Topical minoxidil therapy for hair regrowth

The pathogenesis of hair loss, the postulated mechanisms of minoxidil action on hair growth, and clinical trials, adverse reactions, experimental formulations, and percutaneous absorption of topical minoxidil preparations are reviewed. Topical minoxidil seems to normalize hair follicles and increase blood flow to the scalp. In clinical trials of various formulations, results have varied. Improved hair growth occurred after four to six months of therapy; twice-daily application seems to be indicated. The most frequently reported adverse reactions are mild scalp dryness and irritation and, rarely, allergic contact dermatitis. Current recommendations are to reserve topical minoxidil for patients with normal cardiovascular status and to routinely monitor blood pressure, heart rate, and electrocardiographic changes. A new drug application is pending with FDA for use of topical minoxidil in androgenetic alopecia (male-pattern baldness), which is genetically determined and apparently stimulated by androgens. For alopecia areata, which involves hair loss on the body or scalp, usually patchy and of sudden onset, no reliable treatment has been found, although minoxidil may be efficacious in some patients. Minoxidil has generated new interest in hair-loss research. The etiology of hair loss must be better understood before more effective treatment regimens can be designed.     

Topical minoxidil. A preliminary review of its pharmacodynamic properties and therapeutic efficacy in alopecia areata and alopecia androgenetica

When minoxidil is administered orally for periods in excess of 1 month, hypertrichosis occurs as a side effect in a majority of patients. Consequently, topical minoxidil has been developed to try to improve hair growth in patients with alopecia areata and alopecia androgenetica. Preliminary studies have shown that topical minoxidil promotes cosmetically acceptable hair regrowth in a variable proportion of patients with alopecia areata. Data from a large multicentre trial indicate that cosmetically worthwhile results are achieved in about one-third of subjects with alopecia androgenetica after 1 year of treatment. A much higher proportion (about 80%) of patients with alopecia androgenetica exhibited some non-vellus hair regrowth after 1 year, and whether more of these patients would develop a cosmetically acceptable result with a longer treatment period is an important area of future investigation. Initial indications suggest that less severe disease is a predictor of likely response. Thus, topical minoxidil would seem to be a useful treatment modality for patients with alopecia androgenetica--a disease for which no other safe and effective drug therapy exists. Results from treating patients with alopecia areata with topical minoxidil, although encouraging, have been more variable and require further evaluation. Even though a number of questions remain to be answered about topical minoxidil (as would be expected at this stage in its development), it would seem to be the first available drug with the potential to promote substantial hair regrowth in these divergent diseases.     

加味二至丸联合外用米诺地尔酊治疗青年型男性脱发的临床观察

目的 探讨加味二至丸联合外用米诺地尔酊对青年型男性脱发的疗效.方法 选取男性型脱发患者126例,按随机数字表法分为三组,即西药组(米诺地尔酊外用)、中药组(加味二至丸)和联合治疗组(加味二至丸加米诺地尔酊外用),每组42例.超声仪检测三组患者治疗前后血流动力学特征变化;高分辨率扫描电子显微镜-X射线能谱仪测定秃发区微量元素Ca、Fe、Zn、Cu的含量;检测各组治疗后毛发生长速度、生长长度和毛囊状况,最后进行疗效判定.结果 与治疗前相比,三组患者治疗后血流阻力指数(RI)明显下降,流速时间积分(VT1)和峰值流速(Vmax)明显升高,且联合治疗组血流动力学改善效果较西药组和中药组明显(P＜0.05);联合治疗组发中微量元素Fe、Ca、Zn、Cu含量明显升高,且升高幅度大于单纯西药和中药组(P＜0.05);联合治疗组毛发生长速度为(12.605 ±3.271) ×10-2 mm·d-1,治疗后总有效率高达92.9％,明显高于单纯中药组(76.2％)和西药组(54.8％),且联合治疗组毛囊生长期较另外两组延长(P＜0.05).结论 加味二至丸联合外用米诺地尔酊对男性型脱发患者疗效确切,值得临床推广应用.     

