Local Estrogen Therapy for Pelvic Organ Prolapse in Postmenopausal Women: A Systematic Review and Meta-Analysis
-
Xia Yu
,
Li He
,
Yanjun Wang
,
Li Wang
,
Zhenlin Yang
,
Yonghong Lin
Abstract
Background: The prevalence of pelvic organ prolapse (POP) is expected to increase in the next few decades, imposing a substantial medical burden. The effect of local estrogen therapy (LET) on POP in postmenopausal women is still controversial; therefore, we aimed to provide reliable evidence to address this issue from the perspective of vaginal health and quality of life (QoL).
Methods: We searched in the PubMed, the Web of Science, Embase and the Cochrane Library databases for eligible RCTs from beginning to Apr 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in our study.
Results: Seven RCTs(n=570) were included. No significant improvement of the epithelial thickness (SMD=1.38, 95%CI -0.54 to 3.31, P=0.16) or vaginal pH (SMD=-0.98, 95%CI -2.65 to 0.69, P=0.25) after LET compared with the control. A slight increase was observed in the VMI (MD=16.58, 95%CI 1.14 to 32.02, P=0.04). Regarding QoL, no significant differences between the estrogen group and the control group in PFIQ-7 (6m: MD=3.60, 95%CI –3.13 to 10.33, P=0.29; 12m: MD=3.53, 95%CI -3.35 to 10.41, P=0.31), PISQ-12(6m: MD=0.62, 95%CI –0.73 to 1.98, P=0.37; 12m: MD=0.36, 95%CI –1.06 to 1.77, P=0.62), or PGI-I (6m: RR=0.99, 95%CI 0.92 to 1.07, P=0.88; 12m: RR=1.01, 95%CI 0.95 to 1.07, P=0.72) score. Moreover, no more specific adverse events (AEs) (RR=1.11, 95%CI 0.84 to 1.48, P=0.46) were observed in the interventional group.
Conclusion: Not find LET caused either a significant improvement in vaginal health and QoL or more AEs.
1. Collins SA, O'Shea M, Dykes N, Ramm O, Edenfield A, Shek KL, van Delft K, Beestrum M, Kenton K (2021). International Urogynecological Consultation: clinical definition of pelvic organ prolapse. Int Urogynecol J, 32:2011-2019.
2. Drage KJ, Aghera M, MacKellar P, et al (2022). The relationship between symptom severity, bother and psychological factors in women with pelvic organ prolapse: A cross-sectional observational study. Neurourol Urodyn, 41:423-431.
3. Rortveit G, Brown JS, Thom DH, et al (2007). Symptomatic pelvic organ prolapse: prevalence and risk factors in a population-based, racially diverse cohort. Obstet Gynecol, 109:1396-403.
4. Svihrova V, Svihra J, Luptak J, Swift S, Digesu GA (2014). Disability-adjusted life years (DALYs) in general population with pelvic organ prolapse: a study based on the prolapse quality-of-life questionnaire (P-QOL). Eur J Obstet Gynecol Reprod Biol, 182:22-6.
5. Robinson D, Prodigalidad LT, Chan S, et al (2022). International Urogynaecology Consultation chapter 1 committee 4: patients' perception of disease burden of pelvic organ prolapse. Int Urogynecol J, 33:189-210.
6. Davidson ERW, Myers EM, De La Cruz JF, Connolly A (2019). Baseline Understanding of Urinary Incontinence and Prolapse in New Urogynecology Patients. Female Pelvic Med Reconstr Surg, 25:67-71.
7. Brown HW, Hegde A, Huebner M, et al (2022). International urogynecology consultation chapter 1 committee 2: Epidemiology of pelvic organ prolapse: prevalence, incidence, natural history, and service needs. Int Urogynecol J, 33:173-187.
8. Wu JM, Hundley AF, Fulton RG, Myers ER (2009). Forecasting the prevalence of pelvic floor disorders in U.S. Women: 2010 to 2050. Obstet Gynecol, 114:1278-1283.
