Skip to main content

Advertisement

SpringerLink
Log in

Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

To provide dermatologists and oncologists with a foundation for practical understanding and uses of 5α-reductase inhibitors and spironolactone for breast cancer patients and survivors receiving endocrine therapies (ETs), including the effect of these treatments on sex hormone levels, any reported drug interactions, and any risk of malignancy.

Methods

All published studies from January 1978 through April 2018 were considered, using databases such as PubMed, Google Scholar, and Science Direct. Forty-seven studies were included in this review.

Results

There is no evidence of interactions between 5α-reductase inhibitors and spironolactone with ETs used in breast cancer. Sex hormone alteration with 5α-reductase inhibitor or spironolactone use is variable. Three randomized controlled trials, 1 case–control study, and 6 retrospective cohort studies, including 284 female patients, studied the effects of 5α-reductase inhibitors on serum estrogen levels. Levels were increased in 97 of 284 (34%) patients, decreased in 15 of 284 (5.3%) patients, and unchanged in 162 of 284 (57%) patients. Four retrospective cohort studies, 1 case study, and 1 double-blinded crossover study, including 95 female patients, assessed the effect of spironolactone on estrogen levels. Levels were increased in 25 of 95 (26%) patients, decreased in 6 of 95 (6.3%) patients, and unchanged in 64 of 95 (67%) patients. Ultimately, most patients did not have a significant alteration in the level of estrogen when using 5α-reductase inhibitors or spironolactone. No consistent evidence of increased risk of female breast cancer while on spironolactone was reported in 3 studies including 49,298 patients; the risk of breast cancer with the use of 5α-reductase inhibitors has not been studied.

Conclusions

Most patients did not show increased estrogen levels with spironolactone and there were no data suggesting increased risk of breast cancer. Based on hormonal and pharmacological activity, spironolactone may be considered for further research on alopecia and hirsutism in breast cancer patients.

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

Similar content being viewed by others

References

  1. World Health Organization. WHO | breast cancer: prevention and control. http://www.who.int/cancer/detection/breastcancer/en/. Accessed 26 Nov 2017

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics (2018) CA Cancer J Clin 2018 68(1):7–30. https://doi.org/10.3322/caac.21442

    Article  Google Scholar 

  3. Moscetti L, Agnese Fabbri M, Sperduti I et al (2015) Adjuvant aromatase inhibitor therapy in early breast cancer: what factors lead patients to discontinue treatment? Tumori 101(5):469. https://doi.org/10.5301/tj.5000376

    Article  CAS  PubMed  Google Scholar 

  4. Saggar V, Wu S, Dickler MN, Lacouture ME (2013) Alopecia with endocrine therapies in patients with cancer. Oncologist 18(10):1126–1134. https://doi.org/10.1634/theoncologist.2013-0193. Epub 13 Sep 2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Smith IE, Dowsett M (2003) Aromatase inhibitors in breast cancer. N Engl J Med 348(24):2431–2442. https://doi.org/10.1056/NEJMra023246. Accessed 6 April 2018

  6. Freites-Martinez A, Shapiro J, van den Hurk C, et al (2018) CME part 2: hair disorders in cancer survivors persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, and hair growth disorders related to endocrine therapy or cancer surgery. J Am Acad Dermatol. https://doi.org/10.1016/j.jaad.2018.03.056

    Article  PubMed  Google Scholar 

  7. Freites-Martinez A, Shapiro J, Chan D et al (2018) Endocrine therapy-induced alopecia in patients with breast cancer. JAMA Dermatol. https://doi.org/10.1001/jamadermatol.2018.0454

  8. Bourgeois H, Kerbrat P, Combe M et al (2010) Long term persistent alopecia and suboptimal hair regrowth after adjuvant chemotherapy for breast cancer: alert for an emerging side effect: French ALOPERS Observatory. Ann Oncol 21:83–84

    Google Scholar 

  9. Kang D, Kim IR, Lee D et al (2017) Incidence of permanent chemotherapy-induced alopecia among breast cancer patients: a five-year prospective cohort study. Ann Oncol 28:22

    Article  Google Scholar 

  10. Kim S, Park H, Kim J et al (2016) Irreversible chemotherapy-induced alopecia in breast cancer patient. Cancer Res. https://doi.org/10.1158/1538-7445.SABCS15-P1-15-04

