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... Not only convenient and simple, natural hair loss treatments are also quite effective and cost-effective. Therefore, we can absolutely use natural ingredients at home to treat hair loss in the following ways [7][8][9]. Most oils including coconut oil, olive oil, jojoba oil, etc. all work very well with hair. ...
Finding out methods or ways to improve people's health is always focused. How to have beautiful hair is what both men and women want. In order to achieve that, people used natural ingredients to nourish their hair in addition to modern Western medical therapies. The paper was based on sources of journals, documents as well as the survey results completed by patients and foreigners living in Ho Chi Minh city, Vietnam. The research paper once again determines the importance of folk therapies as well as some great herbs in this country.
Alopecia is a non-specific term for hair loss clinically diagnosed by the hair loss pattern and histological analysis of patient scalp biopsies. The immune-mediated alopecia subtypes, including alopecia areata, lichen planopilaris, frontal fibrosing alopecia, and central centrifugal cicatricial alopecia, are common, significant forms of alopecia subtypes. For example, alopecia areata is the most common autoimmune disease with a lifetime incidence of approximately 2% of the world's population. In this perspective, we discuss major results from studies of immune-mediated alopecia subtypes. These studies suggest the key event in disease onset as the collapse in immune privilege, which alters the hair follicle microenvironment, e.g., upregulation of major histocompatibility complex molecules and increase of cytokine production, and results in immune cell infiltration, inflammatory responses, and damage of hair follicles. We note that previous studies have established that the hair follicle has a complex mechanical microenvironment, which may regulate the function of not only tissue cells but also immune cell infiltrates. This suggests a potential for mechanobiology to contribute to alopecia research by adding new methods, new approaches, and new ways of thinking, which is missing in the existing literature. To fill this a gap in the alopecia research space, we develop a mechanobiological hypothesis that alterations in the hair follicle microenvironment, specifically in the mechanically responsive tissues and cells, partially due to loss of immune privilege, may be contributors to disease pathology. We further focus our discussion on the potential for applying mechanoimmunology to the study of T cell infiltrates in the hair follicle, as they are considered primary contributors to alopecia pathology. To establish the connection between the mechanoimmunological hypothesis and immune-mediated alopecia subtypes, we discuss what is known about the role of T cells in immune-mediated alopecia subtypes, using the most extensively studied AA as our model.
Background
Although the structural changes of the scalp in androgenetic alopecia (AGA) have been reported, these changes have been poorly understood. It is expected that modern MRI would visualize the scalp anatomy in vivo. This study aimed to explore whether AGA causes (a) changes in the thickness of the scalp, (b) anatomical changes in the hair follicles, and (c) changes in the signal intensity of MRI.
Materials and Methods
Twenty‐seven volunteers underwent MRI for hair and scalp (MRH) and were categorized into two according to the Hamilton‐Norwood Scale: the “AGA group” and the “normal group.” Two radiologists analyzed the thickness and signal intensity of the scalp, and the depth of hair follicles. These measurements were compared between the two groups.
Results
The thickness of the hypodermis and the entire scalp was significantly thinner in the AGA group than in the control group. The AGA group had significantly shallower depth of hair follicles and relative depth of the hair follicles to that of the entire scalp than the normal group. The hypodermis showed higher signal intensity in the AGA group than the normal group.
Conclusion
MRH allowed noninvasive visualization of the scalp anatomy and demonstrated the thinner nature of the entire scalp and hypodermis, along with the shallower depth of the hair follicles in the AGA group in comparison to the normal group. Additionally, MRH demonstrated the increased MR signal intensity in the scalp associated with AGA. MRH may be a promising new method for quantitative and objective analyses of AGA.
I will review structural and biologic characteristics of hair follicles in different body regions and discuss regulatory factors influencing both normal and abnormal hair growth, with emphasis on androgenic action associated with both hirsutism and androgenic alopecia.
A double-blind clinicopathologic study was designed to assess the efficacy and safety of topical minoxidil in the treatment of male-pattern baldness. Twenty-one bald but otherwise healthy male volunteers were randomly assigned (7 per group) to receive a 1% or 5% minoxidil solution in a vehicle of ethanol-water-propylene glycol or the vehicle alone applied twice daily to the bald scalp. The 15 white and 6 black subjects were aged 24 to 46 years. Scalp biopsies were done pretreatment and at weeks 12 and 24 after treatment began. Ten normal subjects from the same population, matched for age, served as controls for histopathologic studies. Increased hair growth was seen in both minoxidil-treated and placebo-treated groups, and there was no statistically significant difference between groups at 15.7 weeks when treatment was discontinued. Hair growth appeared to be limited to hypertrophy of pre-existent follicles; there was no good evidence for follicular neogenesis. It was concluded that topical application of up to 5% minoxidil solution was safe within the limits of this study.
