Bicalutamide improves minoxidil-induced hypertrichosis in female pattern hair loss: A retrospective review of 35 patients

米诺地尔 医学 多毛症 脱发 皮肤病科 抗雄激素 毛发生长 卡贝洛 毛发病 男性型秃发 非那雄胺 头皮 内科学 雄激素 生理学 癌症 前列腺 激素
作者
Anthony Moussa,Ahmed Kazmi,Laita Bokhari,Rodney Sinclair
出处
期刊:Journal of The American Academy of Dermatology [Elsevier BV]
卷期号:87 (2): 488-490 被引量:7
标识
DOI:10.1016/j.jaad.2021.10.048
摘要

To the Editor: Low-dose systemic minoxidil in combination with antiandrogen therapy has been successfully used to treat female pattern hair loss (FPHL).1Sinclair R.D. Female pattern hair loss: a pilot study investigating combination therapy with low-dose oral minoxidil and spironolactone.Int J Dermatol. 2018; 57: 104-109https://doi.org/10.1111/ijd.13838Crossref PubMed Scopus (61) Google Scholar Although minoxidil has a favorable safety profile, hypertrichosis occurs in up to 24% of patients.2Jimenez-Cauhe J. Saceda-Corralo D. Rodrigues-Barata R. et al.Safety of low-dose oral minoxidil treatment for hair loss. A systematic review and pooled-analysis of individual patient data.Dermatol Ther. 2020; 33: e14106https://doi.org/10.1111/dth.14106Crossref PubMed Scopus (11) Google ScholarBicalutamide is a pure, nonsteroidal androgen receptor inhibitor that has been successfully used in the treatment of FPHL.3Fernandez-Nieto D. Saceda-Corralo D. Jimenez-Cauhe J. et al.Bicalutamide: a potential new oral antiandrogenic drug for female pattern hair loss.J Am Acad Dermatol. 2020; 83: e355-e356https://doi.org/10.1016/j.jaad.2020.04.054Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Low-dose bicalutamide (25 mg/daily) has also been used to treat moderate-to-severe hirsutism with significant efficacy.4Müderris I.I. Bayram F. Ozçelik B. Güven M. New alternative treatment in hirsutism: bicalutamide 25 mg/day.Gynecol Endocrinol. 2002; 16: 63-66Crossref PubMed Scopus (30) Google Scholar Our aim was to determine whether oral bicalutamide decreases the risk of minoxidil-induced hypertrichosis.We retrospectively reviewed the records of all FPHL patients at our institution with minoxidil-induced hypertrichosis that were concurrently treated with oral bicalutamide between May 2016 and May 2021. Those treated with laser hair removal, electrolysis, depilatory creams, or concomitant drugs with antiandrogen potential (eg, drospirenone, spironolactone, finasteride, or dutasteride) were excluded from the review. Improvement in hypertrichosis was determined via a combination of clinician assessment, review of photography, and subjective reporting by patients.We identified 35 patients who demonstrated clear improvement of minoxidil-induced hypertrichosis after commencement or up-titration of oral bicalutamide (Table I). The mean age of patients was 53.5 years (SD, 16.82; range, 20-84 years). Daily minoxidil dose ranged from 0.25 mg to 10 mg and included oral and sublingual preparations; hypertrichosis occurred in patients taking a mean dose of 1.5 mg/day (SD, 1.07; range, 0.25-5 mg).Table IPatient demographics, drug doses, and follow up in female pattern hair loss patients with minoxidil-induced hypertrichosis treated with oral bicalutamide (n = 35)FeatureResultsAge in y; mean (SD)53.5 (16.82)SexFemale; n (%)35 (100)Fitzpatrick skin phototype Type I; n (%)7 (20) Type II; n (%)17 (49) Type III; n (%)6 (17) Type IV; n (%)2 (6) Type V; n (%)3 (9) Type VI; n (%)0 (0)Duration of follow up (mo); mean (SD)28.9 (25.92)Dose (mg) of minoxidil causing hypertrichosis; mean (SD)1.5 (1.07)Dose (mg) of bicalutamide improving hypertrichosis; mean (SD)14.4 (5.25) 10 mg; n (%)20 (57) 20 mg; n (%)14 (40) 25 mg; n (%)1 (3)Dose (mg) of minoxidil at latest review; mean (SD)2.2 (1.67)Dose (mg) of bicalutamide at latest review; mean (SD)14.7 (6.30) 10 mg; n (%)18 (56) 20 mg; n (%)11 (34) 25 mg; n (%)1 (3) 30 mg; n (%)2 (6)Time (mo) to improvement of hypertrichosis after commencement of bicalutamide; mean (SD)3.4 (1.27)Areas of hypertrichosis improvement Face; n (%)35 (100) Limbs; n (%)4 (11) Body; n (%)4 (11) Open table in a new tab All patients commenced bicalutamide at a dose of 10 mg. The mean dose of bicalutamide that reduced hypertrichosis was 14.4 mg (SD, 5.25 mg). The use of concurrent bicalutamide permitted an increase in the mean daily dose of minoxidil to 2.2 mg (SD, 1.67 mg) without