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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

Long-Lasting Effects of Spironolactone after its Withdrawal in Patients with Hyperandrogenic Skin Disorders

Author(s): Chiara Sabbadin*, Francesca Beggiao, Carlotta Keiko Vedolin, Gloria Orlando, Eugenio Ragazzi, Filippo Ceccato, Mattia Barbot, Luciana Bordin, Gabriella Donà, Alessandra Andrisani, Anna Belloni Fortina, Carla Scaroni and Decio Armanini

Volume 23, Issue 2, 2023

Published on: 07 September, 2022

Page: [188 - 195] Pages: 8

DOI: 10.2174/1871530322666220509051746

Price: $65

Abstract

Objective: Hyperandrogenic skin disorders, such as hirsutism, acne and alopecia, affect approximately 10-20% of women of reproductive age, reducing quality of life and causing psychological impairment. Spironolactone is a commonly used antiandrogen, especially in women who are not sexually active or have contraindications to hormonal contraceptives. The aim of this study was to evaluate the effects of spironolactone, especially after its withdrawal, in patients with hyperandrogenic skin disorders.

Methods: Retrospective analysis of 63 women with hyperandrogenic skin symptoms due to polycystic ovary syndrome (PCOS), treated with spironolactone for at least 6 months as first-line treatment.

Results: After a mean time of treatment of 25.7 months, all patients reported a significant improvement in hyperandrogenic skin disorders; only 5 patients were dissatisfied and required the addition of an oral contraceptive. The therapy was well tolerated and the most frequent side-effect was intermestrual bleeding in 68.2% of cases, affecting mainly classic PCOS phenotype. Thirthyeight patients showed prolonged effects 33.7 months after spironolactone withdrawal, whereas 20 relapsed 17.5 months after discontinuation. No significant difference in clinical and biochemical parameters was observed between these two groups both at baseline and after spironolactone treatment. Ovulatory PCOS patients were treated for a shorter time and reported earlier relapse than classic PCOS patients.

Conclusion: Spironolactone is an effective and safe treatment for hyperandrogenic skin disorders, showing long-lasting effects even several months after its discontinuation.

Keywords: Spironolactone, anti-androgens, PCOS, hyperandrogenism, hirsutism, acne, alopecia.