Background: Multiple HLA class I and class II antigen associations have been described for alopecia areata (AA). As in other immune-mediated diseases, the HLA antigens associated with AA could influence the patient's ability to respond to immune challenge from both self- and non-self-antigens and may offer clues to the cause and prognosis of and potential therapy for the disease. Objective: Our purpose was to determine which HLA class II antigens are associated with two forms of long-standing AA, which we define to be long-standing patchy AA and longstanding alopecia totalis (AT) and alopecia universalis (AU). We also examined other factors such as age at onset of disease and familial and patient histories of autoimmune disease for correlation with the two groupings. Methods: Patients were typed for HLA class I and class II antigens by serologic methods and were typed by molecular methods for the subtypes of the HLA class II antigens. Results: HLA-DR11 (DRB1*1104) and HLA-DQ7 (DQB1*0301) were found to be highly significantly increased in frequency in patients with long-standing AT/AU (group III) but not in patients with long-standing patchy AA (group II); both patient groups showed increased frequencies of HLA-DQ3 (DQB1*03). Group III patients were unique in their early age at onset of disease. Familial incidence of AA was 37% in patients who had their first patch by 30 years of age and 7.1% with the first patch after 30 years of age. Conclusion: The data support the differential association of two well-defined clinical forms of AA, namely long-standing AT/AU and long-standing patchy AA, with specific HLA antigens and age at onset; they also suggest that the broad antigen HLA-DQ3, DQB1*03, is a Likely candidate for general susceptibility to AA. Our findings also suggest a bimodal pat tern of disease with an early-onset form associated with greater severity, long duration, and family history of the disease and a late-onset form characterized by milder severity, shorter duration, and low family incidence.
Background: Androgenetic alopecia (male pattern hair loss) is caused by androgen-dependent miniaturization of scalp hair follicles, with scalp dihydrotestosterone (DHT) implicated as a contributing cause. Finasteride, an inhibitor of type II 5α-reductase, decreases serum and scalp DHT by inhibiting conversion of testosterone to DHT. Objective: Our purpose was to determine whether finasteride treatment leads to clinical improvement in men with male pattern hair loss. Methods: In two 1-year trials, 1553 men (18 to 41 years of age) with male pattern hair loss received oral finasteride 1 mg/d or placebo, and 1215 men continued in blinded extension studies for a second year. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, and review of photographs by an expert panel. Results: Finasteride treatment improved scalp hair by all evaluation techniques at 1 and 2 years (P < .001 vs placebo, all comparisons). Clinically significant increases in hair count (baseline = 876 hairs), measured in a 1-inch diameter circular area (5.1 cm2 ) of balding vertex scalp, were observed with finasteride treatment (107 and 138 hairs vs placebo at 1 and 2 years, respectively; P < .001). Treatment with placebo resulted in progressive hair loss. Patients’ self-assessment demonstrated that finasteride treatment slowed hair loss, increased hair growth, and improved appearance of hair. These improvements were corroborated by investigator assessments and assessments of photographs. Adverse effects were minimal. Conclusion: In men with male pattern hair loss, finasteride 1 mg/d slowed the progression of hair loss and increased hair growth in clinical trials over 2 years. (J Am Acad Dermatol 1998;39:578-89.)
To investigate the relation between androgens and hair growth, testosterone-1,2-³H metabolism was assessed under standardized conditions in growing (anagen) and resting (telogen) hair roots from 10 anatomical sites from 4 women and 14 men, 6 of whom had varying degrees of male pattern baldness. A micromethod was developed to quantitate androgen metabolism in only a few hair roots.
In all hairs examined, 5α-reduced and 17-ketosteroids were the major metabolites of testosterone. No significant relation was found between androgen-mediated growth of hair and the capacity to form 5α-metabolites, e.g., scalp hair of women performed 5α-reduction to approximately the same degree as beard hair from men. The formation of 17-ketometabolites was decreased in telogen hairs from all body sites, whereas the formation of dihydrotestosterone was decreased in telogen hairs only from the scalp.
In general a higher formation of 5α-reduced metabolites and 17-ketosteroid metabolites was observed at all sites of the scalp of bald men as compared to hair obtained from the corresponding sites of women and nonbalding men, and a significantly higher rate of metabolism was found at the frontal area of the bald men. It is not clear at present whether these changes are secondary to the balding process or are related causally to the hair loss.
On the basis of these studies it is concluded that regional differences in androgen-mediated hair growth cannot be the result of variations in testosterone metabolism in the hair follicles.