development of hypertrichosis.Fifteen (43%) patients were started on bicalutamide after developing hypertrichosis from minoxidil. Twenty patients (57%) were started on bicalutamide with minoxidil concurrently, and improvement of hypertrichosis was observed in this group on up-titration of the bicalutamide dose. Patients were followed up for a mean duration of 28.9 months (SD, 25.92 months). The mean time to documented improvement of hypertrichosis was 3.4 months (SD, 1.27 months) after commencing a stable dose of bicalutamide.Safety and efficacy of systemic minoxidil and oral bicalutamide were evaluated as secondary objectives. The mean Sinclair stage at baseline was 2.82. The mean reduction in Sinclair stage was 0.54 (19.1%) at 6 months and 0.66 (23.4%) at 12 months. Bicalutamide and minoxidil were well tolerated overall. Bicalutamide-related adverse effects occurred in 5 patients (14%) and are outlined in Table II; adverse effects led to a dose reduction in 3 patients and discontinuation of therapy in 2 patients (due to transaminitis and scalp dysesthesia). Systemic minoxidil had a favorable safety profile; adverse effects included dizziness (n = 1, 3%) and palpitations (n = 1, 3%) leading to dose reductions. One patient discontinued both minoxidil and bicalutamide due to a perceived lack of efficacy.Table IIBicalutamide-related adverse effects and discontinuation of therapyAdverse effectsPatients, No. (%)Discontinuation, No. (%)Dose reduction, No. (%)Scalp dysesthesia1 (3)1 (3)0 (0)Headaches1 (3)0 (0)1 (3)Peri-orbital edema1 (3)0 (0)1 (3)Transaminitis2 (6)1 (3)1 (3) Open table in a new tab Oral bicalutamide appears to be beneficial in mitigating hypertrichosis caused by minoxidil in FPHL patients. Daily bicalutamide (mean dose, 14.4 mg) both reduced hypertrichosis and permitted an increase in the mean dosing of minoxidil by 0.7 mg/day without further hypertrichosis. This observation calls into question the suggestion that minoxidil-induced hypertrichosis is androgen independent and indeed the distinction between hypertrichosis and hirsutism. Although unclear, minoxidil may in fact influence the androgen receptor or its downstream signaling.5Hsu C.L. Liu J.S. Lin A.C. Yang C.H. Chung W.H. Wu W.G. Minoxidil may suppress androgen receptor-related functions.Oncotarget. 2014; 5: 2187-2197https://doi.org/10.18632/oncotarget.1886Crossref PubMed Scopus (27) Google Scholar This study is limited by small patient numbers, the lack of a control arm, its retrospective design, and the absence of formal hypertrichosis scoring. Prospective placebo-controlled studies are required to support this conclusion. To the Editor: Low-dose systemic minoxidil in combination with antiandrogen therapy has been successfully used to treat female pattern hair loss (FPHL).1Sinclair R.D. Female pattern hair loss: a pilot study investigating combination therapy with low-dose oral minoxidil and spironolactone.Int J Dermatol. 2018; 57: 104-109https://doi.org/10.1111/ijd.13838Crossref PubMed Scopus (61) Google Scholar Although minoxidil has a favorable safety profile, hypertrichosis occurs in up to 24% of patients.2Jimenez-Cauhe J. Saceda-Corralo D. Rodrigues-Barata R. et al.Safety of low-dose oral minoxidil treatment for hair loss. A systematic review and pooled-analysis of individual patient data.Dermatol Ther. 2020; 33: e14106https://doi.org/10.1111/dth.14106Crossref PubMed Scopus (11) Google Scholar Bicalutamide is a pure, nonsteroidal androgen receptor inhibitor that has been successfully used in the treatment of FPHL.3Fernandez-Nieto D. Saceda-Corralo D. Jimenez-Cauhe J. et al.Bicalutamide: a potential new oral antiandrogenic drug for female pattern hair loss.J Am Acad Dermatol. 2020; 83: e355-e356https://doi.org/10.1016/j.jaad.2020.04.054Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Low-dose bicalutamide (25 mg/daily) has also been used to treat moderate-to-severe hirsutism with significant efficacy.4Müderris I.I. Bayram F. Ozçelik B. Güven M. New alternative treatment in hirsutism: bicalutamide 25 mg/day.Gynecol Endocrinol. 