  11. Masidonski P (2009) Permanent alopecia in women being treated for breast cancer. Clin J Oncol Nurs 13(1):13–15. https://doi.org/10.1188/09.CJON.13-14

    Article  PubMed  Google Scholar 

  12. Bertrand M, Mailliez A, Vercambre S, Kotecki N, Mortier L, Bonneterre J(2013) Permanent chemotherapy induced alopecia in early breast cancer patients after (neo)adjuvant chemotherapy: long term follow up. Cancer Res. https://doi.org/10.1158/0008-5472.SABCS13-P3-09-15

    Article  Google Scholar 

  13. Fonia A, Cota C, Setterfield JF, Goldberg LJ, Fenton DA, Stefanato CM (2017) Permanent alopecia in patients with breast cancer after taxane chemotherapy and adjuvant hormonal therapy: clinicopathologic findings in a cohort of 10 patients. J Am Acad Dermatol 76(5):948–957. https://doi.org/10.1016/j.jaad.2016.12.027

    Article  CAS  PubMed  Google Scholar 

  14. Kluger N, Jacot W, Frouin E et al (2012) Permanent scalp alopecia related to breast cancer chemotherapy by sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel: a prospective study of 20 patients. Ann Oncol 23(11):2879–2884. https://doi.org/10.1093/annonc/mds095. Epub 9 May 2012

    Article  CAS  PubMed  Google Scholar 

  15. Thorp N, Swift F, Arundell D, Wong H (2015) Long term hair loss in patients with early breast cancer receiving docetaxel chemotherapy. Cancer Res. https://doi.org/10.1158/1538-7445.SABCS14-P5-17-04

    Article  Google Scholar 

  16. Otberg N, Shapiro J (2012) Chapter 88. Hair growth disorders. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K (eds) Fitzpatrick’s dermatology in general medicine, 8th edn. The McGraw-Hill Companies, New York. http://accessmedicine.mhmedical.com/content.aspx?aid=56049509. Accessed 25 March 2018

  17. Sinclair R, Wewerinke M, Jolley D (2005) Treatment of female pattern hair loss with oral antiandrogens. Br J Dermatol 152(3):466–473. https://doi.org/10.1111/j.1365-2133.2005.06218.x

    Article  CAS  PubMed  Google Scholar 

  18. van Zuuren EJ, Fedorowicz Z (2017) Interventions for female pattern hair loss. JAMA Dermatol 153(3):329–330. https://doi.org/10.1001/jamadermatol.2016.5790

    Article  PubMed  Google Scholar 

  19. Clinical efficacy of oral administration of finasteride at a dose of 2.5 mg/day in women with female pattern hair loss (2018). Dermatol Ther 31(2):e12588. https://doi.org/10.1111/dth.12588

  20. Camacho-Martinez F (2009) Hair loss in women. Semin Cutan Med Surg 28(1):19–32. https://doi.org/10.1016/j.sder.2009.01.001

    Article  CAS  PubMed  Google Scholar 

  21. Trüeb RM (2004) Finasteride treatment of patterned hair loss in normoandrogenic postmenopausal women. Dermatology 209(3):202–207. https://doi.org/10.1159/000079890. Accessed 20 March 2018

  22. Seale LR, Eglini AN, McMichael AJ (2016) Side effects related to 5 α-reductase inhibitor treatment of hair loss in women: a review. J Drugs Dermatol 15(4):414–419

    CAS  PubMed  Google Scholar 

  23. Gupta AK, Charrette A (2014) The efficacy and safety of 5α-reductase inhibitors in androgenetic alopecia: a network meta-analysis and benefit-risk assessment of finasteride and dutasteride. J Dermatol Treat 25(2):156–161. https://doi.org/10.3109/09546634.2013.813011. Accessed 26 March 2018

  24. Boychenko O, Bernstein RM, Schweiger ES (2012) Finasteride in the treatment of female pattern (androgenic) alopecia: a case report and review of the literature. Cutis 90(2):73–76

    PubMed  Google Scholar 

  25. Yeon JH, Jung JY, Choi JW et al (2011) 5 mg/day finasteride treatment for normoandrogenic asian women with female pattern hair loss. J Eur Acad Dermatol Venereol 25(2):211–214. https://doi.org/10.1111/j.1468-3083.2010.03758.x. Accessed 26 March 2018

