use of promestriene in women with breast cancer who suffer from genitourinary syndrome of menopause.
Keywords
Efficacy; Safety; Therapeutics; Hormone Replacement Therapy; Estradiol; Menopause.Eficacia; Seguridad; Terapéutica; Terapia de Reemplazo de Hormonas; Estradiol; Menopausia.
References
1) Barzaman K, Karami J, Zarei Z, Hosseinzadeh A, Kazemi MH, Moradi-Kalbolandi S, Safari E, Farahmand L. Breast cancer: Biology, biomarkers, and treatments. Int Immunopharmacol. 2020 Jul;84:106535. https://doi.org/10.1016/j.intimp.2020.106535.
2) Canadian Cancer Statistics Advisory Committee, Canadian Cancer Society, Statistics Canada, the Public Health Agency of Canada. Canadian Cancer Statistics 2021. Toronto, Canada: Canadian Cancer Society; 2021.
3) Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL, Siegel RL. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019 Sep;69(5):363-385. https://doi.org/10.3322/caac.21565.
4) Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. https://doi.org/10.1002/ijc.29210.
5) Ministerio de Salud y Protección Social-Colciencias. Instituto Nacional de Cancerología ESE. Instituto de Evaluación Tecnológica en Salud IETS. Guía de práctica clínica (GPC) para la detección temprana, tratamiento integral, seguimiento y rehabilitación del cáncer de mama. Versión para profesionales de la salud – 2013 Guía No. GPC-2013-19. ISBN: 978-958-8838-28-1. Bogotá, Colombia Abril de 2013.
6) Brenner DR, Weir HK, Demers AA, Ellison LF, Louzado C, Shaw A, Turner D, Woods RR, Smith LM; Canadian Cancer Statistics Advisory Committee. Projected estimates of cancer in Canada in 2020. CMAJ. 2020 Mar 2;192(9):E199-E205. https://doi.org/10.1503/cmaj.191292.
7) Geiersbach KB, Chen H, Emmadi R, Haskell GT, Lu X, Liu YJ, Swisshelm K. Current concepts in breast cancer genomics: An evidence based review by the CGC breast cancer working group. Cancer Genet. 2020 Jun;244:11-20. https://doi.org/10.1016/j.cancergen.2020.02.002.
8) Waks AG, Winer EP. Breast Cancer Treatment: A Review. JAMA. 2019 Jan 22;321(3):288-300. https://doi.org/10.1001/jama.2018.19323.
9) Garmpis N, Damaskos C, Garmpi A, Nikolettos K, Dimitroulis D, Diamantis E, et al. Molecular Classification and Future Therapeutic Challenges of Triple-negative Breast Cancer. In Vivo. 2020 Jul-Aug;34(4):1715-1727. https://doi.org/10.21873/invivo.11965.
10) Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019 Oct 1;30(10):1674. https://doi.org/10.1093/annonc/mdz189.
11) Bevers TB, Helvie M, Bonaccio E, Calhoun KE, Daly MB, Farrar WB, et al. Breast Cancer Screening and Diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018 Nov;16(11):1362-1389. https://doi.org/10.6004/jnccn.2018.0083.
12) Merino Bonilla JA, Torres Tabanera M, Ros Mendoza LH. Breast cancer in the 21st century: from early detection to new therapies. Radiologia. 2017 Sep-Oct;59(5):368-379. English, Spanish. https://doi.org/10.1016/j.rx.2017.06.003.
13) Peart O. Breast intervention and breast cancer treatment options. Radiol Technol. 2015 May-Jun;86(5):535M-558M; quiz 559-62.
14) Moreno AC, Sikka SK, Thacker HL. Genitourinary syndrome of menopause in breast cancer survivors:Treatments are available. Cleve Clin J Med. 2018 Oct;85(10):760-766. https://doi.org/10.3949/ccjm.85a.17108.
15) Ganz PA. Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century. Am J Med. 2005 Dec 19;118 Suppl 12B:136-41. https://doi.org/10.1016/j.amjmed.2005.09.047.
16) Bluming AZ. Hormone Replacement Therapy After Breast Cancer: It Is Time. Cancer J. 2022 May-Jun 01;28(3):183-190. https://doi.org/10.1097/PPO.0000000000000595.
17) Poggio F, Del Mastro L, Bruzzone M, Ceppi M, Razeti MG, Fregatti P, et al. Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis. Breast Cancer Res Treat. 2022 Jan;191(2):269-275. https://doi.org/10.1007/s10549-021-06436-9.
18) Gaudefroy M, Pigache JP. Etude des effects estrogéniques du promestriène [Study of estrogenic effects of promestriene]. Arch Anat Cytol Pathol. 1977;25(2):125-8.