2002; 16: 63-66Crossref PubMed Scopus (30) Google Scholar Our aim was to determine whether oral bicalutamide decreases the risk of minoxidil-induced hypertrichosis. We retrospectively reviewed the records of all FPHL patients at our institution with minoxidil-induced hypertrichosis that were concurrently treated with oral bicalutamide between May 2016 and May 2021. Those treated with laser hair removal, electrolysis, depilatory creams, or concomitant drugs with antiandrogen potential (eg, drospirenone, spironolactone, finasteride, or dutasteride) were excluded from the review. Improvement in hypertrichosis was determined via a combination of clinician assessment, review of photography, and subjective reporting by patients. We identified 35 patients who demonstrated clear improvement of minoxidil-induced hypertrichosis after commencement or up-titration of oral bicalutamide (Table I). The mean age of patients was 53.5 years (SD, 16.82; range, 20-84 years). Daily minoxidil dose ranged from 0.25 mg to 10 mg and included oral and sublingual preparations; hypertrichosis occurred in patients taking a mean dose of 1.5 mg/day (SD, 1.07; range, 0.25-5 mg). All patients commenced bicalutamide at a dose of 10 mg. The mean dose of bicalutamide that reduced hypertrichosis was 14.4 mg (SD, 5.25 mg). The use of concurrent bicalutamide permitted an increase in the mean daily dose of minoxidil to 2.2 mg (SD, 1.67 mg) without development of hypertrichosis. Fifteen (43%) patients were started on bicalutamide after developing hypertrichosis from minoxidil. Twenty patients (57%) were started on bicalutamide with minoxidil concurrently, and improvement of hypertrichosis was observed in this group on up-titration of the bicalutamide dose. Patients were followed up for a mean duration of 28.9 months (SD, 25.92 months). The mean time to documented improvement of hypertrichosis was 3.4 months (SD, 1.27 months) after commencing a stable dose of bicalutamide. Safety and efficacy of systemic minoxidil and oral bicalutamide were evaluated as secondary objectives. The mean Sinclair stage at baseline was 2.82. The mean reduction in Sinclair stage was 0.54 (19.1%) at 6 months and 0.66 (23.4%) at 12 months. Bicalutamide and minoxidil were well tolerated overall. Bicalutamide-related adverse effects occurred in 5 patients (14%) and are outlined in Table II; adverse effects led to a dose reduction in 3 patients and discontinuation of therapy in 2 patients (due to transaminitis and scalp dysesthesia). Systemic minoxidil had a favorable safety profile; adverse effects included dizziness (n = 1, 3%) and palpitations (n = 1, 3%) leading to dose reductions. One patient discontinued both minoxidil and bicalutamide due to a perceived lack of efficacy. Oral bicalutamide appears to be beneficial in mitigating hypertrichosis caused by minoxidil in FPHL patients. Daily bicalutamide (mean dose, 14.4 mg) both reduced hypertrichosis and permitted an increase in the mean dosing of minoxidil by 0.7 mg/day without further hypertrichosis. This observation calls into question the suggestion that minoxidil-induced hypertrichosis is androgen independent and indeed the distinction between hypertrichosis and hirsutism. Although unclear, minoxidil may in fact influence the androgen receptor or its downstream signaling.5Hsu C.L. Liu J.S. Lin A.C. Yang C.H. Chung W.H. Wu W.G. Minoxidil may suppress androgen receptor-related functions.Oncotarget. 2014; 5: 2187-2197https://doi.org/10.18632/oncotarget.1886Crossref PubMed Scopus (27) Google Scholar This study is limited by small patient numbers, the lack of a control arm, its retrospective design, and the absence of formal hypertrichosis scoring. Prospective placebo-controlled studies are required to support this conclusion. Prof Sinclair, Director and Founder of Samson Medical Pty Ltd, participates on the pharmaceutical advisory board for Eli Lilly, Pfizer, and Leo Pharmaceutical; is on the speakers bureau for Abbvie and Novartis; and is principal investigator in clinical trials for Amgen, Novartis, Arcutis Biotherapeutics, Aerotech, Merck & Co, Celgene, Coherus BioSciences, Jannsen, Regeneron, MedImmune, Glaxo Smith Kline, Samson Clinical, Boehringer Ingelheim, Oncobiologics, Roche, Ascend, Dermira, AstraZeneca, Akesobio, Reistone Biopharma, UCB, Sanofi, Connect, Arena, Sun Pharma, Bristol Myer Squibb, and Galderma. Drs Moussa and Kazmi and author Bokhari have no conflicts of interest to disclose.
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