  26. Mella JM, Perret MC, Manzotti M, Catalano HN, Guyatt G (2010) Efficacy and safety of finasteride therapy for androgenetic alopecia: a systematic review. Arch Dermatol 146(10):1141–1150. https://doi.org/10.1001/archdermatol.2010.256. Accessed 26 March 2018

  27. Iorizzo M, Vincenzi C, Voudouris S, Piraccini BM, Tosti A (2006) Finasteride treatment of female pattern hair loss. Arch Dermatol 142(3):298–302. https://doi.org/10.1001/archderm.142.3.298. Accessed 26 March 2018

  28. Price VH, Roberts JL, Hordinsky M et al (2000) Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia. J Am Acad Dermatol 43(5 Pt 1):768–776. https://doi.org/10.1067/mjd.2000.107953. Accessed 20 March 2018

  29. Moghetti P, Castello R, Magnani CM et al (1994) Clinical and hormonal effects of the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism. J Clin Endocrinol Metab 79(4):1115–1121. https://doi.org/10.1210/jcem.79.4.7962284. Accessed 11 April 2018

  30. Wong IL, Morris RS, Chang L, Spahn MA, Stanczyk FZ, Lobo RA (1995) A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J Clin Endocrinol Metab 80(1):233–238. https://doi.org/10.1210/jcem.80.1.7829618

    Article  CAS  PubMed  Google Scholar 

  31. Castello R, Tosi F, Perrone F, Negri C, Muggeo M, Moghetti P (1996) Outcome of long-term treatment with the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism: clinical and hormonal effects during a 1-year course of therapy and 1-year follow-up. Fertil Steril 66(5):734–740. http://www.ncbi.nlm.nih.gov/pubmed/8893676

  32. Venturoli S, Marescalchi O, Colombo FM et al (1999) A prospective randomized trial comparing low dose flutamide, finasteride, ketoconazole, and cyproterone acetate-estrogen regimens in the treatment of hirsutism. J Clin Endocrinol Metab 84(4):1304–1310. https://doi.org/10.1210/jcem.84.4.5591

    Article  CAS  PubMed  Google Scholar 

  33. Shum KW, Cullen DR, Messenger AG (2002) Hair loss in women with hyperandrogenism: four cases responding to finasteride. J Am Acad Dermatol 47(5):733–739

    Article  PubMed  Google Scholar 

  34. Somani N (2014) Hirsutism: an evidence-based treatment update. Am J Clin Dermatol 15(3):247–267. https://doi.org/10.1007/s40257-014-0078-4

    Article  PubMed  Google Scholar 

  35. Rossi A, Iorio A, Scali E et al (2013) Aromatase inhibitors induce ‘male pattern hair loss’ in women? Ann Oncol Off J Eur Soc Med Oncol 24(6):1710. https://doi.org/10.1093/annonc/mdt170

    Article  CAS  Google Scholar 

  36. Price VH (1975) Testosterone metabolism in the skin. A review of its function in androgenetic alopecia, acne vulgaris, and idiopathic hirsutism including recent studies with antiandrogens. Arch Dermatol 111(11):1496–1502

    Article  CAS  PubMed  Google Scholar 

  37. Kaufman KD (1996) Androgen metabolism as it affects hair growth in androgenetic alopecia. Dermatol Clin 14(4):697–711

    Article  CAS  PubMed  Google Scholar 

  38. Price VH (1999) Treatment of hair loss. N Engl J Med 341(13):964–973. https://doi.org/10.1056/NEJM199909233411307. Accessed 19 March 2018

  39. Vexiau P, Chaspoux C, Boudou P et al (2000) Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism. Arch Dermatol Res 292(12):598–604

    Article  CAS  PubMed  Google Scholar 

  40. Ohnemus U, Uenalan M, Inzunza J, Gustafsson J, Paus R (2006) The hair follicle as an estrogen target and source. Endocr Rev 27(6):677–706. https://doi.org/10.1210/er.2006-0020. Accessed 31 May 2018