• It has been shown previously that alopecia areata can be treated with dinitrochlorobenzene (DNCB) and other contact allergens. Whether these agents work by inducing immunologic stimulation or simply a nonspecific inflammatory reaction has not been definitively demonstrated. To test the relative importance of these two mechanisms, we have randomly studied 22 patients with alopecia areata to whom either DNCB or croton oil was applied topically. Sixty-three percent of patients without spontaneous regrowth of hair regrew hair after DNCB application. None of those treated with croton oil responded. Patients initially treated with croton oil regrew hair when treated later with DNCB. Therefore, a proved contact allergen was shown to be required for therapeutic success. Patient acceptance of the induced contact dermatitis was excellent. In light of recent data on the mutagenicity of DNCB to bacteria, other contact allergens for topical immunotherapy are being sought.(Arch Dermatol 1981;117:384-387)
Objective To examine changes in the free-to-total (f/t) serum prostate-specific antigen (PSA) ratio among men treated with finasteride for benign prostatic hypertrophy.Patients and methods Blood samples were taken from 20 men (mean age 71 years, range 61–87) before and after a minimum of 9 months of treatment with finasteride and the f/tPSA ratio determined using the Immulite assay system.Results Although mean total and free PSA levels decreased significantly, the mean f/tPSA ratio increased only slightly and not significantly; the ratios remained unchanged in men with an initially low or high (<>10%) ratio.Conclusions Concern has been expressed over the loss of the discriminatory power of serum PSA in a patient receiving treatment with finasteride. The f/tPSA ratio, currently used to help differentiate benign from malignant processes in the prostate, remains valid during treatment with finasteride; it does not affect the f/tPSA ratio.
Fourteen years have elapsed since publication of the second edition of this highly regarded book and in that time a vast new knowledge relating to the biology of skin has accumulated. Nevertheless, the third edition remains the same size as the second and covers the same basic subject matter, but here the similarity ends, for the book has been totally rewritten and the content only superficially resembles that of the earlier edition. The book presents a systematic discussion of the epidermis, dermis, and their modifications and constituents such as blood supply, cutaneous nerves, hair apparatus, nails, and glands. These topics are presented with discussions of gross, light microscopic, and electron microscopic morphology; embryology; function; cell kinetics and metabolism; and histochemistry. The picture of skin that evolves is that of a highly complex and dynamic organ for which the authors have a deep affection. The style is easily readable, and the
Current concepts of testosterone metabolism in the human skin are reviewed, and the role of dihydrotestosterone in the pathophysiology of androgenetic alopecia, acne vulgaris, and idiopathic hirsutism is discussed. The hypothesis is submitted that a temporary, increased dihydrotestosterone formation at specific skin target sites at different ages causes the normal development of certain sexual characteristics, as well as the androgen-dependent skin disorders. Future treatment of these conditions is discussed in light of recent studies with antiandrogens.
Androgenetic alopecia in the female occurs much more frequently than is generally believed. The condition is still considered infrequent, for it differs, in its clinical picture and in the sequence of events leading to it, from common baldness in men. To facilitate an early diagnosis (desirable in view of the therapeutic possibilities by means of antiandrogens) a classification of the stages of the common form (female type) of androgenetic alopecia in women is presented. The exceptionally observed male type of androgenetic alopecia can be classified according to Hamilton or to the modification of this classification proposed by Ebling & Rook.
A distinctive form of hereditary male pseudohermaphroditism is described in 24 members of 13 families in an isolated village of the Dominican Republic with a population of 4,300. The affected males are born with ambiguous external genitalia and in the past they were raised as girls. At puberty they develop typical male phenotype and male psychosexual orientation. Their karyotype is 46 XY. The condition is due to deficiency of Δ4 5α reductase which results in diminished transformation of testosterone and other deoxysteroids to 5α metabolites. The biochemical defect is inherited in an autosomal recessive fashion. Both male and female homozygotes are found but the biochemical defect is expressed only in males. Obligate heterozygotes are phenotypically normal but have a reductase deficiency, intermediate between that of normal and affected. The isolation of the village and demonstration of common ancestry in pedigrees suggests that the increase in gene frequency is a consequence of founder effects. (Myrianthopoulos - Bethesda, Md.)