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[1]
Redmond, G.P. Androgens and women’s health. Int. J. Fertil. Womens Med., 1998, 43(2), 91-97.
[PMID: 9609208]
[2]
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syn-drome (PCOS). Hum. Reprod., 2004, 19(1), 41-47.
[http://dx.doi.org/10.1093/humrep/deh098]
[3]
Legro, R.S.; Arslanian, S.A.; Ehrmann, D.A.; Hoeger, K.M.; Murad, M.H.; Pasquali, R.; Welt, C.K. Diagnosis and treatment of polycystic ovary syndrome: An Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab., 2013, 98(12), 4565-4592.
[http://dx.doi.org/10.1210/jc.2013-2350] [PMID: 24151290]
[4]
Martin, K.A.; Anderson, R.R.; Chang, R.J.; Ehrmann, D.A.; Lobo, R.A.; Murad, M.H.; Pugeat, M.M.; Rosenfield, R.L. Evaluation and treatment of hirsutism in premenopausal women: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab., 2018, 103(4), 1233-1257.
[http://dx.doi.org/10.1210/jc.2018-00241] [PMID: 29522147]
[5]
Armanini, D.; Andrisani, A.; Bordin, L.; Sabbadin, C. Spironolactone in the treatment of polycystic ovary syndrome. Expert Opin. Pharmacother., 2016, 17(13), 1713-1715.
[http://dx.doi.org/10.1080/14656566.2016.1215430] [PMID: 27450358]
[6]
Lobo, R.A.; Shoupe, D.; Serafini, P.; Brinton, D.; Horton, R. The effects of two doses of spironolactone on serum andro-gens and anagen hair in hirsute women. Fertil. Steril., 1985, 43(2), 200-205.
[http://dx.doi.org/10.1016/S0015-0282(16)48373-1] [PMID: 3967781]
[7]
Carmina, E.; Lobo, R.A. Peripheral androgen blockade versus glandular androgen suppression in the treatment of hirsutism. Obstet. Gynecol., 1991, 78(5 Pt 1), 845-849.
[PMID: 1833685]
[8]
Sabbadin, C.; Andrisani, A.; Zermiani, M.; Donà, G.; Bordin, L.; Ragazzi, E.; Boscaro, M.; Ambrosini, G.; Armanini, D. Spi-ronolactone and intermenstrual bleeding in polycystic ovary syndrome with normal BMI. J. Endocrinol. Invest., 2016, 39(9), 1015-1021.
[http://dx.doi.org/10.1007/s40618-016-0466-0] [PMID: 27072668]
[9]
Moghetti, P.; Tosi, F.; Tosti, A.; Negri, C.; Misciali, C.; Perrone, F.; Caputo, M.; Muggeo, M.; Castello, R. Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: A randomized, double blind, placebo-controlled trial. J. Clin. Endocrinol. Metab., 2000, 85(1), 89-94.
[http://dx.doi.org/10.1210/jc.85.1.89] [PMID: 10634370]
[10]
Ezeh, U.; Huang, A.; Landay, M.; Azziz, R. Long-term re-sponse of hirsutism and other hyperandrogenic symptoms to combination therapy in polycystic ovary syndrome. J. Womens Health (Larchmt.), 2018, 27(7), 892-902.
[http://dx.doi.org/10.1089/jwh.2017.6833] [PMID: 29878857]
[11]
Charny, J.W.; Choi, J.K.; James, W.D. Spironolactone for the treatment of acne in women, a retrospective study of 110 pa-tients. Int. J. Womens Dermatol., 2017, 3(2), 111-115.
[http://dx.doi.org/10.1016/j.ijwd.2016.12.002] [PMID: 28560306]
[12]
Roberts, E.E.; Nowsheen, S.; Davis, M.D.P.; McEvoy, M.T.; Newman, C.C.; Sartori Valinotti, J.C.; Sciallis, G.F.; Torgerson, R.R.; Wetter, D.A. Treatment of acne with spironolactone: A retrospective review of 395 adult patients at Mayo Clinic, 2007-2017. J. Eur. Acad. Dermatol. Venereol., 2020, 34(9), 2106-2110.
[http://dx.doi.org/10.1111/jdv.16302] [PMID: 32078195]
[13]
van Zuuren, E.J.; Fedorowicz, Z.; Schoones, J. Interventions for female pattern hair loss. Cochrane Database Syst. Rev., 2016, 2016(5), CD007628.
[PMID: 27225981]
[14]
Sinclair, R.; Wewerinke, M.; Jolley, D. Treatment of female pattern hair loss with oral antiandrogens. Br. J. Dermatol., 2005, 152(3), 466-473.
[http://dx.doi.org/10.1111/j.1365-2133.2005.06218.x ] [PMID: 15787815]
[15]
Lumachi, F.; Rondinone, R. Use of cyproterone acetate, finasteride, and spironolactone to treat idiopathic hirsutism. Fertil. Steril., 2003, 79(4), 942-946.
[http://dx.doi.org/10.1016/S0015-0282(02)04927-0] [PMID: 12749435]
[16]
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syn-drome. Fertil. Steril., 2004, 81(1), 19-25.
[http://dx.doi.org/10.1016/j.fertnstert.2003.10.004]
[17]
Escobar-Morreale, H.F.; Carmina, E.; Dewailly, D.; Gam-bineri, A.; Kelestimur, F.; Moghetti, P.; Pugeat, M.; Qiao, J.; Wijeyaratne, C.N.; Witchel, S.F.; Norman, R.J. Epidemiology, diagnosis and management of hirsutism: A consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum. Reprod. Update, 2012, 18(2), 146-170.
[http://dx.doi.org/10.1093/humupd/dmr042] [PMID: 22064667]