9. Geoffrion R, Larouche M (2021). Guideline No. 413: Surgical Management of Apical Pelvic Organ Prolapse in Women. J Obstet Gynaecol Can, 43:511-523.e1.
10. Srikrishna S, Robinson D, Cardozo L (2010). A longitudinal study of patient and surgeon goal achievement 2 years after surgery following pelvic floor dysfunction surgery. BJOG, 117:1504-11.
11. Al-Badr A, Saleem Z, Kaddour O, et al (2022). Prevalence of pelvic floor dysfunction: a Saudi national survey. BMC Womens Health, 22:27.
12. Reddy RA, Cortessis V, Dancz C, Klutke J, Stanczyk FZ (2020). Role of sex steroid hormones in pelvic organ prolapse. Menopause, 27:941-951.
13. Deng ZM, Dai FF, Yuan MQ, et al (2021). Advances in molecular mechanisms of pelvic organ prolapse (Review). Exp Ther Med, 22:1009.
14. Yi M, Wang S, Wu T, et al (2021). Effects of exogenous melatonin on sleep quality and menopausal symptoms in menopausal women: a systematic review and meta-analysis of randomized controlled trials. Menopause, 28:717-725.
15. Lien YS, Chen GD, Ng SC (2012). Prevalence of and risk factors for pelvic organ prolapse and lower urinary tract symptoms among women in rural Nepal. Int J Gynaecol Obstet, 119:185-8.
16. The NAMS 2020 GSM Position Statement Editorial Panel (2020). The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause, 27:976-992.
17. Higgins JPT, Thomas J, Chandler J, et al (2021). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). https://training.cochrane.org/handbook
18. Felding C, Mikkelsen AL, Clausen HV, et al (1992). Preoperative treatment with oestradiol in women scheduled for vaginal operation for genital prolapse. A randomised, double-blind trial. Maturitas, 15:241-9.
19. Karp DR, Jean-Michel M, Johnston Y, et al (2012). A randomized clinical trial of the impact of local estrogen on postoperative tissue quality after vaginal reconstructive surgery. Female Pelvic Med Reconstr Surg, 18:211-5.
20. Rahn DD, Good MM, Roshanravan SM, et al (2014). Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab, 99:3728-36.
21. Sun Z, Zhu L, Xu T, Shi X, Lang J (2016). Effects of preoperative vaginal estrogen therapy for the incidence of mesh complication after pelvic organ prolapse surgery in postmenopausal women: is it helpful or a myth? A 1-year randomized controlled trial. Menopause, 23:740-8.
22. Tontivuthikul P, Sanmee U, Wongtra-Ngan S, Pongnarisorn C (2016). Effect of Local Estrogen Cream on Vaginal Health after Pessary Use for Prolapsed Pelvic Organ: A Randomized Controlled Trial. J Med Assoc Thai, 99:757-63.
23. Vaccaro CM, Mutema GK, Fellner AN, et al (2013). Histologic and cytologic effects of vaginal estrogen in women with pelvic organ prolapse: a randomized controlled trial. Female Pelvic Med Reconstr Surg, 19:34-9.
24. Verghese TS, Middleton L, Cheed V, et al (2020). Randomised controlled trial to investigate the effectiveness of local oestrogen treatment in postmenopausal women undergoing pelvic organ prolapse surgery (LOTUS): a pilot study to assess feasibility of a large multicentre trial. BMJ Open, 10(9):e025141.
25. Chiengthong K, Ruanphoo P, Chatsuwan T, Bunyavejchevin S (2022). Effect of vaginal estrogen in postmenopausal women using vaginal pessary for pelvic organ prolapse treatment: a randomized controlled trial. Int Urogynecol J, 33(7):1833-1838.
26. Marschalek ML, Bodner K, Kimberger O, et al (2021). Surgical Assessment of Tissue Quality during Pelvic Organ Prolapse Repair in Postmenopausal Women Pre-Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial. J Clin Med, 10(11):2531.
27. de Albuquerque Coelho SC, Giraldo PC, et al (2021). ESTROgen use for complications in women treating pelvic organ prolapse with vaginal PESSaries (ESTRO-PESS)-a randomized clinical trial. Int Urogynecol J, 32:1571-1578.