A 5 alpha-reductase inhibitor, finasteride, was administered orally at 0.5 mg/day, alone or in combination with topical 2% minoxidil, for 20 weeks to determine the effects on scalp hair growth in balding adult male stumptail macaque monkeys. A 7-day dose-finding study showed that both 0.5- and 2.0-mg doses of the drug produced a similar diminution in serum dihydrotestosterone (DHT) in male stumptails. Hair growth was evaluated by shaving and weighing scalp hair at baseline and at 4-week intervals during treatment to obtain cumulative delta hair weight (sum of the 4-week changes in hair weight from baseline) for the 20-week study. The activity of the 5 alpha-reductase enzyme was assessed by RIA of serum testosterone (T) and DHT at 4-week intervals. The combination of finasteride and minoxidil generated significant augmentation of hair weight (additive effect) compared to either drug alone. Finasteride increased hair weight in four of five monkeys. When the data of the one nonresponsive monkey were excluded, finasteride elicited a significant elevation in hair weight compared to topical vehicle alone. Minoxidil also evoked a significant increase in hair weight compared to vehicle alone. Serum T was unchanged, whereas serum DHT was significantly depressed in monkeys that received either finasteride or the combination of finasteride and minoxidil. These data suggest that inhibition of the conversion of T to DHT by this 5 alpha-reductase inhibitor reverses the balding process and enhances hair regrowth by topical minoxidil in the male balding stumptail macaque.
Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction.
In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period.
As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups.
The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.
Although it is clear from the foregoing that some of the drugs and chemicals used to treat severe alopecia areata are efficacious to some degree, it is impossible to draw any meaningful comparisons among the data outlined in Tables 1 and 2. Virtually all of the studies were designed differently. Differences in chronicity and extent of disease as well as history of previous treatment resistance may significantly affect efficacy data even as two investigators compare the same drug. Drug-induced hair regrowth in alopecia areata may be very slow; a cosmetic response may take 1 to 2 years to achieve. Efficacy determinations made at shorter intervals may, therefore, not reflect true therapeutic potential. Efficacy end points vary significantly and need to be standardized. From a practical standpoint, scalp hair coverage that is deemed by the patient to be cosmetically acceptable seems to be a reasonable efficacy end point to report. Maintenance of cosmetic effect with continued treatment and/or following discontinuation of treatment also is useful to document. Table 3 outlines my approach to therapy of alopecia areata. Topical treatments often must be used for as long as 3 months before evidence of regrowth can be seen. In my experience with severe disease, if topical treatments cannot control a flare or induce regrowth, then the patient will often require either lengthy or frequent courses of systemic steroids. In my experience, prednisone doses as low as 20 mg/d may be associated with aseptic neurosis of the hip or severe gastrointestinal bleeding. Severe alopecia areata is a disease for which all therapies are, at best, palliative and, at worst, potentially harmful to patients who are usually otherwise very healthy. The psychosocial significance of this disease is enormous. The insights shared by a long-time sufferer of the disease mirror those expressed by the many patients with whom I have worked during the past 12 years. Three key elements to effectively treat the patient are (1) to help the patient understand the disease; (2) to encourage the patient to share his or her feelings with the physician, family, friends, and other sufferers of the disease; and (3) to help the patient to maintain a sense of hope for future scientific knowledge and treatment of the disease. With a thorough knowledge of the potential benefits and risks of each treatment or combination treatment, the physician with the patient's understanding and cooperation may then embark on what may be in severe cases a lengthy and sometimes unproductive therapeutic process.
Thirty-two patients with mild to extensive alopecia areata, including 16 patients with alopecia totalis or universalis, entered a randomized, controlled trial of a 6-week taper of prednisone followed by either 2% topical minoxidil or vehicle applied three times daily for an additional 14 weeks. The results of this study were compared with an open trial of 48 patients with alopecia areata treated with a similar taper of prednisone with concomitant 2% topical minoxidil applied twice daily. Only terminal hair growth was considered and was quantitated as 1% to 24%, 25% to 49%, 50% to 74%, and 75% to 100%: only those with more than 25% terminal hair regrowth were considered to have had an objective response.
At the end of 6 weeks of prednisone, 47% (15/32) of patients had more than 25% regrowth, including nine of 20 patients who had had at least 75% hair loss at baseline. Side effects of prednisone were primarily weight gain and mood changes/emotional lability. At 3 months, six of seven minoxidil-treated patients vs one of six vehicle-treated patients who had an objective response to prednisone maintained or augmented this hair growth: at the 20-week visit, these numbers were three of seven and zero of four patients, respectively. In the open trial, objective hair growth with prednisone was 30%, related to the extent of hair loss at baseline, and this growth persisted in more than 50% of patients at 6 months with the use of 2% topical minoxidil.
A 6-week taper of prednisone offers potential for more than 25% regrowth in 30% to 47% of patients with alopecia areata with predictable and transient side effects. Two percent topical minoxidil three times daily appears to help limit poststeroid hair loss.
Despite the prevalence of androgenetic alopecia among men, little is known about its psychological effects.
This investigation examined the psychosocial sequelae that balding men attribute to hair loss and compared balding and nonbalding men in personality functioning.
Subjects included 63 men with modest balding, 40 men with more extensive balding, and 42 nonbalding controls. All anonymously completed a battery of standardized psychological measures.