19) Del Pup L, Di Francia R, Cavaliere C, Facchini G, Giorda G, De Paoli P, Berretta M. Promestriene, a specific topic estrogen. Review of 40 years of vaginal atrophy treatment: is it safe even in cancer patients? Anticancer Drugs. 2013 Nov;24(10):989-98. https://doi.org/10.1097/CAD.0b013e328365288e.
20) Espitia De La Hoz FJ. Promestrieno: evaluación de su uso e impacto en los niveles séricos de estradiol en mujeres con cáncer de mama y síndrome genitourinario de la menopausia. ARMENIA, COLOMBIA, 2017-2018. Arch Med (Manizales). 2022. 22(2):206-220. https://doi.org/10.30554/archmed.22.2.4036.2022
21) Esch M, Schadewald DM. Treatment-Induced Ovarian Insufficiency and Early Menopause in Breast Cancer Survivors. Clin J Oncol Nurs. 2023 Jan 25;27(1):7-12. https://doi.org/10.1188/23.CJON.7-12.
22) Derakhshan F, Reis-Filho JS. Pathogenesis of Triple-Negative Breast Cancer. Annu Rev Pathol. 2022 Jan 24;17:181-204. https://doi.org/10.1146/annurev-pathol-042420-093238.
23) Bachmann GA, Notelovitz M, Kelly SJ, Thompson C, Owens A. Long-term non-hormonal treatment of vaginal dryness. Clin Pract Sexuality 1992; 8:3-8.
24) Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, et al. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000 Apr-Jun;26(2):191-208. https://doi.org/10.1080/009262300278597.
25) Wiegel M, Meston C, Rosen R. The female sexual function index (FSFI): cross-validation and development of clinical cutoff scores. J Sex Marital Ther. 2005 Jan-Feb;31(1):1-20. https://doi.org/10.1080/00926230590475206.
26) Espitia De La Hoz FJ. Prevalencia y caracterización de las disfunciones sexuales en mujeres, en 12 ciudades colombianas, 2009-2016. Rev Colomb Obstet Ginecol. 2023 Nov 05;69(1):9-21. https://doi.org/10.18597/rcog.3035.
27) Santos LPA, Bonduki CE, Dardes RCM, Heinke T, Patriarca MT. Effects of oxytocin versus promestriene on genitourinary syndrome: a pilot, prospective, randomized, double-blind study. Clinics (Sao Paulo). 2022 Oct 1;77:100116. https://doi.org/10.1016/j.clinsp.2022.100116.
28) Santos I, Clissold S. Urogenital disorders associated with oestrogen deficiency: the role of promestriene as topical oestrogen therapy. Gynecol Endocrinol. 2010 Sep;26(9):644-51. https://doi.org/10.3109/09513591003767948.
29) Lubián López DM. Management of genitourinary syndrome of menopause in breast cancer survivors: An update. World J Clin Oncol. 2022 Feb 24;13(2):71-100. https://doi.org/10.5306/wjco.v13.i2.71.
30) Wiśniewska I, Jochymek B, Lenart-Lipińska M, Chabowski M. The pharmacological and hormonal therapy of hot flushes in breast cancer survivors. Breast Cancer. 2016 Mar;23(2):178-82. https://doi.org/10.1007/s12282-015-0655-2.
31) Baumgart J, Nilsson K, Evers AS, Kallak TK, Poromaa IS. Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer. Menopause. 2013 Feb;20(2):162-8. https://doi.org/10.1097/gme.0b013e31826560da.
32) Sun AJ, Lin SQ, Jing LH, Wang ZY, Ye JL, Zhang Y. [Safety of promestriene capsule used in postmenopausal atrophic vaginitis]. Zhonghua Fu Chan Ke Za Zhi. 2009 Aug;44(8):593-6. Chinese.
33) 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. https://doi.org/10.3390/jpm5020050.
34) Wills S, Ravipati A, Venuturumilli P, Kresge C, Folkerd E, Dowsett M, Hayes DF, Decker DA. Effects of vaginal estrogens on serum estradiol levels in postmenopausal breast cancer survivors and women at risk of breast cancer taking an aromatase inhibitor or a selective estrogen receptor modulator. J Oncol Pract. 2012 May;8(3):144-8. https://doi.org/10.1200/JOP.2011.000352.
35) Chin SN, Trinkaus M, Simmons C, Flynn C, Dranitsaris G, Bolivar R, Clemons M. Prevalence and severity of urogenital symptoms in postmenopausal women receiving endocrine therapy for breast cancer. Clin Breast Cancer. 2009 May;9(2):108-17. https://doi.org/10.3816/CBC.2009.n.020.
