Efficacy and safety profile of oral spironolactone use for androgenic alopecia: A systematic review

To the Editor: Androgenic alopecia (AGA) is a psychologically taxing dermatologic condition estimated to affect nearly 50% of women by the age of 50.1Ho C.H. Sood T. Zito P.M. Androgenetic alopecia.in: StatPearls. StatPearls Publishing, 2021https://pubmed.ncbi.nlm.nih.gov/28613674/Date accessed: January 25, 2021Google Scholar Currently, the only medications approved by the United States Food and Drug Administration in the treatment of hair loss are topical minoxidil and oral finasteride. Considering the limited treatment options available for women, it is important to consider additional therapeutic agents. Although not currently approved by the Food and Drug Administration for dermatologic conditions, spironolactone has been proposed as a potential treatment agent for AGA due to its ability to decrease circulating androgens and counteract androgen effects on hair follicles.2Rathnayake D. Sinclair R. Innovative use of spironolactone as an antiandrogen in the treatment of female pattern hair loss.Dermatol Clin. 2010; 28: 611-618https://doi.org/10.1016/j.det.2010.03.011Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar This review will establish the efficacy and safety of spironolactone for the treatment of AGA in women. On September 27, 2020, a systematic search of PubMed, Embase, and Web of Science databases was conducted using the search terms “spironolactone” and “alopecia.” Methodology for study selection has been described in Fig 1. The search terms used in each search are included in Supplemental Text 1 (available via Mendeley at https://doi.org/10.17632/vjkzv33jyv.1). A total of 12 studies with 286 participants were included and have been summarized in Table I.Table ISummary of studies evaluating the treatment of androgenic alopecia in women with oral spironolactoneDesignGrade of recommendationDiagnosisNTreatment regimenOutcomeAdverse effects (% affected)Risk of biasCase series4AGA4Oral spironolactone 100 mg twice daily for 6 monthsAll 4 patients (100%) experienced a 50% to 62.9% decrease in hair loss compared with pretreatment assessment and had improvement in their trichogram scoreReduction in blood pressure (100)Some concernsCase report4AGA1Oral spironolactone initially at 50 mg daily with topical minoxidil solution for 3 months, increased to 100 mg daily for 2 monthsNo improvement in hair lossSymptoms of recurrent intracranial hypertension (dizziness, tinnitus, frontal headache); facial hair growth (100)HighCase series4AGA7Oral spironolactone 200 mg daily for 6 monthsSubjective assessment of improvement per patient report in 86% of study participantsNRSome concernsRetrospective analysis2bAGA79Average oral spironolactone dose of 100 mg daily. Of all patients, 28% were started on concomitant therapies with spironolactone, including topical minoxidil, low-level laser light device, and iron supplementation.Duration of use: 6 months (n = 31),1 year (n = 23), and >1 year (n = 22)Patients with a Sinclair score of 2.5 or higher had almost a full integer improvement in their Sinclair score independent of concomitant therapies or menopausal status. Optimal Sinclair scores were noted after at least 1 year of treatment with spironolactoneLightheadedness/dizziness (16), unable to tolerate therapy (4), menstrual irregularities (3), nausea (3), urinary changes (3), rash (3), breast tenderness (1), hyperkalemia (1)Some concernsRetrospective survey/analysis2bAGA39Oral spironolactone at mean dose of 110 mg daily in combination with topical minoxidil or other unspecified agentsStabilization or improvement in disease in 74.3% of patientsNRHighCase report4AGA1Oral spironolactone at an initial dose of 25 mg daily, increased to 200 mg daily over 6 weeks for 2 years as a monotherapy. Topical minoxidil 5% solution 1 mL was used in combination with oral spironolactone for 2 additional yearsImprovement in hair regrowth evidenced after 12 months of oral spironolactone 200 mg daily, with plateau after 2 years of therapy. Evidence of additional hair regrowth following concurrent application of 1 mL of topical minoxidil 5% solution daily with maintenance of results at 4-year follow upNRHighRandomized controlled trial1bAGA12Oral spironolactone 75 mg or 100 mg daily for 12 months; 2 subjects from treatment group increased their dose to 