28. Weber MA, Diedrich CM, Ince C, Roovers JP (2016). Focal depth measurements of the vaginal wall: a new method to noninvasively quantify vaginal wall thickness in the diagnosis and treatment of vaginal atrophy. Menopause, 23:833-8.
29. Crandall CJ, Hovey KM, Andrews CA, et al (2018). Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study. Menopause, 25:11-20.
30. Zbucka-Kretowska M, Marcus-Braun N, Eboue C, et al (2011). Expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women presenting pelvic organ prolapse. Folia Histochem Cytobiol, 49:521-7.
31. Fuermetz A, Schoenfeld M, Ennemoser S, et al (2015). Change of steroid receptor expression in the posterior vaginal wall after local estrogen therapy. Eur J Obstet Gynecol Reprod Biol, 187:45-50.
32. Weber MA, Limpens J, Roovers JP (2015). Assessment of vaginal atrophy: a review. Int Urogynecol J, 26:15-28.
33. Mitchell CM, Reed SD, Diem S, et al (2018). Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial. JAMA Intern Med, 178:681-690.
34. Manzini C, van den Noort F, Grob ATM, et al (2021). The effect of pessary treatment on puborectalis muscle function. Int Urogynecol J, 32:1409-1417.
35. Barber MD, Kuchibhatla MN, Pieper CF, Bump RC (2001). Psychometric evaluation of 2 comprehensive condition-specific quality of life instruments for women with pelvic floor disorders. Am J Obstet Gynecol, 185:1388-95.
36. Rogers RG, Kammerer-Doak D, Villarreal A, et al (2001). A new instrument to measure sexual function in women with urinary incontinence or pelvic organ prolapse. Am J Obstet Gynecol, 184:552-8.
37. Barber MD, Walters MD, Bump RC (2005). Short forms of two condition-specific quality-of-life questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7). Am J Obstet Gynecol, 193:103-13.
38. Rogers RG, Coates KW, Kammerer-Doak D, Khalsa S, Qualls C (2003). A short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Int Urogynecol J Pelvic Floor Dysfunct, 14:164-8; discussion 168.
39. Mattsson NK, Karjalainen PK, Tolppanen AM, et al (2020). Pelvic organ prolapse surgery and quality of life-a nationwide cohort study. Am J Obstet Gynecol, 222:588. e1-588.e10.
40. Srikrishna S, Robinson D, Cardozo L (2010). Validation of the Patient Global Impression of Improvement (PGI-I) for urogenital prolapse. Int Urogynecol J, 21:523-8.
41. Rahkola-Soisalo P, Mikkola TS, Altman D, Falconer C (2019). Pelvic Organ Prolapse Repair Using the Uphold Vaginal Support System: 5-Year Follow-Up. Female Pelvic Med Reconstr Surg, 25:200-205.
2. Drage KJ, Aghera M, MacKellar P, et al (2022). The relationship between symptom severity, bother and psychological factors in women with pelvic organ prolapse: A cross-sectional observational study. Neurourol Urodyn, 41:423-431.
3. Rortveit G, Brown JS, Thom DH, et al (2007). Symptomatic pelvic organ prolapse: prevalence and risk factors in a population-based, racially diverse cohort. Obstet Gynecol, 109:1396-403.
4. Svihrova V, Svihra J, Luptak J, Swift S, Digesu GA (2014). Disability-adjusted life years (DALYs) in general population with pelvic organ prolapse: a study based on the prolapse quality-of-life questionnaire (P-QOL). Eur J Obstet Gynecol Reprod Biol, 182:22-6.
5. Robinson D, Prodigalidad LT, Chan S, et al (2022). International Urogynaecology Consultation chapter 1 committee 4: patients' perception of disease burden of pelvic organ prolapse. Int Urogynecol J, 33:189-210.
6. Davidson ERW, Myers EM, De La Cruz JF, Connolly A (2019). Baseline Understanding of Urinary Incontinence and Prolapse in New Urogynecology Patients. Female Pelvic Med Reconstr Surg, 25:67-71.
