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Clinical utility and validity of minoxidil response testing in androgenetic alopecia
Abstract
Clinical response to 5% topical minoxidil for the treatment of androgenetic alopecia (AGA) is typically observed after 3–6 months. Approximately 40% of patients will regrow hair. Given the prolonged treatment time required to elicit a response, a diagnostic test for ruling out nonresponders would have significant clinical utility. Two studies have previously reported that sulfotransferase enzyme activity in plucked hair follicles predicts a patient's response to topical minoxidil therapy. The aim of this study was to assess the clinical utility and validity of minoxidil response testing. In this communication, the present authors conducted an analysis of completed and ongoing studies of minoxidil response testing. The analysis confirmed the clinical utility of a sulfotransferase enzyme test in successfully ruling out 95.9% of nonresponders to topical minoxidil for the treatment of AGA.
... It is based on the average change in non-vellus hair count [29]. Olsen et al. performed clinical studies in men, where using 5% minoxidil contributed to hair growth in approximately 40% of patients [21,30]. On the other hand, the response to 2% minoxidil is lower. ...
... Sulfotransferases are xenobiotic metabolizing enzymes with the highest expression found in the human liver [32], but hair follicle cells also express it [13,22,30]. The correlation between SULT1A1 expression in the scalp and minoxidil response has been previously reported [33]. ...
... Frame et al. have adapted a colorimetric assay of SULT1A1 activity to measure the conversion of minoxidil in the hair root of a plucked human hair [34]. The expression of SULT1A1 has been localized in the outer root sheet [30]. In the assay, the conversion of minoxidil to minoxidil sulfate is coupled with the conversion of p-nitrophenyl sulfate to p-nitrophenyl, which can be quantified by optical absorbance at 405 nm. ...
Androgenetic alopecia (AGA) is a very common type of alopecia in men and women. It may have a negative effect on the quality of life. The most widely used pharmaceutical treatment for AGA is topical minoxidil and it is also the only external treatment of pattern hair loss. There are two forms of this treatment - 5% and 2% minoxidil. The correlation between SULT1A1 expression in the scalp and minoxidil response has been previously reported. Due to the prolonged treatment time required to elicit a therapeutic response (approximately 6 months) combined with the variable efficacy of minoxidil in the general population, expression of SULT1A1 as a biomarker for predicting treatment response would have a significant clinical utility.
... Sulfotransferase enzymes in the outer root sheath of the hair follicle convert minoxidil to its active form. In a number of studies sampling over 200 subjects, our group has demonstrating the clinical utility and validity of a test to measure the follicular sulfotransferase enzymatic activity in plucked hair as a method to predict minoxidil response (4)(5)(6). The test demonstrates an accuracy of 97.8% in identifying non-responders to minoxidil (4). ...
... The hairs were analyzed using the Minoxidil Response Test (Follea Ltd., Munich, Germany), an in-vitro medical device for determining a patient's response to topical minoxidil. The test procedure has been described previously (4). The value from the test indicates the level of sulfotransferase activity present in the sampled hairs, a value less than 0.4 indicates a person does not have adequate sulfotransferase activity to respond to topical minoxidil. ...
... In our previous work, we have demonstrated that the enzymatic activity of the sulfotransferase enzymes in hair follicles predicts minoxidil response (4)(5)(6). In this study, we further built on our findings and demonstrated that topical tretinoin application up-regulates follicular sulfotransferase enzymes for subjects with low basal expression. ...
Minoxidil sulfate is the active metabolite required to exert the vasodilatory and hair growing effects of minoxidil. For hair growth, sulfotransferase enzymes expressed in outer root sheath of the hair follicle sulfonate minoxidil. The large intra‐subject variability in follicular sulfotransferase was found to predict minoxidil response and thus explain the low response rate to topical minoxidil in the treatment of androgenetic alopecia. A method to increase minoxidil response would be of significant clinical utility. Retinoids have been reported to increase minoxidil response. The purported mechanism of action was retinoid modulation of skin permeation to minoxidil, however, evidence to the contrary supports retinoids increase dermal thickness. In order to elucidate the effect of topical retinoids on minoxidil response, we studied the effect of topical tretinoin on follicular sulfotransferase. In this study, we demonstrate that topical tretinoin application influences the expression of follicular sulfotransferase. Of clinical significance, in our cohort, 43% of subjects initially predicted to be non‐responders to minoxidil were converted to responders following 5 days of topical tretinoin application. To our knowledge, this is the first study to elucidate the interaction mechanism between topical minoxidil and retinoids and thus provides a pathway for the development of future androgenetic alopecia treatments.
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... 7,8 SULT1A1 activity has been used as a diagnostic to predict the likelihood of minoxidil response for individuals to help guide treatment for alopecia. 9 However, predicting minoxidil response has limited utility because there is currently no treatment option to remedy low SULT1A1. ...
... SULT1A1 activity in the scalp is required for minoxidil efficacy. 9 Here, we demonstrate in a randomized blinded controlled study that a SULT1A1 inducing topical formula is an effective adjuvant for improving minoxidil response. After 60 days of use, subjects who used both minoxidil and SULT1A1 adjuvant demonstrated more than twice the response to those using minoxidil and sham adjuvant. ...
Background
Minoxidil is a widely used over the counter topical treatment for hair loss. The response rate for topical minoxidil is relatively low. Minoxidil is a pro-drug, converted to its active form, minoxidil sulfate, by SULT1A1 enzymes located in the scalp. Recently, a novel topical formula that increases the activity of SULT1A1 in hair follicles was reported.
Aims
To evaluate any benefit of applying the SULT1A1 enzyme booster prior to daily 5% minoxidil treatment.
Methods
Male androgenic alopecia patients were recruited to a randomized blinded placebo controlled study. Patients were randomized to receive 5% topical minoxidil plus the novel formula or minoxidil plus a sham adjuvant. Patient’s hair growth was monitored using global photography over 60 days.
Results
Twenty-four males with androgenic alopecia (Norwood scale average 4.4, range 2-6) were randomized and completed the trial; 12 in the active arm and 12 in placebo. 75% of the subjects who used the SULT1A1 adjuvant with their daily minoxidil treatments for 60 days regrew hair verses 33% of those using the placebo adjuvant (p=0.023).
Conclusions
In a small cohort of androgenetic alopecia men, adding the SULT1A1 adjuvant to their daily minoxidil treatment regimen improved hair regrowth.
... Therefore, it is expected that cosmetic formulations containing an exogenous source of a ceramide-like molecule may present a repairing effect for skin by hindering, at least partially, the undesirable effects associated with aging [19]. The second compound is a beta-blocker, which is frequently used in both medical products and cosmetic formulations for the prevention and treatment of alopecia due to its recognized role on the stimulation of the circulatory flow within the hair follicles [20,21]. Despite the fact that the real mechanism underlying the performance of the above molecules is almost unknown, different studies have evidenced their effectiveness, which has fostered many research efforts trying to optimize commercial formulations containing such molecules. ...
... Oleic acid (purity > 99%) supplied by Sigma-Aldrich (Saint Louis, MO, USA), were used as oil phase of the different prepared nanoemulsions. Polyoxyethylene (20)sorbitan monooleate (Tween 80) purchased from Sigma-Aldrich (Saint Louis, MO, USA) was used for nanoemulsion stabilization. The two hydrophobic compounds to be encapsulated: (9Z)-N-(1,3-dihydroxyoctadecan-2-yl)octadec-9-enamide (CER) and 2,6-diamino-4-(piperidin-1-yl)pyrimidine 1-oxide (MIN) were supplied by Avanti Polar Lipids, Ltd. (Alabaster, AL, USA) and Sigma Aldrich (Saint Louis Sigma, Aldrich, MO, USA), respectively. ...
