Coming full circle (almost): Low dose oral minoxidil for alopecia
By Warren R. Heymann, MD, FAAD
January 5, 2022
Vol. 4, No. 1
I presume that virtually every dermatologist reading this commentary has recommended topical minoxidil (TM) for their patients with androgenetic alopecia (AGA) and other alopecias (telogen effluvium, alopecia areata [AA], hair shaft abnormalities, and eyebrow hypotrichosis). I recall the excitement in 1988 when the FDA approved TM for AGA in men and in 1991 for women. (1)
The late dermatologist Guinter Kahn was instrumental in the development of TM. The following is from his obituary: “Upjohn originally synthesized minoxidil to treat high blood pressure in the early 1960s. When Charles Chidsey — one of the company’s consultants working at the University of Colorado’s medical school — noticed that the drug stimulated hair growth, Chidsey went to Dr. Kahn and his medical assistant, Paul Grant. Dr. Kahn was running the school’s dermatology department at the time.” According to the Miami Herald, Dr. Kahn and Grant eventually developed a topical solution for minoxidil in 1971. In 1986, after a 15-year legal battle with Upjohn, Dr. Kahn’s name was added to the patent. The pair earned royalties, said to be 2 to 5%, from Upjohn’s $200 million of wholesale annual revenues from Rogaine in the late 1980s. (2)
The thought of using oral minoxidil for alopecia never crossed my mind. Minoxidil is indicated for refractory hypertension and carries a black box warning for the risk of developing a pericardial effusion that may progress to cardiac tamponade and angina pectoris exacerbation. (3) As an antihypertensive, oral minoxidil is usually dosed between 5 and 40 mg daily. The most common adverse reactions are generalized hypertrichosis, tachycardia, and pedal edema. Interestingly, the drug has a minimal hypotensive effect in normotensive patients. (1) Recently, there have been multiple studies exploring the use of low-dose oral minoxidil (LDOM, < 5mg daily) for treating many forms of alopecia, with the goal of gaining hair while keeping adverse reactions at bay.
Even after decades of use, we still do not completely understand how minoxidil improves alopecia. According to Sharma et al, vasodilatory effects are propagated by upregulation of vascular endothelial growth factor (VEGF), increasing cutaneous blood flow with resultant increase in oxygen and growth factor delivery to the hair follicle. Additionally, minoxidil leads to hair follicle potassium channel activation, prolonging anagen and shortening the telogen phase. Minoxidil may also have T-cell immunomodulatory effects, causing suppression of T-cells that may partially explain its use in autoimmune alopecias. (4) Applied on the scalp, TM is converted to its active form, minoxidil sulfate, by sulfotransferase enzymes located in the follicular outer root sheath. Variations in sulfotransferase activity might clarify why some patients fare better than others with TM. It has been suggested that oral minoxidil may also be converted by liver and platelet sulfotransferase, thereby reaching a higher follicular accumulation. (5)
The following is a brief summation of some systematic reviews of LDOM for alopecias. Please note that the majority of treated cases have been for AGA; only case reports and small series are in the literature for other causes of alopecia. These reviews should not be directly compared to one another — authors have used different criteria in their literature reviews — but despite this reality, one can still get a sense of the utility of LDOM for alopecias.
Safety first. Jiminez-Caughe assessed 14 studies including 442 patients. LDOM was used at doses between 0.25 and 5 mg for 8 different types of alopecia. Hypertrichosis was observed in 24% of patients. Pedal edema occurred in 2% and was also associated with higher doses of LDOM. Postural hypotension and heart rate alterations occurred only in 1.1% and 1.3% of patients, respectively. The authors concluded that LDOM is a safe and well-tolerated treatment for hair loss, presenting a lower adverse effect rate than standard doses. (5) LDOM-induced hypertrichosis usually appears within the first 3 months of therapy, mostly affecting the sideburns and temples. It is usually mild and may be easily managed with dose adjustment or hair removal; discontinuing LDOM is not required for most patients. (6)
Efficacy second. Sharma et al included 10 articles for review comprising a total 19,218 patients (215 women and 19,003 men). LDOM ranged from 0.25 to 5 mg daily to twice daily. The strongest evidence existed for AGA and AA, respectively, with 61–100% and 18–82.4% of patients demonstrating objective clinical improvement. Successful treatment of female pattern hair loss, chronic telogen effluvium, monilethrix, and permanent chemotherapy-induced alopecia was also reported. The most common adverse effects with oral minoxidil included hypertrichosis and postural hypotension. They concluded that LDOM is a safe and successful treatment of androgenic alopecia and AA. (4)
Randolph and Tosti evaluated a total of 16 studies with 622 patients utilizing LDOM as the primary treatment modality for hair loss. AGA was the most studied condition, but other disorders included telogen effluvium, lichen planopilaris, loose anagen hair syndrome, monilethrix, alopecia areata, and permanent chemotherapy-induced alopecia. They found that LDOM was an effective and well-tolerated treatment alternative for healthy patients having difficulty with topical formulations (notably for scalp pruritus, scaling, hypertrichosis, and contact dermatitis). In this review, no severe cardiopulmonary adverse reactions were noted. Regardless, the authors advise providers to remain cautious when using LDOM, monitoring patients’ blood pressure and heart rate and observing for signs of fluid retention (weight gain, pedal edema). (7)
Beach et al retrospectively reported their experience in prescribing LDOM for patients with non-scarring and scarring alopecias (1.25 mg daily for at least 3 months) that was confirmed in 51 of 74 patients given the prescription. Increased scalp hair growth was noted in 65% (33/51) and decreased hair shedding in 27% (14/51). Facial hypertrichosis was appreciated in 43% (22/51); 4 patients (8%) reported hypotensive symptoms (lightheadedness) Patients with non-scarring alopecia were most likely to exhibit and acknowledge clinical improvement. (8)
There is a dearth of information regarding LDOM in the pediatric population. TM is not approved for patients under 18 years of age. (I have been using TM off-label in children for decades). Rodino Lemes et al note that the starting dose for oral minoxidil in children (as an antihypertensive agent) is 0.2 mg/kg/day. In their review of TM and LDOM in children, there was only one report of using LDOM — a child with loose anagen syndrome who had a good response. The authors contend that TM should be used first in children, although there may be circumstances where LDOM is indicated, such as severe AGA or AA. Clearly, more studies on the use of LDOM in children are warranted. (1)
Beach asserts that there are 5 practical advantages to LDOM for alopecia (the 5 “Cs”) – Convenience (it is easier to swallow a pill); Cosmesis (no residue or color change); Cost (LDOM is less expensive that TM); Co-therapy (concurrently with other approaches such as commercial keratin fibers); and Compliance (adherence). (9) In conclusion, as a dermatologist who was anxiously awaiting the arrival of a proprietary formulation of topical minoxidil decades ago, I am bemused by the fact that LDOM may actually be a reasonable alternative for many alopecia patients.