  41. Conrad F, Ohnemus U, Bodo E et al (2005) Substantial sex-dependent differences in the response of human scalp hair follicles to estrogen stimulation in vitro advocate gender-tailored management of female versus male pattern balding. J Investig Dermatol Symp Proc 10(3):243–246. https://doi.org/10.1111/j.1087-0024.2005.10115.x.Accessed 31 May 2018

  42. Langan EA, Paus R (2010) Female pattern hair loss: beyond an androgenic aetiology? Br J Dermatol 163(5):1142. https://doi.org/10.1111/j.1365-2133.2010.09955.x. Accessed 31 May 2018

  43. Bickenbach KA, Jaskowiak N (2006) Aromatase inhibitors: an overview for surgeons. J Am Coll Surg 203(3):376–389. https://doi.org/10.1016/j.jamcollsurg.2006.05.291. Accessed 19 March 2018

  44. Yu H, Shu X, Shi R et al (2003) Plasma sex steroid hormones and breast cancer risk in Chinese women. Int J Cancer 105(1):92–97. https://doi.org/10.1002/ijc.11034. Accessed 19 March 2018

  45. Del Re M, Michelucci A, Simi P, Danesi R (2012) Pharmacogenetics of anti-estrogen treatment of breast cancer. Cancer Treat Rev 38(5):442–450. https://doi.org/10.1016/j.ctrv.2011.08.003

    Article  CAS  PubMed  Google Scholar 

  46. Boutin JA (1994) Tyrosine protein kinase inhibition and cancer. Int J Biochem 26(10–11):1203–1226

    Article  CAS  PubMed  Google Scholar 

  47. Fortunati N (1999) Sex hormone-binding globulin: not only a transport protein. What news is around the corner? J Endocrinol Investig 22(3):223–234. https://doi.org/10.1007/BF03343547. Accessed 19 March 2018

  48. Yip L, Zaloumis S, Irwin D et al (2009) Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss. Br J Dermatol 161(2):289–294. https://doi.org/10.1111/j.1365-2133.2009.09186.x. Accessed 20 March 2018

  49. Yip L, Rufaut N, Sinclair R (2011) Role of genetics and sex steroid hormones in male androgenetic alopecia and female pattern hair loss: an update of what we now know. Australas J Dermatol 52(2):81–88. https://doi.org/10.1111/j.1440-0960.2011.00745.x. Accessed 20 March 2018

  50. Mirmirani P (2011) Hormonal changes in menopause: do they contribute to a ‘midlife hair crisis’ in women? Br J Dermatol 165(Suppl 3):7–11. https://doi.org/10.1111/j.1365-2133.2011.10629.x. Accessed 20 March 2018

  51. Neven P, Paridaens R, Pelgrims G et al (2008) Fulvestrant (faslodex) in advanced breast cancer: clinical experience from a Belgian Cooperative Study. Breast Cancer Res Treat 109(1):59–65. https://doi.org/10.1007/s10549-007-9628-2. Accessed 19 March 2018

  52. Atanaskova Mesinkovska N, Bergfeld WF (2013) Hair: what is new in diagnosis and management? Female pattern hair loss update: diagnosis and treatment. Dermatol Clin 31(1):119–127. https://doi.org/10.1016/j.det.2012.08.005. Accessed 20 March 2018

  53. Gallicchio L, Calhoun C, Helzlsouer KJ (2013) Aromatase inhibitor therapy and hair loss among breast cancer survivors. Breast Cancer Res Treat 142(2):435–443. https://doi.org/10.1007/s10549-013-2744-2. Accessed 19 March 2018

  54. Futterweit W, Dunaif A, Yeh HC, Kingsley P (1988) The prevalence of hyperandrogenism in 109 consecutive female patients with diffuse alopecia. J Am Acad Dermatol 19(5 Pt 1):831–836

    Article  CAS  PubMed  Google Scholar 

  55. Fruzzetti F, de Lorenzo D, Parrini D, Ricci C (1994) Effects of finasteride, a 5 alpha-reductase inhibitor, on circulating androgens and gonadotropin secretion in hirsute women. J Clin Endocrinol Metab 79(3):831–835. https://doi.org/10.1210/jcem.79.3.8077369

    Article  CAS  PubMed  Google Scholar 

  56. Ciotta L, Cianci A, Calogero AE et al (1995) Clinical and endocrine effects of finasteride, a 5 alpha-reductase inhibitor, in women with idiopathic hirsutism. Fertil Steril 64(2):299–306. http://www.ncbi.nlm.nih.gov/pubmed/7615107