This work analyzes the dispersion of two highly hydrophobic actives, (9Z)-N-(1,3-dihydroxyoctadecan-2-yl)octadec-9-enamide (ceramidelike molecule) and 2,6-diamino-4-(piperidin-1-yl)pyrimidine 1-oxide (minoxidil), using oil-in-water nanoemulsions with the aim of preparing stable and safe aqueous-based formulations that can be exploited for enhancing the penetration of active compounds through cosmetic substrates. Stable nanoemulsions with a droplet size in the nanometric range (around 200 nm) and a negative surface charge were prepared. It was possible to prepare formulations containing up to 2 w/w% of ceramide-like molecules and more than 10 w/w% of minoxidil incorporated within the oil droplets. This emulsions evidenced a good long-term stability, without any apparent modification for several weeks. Despite the fact that this work is limited to optimize the incorporation of the actives within the nanoemulsion-like formulations, it demonstrated that nanoemulsions should be considered as a very promising tool for enhancing the distribution and availability of hydrophobic molecules with technological interest.
... 3 Several studies have determined that topical MXD applications can promote hair growth (HG) in both males and females with AGA. However, previous studies have also reported that <40% of patients respond to MXD, 4 and the efficacy of MXD is lower than that of low-laser therapy and oral finasteride treatment. 5 MXD takes at least 16-32 weeks to work by increasing the hair count in the scalp, 6,7 and hair loss recurs after 24 weeks once the MXD treatment is discontinued. ...
... Previous studies have shown that MXD treatment results in HG, shortens the telogen-anagen phase transition, 27 and may also enlarge the hair follicle size and increase the hair diameter, leading to increased hair density and T/V ratio. 28,29 Nonetheless, MXD yielded a lower HG response, with *40% efficacy after 16 weeks of usage, 4 and was less effective than finasteride and low-level laser treatment. 5 High MXD concentrations increased the therapeutic effect, but with an increased incidence of adverse events. ...
Background: Minoxidil (MXD) is an U.S. Food and Drug Administration-approved drug for the topical treatment of androgenetic alopecia (AGA) with minor side effects, but its hair growth (HG) effect is unsatisfactory. Methods: A double-blinded within-subjects randomized clinical trial was conducted on 16 male AGA patients who showed limited improvement after MXD treatment. Eligible participants received three concentrated growth factor (CGF) injections on half of the scalp and the placebo on the other side at 4-week intervals, and MXD was applied twice daily on both sides throughout the follow-up period. The primary endpoint was the HG ratio at V4. The secondary endpoints included the HG ratios at V2, V3, and V5; hair density and T/V ratio at V2, V3, V4, and V5; Global Aesthetic Improvement Scale (GAIS) scores at V4 and V5; and participant satisfaction at V4. Results: Each group included 16 subjects; each half of the scalp was randomly assigned to the MXD+CGF or MXD group. The HG ratio at V4 was higher in the MXD+CGF group than in the MXD group. The MXD+CGF group had significant improvements in hair density, HG ratio, and T/V ratio compared with the MXD group over the follow-up period. The GAIS scores and participant satisfaction were higher in the MXD+CGF group than in the MXD group. Unexpectedly, the MXD+CGF treatment hastened HG, which was sustained for 3 months after discontinuation. No severe adverse events occurred. Conclusions: The combined treatment of MXD and CGF is safe and more efficient for AGA patients. Combining CGF can expedite the potency of MXD and provide patients with fast and lasting HG.
... Minoxidil [13], 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. Minoxidil also appears to stimulate the Vessel Endothelial Growth Factor (VEGF), which could promote the production of mesenchymal cells and anagen phase, at the level of the sub-follicular capillary microcirculation. ...
... Synthetic drugs including Minoxidil, Finasteride immunosuppressive drugs, etc. are widely used to treat hair loss. According to data published by the National Center for Biotechnological Information (NCBI), in 2018 Minoxidil (6-(1-piperidinyl) -2,4-pyrimidinediamine-3-oxide), which is also an antihypertensive peripheral vasodilator was the most common drug used topically for the treatment of hair loss, mainly with androgenic alopecia [4,16]. However, these synthetic drugs possess side effects such as hormonal disorders, scalp itching, and scaling [17]. ...
Background: Hair loss or alopecia is a common dermatological problem that occurs in up to 2% of the human population. Often it is hereditary male- or female-pattern baldness. However, different environmental factors, unbalanced diet and chronic diseases result in hair loss. Hair loss is not a life-threatening sickness, but it may result in anxiety and depression, and other serious psychological problems affecting the individual`s quality of life. Objective: Different treatments for hair loss, including synthetic or/and natural drugs such as Minoxidil and Finasteride, approved
by the Food and Drug Administration (FDA) for hair growth. These drugs are effective, but they have potential side
effects. Natural remedies that are used for the treatment of various diseases have been proposed for hair loss healing
because many chronic disorders cause alopecia. Therefore, the main focus of our study was search for alternative
efficient treatment agents, particularly medicinal plants, with limited side effects. Methods: To find relevant information, different databases, including Scopus, PubMed and Google Scholar, were used, and various search terms such as “Hair loss”, “Alopecia”, “Hair loss AND Natural remedies”, “Alopecia AND natural remedies”, “Herbal treatment AND Hair loss” etc. were applied to extract related articles. Results: Different herbs and other natural compounds are believed to reduce hair loss due to their anti-inflammatory and antioxidant potential as well as due to the ability to improve local metabolism when applied externally. As per the literature, herbal extracts and formulations
made from Urtica dioica, Humulus lupulus, Serenoa repens, Pygeum africanum, Vitis vinifera, Cucurbita pepo, Crocus sativus, Medicago sativa, Linum usitatissimum, Broccoli, etc., and some individual herbal compounds, micronutrients, bee products, and keratin have potential to reduce hair loss directly or indirectly. Conclusion: Medicinal plants and several promising natural molecules can promote hair growth and prevent alopecia by reducing the activity of the 5-α-reductase enzyme
... [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. ...
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.
... Thus, polymer-based synthetic nanotechnology-based formulations have gained growing interest since the last decade as a follicular drug delivery treatment. ( continued on next page ) [70] ( continued on next page ) [79] ( continued on next page ) Though topical minoxidil is generally well tolerated, the efficacy of drug treatments remains low [89] . The low effectiveness is likely due to low absorption: about 1.4% of topically applied minoxidil can be absorbed through a normal intact scalp [90] . ...
The hair follicle is not only a critical penetration route in percutaneous absorption but also has been recognized to be a target for hair follicle-associated disorders, such as androgenetic alopecia (AGA) and acne vulgaris. Hair follicle-targeting drug delivery systems allow for controlled drug release and enhance therapeutic efficacy with minimal side effects, exerting a promising method for the management of hair follicle-associated dysfunctions. Therefore, they have obtained much attention in several fields of research in recent years. This review gives an overview of potential follicle-targeting drug delivery formulations currently applied based on the particularities of the hair follicles, including a comprehensive assessment of their preclinical and clinical performance.
... Based on the previous reports, it affects almost 50% of the population with the age over 50 years. [1,2] It was reported that it also affects 6%-38% of healthy females. [3] The reason behind the importance of treatment in these patients is the great discomfort, isolation, and reduction in quality of life this disease could cause. ...
Background and Purpose: Using the commercially manufactured forms of minoxidil, the only approved topical drug preparation for hair regrowth in patients with androgenetic alopecia (AGA) comes across with challenges such as limited permeation through the superficial layers of the skin to reach the site of action and topical adverse reactions like itching and inflammation occur because of the ethanol in the formulations. In this study, a novel nanosuspension formulation with an aqueous base was prepared and evaluated to overcome the discussed challenges. Materials and Methods: The nanosuspension formulation was characterized by size, zeta potential, morphology, and in vitro release. Seventy patients were subjected to use either 1 mL of nanosuspension or the commercial product twice daily for six months and were then examined for changes in hair follicle diameter and hair density within a 1 × 1-cm2 area of the scalp as the primary endpoints besides any adverse reaction manifestation as the secondary endpoint. Results: The nanosuspension formulation showed uniform morphology, 200-nm particle size, and suitable zeta potential that ensures the stability. The in vitro release study exhibited almost 90% release in the first 6 h. It was observed that there were no significant differences between the efficacy of aqueous-based topical 2% nanosuspension of minoxidil and the commercial product in the treatment of AGA (P > 0.05). However, the aqueous-based topical 2% nanosuspension formulation showed better safety and tolerability compared to the marketed profile. Conclusions: It could be concluded that aqueous-based topical 2% nanosuspension is a suitable form with enhanced patient compliance compared to commercially manufactured products.
