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| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 8
| Issue : 1 | Page : 1-6 |
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Oral minoxidil in trichology: A review
Priyanka Arun Kowe1, Bhushan Madke2, Shashank Hemant Bansod3
1 Department of Dermatology, AIIMS Bhubaneshwar, Odisha, India
2 Department of Dermatology, Venereology and Leprology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi Meghe, Wardha, Maharashtra, India
3 Department of Dermatology, Consultant Dermatologist, Hi-Tech Skin Clinic and hair Transplant Centre, Nagpur, Maharashtra, India
| Date of Submission | 15-Aug-2021 |
| Date of Acceptance | 21-Apr-2022 |
| Date of Web Publication | 11-Jun-2022 |
Correspondence Address:
Priyanka Arun Kowe
Department of Dermatology, All India Institute of Medical Sciences, Bhubaneshwar, Odisha
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijdd.ijdd_35_21
Minoxidil, a pro-drug has been used as an oral antihypertensive drug since the 1960s. Though it was initially introduced as a therapy to control hypertension, it became popular after its coincidental finding on the promotion of hair growth and stimulation of new hair production. This has led to the usefulness of minoxidil in treating several hair loss disorders in both topical and oral forms. In 1988, Food and drug administration (FDA) approved topical minoxidil (TM) 2% for the treatment of male androgenetic alopecia (AGA) and in 1992, it got approval for female pattern hair loss (FPHL). Since then the use of TM has increased tremendously. However, there are frequent reports of TM and/or its vehicle-induced contact dermatitis which has reduced the compliance in the patients resulted in a poor outcome. Oral minoxidil (OM) has been tried and found useful in AGA, alopecia areata (AA), traction alopecia (TA), chronic telogen effluvium (CTE), chemotherapy-induced alopecia, monilethrix, and several other alopecia’s; however, the exact mechanism of action and efficacy of oral minoxidil in these disorders remains undetermined. Also, when given in low dose, side effect profile of OM has been found comparable to that of TM. The above data was supported by case series, randomized control trials, and case reports with a low quality of evidence. In this review, we aimed to summarize the different indications of oral minoxidil. We reiterate the claim that high-quality studies are needed before advocating use of oral minoxidil in hair disorders. Keywords: Androgenetic alopecia, oral minoxidil, sulfotransferase, vasodilator
How to cite this article:
Kowe PA, Madke B, Bansod SH. Oral minoxidil in trichology: A review. Indian J Drugs Dermatol 2022;8:1-6 |
| Introduction | |  |
Alopecia has affected men and women with no age preference. It has a significant influence on the social, mental, and psychological well-being of an individual. Although alopecia has multiple etiologies, detailed history, close examination, and required investigations can point to the exact cause and potential diagnosis. The management of alopecia consists of treatment of underlying causes and medical therapy. Minoxidil, a vasodilator is effective medical therapy for the treatment of hair loss disorder as it increases the blood supply to the hair follicle and promotes hair growth. Its been over 50 years, topical minoxidil is used for AGA in both men and women of all ages and also found effective for other alopecias.[1] The effect of minoxidil therapy is reversible and hair growth comes to the pre-treatment stage in 3–6 months after the stoppage of treatment.[2] Since it requires a lifelong application as maintenance therapy, the cost, its frequent adverse effect of irritant and allergic contact dermatitis (manifesting as scalp pruritus, scaling, altered hair texture) and, hair growth at an unwanted site, there is poor compliance from the patient side. To overcome this OM has been considered as an alternative option for the treatment of alopecia. OM has been tried alone or in combination with other drugs for the treatment of FPHL, CTE, AA, TA, chemotherapy-induced alopecia, etc.with variable success.[3],[4],[5],[6],[7] This review aims to familiarize the indications of oral minoxidil in the treatment of various types of alopecia. For this purpose, we searched multiple databases such as Pubmed, Google Scholar, and Scopus with the keywords as “oral minoxidil for alopecia”, “oral minoxidil in hair disorders” and “minoxidil and hair disorders” and included data from a systematic review, original articles, case reports, and case series.
| Pharmacology of Oral Minoxidil | | |
Minoxidil is chemically a “2,6-diamino-4-piperidino pyrimidine-1-oxide” compound with a chemical composition of C9H15N5O [Figure 1].[8] OM is metabolized in liver by glucuronic acid conjugation and excreted through the kidney in 3 to 4 hours after administration.[1] Its half-life is 4.2 hours and has a high volume of distribution. Its peak plasma concentration reaches in 1 hour and 10% of the drug is eliminated unchanged in urine.