  57. Bayhan G, Bahceci M, Demirkol T, Ertem M, Yalinkaya A, Erden AC (2000) A comparative study of a gonadotropin-releasing hormone agonist and finasteride on idiopathic hirsutism. Clin Exp Obstet Gynecol 27(3–4):203–206. http://www.ncbi.nlm.nih.gov/pubmed/11214952

  58. Bayram F, Muderris II, Guven M, Kelestimur F (2002) Comparison of high-dose finasteride (5 mg/day) versus low-dose finasteride (2.5 mg/day) in the treatment of hirsutism. Eur J Endocrinol 147(4):467–471. http://www.ncbi.nlm.nih.gov/pubmed/12370107

  59. Tartagni M, Schonauer MM, Cicinelli E et al (2004) Intermittent low-dose finasteride is as effective as daily administration for the treatment of hirsute women. Fertil Steril 82(3):752–755. https://doi.org/10.1016/j.fertnstert.2004.02.118

    Article  CAS  PubMed  Google Scholar 

  60. Fruzzetti F, Bersi C, Parrini D, Ricci C, Genazzani AR (1999) Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects. Fertil Steril 71(3):445–451. http://www.ncbi.nlm.nih.gov/pubmed/10065780

  61. Moghetti P, Tosi F, Tosti A et al (2000) Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a randomized, double blind, placebo-controlled trial. J Clin Endocrinol Metab 85(1):89–94. https://doi.org/10.1210/jcem.85.1.6245

    Article  CAS  PubMed  Google Scholar 

  62. Beigi A, Sobhi A, Zarrinkoub F (2004) Finasteride versus cyproterone acetate-estrogen regimens in the treatment of hirsutism. Int J Gynaecol Obstet 87(1):29–33. https://doi.org/10.1016/j.ijgo.2004.06.003

    Article  CAS  PubMed  Google Scholar 

  63. Faloia E, Filipponi S, Mancini V, Di Marco S, Mantero F (1998) Effect of finasteride in idiopathic hirsutism. J Endocrinol Investig 21(10):694–698. https://doi.org/10.1007/BF03350800

    Article  CAS  Google Scholar 

  64. Sahin Y, Bayram F, Kelestimur F, Muderris I (1998) Comparison of cyproterone acetate plus ethinyl estradiol and finasteride in the treatment of hirsutism. J Endocrinol Investig 21(6):348–352. https://doi.org/10.1007/BF03350769

    Article  CAS  Google Scholar 

  65. Bayram F, Muderris II, Sahin Y, Kelestimur F (1999) Finasteride treatment for one year in 35 hirsute patients. Exp Clin Endocrinol Diabetes 107(3):195–197. https://doi.org/10.1055/s-0029-1212097

    Article  CAS  PubMed  Google Scholar 

  66. Bayram F, Müderris I, Güven M, Ozçelik B, Keleştimur F (2003) Low-dose (2.5 mg/day) finasteride treatment in hirsutism. Gynecol Endocrinol 17(5):419–422

    Article  CAS  PubMed  Google Scholar 

  67. Muderris II, Bayram F, Guven M (2000) A prospective, randomized trial comparing flutamide (250 mg/day) and finasteride (5 mg/day) in the treatment of hirsutism. Fertil Steril 73(5):984–987. http://www.ncbi.nlm.nih.gov/pubmed/10785225

  68. Lakryc EM, Motta EL, Soares Jr JM, Haidar MA, de Lima GR, Baracat EC (2003) The benefits of finasteride for hirsute women with polycystic ovary syndrome or idiopathic hirsutism. Gynecol Endocrinol 17(1):57–63. http://www.ncbi.nlm.nih.gov/pubmed/12724020

  69. Falsetti L, Gambera A, Legrenzi L, Iacobello C, Bugari G (1999) Comparison of finasteride versus flutamide in the treatment of hirsutism. Eur J Endocrinol 141(4):361–367. http://www.ncbi.nlm.nih.gov/pubmed/10526249

  70. Olsen EA, Hordinsky M, Whiting D et al (2006) The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride. J Am Acad Dermatol 55(6):1014–1023. https://doi.org/10.1016/j.jaad.2006.05.007