... This metabolite is more potent than the parent drug [26] . Testing for sulfotransferase enzyme activity might predict minoxidil responders among androgenetic alopecia patients [27] . ...
... Minoxidil, the pro-drug of minoxidil sulphate, was discovered by coincidence as a treatment for hair thinning and is a Food and Drug Administration (FDA) approved topical drug for androgenetic alopecia (AGA) since 1988. Several studies demonstrated that response to topical minoxidil is predicted by the sulfotransferase enzymatic activity in plucked HF [120,121]. The product will not influence the local immunological problem but works on the blood flow at the HF by angiogenesis, vasodilatation, increased cell proliferation or influencing potassium channels [49,107,122]. ...
Patients suffering from alopecia areata (AA) can lose hair in focal regions, the complete scalp, including eyelashes and eyebrows, or even the entire body. The exact pathology is not yet known, but the most described theory is a collapse of the immune privilege system, which can be found in some specific regions of the body. Different treatment options, local and systemic, are available, but none of them have been proven to be effective in the long term as well for every treatment there should be considered for the possible side effects. In many cases, treated or non-treated, relapse often occurs. The prognosis is uncertain and is negatively influenced by the subtypes alopecia totalis and alopecia universalis and characteristics such as associated nail lesions, hair loss for more than 10 years and a positive familial history. The unpredictable course of the disease also makes it a mental struggle and AA patients are more often associated with depression and anxiety compared to the healthy population. Research into immunology and genetics, more particularly in the field of dendritic cells (DC), is recommended for AA as there is evidence of the possible role of DC in the treatment of other autoimmune diseases such as multiple Sclerosis and cancer. Promising therapies for the future treatment of AA are JAK-STAT inhibitors and PRP.
... For that reason, several recently published studies aimed to reduce adverse effects of minoxidil formulations and to improve the effectiveness by stimulating the accumulation of the drug into the hair follicles (3) using nanostructured delivery systems, such as polymeric nanoparticles (4)(5)(6), liposomes (7)(8)(9), and solid lipid nanoparticles (10)(11)(12)(13). Despite the promising results achieved with these novel minoxidil formulations, a large portion of patients are unresponsive to treatment with this drug (14). Thus, studies to insert new molecules and efficient formulations for the treatment of alopecia are demanded. ...
Latanoprost has recently been used to treat alopecia as it causes an increase in the capillary density of patients. This work presents for the first time the development of polymeric nanocapsules containing latanoprost for the topical treatment of alopecia. Poly-ε-caprolactone nanocapsules loading latanoprost were developed by nanoprecipitation of the polymer on the surface of drug oily nanodroplets. The method encapsulated 93.9 ± 0.4% of the drug into nanocapsules of 197.8 (± 1.2) nm (PdI = 0.15 ± 0.01). The nanosystem presented a zeta potential equal to − 30.1 ± 1.8 mV and was stable for at least 90 days when stored at 6°C. The colloidal aqueous dispersion was non-irritating, according to the in vitro HET-CAM test. The nanocapsules improved latanoprost accumulation into the hair follicles when topically applied on porcine skin, delivering 30% more drug to these skin structures relative to the control solution (P < 0.05). Also, with a simple manual massage, latanoprost accumulation was increased by twofold (P < 0.05). In conclusion, in addition to being a stable and safe formulation, nanocapsules enhanced latanoprost accumulation into the hair follicles, being a nanosystem with high potential for use as a topical formulation for the treatment of androgenic alopecia.
... Minoxidil is increasingly been considered as a treatment option in CAF. It is already well established as a therapy for male and female pattern baldness [34,35]. As a potassium channel opener, it relaxes vascular smooth muscle cells causing reduced blood pressure and peripheral vascular resistance [36,37]. ...
IntroductionAnal fissure is the most common cause of severe anorectal pain in adults, contributing significantly to coloproctology workloads. There are a wide variety of management options available, including topical nitrites, calcium channel blockers, botulinum toxin injection and sphincterotomy. The aim of this study was to review current options for the treatment of chronic anal fissure.MethodsA comprehensive search identifying randomized controlled trials comparing treatment options for anal fissure published between January 2000 and February 2020 was performed. The primary outcome assessed was healing at 8 weeks post commencing treatment. Secondary outcomes included recurrence, intolerance of treatment and complications.ResultsA total of 2822 studies were identified. After removal of duplicates and non-relevant studies, we identified nine randomized controlled trials which met pre-defined criteria. There was a total of 775 patients. At 8 weeks, healing rates were 95.13% in those treated with sphincterotomy, 66.7% in the botulinum toxin group, 63.8% in the nitrate group, 52.3% for topical diltiazem and 50% for topical minoxidil. Recurrence was highest amongst those treated with botulinum toxin injection (41.7%) and lowest for sphincterotomy (6.9%). Although the absolute number is low, there was a risk of permanent incontinence with sphincterotomy.Conclusion
This review of the randomized control data demonstrates that healing was significantly higher amongst those treated with sphincterotomy versus more conservative modalities. Topical nitrites had similar outcomes to botulinum toxin injection but were poorly tolerated in comparison to other treatments. The benefit of sphincterotomy was at a cost of increased complications, notably permanent incontinence.
... A study done by Chitalia et al. demonstrated the low response to minoxidil in individuals with low sulfotransferase activity [25]. Pre-treatment measurement of sulfonyltransferase is hence a useful tool to determine its efficacy in patients [26]. ...
Androgenetic alopecia (AGA), also termed as androgenic alopecia or common baldness, is a condition where there is androgen mediated conversion of susceptible terminal hair into vellus hair. Although it is reported more commonly in males, it also affects females but the incidence is relatively unknown. AGA tremendously affects the psychology of the patient due to its chronicity of treatment and cosmetic implications. There are numerous treatment options available for AGA but the choice of treatment has to often be tailored according to the patient’s needs, affordability, and compliance. This review focusses on the various treatment options available, with special emphasis on the role of low-level laser therapy (LLLT) in the management of AGA. The literature research considered published journal articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) and reference lists of respective articles. Only articles available in English were considered for this review.
... On the other hand, minoxidil induces smooth muscle hyperpolarization by the opening of potassium channels and closure of voltage-operated calcium channels, resulting in relaxation of IAS and blood vessel smooth muscles [8]. Minoxidil is known to be a potent vasodilator agent that is mainly used in the treatment of alopecia by allowing more blood flow and nutrients to the hair follicles [14]. ...
Background:
Chronic anal fissure (CAF) is a common painful anal condition. Medical treatment of CAF involves the use of agents that induce chemical sphincterotomy. The present trial aimed to compare the efficacy and safety of topical minoxidil and glyceryl trinitrate (GTN) preparations in treatment of CAF.
Methods:
Adult patients with CAF were randomly assigned to one of two equal groups; group I received topical 5% minoxidil gel and group II received topical 0.2% GTN cream. The main outcome measures were healing of anal fissure, duration to healing, relief of symptoms, and adverse effects.
Results:
62 patients (36 female and 26 male) were included to the study. Group I comprised 30 patients and group II comprised 32 patients. Healing of anal fissure was achieved in 23 (76.7%) patients in group I and 15 (46.9%) patients in group II (p=0.03). The average duration to healing in group I was significantly shorter than group II (4.1± 1.9 vs 5.3± 2.7 weeks, p=0.048). Adverse effects were recorded in 2 (6.6%) patients in group I and 13 (40.6%) patients in group II. The post-treatment pain score in the GTN group was significantly lower than the Minoxidil group.