The pregnancy category is C.
Antihypertensive dose of OM ranges from 10 mg to 40 mg which has been extended to 100 mg by some physicians, however for alopecia a low dose oral minoxidil (LDOM) 0.25 mg to 5 mg has been found effective with good safety and efficacy in multiple studies.[9]
| Mechanism of Action | | |
Minoxidil, as an arteriolar dilator opens the potassium channels on the peripheral artery smooth muscle cells leading to hyperpolarization of cell membrane increasing the cutaneous blood flow.[1] As a pro-drug, after entering the body, it gets converted to its active metabolite form “minoxidil sulfate” which is responsible for all actions of minoxidil on hair follicles as well as an antihypertensive.[8] This conversion is carried out by an enzyme called “sulfotransferase”. This enzyme is found in many tissues with the liver being the richest source.[10] It is also expressed by the cells of outer root sheath (ORS) of hair follicle and sulfotransferase activity of ORS is responsible for therapeutic response in TM therapy.[11],[12],[13],[14] Ramos et al, observed that metabolism of OM by the liver adds to a higher concentration of minoxidil in the hair follicle, thus a lower ORS sulfotransferase threshold is needed for bio-activation (sulfation) of OM compared to TM.[11] Therefore, OM can be a good choice for patients who develop allergies to TM and in those patients where TM is not effective due to deficiency of local sulfotransferase enzyme present in hair follicle.
| Effect of Oral Minoxidil on the Hair Cycle | | |
Minoxidil alters the hair cycle via two mechanisms, either it prolongs the anagen phase or shortens the telogen/kenogen phase. It is also found to stimulate new hair production and increase the diameter of hair fiber.[2] The dermal papilla (DP) of the hair follicle actively participate in the anagen phase. It gets stimulation from various factors including β-catenin which is involved in regeneration, differentiation and morphogenesis of follicular keratinocytes into the mature hair shaft, thus promoting hair growth. Thus, minoxidil via β-catenin pathway in the DP prolongs the duration of the anagen phase of the hair cycle.[8] Hypertrichosis seen over the face and other body sites indicate that OM, also prolongs the anagen phase duration over these areas.[8]
| Indications of Oral Minoxidil | | |
[Table 1]
Androgenetic alopecia
AGA was the most studied alopecia with OM as a primary treatment modality. Rodrigues-Barata et al. studied 148 women with FPHL for 9 months and observed a daily dose of 1 mg of OM to be an efficacious therapy for higher grades of FPHL.[15] Sinclair et al, observed a combination of OM 0.25 mg and spironolactone 25 mg in 100 women with FPHL, (spironolactone was added to decrease fluid overload) revealed mean reduction in Sinclair hair loss severity score as well as a reduction in hair shedding score at 6 months and 1 year.[3] Hypotension, urticaria, and hypertrichosis were noted as manageable side effects. He concluded that the combination of OM and spironolactone have synergistic effects in FPHL. Ramos et al, compared 1 mg OM versus 5% TM in 52 patients with FPHL in a randomized open comparative study with an endpoint of change in total hair density in a parietal area from baseline to 6 months and he observed that both OM and TM are equally effective in terms of efficacy and safety (12% women taking OM showed increased total hair density and 7% women applying 5% TM).[16] Beach et al, in their study of 18 patients with AGA and traction alopecia with a daily dose of OM 1.25 mg, observed decreased hair shedding in 33% and increased scalp hair in 28% of patients at 6 months follow-up.