    Article  PubMed  Google Scholar 

  71. Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G (2002) Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 60(3):434–441

    Article  PubMed  Google Scholar 

  72. Drake L, Hordinsky M, Fiedler V et al (1999) The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J Am Acad Dermatol 41(4):550–554

    CAS  PubMed  Google Scholar 

  73. Chau CH, Price DK, Till C et al (2015) Finasteride concentrations and prostate cancer risk: results from the prostate cancer prevention trial. PLoS ONE 10(5):e0126672. http://www.ncbi.nlm.nih.gov/pubmed/25955319

  74. Duijnhoven RG, Straus SM, Souverein PC et al (2014) Long-term use of 5alpha-reductase inhibitors and the risk of male breast cancer. Cancer Causes Control 25(11):1577–1582. https://doi.org/10.1007/s10552-014-0455-6. Epub 19 Aug 2014

    Article  PubMed  Google Scholar 

  75. Bird ST, Brophy JM, Hartzema AG, Delaney JA, Etminan M (2013) Male breast cancer and 5alpha-reductase inhibitors finasteride and dutasteride. J Urol 190(5):1811–1814. https://doi.org/10.1016/j.juro.2013.04.132. Epub 9 May 2013

    Article  CAS  PubMed  Google Scholar 

  76. Meijer M, Thygesen LC, Green A et al (2018) Finasteride treatment and male breast cancer: a register-based cohort study in four Nordic countries. Cancer Med 7(1):254–260. https://doi.org/10.1002/cam4.1273

    Article  CAS  PubMed  Google Scholar 

  77. Gardiner P, Schrode K, Quinlan D et al (1989) Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites. J Clin Pharmacol 29(4):342–347

    Article  CAS  PubMed  Google Scholar 

  78. Li CI, Malone KE, Weiss NS, Boudreau DM, Cushing-Haugen K, Daling JR (2003) Relation between use of antihypertensive medications and risk of breast carcinoma among women ages 65–79 years. Cancer 98(7):1504–1513. https://doi.org/10.1002/cncr.11663

    Article  PubMed  Google Scholar 

  79. Fryzek JP, Poulsen AH, Lipworth L et al (2006) A cohort study of antihypertensive medication use and breast cancer among Danish women. Breast Cancer Res Treat 97(3):231–236. https://doi.org/10.1007/s10549-005-9091-x. Accessed 24 March 2018

  80. Biggar RJ, Andersen EW, Wohlfahrt J, Melbye M (2013) Spironolactone use and the risk of breast and gynecologic cancers. Cancer Epidemiol 37(6):870–875. https://doi.org/10.1016/j.canep.2013.10.004. Epub 1 Nov 2013

    Article  PubMed  Google Scholar 

  81. Mackenzie IS, Macdonald TM, Thompson A, Morant S, Wei L (2012) Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. BMJ 345:e4447

    Article  PubMed  PubMed Central  Google Scholar 

  82. Mackenzie IS, Morant SV, Wei L, Thompson AM, MacDonald TM (2017) Spironolactone use and risk of incident cancers: a retrospective, matched cohort study. Br J Clin Pharmacol 83(3):653–663. https://doi.org/10.1111/bcp.13152. Accessed 17 March 2018

  83. Ober KP, Hennessy JF (1978) Spironolactone therapy for hirsutism in a hyperandrogenic woman. Ann Intern Med 89(5):643–644. http://www.ncbi.nlm.nih.gov/pubmed/717935

  84. Ganie MA, Khurana ML, Nisar S et al (2013) Improved efficacy of low-dose spironolactone and metformin combination than either drug alone in the management of women with polycystic ovary syndrome (PCOS): a six-month, open-label randomized study. J Clin Endocrinol Metab 98(9):3599–3607. https://doi.org/10.1210/jc.2013-1040. Epub 11 July 2013

    Article  CAS  PubMed  Google Scholar 

  85. Boisselle A, Tremblay RR (1979) New therapeutic approach to the hirsute patient. Fertil Steril 32(3):276–279. http://www.ncbi.nlm.nih.gov/pubmed/488407