Conclusion:
Topical 5% minoxidil gel achieved greater and quicker healing of CAF and fewer adverse effects than topical 0.2% GTN cream. Post-treatment pain scores after GTN were significantly lower than minoxidil.
... populations. While our study size was small, the large NPV observed in our Brazilian population is consistent with a previous study that presented NPV of 95.94% (Goren et al., 2015); therefore, among Brazilian women with FPHL, determining the sulfotransferase activity in plucked hair follicles provides clinical utility in guiding treatment regimen. ...
... Since the hair growth-promoting effect of minoxidil is due to the actions of its sulfated metabolite, minoxidil sulfate, for clinical efficacy, minoxidil has to be sulfated by a group of enzymes known as sulfotransferases, some of which are expressed in the hair follicle with wide interindividual variations in the level of enzyme activity. Therefore, enzymatic assay of sulfotransferase activity in plucked hair follicles may predict response to topical minoxidil therapy [7][8][9]. ...
Evidence-based medicine (EBM) aims for the ideal that healthcare professionals make conscientious, explicit, and judicious use of the best available evidence gained from the scientific method to clinical decision-making. It seeks to assess the strength of the evidence for benefits of diagnostic tests and treatments, using techniques from science, engineering, and statistics, such as the systematic review of medical literature, meta-analysis, risk-benefit analysis, and randomized controlled trials. The limited success rate of EBM therapies suggests that the complex nature of hair loss may be inadequately served by the present levels of evidence, and that physicians treating hair loss may have fallen short of adequately researching a robust evidence to underpin their practices. Against this backdrop, the concept of precision medicine (PM) is evolving. PM refers to the customization of medical care to the patient’s individual characteristics based on the patient’s genetic background and other molecular or cellular analysis, while classifying patients into subpopulations that differ in their susceptibility to a particular medical condition, in the biology or prognosis of those medical conditions, or in their response to a specific treatment. With the advances in hair research, the powerful tools of molecular biology and genetics, and innovative technologies, we have the robust scientific data and tools to adapt the concept of PM to the practice of trichiatry. Finally, databases pertaining to the development and efficacy of PM must be analyzed and be used to form the basis of evidence-based personalized trichiatry.
... 40 The enzymatic assay also demonstrated great accuracy by correctly detecting 94% of non-responders. 41 A subsequent study using this assay showed that at the week 8 of topical minoxidil treatment, the sulfotransferase enzyme activity in hairs stabilized. This finding suggests that those who respond to minoxidil will not between baseline and end of the study ...
Minoxidil was first introduced as an antihypertensive medication and the discovery of its common adverse event, hypertrichosis, led to the development of a topical formulation for promoting hair growth. To date, topical minoxidil is the mainstay treatment for androgenetic alopecia and is used as an off-label treatment for other hair loss conditions. Despite its widespread application, the exact mechanism of action of minoxidil is still not fully understood. In this article, we aim to review and update current information on the pharmacology, mechanism of action, clinical efficacy, and adverse events of topical minoxidil.
... This led to an effort to repurpose the drug as a topical treatment for androgenetic alopecia, which was ultimately approved by the FDA for this indication under the branded name Rogaine. Minoxidil has been found to regrow hair in 40% of patients with androgenetic hair loss after 3-6 months of treatment [2]. Maintenance of this hair regrowth requires continued therapy. ...
... AGA is a skin disorder occurring in about 80% of men and 50% of women during their lifetime [1]. The Treatment of choice is still controversial which include medical treatments or surgical hair transplantation [2]. The goal for treating alopecia with AT-ADSCs includes increasing the number of existing follicles [3]. ...
Background: Platelet Rich Plasma (PRP) is based on the release of growth factors stimulating the initiation/
extension of anagen phase as well as promoting vascularization, Adipose Derived Stem Cell (AT-ADSCs) treatment
were recently introduced as an alternative potential therapeutic application for hair growth.
Objective: The aim of this study was to assess the efficacy side effects and safety of AT-ASCs and PRP in the
treatment of androgentic alopecia.
Patients and methods: Sixty randomized patients were treated by PRP, and AT-ASCs. Each patient was
evaluated, and each lesion was treated by those modalities, patients received three sessions with one month
interval for 3 months, follow up after 3 months.
Results: A highly significant improvement <0.001 in terminal hair count of AT-ASCs group evaluated by videodermoscopy
assessment of AGA. That were confirmed by highly significant improvement in inter-mediate hair count
and mean caliber (<0.001) associated with high incidence of side effects especially headache and erythema. In
contrast, PRP group showed significant improvement 0.037 in terminal hair count and non-significant improvement
in inter-mediate hair count and of mean caliber with minimum side effects. AT-ASCs showed a significant
improvement in terminal hair count than PRP, Highly significant improvement in Inter-mediate hair count and hair
caliber. Also, side effects of AT-ASCs showed highly significant pain, headache and erythema but no serious
adverse events.
Conclusion: Our study suggests that the There was significant improvement in AGA after PRP and highly
significant after AT-ASCs therapy with significant difference of ADSC in terminal
... AGA is a skin disorder occurring in about 80% of men and 50% of women during their lifetime [1]. The Treatment of choice is still controversial which include medical treatments or surgical hair transplantation [2]. The goal for treating alopecia with AT-ADSCs includes increasing the number of existing follicles [3]. ...
Background: Platelet Rich Plasma (PRP) is based on the release of growth factors stimulating the initiation/ extension of anagen phase as well as promoting vascularization, Adipose Derived Stem Cell (AT-ADSCs) treatment were recently introduced as an alternative potential therapeutic application for hair growth.Objective: The aim of this study was to assess the efficacy side effects and safety of AT-ASCs and PRP in the treatment of androgentic alopecia.Patients and methods: Sixty randomized patients were treated by PRP, and AT-ASCs. Each patient was evaluated, and each lesion was treated by those modalities, patients received three sessions with one month interval for 3 months, follow up after 3 months.Results: A highly significant improvement <0.001 in terminal hair count of AT-ASCs group evaluated by video-dermoscopy assessment of AGA. That were confirmed by highly significant improvement in inter-mediate hair count and mean caliber (<0.001) associated with high incidence of side effects especially headache and erythema. In contrast, PRP group showed significant improvement 0.037 in terminal hair count and non-significant improvement in inter-mediate hair count and of mean caliber with minimum side effects. AT-ASCs showed a significant improvement in terminal hair count than PRP, Highly significant improvement in Inter-mediate hair count and hair caliber. Also, side effects of AT-ASCs showed highly significant pain, headache and erythema but no serious adverse events.Conclusion: Our study suggests that the There was significant improvement in AGA after PRP and highly significant after AT-ASCs therapy with significant difference of ADSC in terminal hair count and highly significant in caliber. Both modalities could effectively and safely be used to treat AGA.
... Several studies have demonstrated that sulfotransferase enzyme activity in plucked hair follicles predicts topical minoxidil response in patients with FPHL. Moreover, different studies have been conducted to confirm the clinical utility of a sulfotransferase activity assay to guide treatment (Goren et al., 2015). These analysis show that the sulfotransferase enzyme test can successfully rule out 95.9% of nonresponders to topical minoxidil for the treatment of AGA (McCoy et al., 2016). ...
Female pattern hair loss (FPHL) is the most common form of alopecia in women. Affected women may experience psychological distress and impaired social functioning. Early diagnosis and initiation of treatment are desirable because treatments are more effective to avoid the progression of hair loss than stimulating regrowth. Typically, a diagnosis of FPHL can be confirmed by review of a patient's medical history and a physical examination alone. Testing a scalp biopsy is diagnostic but usually not required. In women with signs of hyperandrogenism, an investigation for ovarian or adrenal disorders should be performed. Treatment for FPHL is obscured by myths. The aim of FPHL treatment could be two-fold: Reverse or stabilize the process of hair follicle miniaturization. Mild-to-moderate FPHL in women can be treated with oral antiandrogen therapies (cyproterone acetate and spironolactone) and/or topical minoxidil with good results in many cases. If used correctly, available medical treatments arrest the progression of the disease and reverse miniaturization in most patients with mild-to-moderate FPHL. Hair systems and surgery may be considered for selected cases of severe FPHL.
