Low-dose oral minoxidil for treating alopecia: A 3-year North American retrospective case series

To the Editor: Alopecia remains a therapeutic challenge to dermatologists. Topical 5% minoxidil is a Food and Drug Administration (FDA)–approved treatment for androgenetic alopecia (AGA), with a variable response rate. Studies suggest that low dose oral minoxidil (LDOM) requires decreased follicular enzymatic activity compared with its topical form.1Ramos P. Goren A. Sinclair R. Miot H. Oral minoxidil bioactivation by hair follicle outer root sheath cell sulfotransferase enzymes predicts clinical efficacy in female pattern hair loss.J Eur Acad Dermatol. 2020; 34: 40-41Crossref PubMed Scopus (8) Google Scholar Although reports document its successful use in dermatology, adaptation in North America has been low. It is unclear whether this is due to concern about patient safety or lack of established oral minoxidil dosing for hair loss. Through electronic medical records search (YES! EMR, Toronto, Canada), all patients first prescribed LDOM at 2 community dermatology clinics from December 1, 2016, through November 30, 2019, were identified. The total number of clinic visits for alopecia, encounters pertaining to LDOM, and each prescription duration was tabulated. Clinic notes were reviewed to determine alopecia diagnoses, prescription compliance, dosage, blood pressure changes, LDOM side-effects, and the effect on hair shedding and hair growth. The University of Toronto research ethics board approved this retrospective study. Patients were prescribed oral minoxidil 1.25 mg nightly for 3 months (halved Loniten 2.5 mg tablet; Pfizer Canada). They understood the drug's on-label indication and most common side-effects, including facial hair.2Weber M.A. Schiffrin E.L. White W.B. et al.Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension.J Clin Hypertens (Greenwich). 2014; 16: 14-26Crossref PubMed Scopus (571) Google Scholar Self-assessment of blood pressure and night ingestion of LDOM to help mitigate hypotensive symptoms were encouraged. No prescription recipients had documented cardiac, hepatic, or renal disease. In-clinic photography with standard poses was used to monitor clinical progression where permitted. All patients prescribed minoxidil during the 3-year period were included in this as-treated analysis. This cohort completed 346 alopecia appointments from 2016-2019, including 165 pertaining to LDOM. The average duration of LDOM consumption across all patients who continued therapy was 10 months. There was a total of 509.5 months of LDOM treatment, including a maximum duration of 30 months. Alopecia was diagnosed clinically (n = 64) and with histology (n = 10). These 74 patients received at least one 3-month prescription for 1.25-mg oral minoxidil during the 3-year period (Table I). The follow-up rate was 72% (53/74) and included 2 patients who returned without filling their prescriptions because of concerns about potential adverse effects. Therefore, 51 of 74 patients prescribed LDOM were confirmed to have started their prescription (Table I).Table IPatient demographics and alopecia diagnoses of those who received low-dose oral minoxidilDemographicPatientsInitial recruitmentTotal (n = 74)Men (n = 15)Women (n = 59)Confirmed LDOM prescriptionTotal (n = 51)Men (n = 12)Women (n = 39)Mean age, y423346Hair textures Caucasian-textured (straight)28919 Afro-textured (curly)12111 Asian-textured (straight)1129South Asian927Far East Asian202Type of alopecia AGA23914 Multiple scalp diagnoses∗Multiple scalp diagnoses: men (n = 2), AGA and AA, and AGA and pseudofolliculitis barbae. Women (n = 13), AGA and TE, 4; CCCA and TA, 4; AGA and LPP/FFA, 2; AGA and AA, 1; AGA, TE, and psoriasis, 1; and TE and weathering, 1.15213 LPP or FFA615 TA303 CCCA202 TE101 Chemotherapy-induced alopecia101Previous alopecia therapy Topical minoxidil35629Concurrent or overlapping alopecia therapy 5α-reductase antagonists or other antiandrogen therapy808 (AGA; FFA; AGA and FFA) Spironolactone505 (AGA; AGA and AA; AGA and TE) Immunomodulators (methotrexate, hydroxychloroquine, pioglitazone)404 (FFA; AGA and LPP/FFA) Platelet-rich plasma505 (AGA) Antibiotics (doxycycline)202 (CCCA) Retinoids (acitretin)202 (FFA/LPP)Abbreviations denote subtypes of alopecia.AA, Alopecia areata; AGA, androgenetic alopecia; CCCA, central centrifugal cicatricial alopecia; FFA, frontal fibrosing alopecia; LDOM, low-dose oral minoxidil; LPP, lichen planopilaris; TA, traction alopecia; TE, telogen effluvium.