7. Brown HW, Hegde A, Huebner M, et al (2022). International urogynecology consultation chapter 1 committee 2: Epidemiology of pelvic organ prolapse: prevalence, incidence, natural history, and service needs. Int Urogynecol J, 33:173-187.
8. Wu JM, Hundley AF, Fulton RG, Myers ER (2009). Forecasting the prevalence of pelvic floor disorders in U.S. Women: 2010 to 2050. Obstet Gynecol, 114:1278-1283.
9. Geoffrion R, Larouche M (2021). Guideline No. 413: Surgical Management of Apical Pelvic Organ Prolapse in Women. J Obstet Gynaecol Can, 43:511-523.e1.
10. Srikrishna S, Robinson D, Cardozo L (2010). A longitudinal study of patient and surgeon goal achievement 2 years after surgery following pelvic floor dysfunction surgery. BJOG, 117:1504-11.
11. Al-Badr A, Saleem Z, Kaddour O, et al (2022). Prevalence of pelvic floor dysfunction: a Saudi national survey. BMC Womens Health, 22:27.
12. Reddy RA, Cortessis V, Dancz C, Klutke J, Stanczyk FZ (2020). Role of sex steroid hormones in pelvic organ prolapse. Menopause, 27:941-951.
13. Deng ZM, Dai FF, Yuan MQ, et al (2021). Advances in molecular mechanisms of pelvic organ prolapse (Review). Exp Ther Med, 22:1009.
14. Yi M, Wang S, Wu T, et al (2021). Effects of exogenous melatonin on sleep quality and menopausal symptoms in menopausal women: a systematic review and meta-analysis of randomized controlled trials. Menopause, 28:717-725.
15. Lien YS, Chen GD, Ng SC (2012). Prevalence of and risk factors for pelvic organ prolapse and lower urinary tract symptoms among women in rural Nepal. Int J Gynaecol Obstet, 119:185-8.
16. The NAMS 2020 GSM Position Statement Editorial Panel (2020). The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause, 27:976-992.
17. Higgins JPT, Thomas J, Chandler J, et al (2021). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). https://training.cochrane.org/handbook
18. Felding C, Mikkelsen AL, Clausen HV, et al (1992). Preoperative treatment with oestradiol in women scheduled for vaginal operation for genital prolapse. A randomised, double-blind trial. Maturitas, 15:241-9.
19. Karp DR, Jean-Michel M, Johnston Y, et al (2012). A randomized clinical trial of the impact of local estrogen on postoperative tissue quality after vaginal reconstructive surgery. Female Pelvic Med Reconstr Surg, 18:211-5.
20. Rahn DD, Good MM, Roshanravan SM, et al (2014). Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial. J Clin Endocrinol Metab, 99:3728-36.
21. Sun Z, Zhu L, Xu T, Shi X, Lang J (2016). Effects of preoperative vaginal estrogen therapy for the incidence of mesh complication after pelvic organ prolapse surgery in postmenopausal women: is it helpful or a myth? A 1-year randomized controlled trial. Menopause, 23:740-8.
22. Tontivuthikul P, Sanmee U, Wongtra-Ngan S, Pongnarisorn C (2016). Effect of Local Estrogen Cream on Vaginal Health after Pessary Use for Prolapsed Pelvic Organ: A Randomized Controlled Trial. J Med Assoc Thai, 99:757-63.
23. Vaccaro CM, Mutema GK, Fellner AN, et al (2013). Histologic and cytologic effects of vaginal estrogen in women with pelvic organ prolapse: a randomized controlled trial. Female Pelvic Med Reconstr Surg, 19:34-9.
24. Verghese TS, Middleton L, Cheed V, et al (2020). Randomised controlled trial to investigate the effectiveness of local oestrogen treatment in postmenopausal women undergoing pelvic organ prolapse surgery (LOTUS): a pilot study to assess feasibility of a large multicentre trial. BMJ Open, 10(9):e025141.
25. Chiengthong K, Ruanphoo P, Chatsuwan T, Bunyavejchevin S (2022). Effect of vaginal estrogen in postmenopausal women using vaginal pessary for pelvic organ prolapse treatment: a randomized controlled trial. Int Urogynecol J, 33(7):1833-1838.