... AGA is a skin disorder occurring in about 80% of men and 50% of women during their lifetime [1]. The Treatment of choice is still controversial which include medical treatments or surgical hair transplantation [2]. The goal for treating alopecia with AT-ADSCs includes increasing the number of existing follicles [3]. ...
... Our opinion is that topical MX base remains the first-line topical agent for treatment of male and female AGA, unless the patient proves to be unresponsive, then a formulation of MXS at probably higher concentrations may present an alternative with enhanced efficacy. For this purpose, a novel enzymatic assay may predict MX response [10]. ...
... This enzyme is the one responsible to convert minoxidil into its active form, minoxidil sulfate that stimulates hair follicles [17,18]. Recently, three studies [19][20][21] pointed out the importance of testing for minoxidil response given the lengthy treatment time required to ascertain individual efficacy of minoxidil. They performed Sulfotransferase assay test which yielded an accuracy of 95.9% in ruling out non responders to minoxidil. ...
Background:
Female pattern hair loss (FPHL) is the most common form of hair loss in women. Nevertheless, its management represents a real challenge. Among the FDA approved therapeutic modalities for FPHL are topical minoxidil and more recently low-level light therapy (LLLT).
Aim of work:
Assess the efficacy and safety of LLLT in comparison to topical minoxidil 5% and to a combination of both therapies in the treatment of FPHL.
Patients and methods:
This study included 45 female patients with proven FPHL. They were randomly divided into three equal groups, where group (i) patients were instructed to apply topical minoxidil 5% twice daily, group (ii) patients received LLLT using the helmet iGrow® device for 25 minutes 3 days weekly, and group (iii) patients received a combination of both topical minoxidil 5% twice daily and LLLT for 25 minutes 3 days weekly for 4 months (study duration). Evaluation was done according to clinical, dermoscopic (folliscopic), and ultrasound bio-microscopic (UBM) parameters. Patient satisfaction and side effects were reported.
Results:
The efficacy and safety of both topical minoxidil and LLLT were highlighted with comparable results in all parameters. The combination group (iii) occupied the top position regarding Ludwig classification and patient satisfaction. UBM and dermoscopic findings showed significant increase in the number of regrowing hair follicles at 4 months in all groups, whereas only UBM showed such significant increase at 2 months in the combination group (iii). A non-significant increase in the hair diameter was also documented in the three groups.
Conclusion:
LLLT is an effective and safe tool with comparable results to minoxidil 5% in the treatment of FPHL. Owing to the significantly better results of combination therapy, its usage is recommended to hasten hair regrowth. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc.
... Although the mechanism by which minoxidil promotes hair growth is not fully understood, it is believed that minoxidil can dilate blood vessels and open potassium channels, which allow flow of more oxygen, blood, and nutrients into the follicles. This may cause follicles in the telogen phase to shed, which are then replaced by thicker hair in a new anagen phase [5,6]. ...
Minoxidil dissolved in organic solvents is commonly used in the treatment of androgenic alopecia because it is hydrophobic and poorly soluble in water. The aim of this investigation was to develop an aqueous minoxidil solution without addition of organic solvents. To this end, minoxidil was encapsulated in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to form a minoxidil–HP-β-CD inclusion complex with aqueous solubility higher than that of pure minoxidil. Minoxidil–HP-β-CD inclusion complexes were prepared using a freeze-drying method from minoxidil and HP-β-CD at a molar ratio of 1:1. Complex formation was confirmed by nuclear magnetic resonance, thermogravimetric analysis, and thin layer chromatography. The structure of the complex was determined using two-dimensional rotating frame overhauser effect spectroscopy. Minoxidil–HP-β-CD inclusion complexes were dissolved in water to form a homogeneous aqueous solution, and its effect on the hair cycle of mice was evaluated in vivo. The results support the feasibility of using HP-β-CD to prepare an aqueous minoxidil solution to replace organic solvent-based solutions.
Background:
Androgenetic alopecia is defined as a patterned hair loss resulting from the effect of androgen on hair follicles and characterized by non-scarring, progressive miniaturization of the hair follicles. Minoxidil and finasteride are regarded as the first line treatments with antiandrogens and flutamide are considered as the alternative choices. In the current study, we evaluated the efficacy of combination therapy with topical 2%Flutamide plus 5%minoxidil versus %5 minoxidil alone in the treatment of the androgenetic alopecia.
Material and methods:
This was a randomized, double-blinded clinical trial in 40 patients with androgenetic alopecia. Patients were randomized to receive either topical minoxidil versus topical flutamide plus minoxidil for 6 months. At the end of study, patients were compared regarding mean hair density and mean hair thickness and patient's satisfaction. Collected data were analyzed using T-test, Ki square and Kolmogorov-Smirnov tests.
Results:
Topical flutamide plus minoxidil solution was significantly more effective than minoxidil in terms of hair density, hair thickness and patient's satisfaction (p<0.05).
Conclusion:
Topical hydro alcoholic solution of flutamide plus minoxidil may be promising treatment for the androgenetic alopecia. To better evaluate the efficacy of topical flutamide, more prolonged studies with higher number of patients and use of different vehicles and different ingredients are recommended.
Hair is a deeply rooted component of identity and culture. Recent articles in this series have focused on scientific evidence relating to hair growth and new insights into the pathogenesis and mechanism of hair loss. This article reviews emerging evidence that has advanced our understanding of hair growth in both of these areas to provide a context for outlining current and emerging therapies. These include finasteride, minoxidil, topical prostaglandins, natural supplements, microneedling, low-level laser light, platelet-rich plasma, fractional lasers, cellular therapy, Wnt activators and SFRP1 antagonism.
Male and female pattern hair loss (PHL) is an innocuous condition, but it has a major psychological impact on the sufferer. This paper aims to provide a simple algorithmic approach toward diagnosis, staging, and treatment of PHL in males and females. It also aims at simplifying the decision-making process for the surgeon with regard to timing and extent of procedure for hair transplant surgeries. Various treatment options, their merits and demerits, along with scientific evidence supporting or not supporting the treatment options are discussed in detail.
Pattern hair loss (PHL) is the most frequent cause of hair loss in men and women, accounting for 65% of consultations in a hair referral center. PHL is understood to represent a hereditary, age-dependent progressive thinning of the scalp hair, which follows distinct clinical patterns with notable differences depending on sex and age of onset. Clinical and investigative advances have helped us to understand some of the pathogenic steps, leading to PHL. Besides genetic factors and peculiarities of androgen metabolism, additional pathogenic factors that are suspected include microbiomata, oxidative stress, and microinflammation. While further suspects are likely to be exposed, individual diversity of causal agents, as well as of the sequence of events, or combined factors, must be kept in mind. A large number of therapeutic molecules claimed to be active and patented in this field, and their limited efficacy in offering a definitive cure of PHL confirm the complexity of PHL. The aim of therapy is to retard progression of hair thinning and increase hair coverage of the scalp. As yet, two FDA-approved drugs are available for this purpose, oral finasteride, and topical solution of minoxidil. Variations in posology and formulation allow for an enhancement of patient comfort and treatment efficacy. Antiandrogen treatments in women with normal androgen levels have questionable efficacy while having health risks.
Low-dose oral minoxidil (OM) has increasingly been used by many doctors around the world as a treatment option for hair loss. Sufficient data regarding its effect and side effect profile are lacking. An online search was done on PUBMED and GOOGLE SCHOLAR for articles that used OM as a treatment option for hair loss. Doses ranging from 0.25 to 5 mg have been used for treatment in various studies. Good compliance and tolerability have been noticed with low-dose OM therapy. Adverse effects are few and are mild with hypertrichosis being the most common adverse effect in a majority of the studies, the risk of which increases with an increase in dosage of the drug.