Point to Remember: Low dose oral minoxidil may be a valuable treatment option for patients with androgenetic and other forms of alopecia. An abridged version of this commentary was published in the March 2021 JAAD as “A Clinician's Perspective.”
Our expert’s viewpoint
Antonella Tosti, MD
Fredric Brandt Endowed Professor of Dermatology and Cutaneous Surgery, University of Miami
Consider prescribing low dose oral minoxidil in all hair diseases. It improves thickness and overall hair volume. Patients prefer an oral treatment to topical therapy and compliance is usually very good. Hypertrichosis is common, but most patients are so happy with results that they would rather epilate/depilate and continue treatment!
Dr Tosti had disclosed financial relationships with the following to the AAD at the time of publication: Almirall, DS Laboratories, Eli Lilly and Company, Fotofinder, Kythera, LEO Laboratories Ltd (LEO Pharma), Monat Global, Pfizer Inc., Springer Science & Business Media, Taylor & Francis, Thirty Madison, Inc. Full disclosure information is available.
Lemes LR, Melo DF, de Oliveira DS, de La-Rocque M, Zompero C, Ramos PM. Topical and oral minoxidil for hair disorders in pediatric patients: What do we know so far? Dermatol Ther. 2020 Jul 2:e13950. doi: 10.1111/dth.13950. Epub ahead of print. PMID: 32614119.
Guinter Kahn, dermatologist who helped develop baldness remedy, dies at 80. Associated Press, September 26, 2014.
Epocrates, accessed November 1, 2020.
Sharma AN, Michelle L, Juhasz M, Muller Ramos P, Atanaskova Mesinkovska N. Low-dose oral minoxidil as treatment for non-scarring alopecia: a systematic review. Int J Dermatol. 2020 Aug;59(8):1013-1019. doi: 10.1111/ijd.14933. Epub 2020 Jun 9. PMID: 32516434.
Jimenez-Cauhe J, Saceda-Corralo D, Rodrigues-Barata R, Moreno-Arrones OM, Ortega-Quijano D, Fernandez-Nieto D, Jaen-Olasolo P, Vaño-Galvan S. Safety of low-dose oral minoxidil treatment for hair loss. A systematic review and pooled-analysis of individual patient data. Dermatol Ther. 2020 Aug 5:e14106. doi: 10.1111/dth.14106. Epub ahead of print. PMID: 32757405.
Randolph M, Tosti A. Oral minoxidil treatment for hair loss: A review of efficacy and safety. J Am Acad Dermatol. 2020 Jul 1:S0190-9622(20)32109-5. doi: 10.1016/j.jaad.2020.06.1009. Epub ahead of print. PMID: 32622136.
Beach RA, McDonald KA, Barrett BM. Tolerated, Effective, Successful: Low Dose Oral Minoxidil for Treating Alopecia, A 3-Year North American Retrospective Case Series. J Am Acad Dermatol. 2020 Oct 21:S0190-9622(20)32844-9. doi: 10.1016/j.jaad.2020.10.032. Epub ahead of print. PMID: 33098962.
Jimenez-Cauhe J, Saceda-Corralo D, Rodrigues-Barata R, Hermosa-Gelbard A, Moreno-Arrones OM, Gil-Redondo R, Ortega-Quijano D, Fernandez-Nieto D, Jaen-Olasolo P, Vaño-Galvan S. Characterization and management of hypertrichosis induced by low-dose oral minoxidil in the treatment of hair loss. J Am Acad Dermatol. 2020 Sep 11:S0190-9622(20)32594-9. doi: 10.1016/j.jaad.2020.08.124. Epub ahead of print. PMID: 32926970.
Beach RA. Case series of oral minoxidil for androgenetic and traction alopecia: Tolerability & the five C's of oral therapy. Dermatol Ther. 2018 Nov;31(6):e12707. doi: 10.1111/dth.12707. Epub 2018 Sep 24. PMID: 30246901; PMCID: PMC6586015.
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