[6] Jha et al. studied a dose of 1.25 mg in male AGA with improvement in hair shedding and concluded that a higher dosage may be needed in patients without any response in 6 months of treatment.[17] Lueangarun et al, studied 30 patients of male AGA (grade III vertex to grade V) with OM 5 mg daily for 6 months and found a visible increase in total hair counts at week 12. Remarkable improvement was noticed in the further course of treatment with 100% improvement on photographic assessment of vertex area. In addition to the vertex, the frontal area also showed improvement.[18] Another study of 41 patients on male AGA by Jimenez-Cuahe et al, showed improvement on the Norwood-hamilton scale by 1 grade. 10 patients received a daily dose of 2.5 mg and 31 patients received daily 5 mg. 16 patients received OM monotherapy out of which 90% patients showed marked improvement, 9.8% showed stabilization and none of the patients on 5 mg worsened in his study.[19] Side effects were mild and tolerable and mostly associated with a 5 mg dose. Pirmez et al. studied a very low dose of 0.25 mg/day of OM for 24 weeks and found stabilization and improvement in 40% -60% of male AGA patients but in terms of hair thickness and density, the improvement was insignificant.[20]
Current literature suggests that a daily dose of 0.25 mg to 1.25 mg for FPHL and a dose of 2.5 mg to 5 mg for male AGA over 6 months can be considered with caution and tolerable safety profile.
Telogen effluvium
Telogen effluvium (TE) is the commonest type of diffuse hair loss frequently seen in women after a stressful event such as trauma, surgery, pregnancy, nutritional deficiency, and any chronic illness. It is characterized by excessive shedding of telogen hairs 3 to 4 months after the triggering event. Chronic telogen effluvium (CTE) is defined as hair shedding persisting over 6 months. Perera et al, in their systematic review of 36 women with CTE observed the response of OM (0.25 mg to 2.5 mg/day) for 6 months and found a significant reduction in the mean hair shedding score at 6 months and 12 months. No significant adverse effect was found in this study and all patients followed up for 12 months.[4]
Alopecia areata (AA)
In a study by Fiedler-Weiss et al, with 65 patients of severe AA, a dose of 5 mg every 12 hours was found to produce better regrowth of hair compared to 5% TM. Although hair regrowth was rapid and extensive with OM compared to TM, cosmetic improvement was achieved only in 18% of patients. A strict salt control diet was followed to overcome fluid retention effects.[21] Tolerable side effects such as palpitation, headache, facial hypertrichosis were noted and few patients had fluid retention. Another study with a combination of tofacitinib 10 mg/day and 2.5 mg/day OM for women and 5 mg/day for men found that combined treatment with OM is more effective than tofacitinib monotherapy for AA.[22]
Traction alopecia (TA)
OM was found effective in 4 patients of TA with a dose of 1.25 mg daily for 6 months. The improvement was noticed in the form of decreased hair shedding and increased scalp hair.[6]
Monilethrix
It is a genodermatoses with autosomal dominant inheritance. It manifests as fragile hairs, follicular keratotic papules, and beaded hair shaft which is the characteristic sign of monilethrix. Due to hair breakability, it leads to diffuse hair loss. OM has been found as a promising treatment for hair loss in monilethrix. In two cases treated with a low dose of 0.25 mg to 0.5 mg OM for 6 month period, a noticeable improvement was seen in the form of hair growth, decrease hair breakage, increase hair volume and length.[23] The study concluded that low dose OM was well tolerated but long-term maintenance will be needed to prevent relapse of hair loss. Patients were monitored for blood pressure and pulse rate.