36) Espitia De La Hoz FJ. Calidad de vida en mujeres con síndrome genitourinario de la menopausia en el Quindío, Colombia. Rev Colomb Endocrinol Diabet Metab. 2023;10(1):e761. https://doi.org/10.53853/encr.10.1.761.
2) Canadian Cancer Statistics Advisory Committee, Canadian Cancer Society, Statistics Canada, the Public Health Agency of Canada. Canadian Cancer Statistics 2021. Toronto, Canada: Canadian Cancer Society; 2021.
3) Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL, Siegel RL. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019 Sep;69(5):363-385. https://doi.org/10.3322/caac.21565.
4) Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. https://doi.org/10.1002/ijc.29210.
5) Ministerio de Salud y Protección Social-Colciencias. Instituto Nacional de Cancerología ESE. Instituto de Evaluación Tecnológica en Salud IETS. Guía de práctica clínica (GPC) para la detección temprana, tratamiento integral, seguimiento y rehabilitación del cáncer de mama. Versión para profesionales de la salud – 2013 Guía No. GPC-2013-19. ISBN: 978-958-8838-28-1. Bogotá, Colombia Abril de 2013.
6) Brenner DR, Weir HK, Demers AA, Ellison LF, Louzado C, Shaw A, Turner D, Woods RR, Smith LM; Canadian Cancer Statistics Advisory Committee. Projected estimates of cancer in Canada in 2020. CMAJ. 2020 Mar 2;192(9):E199-E205. https://doi.org/10.1503/cmaj.191292.
7) Geiersbach KB, Chen H, Emmadi R, Haskell GT, Lu X, Liu YJ, Swisshelm K. Current concepts in breast cancer genomics: An evidence based review by the CGC breast cancer working group. Cancer Genet. 2020 Jun;244:11-20. https://doi.org/10.1016/j.cancergen.2020.02.002.
8) Waks AG, Winer EP. Breast Cancer Treatment: A Review. JAMA. 2019 Jan 22;321(3):288-300. https://doi.org/10.1001/jama.2018.19323.
9) Garmpis N, Damaskos C, Garmpi A, Nikolettos K, Dimitroulis D, Diamantis E, et al. Molecular Classification and Future Therapeutic Challenges of Triple-negative Breast Cancer. In Vivo. 2020 Jul-Aug;34(4):1715-1727. https://doi.org/10.21873/invivo.11965.
10) Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019 Oct 1;30(10):1674. https://doi.org/10.1093/annonc/mdz189.
11) Bevers TB, Helvie M, Bonaccio E, Calhoun KE, Daly MB, Farrar WB, et al. Breast Cancer Screening and Diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018 Nov;16(11):1362-1389. https://doi.org/10.6004/jnccn.2018.0083.
12) Merino Bonilla JA, Torres Tabanera M, Ros Mendoza LH. Breast cancer in the 21st century: from early detection to new therapies. Radiologia. 2017 Sep-Oct;59(5):368-379. English, Spanish. https://doi.org/10.1016/j.rx.2017.06.003.
13) Peart O. Breast intervention and breast cancer treatment options. Radiol Technol. 2015 May-Jun;86(5):535M-558M; quiz 559-62.
14) Moreno AC, Sikka SK, Thacker HL. Genitourinary syndrome of menopause in breast cancer survivors:Treatments are available. Cleve Clin J Med. 2018 Oct;85(10):760-766. https://doi.org/10.3949/ccjm.85a.17108.
15) Ganz PA. Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century. Am J Med. 2005 Dec 19;118 Suppl 12B:136-41. https://doi.org/10.1016/j.amjmed.2005.09.047.
16) Bluming AZ. Hormone Replacement Therapy After Breast Cancer: It Is Time. Cancer J. 2022 May-Jun 01;28(3):183-190. https://doi.org/10.1097/PPO.0000000000000595.
17) Poggio F, Del Mastro L, Bruzzone M, Ceppi M, Razeti MG, Fregatti P, et al. Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis. Breast Cancer Res Treat. 2022 Jan;191(2):269-275. https://doi.org/10.1007/s10549-021-06436-9.
18) Gaudefroy M, Pigache JP. Etude des effects estrogéniques du promestriène [Study of estrogenic effects of promestriene]. Arch Anat Cytol Pathol. 1977;25(2):125-8.
19) Del Pup L, Di Francia R, Cavaliere C, Facchini G, Giorda G, De Paoli P, Berretta M. Promestriene, a specific topic estrogen. Review of 40 years of vaginal atrophy treatment: is it safe even in cancer patients? Anticancer Drugs. 2013 Nov;24(10):989-98. https://doi.org/10.1097/CAD.0b013e328365288e.