Minoxidil is an antihypertensive agent and hair growth promoter. Minoxidil is a pro‐drug that requires conversion to minoxidil sulfate by the sulfotransferase enzymes to be biologically active. Previously, we identified the sulfotransferases isoenzyme SULT1A1 as the predominant sulfotransferase responsible for minoxidil sulfonation in the outer root sheet (ORS) of hair follicles.
Aims
Minoxidil is a hair growth drug for treating androgenetic alopecia. Although minoxidil is generally administered as a topical formulation, this prodrug must be converted to its active form (minoxidil sulfate) by sulfotransferase in hair follicle tissue. Therefore, its effect may be affected by the sulfureting of minoxidil and de-sulfureting of minoxidil sulfate in hair follicles. To investigate the biotransformation of minoxidil sulfate to minoxidil in hair follicle component cells, a method for simultaneous determination of minoxidil and minoxidil sulfate by high-performance liquid chromatography with UV-detection was established.
Main methods
Minoxidil and minoxidil sulfate were separated by a reversed-phase chromatography. Minoxidil sulfate was incubated with human hair follicle keratinocyte- and dermal papilla cell-derived arylsulfatases as well as snail-derived sulfatase. The enzyme mixture was applied on HPLC system directly.
Key findings
Minoxidil and minoxidil sulfate were separated simultaneously. The limit of detection of minoxidil and minoxidil sulfate was 25 and 100 pg inj⁻¹, respectively. Snail-derived sulfatase as well as human hair follicle keratinocyte- and dermal papilla cell-derived arylsulfatases hydrolyzed minoxidil sulfate to minoxidil. Arylsulfatase in hair follicle metabolized the active form of minoxidil to the inactive form. Inactivation of active minoxidil (sulfate) was inhibited by the natural substrate of arylsulfatase A, ascorbate-2-sulfate.
Significance
Arylsulfatase inhibitors may sustain the effect of minoxidil sulfate in AGA therapy. The developed technique was effective for studies of minoxidil metabolism and bioavailability.
Topical minoxidil has been used as a topical treatment for androgenetic alopecia (AGA) for more than 30 years. Approximately 60 to 70% of patients do not achieve hair growth.
Minoxidil is a pro‐drug. In order to exert biological activity, minoxidil requires conversion to minoxidil sulfate by sulfotransferase enzymes (SULT1A1). We have reported extensively that SULT1A1 activity in the outer root sheath (ORS) of the hair follicle correlates directly with topical minoxidil response. We have demonstrated the clinical utility and validity of a colorimetric test to measure the follicular SULT1A1 activity in plucked hair as a method to predict minoxidil responders. This same test also predicts clinical response to oral minoxidil.
Psoriasis is a complex immune‐mediated systemic disease affecting 1% to 2% of the North‐American population.1 Although observational studies have reported an increased risk of depression with psoriasis severity when compared to the general population, the literature remains scarce with regards to the risk of suicide in psoriasis.2‐4 Two recent meta‐analyses of observational studies reported conflicting results, one showed no association between psoriasis and suicidality,4 while the second showed an increased risk of suicidal ideation and behaviour in psoriasis patients when compared to the general population.3 As psoriasis severity may change over the life course of the disease, we aimed to establish if the risk of suicidal behaviour (hospital admission for suicide attempt and suicide death) in patients with psoriasis increases with the severity of the disease. We also aimed to identify the main predictors of suicidal behaviour in psoriasis patients.
Polymeric nanofibers fabricated by electrospinning either blank (PVA) or loaded with minoxidil sulphate have yielded optimum fibers with an average diameter 273 nm, and 511 nm, respectively. Thermal analysis of nanofibers indicated no chemical interaction. The NMR spectrum confirmed stability of nanofiber as there were no interactions between functional groups. Prepared nanofibers showed a 47.4% encapsulation efficiency and 73% yield. In vitro drug release of minoxidil sulphate from nanofiber exhibited an initial burst release followed by a slower release pattern. Stability studies revealed that minoxidil nanofiber was stable if stored at room temperature and protected from light with only loss of 9.6% of its nominal concentration within 6 months. As a result, the prepared solid/colored formula serves as an ideal formulation for such instable drug in liquid formula taking the advantage of the attractiveness of beauty colored coverage, and the simple, and non-tousled application.
Introduction: Androgenetic alopecia is a common hair loss disorder affecting up to 80% of males by the age of 80. It is characterized by androgen related progressive thinning of hair in a defined pattern. It results in diminished self-esteem, reduced confidence and distress in affected men, irrespective of age or stage of baldness. An effective treatment for hair baldness is needed.
Areas covered: In androgenetic alopecia, hair follicles undergo progressive miniaturization. Genetic factors and androgens are key role-players in disease pathogenesis. Herein the authors review the pharmacologic treatment of androgenetic alopecia, which involves 5 alpha reductase inhibitors, minoxidil and prostaglandins. Non-pharmacologic approaches are also explored.
Expert opinion: Androgenetic alopecia progresses over time and although the current available medical treatments like finasteride and minoxidil are effective in arresting the progression of the disease, they allow only partial regrowth of hair at its best. Early treatment achieves a more optimal outcome. Non-pharmacologic treatments like PRP can be considered in patients refractory to medical treatment.Abbreviations: MPHL: male pattern hair loss; AGA: androgenetic alopecia; DHT: dihydrotestosterone; 5AR: 5-alpha-reductase; VEGF: vascular endothelial growth factor; PG’s: prostaglandins (PG’s); PGD2R: prostaglandin D2 receptor; VPA: valproic aid; SR: Serenoa Repens; PRP: platelet-rich plasma; PDGF: platelet derived growth factor; TGF: transforming growth factor; ERK: extracellular signal-regulated kinase; PKB: protein kinase B; LLLT: low-level laser therapy; ROS: reactive oxygen species; RCT: randomized control trial; SFRP1: secreted frizzled related protein 1; DP: dermal papilla; PDE5: phosphodiesterase 5
Darier's disease (DD) is an autosomal dominant genetic disorder caused by mutations in the ATP2A2 gene which encodes a sarco/endoplasmic reticulum Ca2+ATPase type 2 isoform (SERCA2).1 SERCA2 is expressed in epidermal keratinocytes in the skin and neurocytes in the brain. It is associated with neuropsychiatric diseases, such as mental retardation, mood disorders, schizophrenia and epilepsy. This article is protected by copyright. All rights reserved.
Topical minoxidil (TM) is the only FDA-approved medication for the treatment of female pattern hair loss (FPHL).1 Minoxidil is a pro-drug. TM efficacy in FPHL requires bio-activation into minoxidil sulfate by sulfotransferase enzymes.2 Sulfotransferases are xenobiotic metabolizing enzymes expressed in many tissues with the highest expression found in the human liver.3 Hair follicle outer root sheath cells (ORS) also express sulfotransferase, and ORS sulfotransferase activity predicts TM therapeutic response.
Classically, rHDL has been studied from the viewpoint of antiatherosclerotic therapies. In addition, however, to its demonstrated advantageous effects on HDL as described above, hydrophobic biomolecules, including anti-cancer (Lacko et al. 2002), antifungal (Oda et al. 2006), and anti-viral drugs (Bijsterbosch et al. 1996) have already been incorporated into rHDL. The greatest difficulty with such potent agents is the achievement of specific delivery with high degrees of efficiency. Various size of rHDL were theorized to represent an attractive vehicle for delivery in such cases. Lacko et al. demonstrated that 3 molecules of taxol per rHDL particle could be incorporated into the rHDL complexes (Lacko et al. 2002). Oda et al. reported that amphotericin B-rHDL represented a novel formulation that effectively solubilized the antibiotic, and elicited significant in vitro and in vivo antifungal effects without any observed toxicity at therapeutic doses (Oda et al. 2006). These reports have demonstrated that rHDL might be utilized as efficient drug and gene delivery vehicles for therapeutic agents, owing to the ability of peripheral cells to acquire HDL core components.