Reported effects of balding reflected considerable preoccupation, moderate stress or distress, and copious coping efforts. These effects were especially salient among men with more extensive balding and among younger men, single men, and those with an earlier hair-loss onset. Relative to controls, balding men had less body-image satisfaction yet were comparable on other personality indexes. Personality correlates of the psychological responses to hair loss were identified.
Although most men regard hair loss to be an unwanted, distressing experience that diminishes their body image, balding men actively cope and generally retain the integrity of their personality functioning.
The therapeutic value of topical minoxidil in alopecia areata (AA) has been investigated in recent years, with variable results. Although the mechanism whereby minoxidil may stimulate hair regrowth in some cases of AA has not yet been elucidated, there have been reports of a decrease in the perifollicular infiltrates of mononuclear leukocytes (MNC)--particularly T lymphocytes--that characterize this condition, in patients "responding" to topical minoxidil. In a randomized and double-blind study, we have investigated the effect of 5% topical minoxidil versus placebo (vehicle alone) on the extent and composition of the perifollicular MNC infiltration in 20 patients having extensive AA (26-99% scalp hair loss). The proportions of hair follicles showing perifollicular infiltration by MNC and their main subsets were determined with histologic and immunohistochemical stainings of scalp biopsies obtained before treatment, after 12 weeks of randomized double-blind minoxidil versus placebo treatment, and after 12 additional weeks during which all patients received minoxidil. Six of the patients showed cosmetically acceptable hair regrowth (CAHR) at the end of the 24 weeks and this was associated with a significant decrease in the proportions of follicles infiltrated by total T and B lymphocytes, macrophages, and Langerhans cells at week 12, and by total T lymphocytes at week 24. However, no significant differences in the extent or composition of the perifollicular infiltrates were detected at week 12 between patients receiving minoxidil and placebo, or between the week-12 and week-24 biopsies of those patients who first received placebo and then minoxidil. These findings indicate that in AA the reduction in perifollicular T-cell infiltration associated with CAHR is not attributable to an effect of topical minoxidil.
Finasteride, a 4-aza steroid compound, is an orally active inhibitor of the 5 alpha-reductase enzyme. 5 alpha-Reductase is necessary for the metabolism of testosterone (T) to dihydrotestosterone (DHT) and is found in high levels only in certain tissues such as the prostate. Finasteride has been shown to markedly suppress serum DHT levels in man without lowering testosterone levels. In patients with benign prostate hyperplasia (BPH), finasteride was found to decrease prostate volume by a mean of 28% over a period of 6 months, without causing clinically significant adverse effects. DHT appears to be the primary androgen for prostatic growth. Selective inhibition of 5 alpha-reductase by finasteride may provide a novel approach to BPH therapy by reducing prostate size without affecting T-dependent processes such as fertility, muscle strength, and libido. The clinical development of finasteride for the treatment of benign prostate hyperplasia is reviewed.
We report a cluster of male pseudohermaphrodites from the Simbari Anga linguistic group in the Eastern Highlands of Papua New Guinea. These subjects are born with a rudimentary clitoral-like penis and pseudovaginal perineoscrotal hypospadias. At puberty, the penis enlarges with concurrent growth of pubic and axillary hair and significant muscular development. There is significant facial hair, but it is less than that of their normal male siblings or other male relatives. Plasma collected from four adult subjects revealed elevated plasma testosterone levels, low to low normal dihydrotestosterone levels, and elevated testosterone/dihydrotestosterone ratios. All subjects had high urinary aetiocholanolone/androsterone ratios, and C19 and C21 5 beta/5 alpha metabolite ratios. Decreased 5 alpha-reductase activity was demonstrated in fibroblasts cultured from genital skin. The data indicate a phenotypic and biochemical profile similar to patients studied in the Dominican Republic, except for a greater abundance of facial and body hair. The phenotypic variability, as pertains to facial and body hair, may be related to differences in familial expression, as well as the degree of enzyme deficiency. Infants, thought to be females at birth, were reared as girls until puberty in a society practising one of the strictest gender segregations known. At puberty, these 'girls' were discovered to be boys, and a switch of gender roles was instituted. Recently, however, some Muniri, Dunkwi and northern Simbari hamlets recognize these individuals as male in infancy and rear them as boys, calling them 'kwalatmala' to distinguish them from normal males, accepting them as an intersex destined to occupy male adult roles.
Twelve children with extensive alopecia areata or alopecia totalis were treated with the contact allergen diphencyprone. The duration of treatment ranged from 5 months to 1 year. Eight of the 12 (67%) regrew scalp hair and in four (33%) there was a complete regrowth. Six months after treatment was discontinued three of the four children with complete regrowth maintained their hair, one had lost all the regrowth and a further child with patchy regrowth at the end of treatment subsequently regrew hair completely while off therapy.