Chemotherapy-induced alopecia
Chemotherapeutic agents are known to cause reversible hair loss which resolves 3 to 6 months after completion of treatment. There is a case report of permanent-chemotherapy induced alopecia (PCIA) who was treated with busulphan containing regimen for bone marrow transplant for hematological malignancy. The patient received OM 1 mg/day for 1 year and noticed increased hair growth at 6 weeks and lengthening of hair at 1year. Regrowth was prominent over frontal and parietal areas. Hemodynamically patient was stable.[7]
Loose anagen syndrome (LAS)
Jerjen et al. studied 8 patients (with mean age 5.75 years) of LAS with low dose OM (≤ 0.02 mg kg–1 daily) for 12 months and noticed increased hair length, increase in density of hair, reduction in hair shedding, and 2 patients experienced a change in hair color. The study suggested that LDOM can be a promising therapy for children with severe LAS.[24]
Lichen planopilaris (LPP)
LPP is a type of primary scarring alopecia characterized by perifollicular erythema, peripilar casts and loss of follicular opening. In a study of 51 patients by Vano-Galvan et al, LDOM 0.5 mg for women and 2.5 mg for men was advised for mean duration of 21 months. Improvement was noticed in hair thickness in 39% patients, thickness remains stable for 53% patients. They found that LDOM was more effective for diffuse LPP rather than patchy LPP. Adverse effects were mild.[25]
Other scarring alopecia
Beach et al, tried 1.25 mg of OM for 3 months in patients of central centrifugal cicatritial alopecia (CCCA) and frontal fibrosing alopecia (FFA) and observed hair growth over vertex and reduction in telogen hairs.[26]
Summary of previous studies of OM in various alopecia is given in [Table 2].
Adverse effects [[Table 3]A]
Interactions
Salicylate/ aspirin should not be used concomitantly since it inhibit sulfotransferase activity therby decreases the activity of OM.[1] Guanethidine, an antihypertensive should also be avoided as it precipitate orthostatic hypotension.[1]
Baseline work-up [[Table 3]B]
It shoud be done in all patients particularly pateints with underlying heart disease.
Advise to patients on OM
Reduced salt intake to < 2gm/day.
Keep the record of blood pressure and pulse rate monitoring.
Reduce alcohol intake to prevent sudden fall in blood pressure.
Reduce caffeine containing products and tablets for cold to avoid rapid increase in heart rate.
Future scope
Due to its convenient dosing and hence greater patient compliance, OM can be tried as a first-line of treatment in selected patients where currently its topical counterpart is in use. These include impulse control disorders such as trichotillomania along with antipsychotics, hair shaft disorders, to promote hair growth in beard area where patient won’t agree to undergo a hair transplant procedure and also for sparce hair growth over eyebrows.
| Conclusion | | |
Low dose OM (0.25 mg to 5 mg) though, not as a first-line drug, can be looked as an emerging alternative in young healthy patients who are non compliant to TM with regular blood pressure and heart rate monitoring. OM is a convenient, economical, and cosmetically more acceptable.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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| 2. | Messenger AG, Rundegren J Minoxidil: Mechanisms of action on hair growth. Br J Dermatol 2004;150:186-94. |
| 3. | Sinclair RD Female pattern hair loss: A pilot study investigating combination therapy with low-dose oral minoxidil and spironolactone. Int J Dermatol 2018;57:104-9. |
| 4. | Perera E, Sinclair R Treatment of chronic telogen effluvium with oral minoxidil: A retrospective study. F1000Res 2017;6:1650. |
| 5. | Pratt CH, King LE Jr, Messenger AG, Christiano AM, Sundberg JP Alopecia areata. Nat Rev Dis Primers 2017;3:17011. |
