Skip to main content

Advertisement

SpringerLink
Log in

Systemic and local effects of vaginal dehydroepiandrosterone (DHEA): NCCTG N10C1 (Alliance)

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Background

Dehydroepiandrosterone (DHEA) is helpful for treating vaginal symptoms. This secondary analysis evaluated the impact of vaginal DHEA on hormone concentrations, bone turnover, and vaginal cytology in women with a cancer history.

Methods

Postmenopausal women, diagnosed with breast or gynecologic cancer, were eligible if they reported at least moderate vaginal symptoms. Participants could be on tamoxifen or aromatase inhibitors (AIs). Women were randomized to 3.25 versus 6.5 mg/day of DHEA versus a plain moisturizer (PM) control. Sex steroid hormone levels, biomarkers of bone formation, vaginal pH, and maturation index were collected at baseline and 12 weeks. Analysis included independent t tests and Wilcoxon rank tests, comparing each DHEA arm with the control.

Results

Three hundred forty-five women contributed evaluable blood and 46 contributed evaluable cytology and pH values. Circulating DHEA-S and testosterone levels were significantly increased in those on vaginal DHEA in a dose-dependent manner compared to PM. Estradiol was significantly increased in those on 6.5 mg/day DHEA but not in those on 3.25 mg/day DHEA (p < 0.05 and p = 0.05, respectively), and not in those on AIs. Biomarkers of bone formation were unchanged in all arms. Maturation of vaginal cells was 100% (3.25 mg/day), 86% (6.5 mg/day), and 64% (PM); pH decreased more in DHEA arms.

Conclusion

DHEA resulted in increased hormone concentrations, though still in the lowest half or quartile of the postmenopausal range, and provided more favorable effects on vaginal cytology, compared to PM. Estrogen concentrations in women on AIs were not changed. Further research on the benefit of vaginal DHEA is warranted in hormone-dependent cancers.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Gracia CR, Freeman EW (2004) Acute consequences of the menopausal transition: the rise of common menopausal symptoms. Endocrinol Metab Clin N Am 33(4):675–689. https://doi.org/10.1016/j.ecl.2004.07.003

    Article  CAS  Google Scholar 

  2. Bacon JL (2017) The menopausal transition. Obstet Gynecol Clin N Am 44(2):285–296. https://doi.org/10.1016/j.ogc.2017.02.008

    Article  Google Scholar 

  3. Ganz PA, Cecchini RS, Julian TB et al (2016) Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet 387(10021):857–865

    Article  CAS  PubMed  Google Scholar 

  4. Cella D, Fallowfield LJ (2008) Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat 107(2):167–180. https://doi.org/10.1007/s10549-007-9548-1

    Article  CAS  PubMed  Google Scholar 

  5. Barton DL, Ganz PA (2015) Symptoms: menopause, infertility and sexual health. Adv Exp Med Biol 862:115–141. https://doi.org/10.1007/978-3-319-16366-6_9

    Article  PubMed  Google Scholar 

  6. Lara LA, Useche B, Ferriani RA et al (2009) The effects of hypoestrogenism on the vaginal wall: interference with the normal sexual response. J Sex Med 6(1):30–39. https://doi.org/10.1111/j.1743-6109.2008.01052.x

    Article  PubMed  Google Scholar 

  7. Leclair DM, Ananjarajah G (2002) Review article: Effects of estrogen deprivation: vasomotor symptoms, urogenital atrophy, and psychobiologic effects. Clinics in Fam Pract 4(1):27–39. https://doi.org/10.1016/S1522-5720(03)00049-7

    Article  Google Scholar 

  8. Archer DF (2010) Efficacy and tolerability of local estrogen therapy for urogenital atrophy. Menopause 17(1):194–203

    Article  PubMed  Google Scholar 

  9. Tan O, Bradshaw K, Carr BR (2012) Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women: an up-to-date review. Menopause 19(1):109–117

    Article  PubMed  Google Scholar 

  10. North American Menopause Society (2007) The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause (New York) 14(3 Pt 1):355–369 quiz 370–351

    Google Scholar 

  11. Santen RJ, Pinkerton JV, Conaway M et al (2002) Treatment of urogenital atrophy with low-dose estradiol: preliminary results. Menopause 9(3):179–187