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
Thirty-one men with androgenetic alopecia completed 4 1/2 to 5 years of therapy with 2% and 3% topical minoxidil. Hair regrowth with topical minoxidil tended to peak at 1 year with a slow decline in regrowth over subsequent years. However, at 4 1/2 to 5 years, maintenance of nonvellus hairs beyond that seen at baseline was still evident. Topical minoxidil appears to be effective in helping to maintain nonvellus hair growth in men with androgenetic alopecia.
Quantitative growth of hair over a 40-week period is reported for eight women with androgenetic alopecia. Using a random, double-blind protocol, the women were given either a 2% minoxidil solution or a placebo of vehicle only. Hair in a permanently marked site on the fronto-parietal scalp was pulled through a 1-cm-square clear plastic template, and the outline of the template was drawn on the scalp. The hair was carefully hand clipped and collected at five eight-week intervals (one untreated and four treated), using great care to collect only hairs within the marked area. Subsequent measurements included the total weight of hair grown in the marked area, the total number of hairs, and, on a randomized 50-hair subsample, the weight, lengths, and optical diameters. Calculated quantities included average weight per hair, average length, and average optical width. The average total hair weight of minoxidil-treated subjects increased over the 32-week test period by 42.5%, compared to 1.9% for the placebo-treated subjects (average p = 0.018). Changes for the average number count were 29.9% and -2.6%, respectively (average p = 0.022). These increases, observed using an unusually small number of subjects, clearly distinguished the treated subjects from the untreated. During the same test period, the averaged quantities of weight, diameter, and length from the 50-hair subsample showed insignificant change (p usually greater than 0.5). In addition to showing a larger percentage increase than did the total number, the total weight is not only easier to obtain, but less prone to error during sampling and measurement. Therefore, we recommend that total weight from a defined area be considered as the primary quantitative estimator for hair growth.
Studies in our laboratory have shown that minoxidil prolongs the life of keratinocytes in culture and extends the time after confluence that cells can be subcultured. These data suggest that the drug reduces the rate at which cells are lost from the germinative pool and hence slows senescence. In a dose-response study with minoxidil, the maximal effect of the drug was seen at doses from 6 to 12 micrograms/ml; however, activity could be detected at doses below 1 microgram/ml. Cells subcultured during log growth failed to demonstrate that minoxidil increased the total number of generations attainable under these conditions, although as expected, epidermal growth factor extended the life span of cells. When the experiments were repeated in a keratinocyte cell line that does not require a fibroblast feeder layer, the same results were obtained, indicating that the difference observed between log phase and postconfluence growth cannot be explained by the presence of fibroblasts. Minoxidil's effect on postconfluent cells was blunted by the addition of cholera toxin to the medium, suggesting that elevation of cyclic adenosine monophosphate cannot be a mechanism, although reduction of cyclic adenosine monophosphate is a possibility. Finally, maintaining keratinocytes at a 20 to 40 mM calcium concentration greatly reduced the ability of postconfluent cells to be subcultured, in comparison with the normal calcium concentration of 2 mM. That minoxidil almost completely reversed this inhibitory effect suggests it may work by preventing cross-linking by transglutaminase, which is activated by elevated calcium concentrations.
Minoxidil, a potent vasodilator, stimulates the growth of terminal hair from vellus or miniaturized follicles in balding scalp. To study minoxidil's action on isolated follicles we developed and validated an organ culture system using mouse whisker follicles. Control follicles cultured without minoxidil showed macroscopic changes including kinking of the hair shafts and bending of the follicles. Necrosis was evident in the differentiating epithelial elements forming the cuticle, cortex, and inner root sheath. These abnormalities were eliminated or greatly reduced in minoxidil-treated follicles. The morphology of these follicles was consistent with the production of new hair during culture. Direct measurement demonstrated that minoxidil-treated follicles grew significantly longer than control follicles during the 3-d culture. Minoxidil increased the incorporation of radiolabeled cysteine and glycine in follicles compared with control treatment. Doses of minoxidil up to 1 mM caused increased cysteine incorporation, while higher doses were inhibitory. Experiments with labeled thymidine indicated that minoxidil induced proliferation of hair epithelial cells near the base of the follicle. Autoradiography also showed that cysteine accumulated in the keratogenous zone above the dermal papilla. These studies demonstrate that organ cultured follicles are suitable for determining minoxidil's mechanism of action and may be useful for studying other aspects of hair biology. The results also show that minoxidil's effect on hair follicles is direct. This suggests that minoxidil's action in vivo includes more than just increasing blood flow to hair follicles.