Drug-induced hair disorders

Drugs may induce hair loss, stimulate hair growth or, more rarely, induce changes in the hair shape and colour. Drug-induced hair loss is usually completely reversible and is, in most cases, a consequence of a toxic effect of the drug on the hair follicle matrix. In rare cases alopecia may be permanent. Depending on type of drug, dosage and patient susceptibility, hair loss presents as telogen effluvium, anagen effluvium or both. Telogen effluvium is also commonly observed after discontinuation of drugs that prolong anagen, such as topical minoxidil and oral contraceptives. Although a large number of drugs have been occasionally reported to produce hair loss, only for a few drugs the relation between drug intake and hair loss has been proven.     

Preparation and in vivo evaluation of lecithin-based microparticles for topical delivery of minoxidil

Minoxidil is widely used for treatment of androgenic alopecia. Commercial products containing minoxidil are usually in solution form. Repeated applications of minoxidil solution can lead to adverse effects such as skin irritation and horniness. The aims of this study were to prepare lecithin-based microparticle in minoxidil solution for enhancement of minoxidil topical delivery and skin protection and evaluate the ability of lecithin on in vitro delivery, in vivo hair growth, and skin trouble improvement compared to commercial minoxidil solution. In in vitro skin permeation study, minoxidil solution containing lecithin microparticle showed higher skin penetration rate and higher retention of drug inside the skin compared to minoxidil solution without lecithin. After topical application of minoxidil solutions with or without lecithin to C57BL/6 mice, minoxidil 5% solution containing lecithin microparticle showed hair re-growth as efficient as commercial product of minoxidil 5% solution. It also significantly improved skin troubles while commercial product presented horny substance and crust formation. Therefore, the lecithin-based microparticle in minoxidil 5% solution has good ability to promote hair growth without adverse effects.     

Simultaneous effects of tocopheryl polyethylene glycol succinate (TPGS) on local hair growth promotion and systemic absorption of topically applied minoxidil in a mouse model

In this study, topical minoxidil solutions supplemented with TPGS in cosolvent systems of various compositions consisting of water, alcohol, and polyethylene glycol 400 were designed to evaluate the efficacy of promoting hair growth after topical application and the safety in terms of the amount of minoxidil absorbed through the skin into the circulation using C57BL/6J mice as a model. The commercial product of 2% Regaine) was used as the positive control. The role, which sulfotransferase activity plays in hair growth with treatment using minoxidil, was determined as well. The results revealed that the addition of 0.5% TPGS was able to enhance the proliferation of hair, but an increase in the amount of TPGS to 2% led to deterioration in the enhancement of hair growth. At the higher added amount (2.0%) of TPGS, the promotion of hair growth was slightly reduced for both cosolvent formulations F1 (100% water) and F3 (100% PEG 400), whereas it was reduced to a greater extent for the cosolvent formulations F8-F10. In comparison, the influences of cosolvent compositions with TPGS amounts of 0.0 and 2.0% on the promotion of hair growth were similar. On the contrary, variability in the promotion of hair growth by different solvent formulations was minimal when the added amount of TPGS was 0.5%. In general, a relationship between hair growth and sulfotransferase activities after topical application of 2% Regaine and minoxidil formulations containing various amounts of TPGS was not demonstrated. Plasma concentrations of minoxidil with 2% Regaine were found to be greater than those of 2% minoxidil in those cosolvent formulations containing various amounts of TPGS, while showing insignificant differences among those 10 cosolvent formulations with a fixed amount of TPGS. A tendency for the plasma concentration of minoxidil to increase after the topical administration of minoxidil formulations containing the higher amount of TPGS (2%) was noted.     

Nongenotoxicity of minoxidil in murine hair follicles as determined by the nuclear aberration assay