    Article  PubMed  Google Scholar 

  12. Kendall A, Dowsett M, Folkerd E, Smith I (2006) Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 17(4):584–587. https://doi.org/10.1093/annonc/mdj127

    Article  CAS  PubMed  Google Scholar 

  13. Wills S, Ravipati A, Venuturumilli P, Kresge C, Folkerd E, Dowsett M, Hayes DF, Decker DA (2012) 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 8(3):144–148. https://doi.org/10.1200/JOP.2011.000352

    Article  PubMed  PubMed Central  Google Scholar 

  14. Naessen T, Rodriguez-Macias K, Lithell H (2001) Serum lipid profile improved by ultra-low doses of 17 beta-estradiol in elderly women. J Clin Endocrinol Metab 86(6):2757–2762. https://doi.org/10.1210/jcem.86.6.7524

    CAS  PubMed  Google Scholar 

  15. Naessen T, Berglund L, Ulmsten U (1997) Bone loss in elderly women prevented by ultralow doses of parenteral 17beta-estradiol. Am J Obstet Gynecol 177(1):115–119. https://doi.org/10.1016/S0002-9378(97)70448-4

    Article  CAS  PubMed  Google Scholar 

  16. Reeder-Hayes K, Muss HB (2017) Vaginal estrogens and aromatase inhibitors: how safe is safe enough? JAMA Oncol 3(3):305–306. https://doi.org/10.1001/jamaoncol.2016.3934

    Article  PubMed  Google Scholar 

  17. Labrie F, Archer D, Bouchard C et al (2009) Effect of intravaginal dehydroepiandrosterone (prasterone) on libido and sexual dysfunction in postmenopausal women. Menopause 16(5):923–931

    Article  PubMed  Google Scholar 

  18. Labrie F, Archer D, Bouchard C et al (2009) Intravaginal dehydroepiandrosterone (prasterone), a physiological and highly efficient treatment of vaginal atrophy. Menopause 16(5):907–922

    Article  PubMed  Google Scholar 

  19. Labrie F, Derogatis L, Archer DF, Koltun W, Vachon A, Young D, Frenette L, Portman D, Montesino M, Côté I, Parent J, Lavoie L, Beauregard A, Martel C, Vaillancourt M, Balser J, Moyneur É, Members of the VVA Prasterone Research Group (2015) Effect of intravaginal prasterone on sexual dysfunction in postmenopausal women with vulvovaginal atrophy. J Sex Med 12(12):2401–2412. https://doi.org/10.1111/jsm.13045

    Article  CAS  PubMed  Google Scholar 

  20. Labrie F, Martel C, Berube R et al (2013) Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens. J Steroid Biochem Mol Biol 138:359–367. https://doi.org/10.1016/j.jsbmb.2013.08.002

    Article  CAS  PubMed  Google Scholar 

  21. Samaras N, Samaras D, Frangos E, Forster A, Philippe JA (2013) Review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: is treatment beneficial? Rejuvenation Res 16(4):285–294. https://doi.org/10.1089/rej.2013.1425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hlaing TT, Compston JE (2014) Biochemical markers of bone turnover—uses and limitations. Ann Clin Biochem 51(2):189–202. https://doi.org/10.1177/0004563213515190

    Article  PubMed  Google Scholar 

  23. Peris P, Alvarez L, Monegal A et al (1999) Biochemical markers of bone turnover after surgical menopause and hormone replacement therapy. Bone 2(3):349–353

    Article  Google Scholar 

  24. Tuntiviriyapun P, Panyakhamlerd K, Triratanachat S, Chatsuwan T, Chaikittisilpa S, Jaisamrarn U, Taechakraichana N (2015) Newly developed vaginal atrophy symptoms II and vaginal pH: a better correlation in vaginal atrophy? Climacteric 18(2):246–251. https://doi.org/10.3109/13697137.2014.981520

    Article  CAS  PubMed  Google Scholar 

  25. 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/s00192-014-2464-0

    Article  CAS  PubMed  Google Scholar 

  26. Labrie F, Archer D, Bouchard C et al (2009) Serum steroid levels during 12-week intravaginal dehydroepiandrosterone administration. Menopause 16(5):897–906