Anthralin cream 0.5% to 1.0% was used to treat 68 patients with severe alopecia areata. Therapy was relatively well tolerated, although all patients experienced pruritus and local erythema and scaling. Cosmetic response was seen in 17 (25%) of the patients, and was maintained during therapy in 12 (71%) of the 17 cosmetic responders. For the patients treated with 0.5% anthralin, the mean time to response (44 of 66 patients) was 11 weeks; the mean time to cosmetic response (13 of 66 patients) was 23 weeks. Duration of the current episode of hair loss did not correlate with cosmetic response. Compared with other currently available topical treatments, anthralin appears to be a reasonable therapeutic option for severe alopecia areata.
Topical minoxidil solution can induce hair regrowth in alopecia areata. A dose-response effect was demonstrated when 48 patients treated with topical 1% minoxidil were compared with 47 patients treated with topical 5% minoxidil. A total of 66 patients were enrolled, 26 of them participating in both study groups. Patients with extensive (75% or greater) scalp hair loss showed a response rate of 38%, defined as terminal hair regrowth, with 1% minoxidil versus an 81% response rate with 5% minoxidil. The current 2% formulation is most likely to elicit cosmetically acceptable regrowth in those with patchy alopecia areata. Occlusion of the treated area appears to be necessary to achieve and maintain maximum results. Nonresponders are most likely to be found among those with the most extensive scalp hair loss. No other clinical features correlate with response to treatment. However, a finding of increased T cell blastogenesis before treatment may predict response. In patients with severe alopecia areata, hair loss generally recurs after treatment is stopped and may recur during treatment. Systemic absorption of topically applied and occluded minoxidil solutions (1% and 5%) was minimal; no clinically significant changes in blood pressure, weight, cardiovascular status, electrocardiogram, electrolytes, complete blood count, or urinalysis were seen. Mild local irritation occurred, and two of the 66 patients developed allergic contact dermatitis to minoxidil, as confirmed by patch tests.
This study was conducted to further evaluate the safety and efficacy of 3% topical minoxidil in the treatment of extensive alopecia areata. Patients were assigned to one of two treatment regimens in a double-blind manner. One group applied 3% minoxidil to the scalp twice daily for 64 weeks; the other group applied placebo for the initial 12 weeks and then switched to 3% minoxidil for the remaining 52 weeks. Thirty male and female subjects, ages 7 to 63 years, with extensive alopecia areata affecting 25% to 100% of the scalp were enrolled, fifteen subjects to each treatment group. Twenty-four of the thirty subjects had greater than 75% scalp hair loss. At 12 weeks the group treated with 3% minoxidil had slightly more hair growth than the placebo group, but the difference was not statistically significant. At 64 weeks, thirteen of twenty subjects (65%) who began with less than full scalp involvement (25% to 99% scalp hair loss) had terminal hair growth that was incomplete or cosmetically acceptable; of these, nine (45%) were cosmetically acceptable, a response that is significant in patients with severe alopecia areata. No hair growth or only slight growth was seen in all nine patients with 100% scalp hair loss at baseline. Thus the extent of hair loss at baseline was correlated with response at 64 weeks. Twenty-one of the patients continued treatment for a second year. Of these, thirteen showed further growth, three had no further growth, and five who had cosmetically acceptable hair growth during the first year had some hair loss.(ABSTRACT TRUNCATED AT 250 WORDS)
A randomized, double-blind trial was conducted to determine the relative efficacy and safety of topical minoxidil solution for progressive male pattern baldness. One hundred fifty men with a discernible vertex balding spot were randomly assigned to treatment with either 2% topical minoxidil, 3% topical minoxidil, or placebo. After 4 months, patients receiving placebo were crossed over to 3% minoxidil. The study was concluded after 12 months of treatment, at which time 100 subjects were evaluable. Efficacy was determined primarily by objective hair counts at monthly intervals and by subjective patient evaluations at 4 and 12 months. Patients applying active medication had significantly greater growth of nonvellus hairs at 4 months than did their placebo counterparts (p = 0.0018 for 2% minoxidil vs placebo; p = 0.0167 for 3% minoxidil vs placebo). In patients crossed over from placebo to 3% minoxidil, the rate of growth of nonvellus hairs increased to fifteen hairs a month during the next 4 months and slowed to ten hairs a month during the last 4 months. Within-group analyses for month 12 evaluable patients demonstrated significant increases in total hair counts for all three groups (p less than or equal to 0.0001). According to investigator evaluations at month 12, 82% of the 2% minoxidil group, 78% of the 3% minoxidil group, and 83% of the placebo to 3% minoxidil group had new hair growth. Clinically insignificant minoxidil blood levels resulted from scalp absorption. Thirty-six medical events in twenty-six patients were deemed related to the study drug; twenty-seven of these events were dermatologic in nature, and all were mild and self-limiting.
