The effect of vitamin D and E vaginal suppositories on tamoxifen-induced vaginal atrophy in women with breast cancer

Abstract

Purpose

Vaginal atrophy is one of the most common side effects of using tamoxifen in women with breast cancer. Hormone therapy for vaginal atrophy is prohibited in these women. The present study was conducted to investigate the effect of vitamin D and E vaginal suppositories on vaginal atrophy in women with breast cancer receiving tamoxifen.

Methods

Women under breast cancer management receiving tamoxifen and showing symptoms of vaginal atrophy were randomized triple-blind to an 8-week trial on vaginal suppository vitamin E or vitamin D or placebo administered every night before bedtime. The genitourinary atrophy self-assessment tool was administered, and pH was measured in all three groups before the intervention and at the end of weeks 2, 4, and 8 of the intervention. The Vaginal Maturation Index (VMI) was also measured before the intervention and at the end of the eighth week. Data were analyzed with paired t tests, repeated measures analysis of variance, and chi-square test.

Results

Thirty-two patients were randomized in each group. The results obtained showed an increase in the VMI by the end of the eighth week of the intervention in the groups receiving the vitamin D and E vaginal suppositories compared with the placebo group (P < 0.001). The vaginal pH also reduced in both groups compared with that in the placebo group (P < 0.001). The symptoms of self-reported genitourinary atrophy also improved in the two intervention groups compared with those in the placebo group by the end of the eighth week (P < 0.001).

Conclusion

These data support that vitamin D and E vaginal suppositories were beneficial in improving vaginal atrophy in women with breast cancer receiving tamoxifen. Given the prohibition on hormone therapy in these women, the suppositories can be used as an alternative therapy to improve these symptoms.

This is a preview of subscription content, log in to check access.

Fig. 1

References

  1. 1.

    Berek JS (2012) Berek and Novak’s gynecology. Lippincott Williams and Wilkins, Philadelphia

    Google Scholar 

  2. 2.

    Enayatrad M, Amoori N, Salehiniya H (2015) Epidemiology and trends in breast cancer mortality in Iran. Iran J Public Health 44(3):430–431

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Del Mastro L, Boni L, Michelotti A et al (2011) Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA 306(3):269–276. https://doi.org/10.1001/jama.2011.991

    PubMed  Article  Google Scholar 

  4. 4.

    Costa M, Saldanha P (2017) Risk reduction strategies in breast cancer prevention. Eur J Breast Health 13(3):103–112. https://doi.org/10.5152/ejbh.2017.3583

    PubMed  Article  PubMed Central  Google Scholar 

  5. 5.

    Kim NN, Stankovic M, Armagan A, Cushman TT, Goldstein I, Traish AM (2006) Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat. BMC Womens Health 6:14

    PubMed  Article  Google Scholar 

  6. 6.

    Weber MA, Limpens J, Roovers JPWR (2015) Assessment of vaginal atrophy: a review. Int Urogynecol J 26(1):15–28. https://doi.org/10.1007/s00192-017-3490-5

    PubMed  CAS  Article  Google Scholar 

  7. 7.

    Portman DJ, Bachmann GA, Simon JA, Group OS (2013) Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause 20(6):623–630. https://doi.org/10.1097/gme.0b013e318279ba64

    PubMed  Article  Google Scholar 

  8. 8.

    Simin J, Tamimi R, Lagergren J, Adami HO, Brusselaers N (2017) Menopausal hormone therapy and cancer risk: an overestimated risk? Eur J Cancer 84:60–68. https://doi.org/10.1016/j.ejca.2017.07.012

    PubMed  CAS  Article  Google Scholar 

  9. 9.

    Trabert B, Wentzensen N, Yang HP, Sherman ME, Hollenbeck AR, Park Y, Brinton LA (2013) Is estrogen plus progestin menopausal hormone therapy safe with respect to endometrial cancer risk? Int J Cancer 132(2):417–426. https://doi.org/10.1002/ijc.27623

    PubMed  CAS  Article  Google Scholar 

  10. 10.

    Brown SB, Hankinson SE (2015) Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Steroids 99:8–10. https://doi.org/10.1016/j.steroids.2014.12.013

    PubMed  CAS  Article  Google Scholar 

  11. 11.