26. Marschalek ML, Bodner K, Kimberger O, et al (2021). Surgical Assessment of Tissue Quality during Pelvic Organ Prolapse Repair in Postmenopausal Women Pre-Treated Either with Locally Applied Estrogen or Placebo: Results of a Double-Masked, Placebo-Controlled, Multicenter Trial. J Clin Med, 10(11):2531.
27. de Albuquerque Coelho SC, Giraldo PC, et al (2021). ESTROgen use for complications in women treating pelvic organ prolapse with vaginal PESSaries (ESTRO-PESS)-a randomized clinical trial. Int Urogynecol J, 32:1571-1578.
28. Weber MA, Diedrich CM, Ince C, Roovers JP (2016). Focal depth measurements of the vaginal wall: a new method to noninvasively quantify vaginal wall thickness in the diagnosis and treatment of vaginal atrophy. Menopause, 23:833-8.
29. Crandall CJ, Hovey KM, Andrews CA, et al (2018). Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study. Menopause, 25:11-20.
30. Zbucka-Kretowska M, Marcus-Braun N, Eboue C, et al (2011). Expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women presenting pelvic organ prolapse. Folia Histochem Cytobiol, 49:521-7.
31. Fuermetz A, Schoenfeld M, Ennemoser S, et al (2015). Change of steroid receptor expression in the posterior vaginal wall after local estrogen therapy. Eur J Obstet Gynecol Reprod Biol, 187:45-50.
32. Weber MA, Limpens J, Roovers JP (2015). Assessment of vaginal atrophy: a review. Int Urogynecol J, 26:15-28.
33. Mitchell CM, Reed SD, Diem S, et al (2018). Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial. JAMA Intern Med, 178:681-690.
34. Manzini C, van den Noort F, Grob ATM, et al (2021). The effect of pessary treatment on puborectalis muscle function. Int Urogynecol J, 32:1409-1417.
35. Barber MD, Kuchibhatla MN, Pieper CF, Bump RC (2001). Psychometric evaluation of 2 comprehensive condition-specific quality of life instruments for women with pelvic floor disorders. Am J Obstet Gynecol, 185:1388-95.
36. Rogers RG, Kammerer-Doak D, Villarreal A, et al (2001). A new instrument to measure sexual function in women with urinary incontinence or pelvic organ prolapse. Am J Obstet Gynecol, 184:552-8.
37. Barber MD, Walters MD, Bump RC (2005). Short forms of two condition-specific quality-of-life questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7). Am J Obstet Gynecol, 193:103-13.
38. Rogers RG, Coates KW, Kammerer-Doak D, Khalsa S, Qualls C (2003). A short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Int Urogynecol J Pelvic Floor Dysfunct, 14:164-8; discussion 168.
39. Mattsson NK, Karjalainen PK, Tolppanen AM, et al (2020). Pelvic organ prolapse surgery and quality of life-a nationwide cohort study. Am J Obstet Gynecol, 222:588. e1-588.e10.
40. Srikrishna S, Robinson D, Cardozo L (2010). Validation of the Patient Global Impression of Improvement (PGI-I) for urogenital prolapse. Int Urogynecol J, 21:523-8.
41. Rahkola-Soisalo P, Mikkola TS, Altman D, Falconer C (2019). Pelvic Organ Prolapse Repair Using the Uphold Vaginal Support System: 5-Year Follow-Up. Female Pelvic Med Reconstr Surg, 25:200-205.
| Files | ||
| Issue | Vol 51 No 8 (2022) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v51i8.10255 | |
| Keywords | ||
| Estrogen Pelvic organ prolapse Postmenopausal women Vaginal health Quality of life | ||
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How to Cite
1.
Yu X, He L, Wang Y, Wang L, Yang Z, Lin Y. Local Estrogen Therapy for Pelvic Organ Prolapse in Postmenopausal Women: A Systematic Review and Meta-Analysis. Iran J Public Health. 2022;51(8):1728-1740.