A 1-cm2 area on the back of CD1 mice was prepared for topical application of minoxidil, N-methyl-N-nitrosourea (MNU), or cyclophosphamide (CY) by clipping or plucking hair from a patch of skin. Plucking stimulates hair follicle cell division while clipping does not. Minoxidil was topically administered for 8 consecutive days. CY or MNU was administered topically once on the eighth day postplucking. The incidence of nuclear aberrations and mitotic figures were measured in hair follicles while frequency of micronuclei and the ratio of RBC/PCE were measured in the bone marrow. Results with minoxidil showed no increase in either nuclear aberrations in the hair follicle or micronuclei in the bone marrow. These results suggest that topically applied minoxidil is not genotoxic. In contrast, a dose-dependent effect of MNU on the incidence of nuclear aberrations in the hair follicle was seen. CY induced a dose-dependent increase in the incidence of micronuclei in the bone marrow and in nuclear aberrations in the hair follicle after topical application. Minoxidil applied to clipped mice significantly increased the incidence of mitotic figures above that seen in both the clipped and plucked controls. This suggests that minoxidil is a mitogenic agent in the hair follicle. These findings are consistent with the success of topically applied minoxidil in the treatment of alopecia areata.     

Update on the pathogenesis, genetics and medical treatment of patterned hair loss

Androgenic alopecia (AGA), or pattern hair loss, is a common condition that affects both men and women has been gradually increasing. The discovery of the androgen receptor (AR) gene and related genes has expanded the knowledge on the genetics of hair loss. These basic science studies, combined with more recent clinical studies, have led to a better understanding of the pathogenesis of AGA in both men and women. These genetic advances have also led to the development of a new screening test for AGA. Recently, in addition to the two currently approved U.S. Food and Drug Administration (FDA) medications (minoxidil and finasteride), a novel device was FDA-approved for the treatment of hair loss, the laser hair comb. Further studies are needed to verify the accuracy and validity of the genetic screening test and the efficacy of the laser hair comb.     

Monilethrix treated with minoxidil

In literature many different therapies are proposed to treat Monilethrix, but a definitive therapy still doe not exist. We decided to treat four patients affected by Monilethrix, with topical minoxidil 2%, 1 ml night and day for 1 year. Minoxidil led to a an increase of normal hair shaft without any side effects in all the patients. Therefore topical minoxidil 2% could be considered a good therapy to treat Monilethrix.     

Minoxidil use in dermatology, side effects and recent patents

Minoxidil, a vasodilator medication known for its ability to slow or stop hair loss and promote hair regrowth, was first introduced, exclusively as an oral drug, to treat high blood pressure. It was however discovered to have the important side-effect of increasing growth or darkening of fine body hairs; this led to the development of a topical formulation as a 2% concentration solution for the treatment of female androgenic alopecia or 5% for treating male androgenic alopecia. Measurable changes disappear within months after discontinuation of treatment. The mechanism by which it promotes hair growth is not fully understood. Minoxidil is a potassium channel opener, causing hyperpolarization of cell membranes and it is also a vasodilator, it is speculated that, by widening blood vessels and opening potassium channels, it allows more oxygen, blood and nutrients to the follicle. This can also cause follicles in the telogen phase to shed, usually soon to be replaced by new, thicker hairs in a new anagen phase. It needs to be applied regularly, once or twice daily, for hair gained to be maintained, and side effects are common. The most common adverse reactions of the topical formulation are limited to irritant and allergic contact dermatitis on the scalp. There have been cases of allergic reactions to the nonactive ingredient propylene glycol, which is found in some topical solution especially if they are galenic. Increased hair loss which can occur during Minoxidil use, is due to the synchronization of the hair cycle that the treatment induces. In this review, we described its mechanism of action, use in dermatology and some patents related to alternative treatment of allergic reactions due to its use.     

The physiological and pharmacological roles of prostaglandins in hair growth

Hair loss is a common status found among people of all ages. Since the role of hair is much more related to culture and individual identity, hair loss can have a great influence on well-being and quality of life. It is a disorder that is observed in only scalp patients with androgenetic alopecia (AGA) or alopecia areata caused by stress or immune response abnormalities. Food and Drug Administration (FDA)-approved therapeutic medicines such as finasteride, and minoxidil improve hair loss temporarily, but when they stop, they have a limitation in that hair loss occurs again. As an alternative strategy for improving hair growth, many studies reported that there is a relationship between the expression levels of prostaglandins (PGs) and hair growth. Four major PGs such as prostaglandin D2 (PGD₂), prostaglandin I2 (PGI₂), prostaglandin E2 (PGE₂), and prostaglandin F2 alpha (PGF₂α) are spatiotemporally expressed in hair follicles and are implicated in hair loss. This review investigated the physiological roles and pharmacological interventions of the PGs in the pathogenesis of hair loss and provided these novel insights for clinical therapeutics for patients suffering from alopecia.     