Several studies have established that sulfotransferase enzyme activity in the outer root sheath of plucked hair follicles predicts response to topical minoxidil in the treatment of pattern hair loss. However, the prevalence of this enzyme activity among Indian patients has not been studied. Additionally, no reports in the literature characterize sulfotransferase activity based on sex, age, duration of hair loss, grade of hair loss, and family history. In this study we utilized a sulfotransferase activity assay first reported by Goren et al. We characterize the follicular sulfotransferase activity of 120 pattern hair loss patients visiting a dermatology outpatient clinic in India. Overall, 40.8% of patients with pattern hair loss had low levels of sulfotransferase. Surprisingly, 49.3% of men had low levels of sulfotransferase compared to 26.6% of women. No correlation was found between sulfotransferase activity and age, duration of hair loss, grade of hair loss, or family history. A sub‐analysis of patient reported outcomes (PRO) validated previous findings that sulfotransferase enzyme activity is a predictive marker for minoxidil response in pattern hair loss patients.
The National Institutes of Health (US NIH, 2018) estimates that in the US approximately 50 million men and 30 million women suffer from AGA (also known as pattern hair loss). Minoxidil is the only topical drug for the treatment of both female and male pattern hair loss. In the US, minoxidil is approved over‐the‐counter (OTC) at a maximum concentration of 5%. In this review, we summarize the findings of the pivotal studies used in support of the drug's approval as well as recent discoveries and novel developments in the use of minoxidil for the treatment of AGA.
It gives me immense pleasure to be the editor of the book Alopecia published by the world leading IntechOpen Publisher. The field of hair restoration is expanding rapidly and the current interest in alopecias is very intense and rising. The overwhelming desire of balding people to look younger has led to great efforts to understand the pathophysiological pathways of alopecias. The diversity in hair loss patterns has led to new classifications of baldness. The diagnosis of hereditary alopecia from non-hereditary alopecia is very important.
Newer theories of hereditary hair loss are being postulated and investigated. These theories have opened new ways in the medical management of hair loss.
The current book has chapters emphasizing the different hereditary and non-hereditary alopecias. Furthermore, the administration of newer drugs may treat hair loss by a variety of mechanisms. All the clinical variants of alopecias are discussed in detail.
The book will help dermatologists, students, hair transplant surgeons, and physicians related to hair loss problems, giving them the opportunity to understand basic pathophysiological, clinical, and medical management options. The basic idea of the book is to diagnose alopecia correctly and outline a treatment plan.
Lastly, I thank my family who provided me with support during the various stages of manuscript preparation by providing the time meant for them.
Dr. Muhammad Ahmad, MD
Plastic & Hair Restoration Surgeon
Islamabad, Pakistan
Objective:
We used JetPeel, combined with topical minoxidil to treat patients with AGA, in order to observe whether the JetPeel can accelerate the recovery of the disease and find a new method for AGA treatment.
Method:
Thirty patients who met the standard were included in the study. The patients were randomly divided into three groups. The first group was treated with JetPeel-assisted topical minoxidil. The second group received topical minoxidil monotherapy. The third group was not given any treatment. We used objective evaluation (amount and diameter of hair, oil secretion level) and subjective evaluation (hair growth score marked by dermatologist and patient) to evaluate the hair growth condition before treatment and every other month. The calculated p values of less than 0.05 were accepted as significant.
Result:
All of the 30 patients finished the study. There was no difference in age, sex, and duration and severity of the disease among groups prior to treatment (p > 0.05). And there was greater improvement in scores of hair growth in the first group compared to the second and third group, which was statistically significant (p < 0.05).
Conclusion:
Compared with topical minoxidil monotherapy, JetPeel-assisted topical minoxidil is more effective during the treatment of androgenetic alopecia.
Clinical trichology should represent an integral part of medical training, and the dermatologist participates with the other medical disciplines in the diagnosis and treatment of all types of hair problems relating to systemic disease. On the other hand, hair loss is an important cause of discomfort and disability. The general physician is not always aware of the significance of hair loss and therefore may fail to refer patients with hair disorders to the dermatologist for appropriate management. Too often, the delay of correct diagnosis, and as a result the delay of appropriate therapy, leads to potentially irreversible loss of hair, prolongs the discomfort, and promotes the disfigurement. Knowledge of the main types of hair loss is prerequisite to providing appropriate patient care.
Emodin is an anthraquinone derivative from the roots of Rheum officinale Baill that possesses a variety of biological activities, including inhibition of 5á-reductase and prostaglandin D2. In this study, we investigated whether emodin promotes hair growth. After emodin was topically applied to the shaved dorsal skin of telogenic C57BL/6 N mice, the hair growth rate and morphological analysis were evaluated in dorsal skin for 15 days. After 13 days of treatment, minoxidil or emodin (0.01% or 0.1%)-treated groups showed remarkable regrowth of hairs relative to the vehicle control group. Scoring of the hair growth and rate of hair growth area for 15 days revealed that groups treated with minoxidil and 0.1% emodin were significantly higher than the vehicle control group. Histological examination revealed the emodin and minoxidil groups markedly recovered the number and morphology of hair follicles, including the subcutis depth, relative to the vehicle group. These results suggest that emodin has an excellent promoting effect in hair growth similar to that of minoxidil and might be useful for treatment of baldness or alopecia.
Introduction:
Hair disorders have a very high social and psychological impact. Treatment is often frustrating and time-consuming both for the patients and the clinicians and requires special skills and expertise. Areas covered: This paper aims to provide an overview of available treatments for the most common forms of alopecia in adults (androgenetic alopecia [AGA], alopecia areata and cicatricial alopecias) after reviewing the literature in PubMed, Google Scholar and ClinicalTrial.gov. Expert opinion: Before starting treatment, it is very important to confirm diagnosis and discuss patient's expectations. Treatment of hair disorders requires time and first results are usually visible a few months after beginning of therapy. Treatment of most hair disorders is mostly not evidenced-based as randomized controlled trials are available only for AGA.
Two percent topical minoxidil is the only US Food and Drug Administration-approved drug for the treatment of female androgenetic alopecia (AGA). Its success has been limited by the low percentage of responders. Meta-analysis of several studies reporting the number of responders to 2% minoxidil monotherapy indicates moderate hair regrowth in only 13–20% of female patients. Five percent minoxidil solution, when used off-label, may increase the percentage of responders to as much as 40%. As such, a biomarker for predicting treatment response would have significant clinical utility. In a previous study, Goren et al. reported an association between sulfotransferase activity in plucked hair follicles and minoxidil response in a mixed cohort of male and female patients. The aim of this study was to replicate these findings in a well-defined cohort of female patients with AGA treated with 5% minoxidil daily for a period of 6 months. Consistent with the prior study, we found that sulfotransferase activity in plucked hair follicles predicts treatment response with 93% sensitivity and 83% specificity. Our study further supports the importance of minoxidil sulfation in eliciting a therapeutic response and provides further insight into novel targets for increasing minoxidil efficacy.
Topical minoxidil is the most common drug used for the treatment of androgenetic alopecia (AGA) in men and women. Although topical minoxidil exhibits a good safety profile, the efficacy in the overall population remains relatively low at 30-40%. To observe significant improvement in hair growth, minoxidil is typically used daily for a period of at least 3-4 months. Due to the significant time commitment and low response rate, a biomarker for predicting patient response prior to therapy would be advantageous. Minoxidil is converted in the scalp to its active form, minoxidil sulfate, by the sulfotransferase enzyme SULT1A1. We hypothesized that SULT1A1 enzyme activity in the hair follicle correlates with minoxidil response for the treatment of AGA. Our preliminary retrospective study of a SULT1A1 activity assay demonstrates 95% sensitivity and 73% specificity in predicting minoxidil treatment response for AGA. A larger prospective study is now under way to further validate this novel assay.