| 6. | Beach RA Case series of oral minoxidil for androgenetic and traction alopecia: Tolerability & the five C’s of oral therapy. Dermatol Ther 2018;31:e12707. |
| 7. | Yang X, Thai KE Treatment of permanent chemotherapy-induced alopecia with low dose oral minoxidil. Australas J Dermatol 2016;57:e130-2. |
| 8. | Rossi A, Cantisani C, Melis L, Iorio A, Scali E, Calvieri S Minoxidil use in dermatology, side effects and recent patents. Recent Pat Inflamm Allergy Drug Discov 2012;6:130-6. |
| 9. | Randolph M, Tosti A Oral minoxidil treatment for hair loss: A review of efficacy and safety. J Am Acad Dermatol 2021;84:737-46. |
| 10. | Falany CN, Kerl EA Sulfation of minoxidil by human liver phenol sulfotransferase. Biochem Pharmacol 1990;40:1027-32. |
| 11. | Ramos PM, Goren A, Sinclair R, Miot HA Oral minoxidil bio-activation by hair follicle outer root sheath cell sulfotransferase enzymes predicts clinical efficacy in female pattern hair loss. J Eur Acad Dermatol Venereol 2020;34:e40-1. |
| 12. | Goren A, Castano JA, McCoy J, Bermudez F, Lotti T Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia. Dermatol Ther 2014;27:171-3. |
| 13. | Goren A, Shapiro J, Roberts J, McCoy J, Desai N, Zarrab Z, et al. Clinical utility and validity of minoxidil response testing in androgenetic alopecia. Dermatol Ther 2015;28:13-6. |
| 14. | Roberts J, Desai N, McCoy J, Goren A Sulfotransferase activity in plucked hair follicles predicts response to topical minoxidil in the treatment of female androgenetic alopecia. Dermatol Ther 2014;27:252-4. |
| 15. | Rodrigues-Barata R, Moreno-Arrones OM, Saceda-Corralo D, Jiménez-Cauhé J, Ortega-Quijano D, Fernández-Nieto D, et al. Low-dose oral minoxidil for female pattern hair loss: A unicenter descriptive study of 148 women. Skin Appendage Disord 2020;6:175-6. |
| 16. | Ramos PM, Sinclair RD, Kasprzak M, Miot HA Minoxidil 1 mg oral versus minoxidil 5% topical solution for the treatment of female-pattern hair loss: A randomized clinical trial. J Am Acad Dermatol 2020;82:252-3. |
| 17. | Jha AK, Sonthalia S, Zeeshan MD, Vinay K Efficacy and safety of very-low-dose oral minoxidil 1.25 mg in male androgenetic alopecia. J Am Acad Dermatol 2020;83:1491-3. |
| 18. | Lueangarun S, Panchaprateep R, Tempark T, Noppakun N Efficacy and safety of oral minoxidil 5 mg daily during 24-week treatment in male androgenetic alopecia. J Am Acad Dermatol 2015;72:AB113. |
| 19. | Jimenez-Cauhe J, Saceda-Corralo D, Rodrigues-Barata R, Hermosa-Gelbard J, Moreno-Arrones OM, Fernandez-Nieto D, et al. Effectiveness and safety of low-dose oral minoxidil in male androgenetic alopecia. J Am Acad Dermatol 2019;81:648-9. |
| 20. | Pirmez R, Salas-Callo CI Very-low-dose oral minoxidil in male androgenetic alopecia: A study with quantitative trichoscopic documentation. J Am Acad Dermatol 2020;82:e21-2. |
| 21. | Fiedler-Weiss VC, Rumsfield J, Buys CM, West DP, Wendrow A Evaluation of oral minoxidil in the treatment of alopecia areata. Arch Dermatol 1987;123:1488-90. |
| 22. | Wambier CG, Craiglow BG, King BA Combination tofacitinib and oral minoxidil treatment for severe alopecia areata. J Am Acad Dermatol 2021;85:743-5. |
| 23. | Sinclair R Treatment of monilethrix with oral minoxidil. Jaad Case Rep 2016;2:212-5. |
| 24. | Jerjen R, Koh WL, Sinclair R, Bhoyrul B Low-dose oral minoxidil improves global hair density and length in children with loose anagen hair syndrome. Br J Dermatol 2021;184: 977-8. |
| 25. | Vañó-Galván S, Trindade de Carvalho L, Saceda-Corralo D, Rodrigues-Barata R, Kerkemeyer KL, Sinclair RD, et al. Oral minoxidil improves background hair thickness in lichen planopilaris. J Am Acad Dermatol 2021;84:1684-6. |
| 26. | Beach RA, McDonald KA, Muylaert Barrett B Low-dose oral minoxidil for treating alopecia: A 3-year north american retrospective case series. J Am Acad Dermatol 2021;84: 761-3. |
[Figure 1]
[Table 1], [Table 2], [Table 3]
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