∗ Multiple scalp diagnoses: men (n = 2), AGA and AA, and AGA and pseudofolliculitis barbae. Women (n = 13), AGA and TE, 4; CCCA and TA, 4; AGA and LPP/FFA, 2; AGA and AA, 1; AGA, TE, and psoriasis, 1; and TE and weathering, 1. Open table in a new tab Abbreviations denote subtypes of alopecia. AA, Alopecia areata; AGA, androgenetic alopecia; CCCA, central centrifugal cicatricial alopecia; FFA, frontal fibrosing alopecia; LDOM, low-dose oral minoxidil; LPP, lichen planopilaris; TA, traction alopecia; TE, telogen effluvium. Most patients requested represcription of LDOM at reassessment (43/51; 84%). Patient reasons for LDOM stoppage were recorded for the remainder (Table II).Table IIPatient-reported reasons for stoppage of low-dose oral minoxidil and adverse effects during low-dose oral minoxidil treatmentStoppage reasonPatient frequencyAversion to pills2Forgetfulness1Nausea1Facial acne1Preference for topical minoxidil1Perceived lack of efficacy and hair shedding1Facial hypertrichosis1Side-effects and symptoms CardiacHypotensive symptoms (reported as lightheadedness)4(2 men; lasted 1 wk; 1 episode)(2 women; lasted several days; reported with coprescription spironolactone)Blood pressure self-assessments Improved measurement2 Unchanged measurement11Palpitations2(1 woman; lasted 3 wk)(1 woman; episodic and preexisted LDOM)Ankle edema1 (woman; lasted 2 wk) HairHair shedding2(1 woman; discontinued therapy)(1 woman; continued therapy and it stabilized)Hypertrichosis22(3 men: temples, cheek)(19 women: skin of lip; eyebrows - deemed beneficial for 2 FFA patients; chin; cheeks; eyelashes) SkinUrticaria1 (woman; 1 episode) OtherParesthesia (arms/hands)1 (woman; intermittently during 4 wk, preexisted LDOM, possibly increased in frequency)FFA, Frontal fibrosing alopecia; LDOM, low-dose oral minoxidil. Open table in a new tab FFA, Frontal fibrosing alopecia; LDOM, low-dose oral minoxidil. At follow-up, escalated 2.5-mg dosing was adopted by 9 of 12 men (75%) and 7 of 39 women (18%) despite known risk of facial hypertrichosis. Side-effects in all patients who continued LDOM were tabulated (Table II). No patient who continued LDOM reported new cardiac diagnoses or morbidity, including pericardial effusions or pericarditis. Results from this retrospective series indicate increased scalp hair growth (33/51; 65%) and decreased hair shedding (14/51; 27%) with LDOM. Patients with nonscarring alopecia were most likely to acknowledge and exhibit clinical improvement (Supplemental Discussion available via Mendeley at https://data.mendeley.com/datasets/4sccxmrfzm/1). The 5 Cs of LDOM are convenience, cosmesis, cost savings, cotherapy feasibility, and compliance.3Beach R.A. Case series of oral minoxidil for androgenetic and traction alopecia: tolerability and the five C's of oral therapy.Dermatol Ther. 2018; 31: e12707Crossref PubMed Scopus (16) Google Scholar The newly proposed sixth C is “crown efficacy,” exhibited by increased hair growth at this scalp region (Supplemental Figs 1-6, https://data.mendeley.com/datasets/4sccxmrfzm/1/files/a99ab998-4da1-42d7-926f-e4de7aca4d73, https://data.mendeley.com/datasets/4sccxmrfzm/1/files/b67819a9-3e1a-46a9-9637-e001a434cba9). Comment on “Low dose oral minoxidil for treating alopecia: A 3-year North American retrospective case series”: Adding further evidence about side effectsJournal of the American Academy of DermatologyVol. 84Issue 5PreviewTo the Editor: We read with interest the article by Beach et al1 addressing the tolerability and effectiveness of low-dose oral minoxidil (LDOM) for treating androgenetic alopecia. With regard to tolerability, a recent review found that, except for hypertrichosis, side effects were infrequent.2,3 Those results are consistent with the ones of the referred study. Full-Text PDF

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