[18]
Tan, J.K.; Tang, J.; Fung, K.; Gupta, A.K.; Thomas, D.R.; Sapra, S.; Lynde, C.; Poulin, Y.; Gulliver, W.; Sebaldt, R.J. Development and validation of a comprehensive acne severity scale. J. Cutan. Med. Surg., 2007, 11(6), 211-216.
[http://dx.doi.org/10.2310/7750.2007.00037] [PMID: 18042334]
[19]
Ludwig, E. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Br. J. Dermatol., 1977, 97(3), 247-254.
[http://dx.doi.org/10.1111/j.1365-2133.1977.tb15179.x ] [PMID: 921894]
[20]
Matthews, D.R.; Hosker, J.P.; Rudenski, A.S.; Naylor, B.A.; Treacher, D.F.; Turner, R.C. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 1985, 28(7), 412-419.
[http://dx.doi.org/10.1007/BF00280883] [PMID: 3899825]
[21]
Sabbadin, C.; Calò, L.A.; Armanini, D. The story of spironolac-tones from 1957 to now: From sodium balance to inflammation. G. Ital. Nefrol., 2016, 33(Suppl. 66), 33.
[22]
Starace, M.; Orlando, G.; Alessandrini, A.; Piraccini, B.M. Female androgenetic alopecia: An update on diagnosis and management. Am. J. Clin. Dermatol., 2020, 21(1), 69-84.
[http://dx.doi.org/10.1007/s40257-019-00479-x] [PMID: 31677111]
[23]
Habeshian, K.A.; Cohen, B.A. Current issues in the treatment of acne vulgaris. Pediatrics, 2020, 145(Suppl. 2), S225-S230.
[http://dx.doi.org/10.1542/peds.2019-2056L] [PMID: 32358215]
[24]
Shenoy, N.K.; Prabhakar, S.M. Finasteride and male breast cancer: Does the MHRA report show a link? J. Cutan. Aesthet. Surg., 2010, 3(2), 102-105.
[PMID: 21031070]
[25]
Mackenzie, I.S.; Macdonald, T.M.; Thompson, A.; Morant, S.; Wei, L. .Spironolactone and risk of incident breast cancer in women older than 55 years: Retrospective, matched cohort study. BMJ, 2012, 345(jul13 1), e4447.
[http://dx.doi.org/10.1136/bmj.e4447] [PMID: 22797844]
[26]
Biggar, R.J.; Andersen, E.W.; Wohlfahrt, J.; Melbye, M. Spironolactone use and the risk of breast and gynecologic cancers. Cancer Epidemiol., 2013, 37(6), 870-875.
[http://dx.doi.org/10.1016/j.canep.2013.10.004] [PMID: 24189467]
[27]
Armanini, D.; Bordin, L.; Donà, G.; Sabbadin, C.; Bakdounes, L.; Ragazzi, E.; Giorgino, F.L.; Fiore, C. Polycystic ovary syn-drome: Implications of measurement of plasma aldosterone, renin activity and progesterone. Steroids, 2012, 77(6), 655-658.
[http://dx.doi.org/10.1016/j.steroids.2012.02.010] [PMID: 22387621]
[28]
Sabbadin, C.; Andrisani, A.; Ambrosini, G.; Bordin, L.; Donà, G.; Manso, J.; Ceccato, F.; Scaroni, C.; Armanini, D. Aldoste-rone in gynecology and its involvement on the risk of hypertension in pregnancy. Front. Endocrinol. (Lausanne), 2019, 10, 575.
[http://dx.doi.org/10.3389/fendo.2019.00575] [PMID: 31507531]
[29]
Zulian, E.; Sartorato, P.; Benedini, S.; Baro, G.; Armanini, D.; Mantero, F.; Scaroni, C. Spironolactone in the treatment of polycystic ovary syndrome: Effects on clinical features, insulin sensitivity and lipid profile. J. Endocrinol. Invest., 2005, 28(1), 49-53.
[http://dx.doi.org/10.1007/BF03345529] [PMID: 15816371]
[30]
Plovanich, M.; Weng, Q.Y.; Mostaghimi, A. Low usefulness of potassium monitoring among healthy young women taking spironolactone for acne. JAMA Dermatol., 2015, 151(9), 941-944.
[http://dx.doi.org/10.1001/jamadermatol.2015.34] [PMID: 25796182]
[31]
Armanini, D.; Castello, R.; Scaroni, C.; Bonanni, G.; Faccini, G.; Pellati, D.; Bertoldo, A.; Fiore, C.; Moghetti, P. Treatment of polycystic ovary syndrome with spironolactone plus licorice. Eur. J. Obstet. Gynecol. Reprod. Biol., 2007, 131(1), 61-67.
[http://dx.doi.org/10.1016/j.ejogrb.2006.10.013] [PMID: 17113210]
[32]
Sabbadin, C.; Bordin, L.; Donà, G.; Manso, J.; Avruscio, G.; Armanini, D. Licorice: From pseudohyperaldosteronism to therapeutic uses. Front. Endocrinol. (Lausanne), 2019, 10, 484.
[http://dx.doi.org/10.3389/fendo.2019.00484] [PMID: 31379750]
[33]
Castello, R.; Tosi, F.; Perrone, F.; Negri, C.; Muggeo, M.; Moghetti, P. 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., 1996, 66(5), 734-740.
[http://dx.doi.org/10.1016/S0015-0282(16)58627-0] [PMID: 8893676]
[34]
Cignarella, A.; Mioni, R.; Sabbadin, C.; Dassie, F.; Parolin, M.; Vettor, R.; Barbot, M.; Scaroni, C. Pharmacological approaches to controlling cardiometabolic risk in women with PCOS. Int. J. Mol. Sci., 2020, 21(24), 9554.
[http://dx.doi.org/10.3390/ijms21249554] [PMID: 33334002]

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