  86. Cumming DC, Yang JC, Rebar RW, Yen SS (1982) Treatment of hirsutism with spironolactone. JAMA 247(9):1295–1298. http://www.ncbi.nlm.nih.gov/pubmed/7199587

  87. Milewicz A, Silber D, Kirschner MA (1983) Therapeutic effects of spironolactone in polycystic ovary syndrome. Obstet Gynecol 61(4):429–432. http://www.ncbi.nlm.nih.gov/pubmed/6828272

  88. Lobo RA, Shoupe D, Serafini P, Brinton D, Horton R (1985) The effects of two doses of spironolactone on serum androgens and anagen hair in hirsute women. Fertil Steril 43(2):200–205. http://www.ncbi.nlm.nih.gov/pubmed/3967781

  89. Shapiro G, Evron S (1980) A novel use of spironolactone: treatment of hirsutism. J Clin Endocrinol Metab 51(3):429–432. https://doi.org/10.1210/jcem-51-3-429

    Article  CAS  PubMed  Google Scholar 

  90. Dorrington-Ward P, McCartney AC, Holland S et al (1985) The effect of spironolactone on hirsutism and female androgen metabolism. Clin Endocrinol (Oxf) 23(2):161–167. http://www.ncbi.nlm.nih.gov/pubmed/4053414

  91. Smals AG, Kloppenborg PW, Hoefnagels WH, Drayer JI (1979) Pituitary–thyroid function in spironolactone treated hypertensive women. Acta Endocrinol 90(4):577–584. http://www.ncbi.nlm.nih.gov/pubmed/107696

  92. Siegberg R, Ylostalo P, Laatikainen T, Pelkonen R, Stenman UH (1987) Endocrine and clinical effects of spironolactone in female hyperandrogenism. Arch Gynecol 240(2):67–73. http://www.ncbi.nlm.nih.gov/pubmed/3566358

  93. Erenus M, Yucelten D, Durmusoglu F, Gurbuz O (1997) Comparison of finasteride versus spironolactone in the treatment of idiopathic hirsutism. Fertil Steril 68(6):1000–1003. http://www.ncbi.nlm.nih.gov/pubmed/9418687

  94. Spritzer PM, Lisboa KO, Mattiello S, Lhullier F (2000) Spironolactone as a single agent for long-term therapy of hirsute patients. Clin Endocrinol (Oxf) 52(5):587–594. http://www.ncbi.nlm.nih.gov/pubmed/10792338

  95. Sert M, Tetiker T, Kirim S (2003) Comparison of the efficiency of anti-androgenic regimens consisting of spironolactone, Diane 35, and cyproterone acetate in hirsutism. Acta Med Okayama 57(2):73–76. http://www.ncbi.nlm.nih.gov/pubmed/12866746

  96. Lumachi F, Rondinone R (2003) Use of cyproterone acetate, finasteride, and spironolactone to treat idiopathic hirsutism. Fertil Steril 79(4):942–946. http://www.ncbi.nlm.nih.gov/pubmed/12749435

  97. Kelestimur F, Everest H, Unluhizarci K, Bayram F, Sahin Y (2004) A comparison between spironolactone and spironolactone plus finasteride in the treatment of hirsutism. Eur J Endocrinol 150(3):351–354. http://www.ncbi.nlm.nih.gov/pubmed/15012621

  98. Yemisci A, Gorgulu A, Piskin S (2005) Effects and side-effects of spironolactone therapy in women with acne. J Eur Acad Dermatol Venereol 19(2):163–166. https://doi.org/10.1111/j.1468-3083.2005.01072.x

    Article  CAS  PubMed  Google Scholar 

  99. Some thyrotropic agents (2001) IARC monographs on the evaluation of carcinogenic risks to humans, No. 79, p 725

  100. Duvic M, Lemak NA, Valero V et al (1996) A randomized trial of minoxidil in chemotherapy-induced alopecia. J Am Acad Dermatol 35(1):74–78. https://doi.org/10.1016/S0190-9622(96)90500-9

    Article  CAS  PubMed  Google Scholar 

  101. Rodriguez R, Machiavelli M, Leone B et al (1994) Minoxidil (mx) as a prophylaxis of doxorubicin-induced alopecia. Ann Oncol 5(8):769–770. http://www.ncbi.nlm.nih.gov/pubmed/7826913