Liposomes and niosomes as potential carriers for dermal delivery of minoxidil

The aim of this work was to formulate minoxidil loaded liposome and niosome formulations to improve skin drug delivery. Multilamellar liposomes were prepared using soy phosphatidylcholine at different purity degrees (Phospholipon 90, 90% purity, soy lecithin (SL), 75% purity) and cholesterol (Chol), whereas niosomes were made with two different commercial mixtures of alkylpolyglucoside (APG) surfactants (Oramix NS10, Oramix CG110), Chol and dicetylphosphate. Minoxidil skin penetration and permeation experiments were performed in vitro using vertical diffusion Franz cells and human skin treated with either drug vesicular systems or propylene glycol-water-ethanol solution (control). Penetration of minoxidil in epidermal and dermal layers was greater with liposomes than with niosomal formulations and the control solution. These differences might be attributed to the smaller size and the greater potential targeting to skin and skin appendages of liposomal carriers, which enhanced globally the skin drug delivery. The greatest skin accumulation was always obtained with non-dialysed vesicular formulations. No permeation of minoxidil through the whole skin thickness was detected in the present study irrespective of the existence of hair follicles. Alcohol-free liposomal formulations would constitute a promising approach for the topical delivery of minoxidil in hair loss treatment.     

Alopecia areata

Alopecia aerata (AA) is an autoimmune disease that presents as well defined patches of nonscarring hair loss with no overt epidermal changes. The life-time risk of AA in the general population is approximately 1.7%. As many as 60% of patients with AA have disease onset before 20 years of age. AA most commonly manifests as sudden loss of hair in well demarcated, localized area in the scalp. The hair loss is usually limited to a single patch. The lesion is usually round or oval. "Exclamation point hairs" are frequently seen at the periphery of the lesion. Because of the high rate of spontaneous recovery especially in those with small areas of hair loss or with a recent onset, not all patients require pharmacological treatment. A "watch-and-wait" approach is often recommended. Psychological support may be offered if necessary. For patients who actively desire treatment, topical corticosteroids and/or minoxidil are the treatment of choice. Interleukin (IL)-31 antibodies and 308-nm Excimer laser as novel treatment modalities appear promising in the armamentarium against this distressing disease. The review also outlined recent patents on the treatment of alopecia.     

Preventive effects of cedrol against alopecia in cyclophosphamide-treated mice

Although numerous hypotheses have been proposed to prevent chemotherapy-induced alopecia (CIA), effective pharmaceuticals have yet to be developed. In our study, the back hairs of C57BL/6 mice were factitiously removed. These mice were then treated with cedrol or minoxidil daily. Mice with early-stage anagen VI hair follicles were treated with cyclophosphamide (CYP, 125 mg/kg) to induce alopecia. The CYP-damaged hair follicles were observed and quantified by using a digital photomicrograph. The results demonstrated that the minoxidil-treated mice suffered from complete alopecia similar to the model 6 days after CYP administration. Simultaneously, the cedrol-treated (200 mg/kg) mice manifested mild alopecia with 40% suppression. Histological observation revealed that anagen hair follicles of the cedrol-pretreated mice (82.5%) likely provided from damage compared with the sparse and dystrophic hair follicles of the model mice (37.0%). Therefore, the use of topical cedrol can prevent hair follicle dystrophy and provide local protection against CIA.     

Pruritic rash with actinic keratosis and impending exfoliation in a patient with hypertension managed with minoxidil

Dermatological toxicity has been reported following initiation of therapy with minoxidil, but no cases have been reported following prolonged use. We report the emergence of an erythematous weeping rash with impending exfoliation three years after the initiation of minoxidil therapy. Minoxidil was withdrawn and the patient responded to therapy with topical corticosteroids. Following minor surgery, the patient was inadvertently rechallenged with minoxidil. Within 24 hours of exposure bullous lesions reappeared in the extremities which again resolved with topical corticosteroids. Dermatological lesions observed on this patient were similar to those reported following acute minoxidil exposure and strongly implicate chronic minoxidil therapy.     