Minoxidil is an antihypertensive agent and hair growth promoter that is metabolized by sulfation to the active compound, minoxidil sulfate. Thermostable phenol sulfotransferase (TS PST or P-PST) was initially thought to catalyze the reaction, and the enzyme was designated minoxidil sulfotransferase (MNX-ST). Information about human ST activities toward minoxidil would be useful in developing the capacity to predict individual responses to minoxidil based on tissue levels of STs. Therefore, human STs were studied from platelet homogenates, partially purified platelets, scalp skin high speed supernatants and COS-1 cell cDNA expressed preparations using a radiochemical enzymatic assay with minoxidil as the substrate. Studies showed the presence of TS PST, TL (thermolabile) PST and MNX-ST activities in human scalp skin. Biochemical properties and correlation studies suggested that in addition to TS PST, the TL PST activity, another ST activity or both were involved in the reaction. Partially purified human platelet TL PST tested with minoxidil and dopamine showed identical thermal stabilities and similar responses to the inhibitors 2,6-dichloro-4-nitrophenol (DCNP) and NaCl. To characterize the activity of TL PST toward minoxidil, several biochemical properties of the enzyme expressed from a human liver cDNA clone were investigated. When assayed with minoxidil and dopamine, thermal stabilities of the expressed enzyme were identical and IC50 values for the inhibitors DCNP and NaCl were similar. It was also demonstrated that cDNA encoded human liver dehydroepiandrosterone sulfotransferase and estrogen sulfotransferase contributed to the sulfation of minoxidil. The results confirm that at least four human STs contribute to minoxidil sulfation. MNX-ST activity represents a combination of ST activities. The data indicate that multiple ST activities should be taken into account in attempts to predict the regulation of minoxidil sulfation and individual responses to minoxidil.
An important step in understanding minoxidil's mechanism of action on hair follicles was to determine the drug's active form. We used organ-cultured vibrissa follicles to test whether it is minoxidil or its sulfated metabolite, minoxidil sulfate, that stimulates hair growth. Follicles from neonatal mice were cultured with or without drugs and effects were assessed by measuring incorporation of radiolabeled cysteine in hair shafts of the treated follicles. Assays of minoxidil sulfotransferase activity indicated that vibrissae follicles metabolize minoxidil to minoxidil sulfate. Dose-response studies showed that minoxidil sulfate is 14 times more potent than minoxidil in stimulating cysteine incorporation in cultured follicles. Three drugs that block production of intrafollicular minoxidil sulfate were tested for their effects on drug-induced hair growth. Diethylcarbamazine proved to be a noncompetitive inhibitor of sulfotransferase and prevented hair growth stimulation by minoxidil but not by minoxidil sulfate. Inhibiting the formation of intracellular PAPS with chlorate also blocked the action of minoxidil but not of minoxidil sulfate. Acetaminophen, a potent sulfate scavenger blocked cysteine incorporation by minoxidil. It also blocked follicular stimulation by minoxidil sulfate apparently by directly removing the sulfate from the drug. Experiments with U-51,607, a potent minoxidil analog that also forms a sulfated metabolite, showed that its activity was inhibited by both chlorate and diethylcarbamazine. These studies show that sulfation is a critical step for hair-growth effects of minoxidil and that it is the sulfated metabolite that directly affects hair follicles.
The in vivo model which may be the most accurate for the ability to predict hair growth in humans, and which was utilized in the preclinical development of minoxidil, is the adult stumptailed macaque. Previous reports have suggested that the enzyme activity which accounts for the activation of minoxidil, i.e., minoxidil sulfotransferase, is present in skin. We have demonstrated that scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity, and further with dissection of that scalp skin into epidermis, dermis and hair follicle, most of sulfotransferase activity was present in the follicle. Sulfotransferase activity in the hair follicle in freeze-dried scalp skin sections from 9 stumptailed macaques ranged from 47 to 84% of the total (mean 61 +/- 12%). Much less minoxidil sulfotransferase activity was measured in the epidermis (mean 18 +/- 11%, with a range of 2-37%) and the dermis (mean 21 +/- 8%, with a range of 4-35%) of these scalp sections. These results indicate that the scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity and this activity is largely localized in the hair follicle which may account for its ability to stimulate hair growth in this animal model.
The first signs of androgenetic alopecia (AGA) may start to develop with the onset of puberty. The prevalence of progressive AGA approaches 50% of Caucasian men and women beyond the age of 40; whereas in Asian, native American and African-American men the prevalence is lower and AGA is less severe. Only exceptionally laboratory tests or scalp biopsies are needed to confirm the diagnosis. Therefore the clinical assessment of AGA is largely a matter of common sense and practice. The loss of hair is often trivialised, but hair loss may have profound effects on a patient's well-being and quality of life. The treatment of AGA is obscured by myths. Many products or procedures are advertized for the treatment of AGA such as vitamins, trace elements, exotic herbs, amino acids, "soft laser", scalp massage, etc. Most of these techniques or substances have never been verified in sound clinical trials. Because of the psychosocial impact of hair loss, however, it is important to explain to patients what they may expect in terms of continuing hair loss, and that response to any therapy may be slow and may include hair regrowth or only retardation of further thinning. The aim of AGA treatment is to reverse or to stabilize the process of HF miniaturization and with this overview we summarize the present treatment modalities for both men and women.
Topical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in individuals with androgenetic alopecia (AGA). Results can be variable, and historical experience suggests that higher concentrations of topical minoxidil may enhance efficacy.
The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of men with AGA.
A total of 393 men (18-49 years old) with AGA applied 5% topical minoxidil solution (n = 157), 2% topical minoxidil solution (n = 158), or placebo (vehicle for 5% solution; n = 78) twice daily. Efficacy was evaluated by scalp target area hair counts and patient and investigator assessments of change in scalp coverage and benefit of treatment.
After 48 weeks of therapy, 5% topical minoxidil was significantly superior to 2% topical minoxidil and placebo in terms of change from baseline in nonvellus hair count, patient rating of scalp coverage and treatment benefit, and investigator rating of scalp coverage. Hair count data indicate that response to treatment occurred earlier with 5% compared with 2% topical minoxidil. Additionally, data from a patient questionnaire on quality of life, global benefit, hair growth, and hair styling demonstrated that 5% topical minoxidil helped improve patients' psychosocial perceptions of hair loss. An increased occurrence of pruritus and local irritation was observed with 5% topical minoxidil compared with 2% topical minoxidil.
In men with AGA, 5% topical minoxidil was clearly superior to 2% topical minoxidil and placebo in increasing hair regrowth, and the magnitude of its effect was marked (45% more hair regrowth than 2% topical minoxidil at week 48). Men who used 5% topical minoxidil also had an earlier response to treatment than those who used 2% topical minoxidil. Psychosocial perceptions of hair loss in men with AGA were also improved. Topical minoxidil (5% and 2%) was well tolerated by the men in this trial without evidence of systemic effects.
An alternative to currently marketed topical minoxidil solutions is desirable.
To assess the efficacy and safety of a new 5% minoxidil topical formulation in a propylene glycol-free foam vehicle in men with androgenetic alopecia (AGA).
This was a 16-week, double-blind, placebo-controlled trial of 5% minoxidil topical foam (MTF) in 352 men, 18 to 49 years old. At week 16, 143 subjects continued on an open-label phase to collect 52 weeks of safety information on 5% MTF.
At week 16 compared with baseline, there was a statistically significant increase in (1) hair counts in the 5% MTF group versus placebo (P < .0001) and (2) subjective assessment of improved hair loss condition (P < .0001) in the 5% MTF group versus placebo. The 5% MTF was well tolerated over a 52-week period.
There was no collection of efficacy data beyond 16 weeks.
We believe that 5% MTF is a safe and effective treatment for men with AGA.