    Article  PubMed  Google Scholar 

  27. Barton DL, Sloan JA, Shuster LT, et al Impact of vaginal dehydroepiandosterone (DHEA) on vaginal symptoms in female cancer survivors: Trial N10C1 (Alliance), J Clin Oncol, 2014 ASCO Annual Meeting Abstracts. Vol 32 No 15_suppl (May 20 Supplement), 2014: 9507

  28. Christiansen C, Christensen MS, Larsen NE, Transbol IB (1982) Pathophysiological mechanisms of estrogen effect on bone metabolism. Dose-response relationships in early postmenopausal women. J Clin Endocrinol Metab 55(6):1124–1130. https://doi.org/10.1210/jcem-55-6-1124

    Article  CAS  PubMed  Google Scholar 

  29. Birrell SN, Butler LM, Harris JM, Buchanan G, Tilley WD (2007) Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer. FASEB J 21(10):2285–2293. https://doi.org/10.1096/fj.06-7518com

    Article  CAS  PubMed  Google Scholar 

  30. Traish AM, Fetten K, Miner M, Hansen ML, Guay A (2010) Testosterone and risk of breast cancer: appraisal of existing evidence. Horm Mol Biol Clin Invest 2(1):177–190

    CAS  Google Scholar 

  31. Hu DG, Selth LA, Tarulli GA et al (2016) Androgen and estrogen receptors in breast cancer coregulate human UDP-glucuronosyltransferases 2B15 and 2B17. Cancer Res 76(19):5881–5893

    Article  CAS  PubMed  Google Scholar 

  32. Labrie F, Luu-The V, Labrie C et al (2003) Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev 24(2):152–182. https://doi.org/10.1210/er.2001-0031

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Cancer Institute of the National Institutes of Health (grant UG1CA189823, to the Alliance for Clinical Trials in Oncology NCORP Grant) and also in part by the Public Health Service (grants U10CA025224, U10CA035090, U10CA035101, U10CA035103, U10CA035113, U10CA035119, U10CA035267, U10CA035269, U10CA035415, U10CA035431, U10CA035448, U10CA037404, U10CA037417, U10CA052352, U10CA063848, U10CA063849, U10CA180790, UG1CA189863, and UG1CA189971). This work was also supported in part by funds from a grant from the Breast Cancer Research Foundation.

Author information

Authors and Affiliations

  1. University of Michigan School of Nursing, 400 N. Ingalls, Room 4304, Ann Arbor, MI, 48109-5482, USA

    Debra L. Barton

  2. Mayo Clinic, Rochester, MN, USA

    Lynne T. Shuster, Jacqueline Thielen, Richa Sood, Jacqueline M. Lafky & Charles L. Loprinzi

  3. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA

    Travis Dockter & Pamela J. Atherton

  4. Dame Roma Mitchell Laboratories, Department of Medicine, University of Adelaide, Adelaide, SA, 5005, Australia

    Stephen N. Birrell

  5. Southeast Clinical Oncology Research (SCOR) Consortium NCORP, Spartanburg Medical Center, Spartanburg, SC, USA

    Patricia Griffin

  6. Sanford NCI Community Oncology Research Program of the North Central Plains, Sanford Roger Maris Cancer Center, Fargo, ND, USA

    Shelby A. Terstriep

  7. Wichita NCI Community Oncology Research Program, Cancer Center of Kansas, Wichita, KS, USA

    Bassam Mattar

Authors
  1. Debra L. Barton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lynne T. Shuster
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Travis Dockter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pamela J. Atherton
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jacqueline Thielen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stephen N. Birrell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Richa Sood
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Patricia Griffin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shelby A. Terstriep
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bassam Mattar
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jacqueline M. Lafky
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Charles L. Loprinzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Debra L. Barton.

Ethics declarations

Conflict of interest

This study was supported by the National Cancer Institute and the Breast Cancer Research Foundation. None of the authors have any conflicts of interest with either of these two funding agencies. The work is solely that of the authors and does not reflect the views of the funding agencies. The data is under the control of the Statistics and Data Management group of the Alliance and can be produced in support of the analysis described in this paper, if required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barton, D.L., Shuster, L.T., Dockter, T. et al. Systemic and local effects of vaginal dehydroepiandrosterone (DHEA): NCCTG N10C1 (Alliance). Support Care Cancer 26, 1335–1343 (2018). https://doi.org/10.1007/s00520-017-3960-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-017-3960-9

Keywords

Search

Navigation