  102. Uno H, Cappas A, Brigham P (1987) Action of topical minoxidil in the bald stump-tailed macaque. J Am Acad Dermatol 16(3 Pt 2):657–668

    Article  CAS  PubMed  Google Scholar 

  103. Hsu C, Liu J, Lin A, Yang C, Chung W, Wu W (2014) Minoxidil may suppress androgen receptor-related functions. OncoTarget 5(8):2187–2197. https://doi.org/10.18632/oncotarget.1886. Accessed 7 April 2018

  104. Buhl AE, Waldon DJ, Kawabe TT, Holland JM (1989) Minoxidil stimulates mouse vibrissae follicles in organ culture. J Investig Dermatol 92(3):315–320

    Article  CAS  PubMed  Google Scholar 

  105. Buhl AE (1991) Minoxidil’s action in hair follicles. J Investig Dermatol 96(5):74S

    Article  Google Scholar 

  106. Burke BM, Cunliffe WJ (1985) Oral spironolactone therapy for female patients with acne, hirsutism or androgenic alopecia. Br J Dermatol 112(1):124–125. http://www.ncbi.nlm.nih.gov/pubmed/3155956

  107. Rathnayake D, Sinclair R (2010) Innovative use of spironolactone as an antiandrogen in the treatment of female pattern hair loss. Dermatol Clin 28(3):611–618. https://doi.org/10.1016/j.det.2010.03.011

    Article  CAS  PubMed  Google Scholar 

  108. Sawaya ME, Price VH (1997) Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. J Investig Dermatol 109(3):296–300. Accessed 19 March 2018

  109. Tolino A, Petrone A, Sarnacchiaro F et al (1996) Finasteride in the treatment of hirsutism: new therapeutic perspectives. Fertil Steril 66(1):61–65. http://www.ncbi.nlm.nih.gov/pubmed/8752612

Download references

Funding

This study was supported in part by the NIH/NCI Cancer Center Support Grant P30 CA008748. This research was additionally funded in part by Beca Excelencia Fundación Piel Sana (Dr. Freites-Martinez) and the RJR Grant. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Dermatology, Memorial Sloan-Kettering Cancer Center, 16 East 60th Street, Suite 407, 4th Floor, New York, NY, 10022, USA

    Raquel N. Rozner, Azael Freites-Martinez & Mario E. Lacouture

  2. The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA

    Jerry Shapiro

  3. Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Eliza B. Geer

  4. Breast Medicine Service, Memorial Sloan Kettering Cancer Center, and Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    Shari Goldfarb

Authors
  1. Raquel N. Rozner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azael Freites-Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jerry Shapiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eliza B. Geer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shari Goldfarb
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mario E. Lacouture
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario E. Lacouture.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest with regard to the preparation of this manuscript.

Disclosures

Mario E. Lacouture has no relevant conflicts of interest with regard to preparation of this manuscript. He has served as consultant for Legacy, Adgero, Debiopharm,Galderma, Johnson and Johnson, Novocure Inc., Merck, Helsinn, Janssen, Menlo Ther, Novartis, Roche, Abbvie, Boehringer Ingelheim, Amgen, E.R. Squibb & Sons, EMD Serono, Genentech, Seattle Genetics, Bayer, Manner SAS,  Lutris, Paxman Coolers, Pfizer, Bristol-Myers Squibb, Silk Therapeutics, Foamix, and Medische Voet. He has received research funding from GSK, Novartis, Veloce, US Biotest, Berg, Bristol-Myers Squibb. Eliza B. Geer has no relevant conflicts of interest with regard to preparation of this manuscript. She has served as the principal investigator of research grants to MSKCC from Novartis, Strongbridge, Chiasma, and IONIS and has received occasional consulting honoraria from Novartis, Strongbridge, Corcept, and Pfizer. Jerry Shapiro has no relevant conflicts of interest with regard to preparation of this manuscript. He has served as a consultant for Aclaris, Samumed, Incyte, Replicel Life Sciences, and Shook, Hardy, Bacon LLP who represent Sanofi Aventis US LLC.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rozner, R.N., Freites-Martinez, A., Shapiro, J. et al. Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies. Breast Cancer Res Treat 174, 15–26 (2019). https://doi.org/10.1007/s10549-018-4996-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-018-4996-3

Keywords

Search

Navigation