20) Espitia De La Hoz FJ. Promestrieno: evaluación de su uso e impacto en los niveles séricos de estradiol en mujeres con cáncer de mama y síndrome genitourinario de la menopausia. ARMENIA, COLOMBIA, 2017-2018. Arch Med (Manizales). 2022. 22(2):206-220. https://doi.org/10.30554/archmed.22.2.4036.2022
21) Esch M, Schadewald DM. Treatment-Induced Ovarian Insufficiency and Early Menopause in Breast Cancer Survivors. Clin J Oncol Nurs. 2023 Jan 25;27(1):7-12. https://doi.org/10.1188/23.CJON.7-12.
22) Derakhshan F, Reis-Filho JS. Pathogenesis of Triple-Negative Breast Cancer. Annu Rev Pathol. 2022 Jan 24;17:181-204. https://doi.org/10.1146/annurev-pathol-042420-093238.
23) Bachmann GA, Notelovitz M, Kelly SJ, Thompson C, Owens A. Long-term non-hormonal treatment of vaginal dryness. Clin Pract Sexuality 1992; 8:3-8.
24) Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, et al. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000 Apr-Jun;26(2):191-208. https://doi.org/10.1080/009262300278597.
25) Wiegel M, Meston C, Rosen R. The female sexual function index (FSFI): cross-validation and development of clinical cutoff scores. J Sex Marital Ther. 2005 Jan-Feb;31(1):1-20. https://doi.org/10.1080/00926230590475206.
26) Espitia De La Hoz FJ. Prevalencia y caracterización de las disfunciones sexuales en mujeres, en 12 ciudades colombianas, 2009-2016. Rev Colomb Obstet Ginecol. 2023 Nov 05;69(1):9-21. https://doi.org/10.18597/rcog.3035.
27) Santos LPA, Bonduki CE, Dardes RCM, Heinke T, Patriarca MT. Effects of oxytocin versus promestriene on genitourinary syndrome: a pilot, prospective, randomized, double-blind study. Clinics (Sao Paulo). 2022 Oct 1;77:100116. https://doi.org/10.1016/j.clinsp.2022.100116.
28) Santos I, Clissold S. Urogenital disorders associated with oestrogen deficiency: the role of promestriene as topical oestrogen therapy. Gynecol Endocrinol. 2010 Sep;26(9):644-51. https://doi.org/10.3109/09513591003767948.
29) Lubián López DM. Management of genitourinary syndrome of menopause in breast cancer survivors: An update. World J Clin Oncol. 2022 Feb 24;13(2):71-100. https://doi.org/10.5306/wjco.v13.i2.71.
30) Wiśniewska I, Jochymek B, Lenart-Lipińska M, Chabowski M. The pharmacological and hormonal therapy of hot flushes in breast cancer survivors. Breast Cancer. 2016 Mar;23(2):178-82. https://doi.org/10.1007/s12282-015-0655-2.
31) Baumgart J, Nilsson K, Evers AS, Kallak TK, Poromaa IS. Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer. Menopause. 2013 Feb;20(2):162-8. https://doi.org/10.1097/gme.0b013e31826560da.
32) Sun AJ, Lin SQ, Jing LH, Wang ZY, Ye JL, Zhang Y. [Safety of promestriene capsule used in postmenopausal atrophic vaginitis]. Zhonghua Fu Chan Ke Za Zhi. 2009 Aug;44(8):593-6. Chinese.
33) 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. https://doi.org/10.3390/jpm5020050.
34) Wills S, Ravipati A, Venuturumilli P, Kresge C, Folkerd E, Dowsett M, Hayes DF, Decker DA. Effects of vaginal estrogens on serum estradiol levels in postmenopausal breast cancer survivors and women at risk of breast cancer taking an aromatase inhibitor or a selective estrogen receptor modulator. J Oncol Pract. 2012 May;8(3):144-8. https://doi.org/10.1200/JOP.2011.000352.
35) Chin SN, Trinkaus M, Simmons C, Flynn C, Dranitsaris G, Bolivar R, Clemons M. Prevalence and severity of urogenital symptoms in postmenopausal women receiving endocrine therapy for breast cancer. Clin Breast Cancer. 2009 May;9(2):108-17. https://doi.org/10.3816/CBC.2009.n.020.
36) Espitia De La Hoz FJ. Calidad de vida en mujeres con síndrome genitourinario de la menopausia en el Quindío, Colombia. Rev Colomb Endocrinol Diabet Metab. 2023;10(1):e761. https://doi.org/10.53853/encr.10.1.761.
Cómo citar
Espitia De La Hoz, F. J. (2024). Efficacy and safety of promestriene in the treatment of genitourinary syndrome of menopause in women with breast cancer. Universitas Medica, 65. https://doi.org/10.11144/Javeriana.umed65.espt
Número
Sección
Artículos originales
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.