Of 149 subjects with androgenetic alopecia, 102 completed 1 year of a double-blind, randomized study comparing 2% minoxidil and 3% minoxidil solutions for safety and efficacy. One third of the subjects used a vehicle placebo for the first 4 months and then switched to 3% minoxidil. At 12 months the 2% minoxidil group switched to a 3% solution. During months 5 to 12 a steady increase in terminal hair counts occurred to an equal degree within the 2% and 3% minoxidil groups and the 3% treatment group switched from placebo. Total hair counts at 12 months increased from a baseline mean of 63.5 to 180.6 in the 2% treatment group, from 61.0 to 179.9 in the 3% group, and from 65.0 to 191.1 in the placebo to 3% crossover group. Although all 102 subjects completing 12 months of the study thought that visible hair growth had resulted, 89 were considered by the investigators to have visible growth. Dense hair growth, defined as hair long enough to cut or comb, was present in 48 subjects by their own evaluation and in 33 subjects by investigator evaluation. There were no serious side effects. Two instances of allergic contact dermatitis and four of pruritus were attributed to use of the drug. Two individuals complained of impotence, which disappeared within a few days of discontinuation of topical minoxidil. This effect has not been reported during the use of minoxidil in its oral form (Loniten) for the treatment of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Perhaps the most intriguing aspect of topical minoxidil is the fact that this drug can promote hair growth in two unrelated conditions: alopecia areata (AA) and androgenetic alopecia. The two conditions have quite different underlying mechanisms. In AA, hair follicles respond to some signal or cell injury by entering a state of aborted cyclical activity; this state can reverse itself spontaneously, or it can be temporarily circumvented with nonspecific immunomodulating agents. In androgenetic alopecia, genetically marked hair follicles undergo progressive, androgen-mediated miniaturization; antiandrogens have been conventionally sought to intercept this process. It is not known how minoxidil promotes hair growth except that living follicles capable of stimulation and hypertrophy are required. It may be that minoxidil influences some fundamental signal to the follicular apparatus, irrespective of the pathophysiology involved. We have used topical minoxidil solution in 90 patients, aged 7-63 years, with extensive AA affecting 25-100% of the scalp. One study was double-blind, and placebo-controlled for an entire year. Minoxidil-treated patients responded better than placebo-treated patients. Both 3 and 5% topical minoxidil solutions have been used, and treatment with the 3% solution has continued for up to 3 years. The results of these studies will be discussed. While topical minoxidil is not very effective for those with 100% scalp hair loss, it is an effective, easy and safe treatment for those with AA affecting 25-99% of the scalp.
Topical 5% minoxidil solution was used to treat 47 patients with severe alopecia areata. Forty patients (85%) had terminal hair regrowth after 48 to 60 weeks of treatment. In the majority of patients, hair regrowth was not cosmetically acceptable. Data were compared with those from a previous study with topical 1% minoxidil solution. Both the percentage of responders and the quality of their hair regrowth were significantly greater with 5% than with 1% topical minoxidil solution. One patient developed an allergic contact dermatitis to minoxidil, but no systemic side effects were detected. The results strongly suggest a dose-response effect for topical minoxidil treatment of alopecia areata and the importance of exploring modifications in dosing and delivery systems to enhance therapeutic efficacy.
Spironolactone (S) has been used successfully for the treatment of hirsutism. We evaluated whether the effects of S on serum androgens and hair growth are dose-related and whether S affects secreted androgens to the same degree as peripherally derived androgens. Two groups of 15 hirsute patients, similarly matched, received either 100 or 200 mg S daily for 3 months. Serum total testosterone (T) decreased significantly (P less than 0.05) and to a similar degree with both dosages, whereas unbound T was unaltered. Dehydroepiandrosterone sulfate was unaltered, whereas androstenedione decreased with 200 mg S (P less than 0.05). Peripherally derived serum dihydrotestosterone decreased to a similar degree with 100 and 200 mg S (P less than 0.05), whereas 5 alpha-androstane-3 alpha-17 beta-diol (3 alpha-diol) increased (P less than 0.05) similarly with both dosages. Serum 3 alpha-diol glucuronide (3 alpha-diol-G) increased with both dosages, but not significantly. Anagen hair shaft diameters decreased significantly in both groups by 19% +/- 8% and 30% +/- 4% (P less than 0.05). No correlation was found between hair growth and serum androgens. Because serum unbound T was largely unaltered by S, it is suggested that the antiandrogenic effects of S are primarily related to its peripheral effect. However, there is no good clinical marker for this effect as levels of 3 alpha-diol and 3 alpha-diol-G increase.