    Bergendal A, Kieler H, Sundström A, Hirschberg AL, Kocoska-Maras L (2016) Risk of venous thromboembolism associated with local and systemic use of hormone therapy in peri- and postmenopausal women and in relation to type and route of administration. Menopause 23(6):593–599. https://doi.org/10.1097/GME.0000000000000611

    PubMed  Article  Google Scholar 

  12. 12.

    Sousa MS, Peate M, Jarvis S, Hickey M, Friedlander M (2017) A clinical guide to the management of genitourinary symptoms in breast cancer survivors on endocrine therapy. Ther Adv Med Oncol 9(4):269–285. https://doi.org/10.1177/1758834016687260

    PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

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

    PubMed  Article  PubMed Central  Google Scholar 

  14. 14.

    Faubion SS, Larkin LC, Stuenkel CA, Bachmann GA, Chism LA, Kagan R, Kaunitz AM, Krychman ML, Parish SJ, Partridge AH, Pinkerton JAV, Rowen TS, Shapiro M, Simon JA, Goldfarb SB, Kingsberg SA (2018) Management of genitourinary syndrome of menopause in women with or at high risk for breast cancer: consensus recommendations from The North American Menopause Society and The International Society for the Study of Women’s Sexual Health. Menopause 25(6):596–608. https://doi.org/10.1097/GME.0000000000001121

    PubMed  Article  Google Scholar 

  15. 15.

    American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice, Farrell R (2016) ACOG Committee Opinion No. 659 Summary: the use of vaginal estrogen in women with a history of estrogen-dependent breast cancer. Obstet Gynecol 127(3):618–619. https://doi.org/10.1097/AOG.0000000000001349

    CAS  Article  Google Scholar 

  16. 16.

    Costantino D, Guaraldi C (2008) Effectiveness and safety of vaginal suppositories for the treatment of the vaginal atrophy in postmenopausal women: an open, non-controlled clinical trial. Eur Rev Med Pharmacol Sci 12(6):411–416

    PubMed  CAS  Google Scholar 

  17. 17.

    Lee YK, Chung HH, Kim JW, Park NH, Song YS, Kang SB (2011) Vaginal pH-balanced gel for the control of atrophic vaginitis among breast cancer survivors: a randomized controlled trial. Obstet Gynecol 117(4):922–927. https://doi.org/10.1097/AOG.0b013e3182118790

    PubMed  Article  Google Scholar 

  18. 18.

    Wurz GT, Soe LH, DeGregorio MW (2013) Ospemifene, vulvovaginal atrophy, and breast cancer. Maturitas 74(3):220–225. https://doi.org/10.1016/j.maturitas.2012.12.002

    PubMed  CAS  Article  Google Scholar 

  19. 19.

    Carter J, Goldfrank D, Schover LR (2011) Simple strategies for vaginal health promotion in cancer survivors. J Sex Med 8(2):549–559. https://doi.org/10.1111/j.1743-6109.2010.01988.x

    PubMed  Article  Google Scholar 

  20. 20.

    Derzko C, Elliott S, Lam W (2007) Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy. Curr Oncol 14(Suppl 1):S20–S40

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Juraskova I, Jarvis S, Mok K, Peate M, Meiser B, Cheah BC, Mireskandari S, Friedlander M (2013) The acceptability, feasibility, and efficacy (phase I/II study) of the OVERcome (Olive Oil, Vaginal Exercise, and MoisturizeR) intervention to improve dyspareunia and alleviate sexual problems in women with breast cancer. J Sex Med 10(10):2549–2558. https://doi.org/10.1111/jsm.12156

    PubMed  Article  Google Scholar 

  22. 22.

    Mazzarello S, Hutton B, Ibrahim MF et al (2015) Management of urogenital atrophy in breast cancer patients: a systematic review of available evidence from randomized trials. Breast Cancer Res Treat 152(1):1–8. https://doi.org/10.1007/s10549-015-3434-z

    PubMed  CAS  Article  Google Scholar 

  23. 23.

    Yildirim B, Kaleli B, Düzcan E, Topuz O (2004) The effects of postmenopausal vitamin D treatment on vaginal atrophy. Maturitas 49(4):334–337

    PubMed  CAS  Article  Google Scholar 

  24. 24.