Preparation of topical bimatoprost with enhanced skin infiltration and in vivo hair regrowth efficacy in androgenic alopecia

To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM–TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM–TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 μM BIM, equivalent to 10 μM minoxidil. Moreover, BIM–TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM–TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM–TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM–TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.     

Treatments for androgenetic alopecia and alopecia areata: current options and future prospects

Androgenetic alopecia and alopecia areata are common disorders of the hair follicle which may heavily influence self esteem and self image. Androgenetic alopecia is caused by the heightened sensitivity of scalp follicles to dihydro- testosterone whereas alopecia areata is induced by an autoimmune reaction. Current drug treatment approaches include the use of regrowth stimulators such as topical minoxidil and oral finasteride for androgenetic alopecia, as well as topical minoxidil, dithranol (anthralin), corticosteroids, contact sensitisers, and psoralen plus ultraviolet A irradiation (PUVA) therapy for alopecia areata. Combination regimens are also proposed. However, extreme cases of either type of alopecia do not generally respond well to these existing treatments. For this reason, new therapeutic strategies are directed towards both improving the targeting of existing agents, as well as the development of novel hypertrichotic modalities.     

2%米诺地尔酊剂外用辅治斑秃的疗效观察

目的观察2%米诺地尔酊剂外用辅治斑秃的临床疗效。方法将120例斑秃患者随机分为观察组和对照组各60例。对照组给予基础对症治疗;观察组在对照组治疗基础上加用2%米诺地尔酊剂,并用生姜汁及生蒜外擦患处,每天2次,1个月为1个疗程。治疗后比较2组疗效及不良反应。结果观察组总有效率为93.3%高于对照组的75.0%,差异有统计学意义(P<0.01)。观察组出现头晕1例,对照组出现下肢水肿1例,经调整用药后均改善。结论 2%米诺地尔酊剂外用辅治斑秃可提高治疗效果,值得临床推广应用。     

The additive effects of minoxidil and retinol on human hair growth in vitro

Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (AGA), whereas retinol significantly improves scalp skin condition and promotes hair growth. We investigated the combined effects of minoxidil and retinol on human hair growth in vitro and on cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT). The combination of minoxidil and retinol additively promoted hair growth in hair follicle organ cultures. In addition, minoxidil plus retinol more effectively elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft elongation demonstrated after minoxidil plus retinol treatment would depend on the dual kinetics associated with the activations of Erk- and Akt-dependent pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.     

Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia

In men who are genetically predisposed to develop androgenetic alopecia (AGA; male pattern hair loss), endogenous androgens alter scalp hair follicles, resulting in production of vellus-like, miniaturised hair, rather than cosmetically significant terminal hair. This change leads to a progressive decline in visible scalp hair density, readily perceived by the patient as thinning and, eventually, baldness. Dihydrotestosterone (DHT), a metabolite of testosterone produced by the enzyme 5alpha-reductase, has been implicated as the specific androgen in the pathogenesis of AGA. Men genetically deficient in the Type 2 isoenzyme of 5alpha-reductase do not develop AGA. Moreover, Type 2 5alpha-reductase has been detected in scalp hair follicles, and balding scalps contain increased Type 2 5alpha-reductase activity and DHT levels. Taken together, these findings provide a rationale for the use of Type 2 5alpha-reductase inhibitors in the treatment of men with AGA. Finasteride, a specific and potent inhibitor of human Type 2 5alpha-reductase, decreases the formation of DHT from testosterone. Originally developed for the treatment of men with benign prostatic hyperplasia (BPH) as a 5 mg tablet, finasteride was subsequently evaluated as a treatment for AGA. Clinical studies in balding men demonstrated that finasteride reduced scalp DHT levels and improved hair growth, confirming the role of DHT in the pathophysiology of AGA. Dose-ranging studies established the optimal dose of 1 mg/day for the treatment of men with this disorder. Large, multicentre studies established the safety and efficacy of finasteride 1 mg, leading to marketing of Propecia (finasteride 1 mg) as a new treatment for men with AGA.