150 mg and 200 mg for an additional 12 monthsNo significant change in total hair density after 12 months in the 75 mg or 100 mg groupThe 2 patients with increased dose to 150 mg and 200 mg daily experienced increased hair densityIrregular periods (25), acne (50)LowObservational open label study2bAGA100Oral spironolactone 25 mg daily in combination with oral minoxidil 0.25 mg daily for 12 monthsTemporary increase in hair shedding 3-6 weeks after imitation of treatment in 22% of participants that resolved with continued use.Improvement in hair loss was noted across study participants. There was a mean reduction in hair loss severity score of 0.85 at 6 months and 1.3 at 12 monthsPostural hypotension (2), urticaria (2), facial hypertrichosis (4)Some concernsOpen label intervention2bAGA40Oral spironolactone 200 mg daily for an average of 16 months10% of patients experienced improvement in hair loss along the scalp vertex, 12.5% along the frontal scalp, and 22.5% in both the frontal and vertex scalpUnable to tolerate therapy requiring dose reduction (12.5)Some concernsCase report4AGA1Oral spironolactone 150 mg daily for 6 monthsImprovement in hair lossNRHighCase report4AGA1Oral spironolactone 50 mg daily for 3 weeks, increased to 100 mg daily for 6 monthsOne point improvement in Sinclair score, decreased hair shedding, and increased follicular densityNRHighCase report4AGA1Oral spironolactone 200 mg daily for 5 years. Topical minoxidil 5% solution 1 mL daily was used for a duration of 6 months in combination with spironolactoneNo change in hair lossNRHighAGA, Androgenic alopecia; NR, not reported. Open table in a new tab AGA, Androgenic alopecia; NR, not reported. Spironolactone was used as a monotherapy in 67 (23.4%) of the 286 patients across all studies and was used in combination with topical minoxidil, oral minoxidil, low-level laser therapy, or iron supplementation in the remaining study participants. Patients were treated with spironolactone at doses ranging between 25 mg and 200 mg for a duration of 6 months to 4 years. Although topical minoxidil was the most common agent used in combination with spironolactone, Burns et al3Burns L.J. De Souza B. Flynn E. Hagigeorges D. Senna M.M. Spironolactone for treatment of female pattern hair loss.J Am Acad Dermatol. 2020; 83: 276-278https://doi.org/10.1016/j.jaad.2020.03.087Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar reported a full integer improvement in Sinclair hair loss severity scale score in women with a baseline Sinclair score of 2.5 or higher on spironolactone independent of concurrent therapies used.4Sinclair R. Wewerinke M. Jolley D. Treatment of female pattern hair loss with oral antiandrogens.Br J Dermatol. 2005; 152: 466-473https://doi.org/10.1111/j.1365-2133.2005.06218.xCrossref PubMed Scopus (137) Google Scholar When employed as a monotherapy, 33 (49.3%) of the 67 patients achieved improvement in follicular density and hair loss on spironolactone. Notably, spironolactone was largely ineffective in studies where the dosage was maintained below 100 mg. Instead, significant improvement was reported after at least 12 months of use at 100 mg to 200 mg daily. This review found oral spironolactone to be an effective, well-tolerated treatment for women with AGA when used in combination with topical minoxidil and, importantly, as a monotherapy. The most commonly reported adverse effect was lightheadedness or dizziness. More severe side effects described in the literature were hypotension, hyperkalemia, and urticarial allergic reaction; however, these affected less than 2% of participants across all studies. Oral spironolactone was generally recommended in nonpregnant women older than 18 years of age at an initial dose of 50 mg daily titrated up to a therapeutic range of 100 mg to 200 mg daily taken for at least 6 months to 1 year to achieve optimal results. This study is limited by the narrow range of data in the literature, which comprises mostly case series and observational studies. Further randomized studies are needed to validate the efficacy of spironolactone as a monotherapy in the treatment of AGA, although the available data support its use in combination with topical minoxidil. Given the positive outcomes, minimal side effects, and economical cost, spironolactone should be regarded as a safe, effective treatment option in women with AGA. None disclosed.