    Rad P, Tadayon M, Abbaspour M, Latifi SM, Rashidi I, Delaviz H The effect of vitamin D on vaginal atrophy in postmenopausal women. Iran J Nurs Midwifery Res 20(2):211–215

  25. 25.

    Lee A, Lee MR, Lee HH et al (2017) Vitamin D proliferates vaginal epithelium through RhoA expression in postmenopausal atrophic vagina tissue. Mol Cell 40(9):677–684

    CAS  Google Scholar 

  26. 26.

    Ziagham S, Abbaspoor Z, Safyari S, Rad P (2013) Effect of vitamin E vaginal suppository on atrophic vaginitis among postmenopausal women. Jundishapur J Chronic Dis Care 2(4):12–19

    Google Scholar 

  27. 27.

    Abban G, Yildirim NB, Jetten AM (2008) Regulation of the vitamin D receptor and cornifin beta expression in vaginal epithelium of the rats through vitamin D3. Eur J Histochem 52:107–104

    PubMed  Article  Google Scholar 

  28. 28.

    Zeyneloglu HB, Oktem M, Haberal NA, Esinler I, Kuscu E (2007) The effect of raloxifene in association with vitamin D on vaginal maturation index and urogenital symptoms in postmenopausal osteoporotic women. Fertil Steril 88(2):530–532

    PubMed  CAS  Article  Google Scholar 

  29. 29.

    Chollet JA, Carter G, Meyn LA, Mermelstein F, Balk JL (2009) Efficacy and safety of vaginal estriol and progesterone in postmenopausal women with atrophic vaginitis. Menopause 16(5):978–983. https://doi.org/10.1097/gme.0b013e3181a06c80

    PubMed  Article  Google Scholar 

  30. 30.

    Speroff L (2003) Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms. Obstet Gynecol 102(4):823–834

    PubMed  CAS  Google Scholar 

  31. 31.

    Lester J, Bernhard L, Ryan-Wenger N (2012) A self-report instrument that describes urogenital atrophy symptoms in breast cancer survivors. West J Nurs Res 34(1):72–96. https://doi.org/10.1177/0193945910391483

    PubMed  Article  Google Scholar 

  32. 32.

    Ziagham Z, Abbaspoor Z, Abbaspour MR (2012) The comparison between the effects of hyaluronic acid vaginal suppository and vitamin e on the treatment of atrophic vaginitis in menopausal women. J Arak Uni Med Sci 15(6):57–64

    Google Scholar 

  33. 33.

    Emamverdikhan AZ, Golmakani N, SharifiSistani N, Shakeri MT, Hasanzade Mofrad M, Sajadi Tabassi A (2014) Comparing two treatment methods of vitamin E suppository and conjugated estrogen vaginal cream on the quality of life in menopausal women with vaginal atrophy. J Midwif Reprod Health 2(4):253–261. https://doi.org/10.22038/JMRH.2014.3246

    Article  Google Scholar 

  34. 34.

    Morali G, Polatti F, Metelitsa EN, Mascarucci P, Magnani P, Marrè GB (2006) Open, non-controlled clinical studies to assess the efficacy and safety of a medical device in form of gel topically and intravaginally used in postmenopausal women with genital atrophy. Arzneimittelforschung 56(3):230–238

    PubMed  Google Scholar 

  35. 35.

    Dinicola S, Pasta V, Costantino D, Guaraldi C, Bizzarri M (2015) Hyaluronic acid and vitamins are effective in reducing vaginal atrophy in women receiving radiotherapy. Minerva Ginecol 67(6):523–531

    PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Roksana Janghorban.

Ethics declarations

The research project was approved by the ethics committee of Shiraz University of Medical Sciences (IR.SUMS.REC 94-01-08-11247) and registered at the Iranian Registry of Clinical Trials (IRCT2016100229683N2).

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Keshavarzi, Z., Janghorban, R., Alipour, S. et al. The effect of vitamin D and E vaginal suppositories on tamoxifen-induced vaginal atrophy in women with breast cancer. Support Care Cancer 27, 1325–1334 (2019). https://doi.org/10.1007/s00520-019-04684-6

Download citation

Keywords

  • Breast cancer
  • Tamoxifen
  • Atrophic vaginitis
  • Vitamin D
  • Vitamin E
  • Vaginal suppository