Peptides. 2005 May;26(5):707-11

Anti-alopecia mechanisms of soymetide-4, an immunostimulating peptide derived from soy beta-conglycinin.
Tsuruki T, Takahata K, Yoshikawa M.

Previously, we found that orally administered soymetide-4 (MITL), an immunostimulating peptide derived from soybean beta-conglycinin alpha’ subunit, suppressed alopecia induced by the anti-cancer drug etoposide in neonatal rats. Soymetide-4 has weak affinity for N-formyl-methionyl-leucyl-phenylalanine (fMLP) receptor. fMLP showed an anti-alopecia effect after intraperitoneal administration, though it was inactive after oral administration. Anti-alopecia effect of fMLP was blocked by pyrilamine or cimetidine, antagonists for histamine H1 or H2 receptor, respectively. However, the anti-alopecia effect of soymetide-4 was not inhibited by the histamine antagonists but by indomethacin, an inhibitor of cyclooxygenase (COX), or AH-23848B, an antagonist of the EP4 receptor for PGE2. Anti-alopecia effect of soymetide-4 was also blocked by pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kappaB (NF-kappa. These results suggest that PGE2, which is produced after activation of COX by soymetide-4, might suppress apoptosis of hair matrix cells and etoposide-induced alopecia by activating NF-kappaB.

South Med J. 2000 Jul;93(7):657-62.

Male pattern baldness

Hogan DJ, Chamberlain M.

BACKGROUND: Male pattern baldness, or androgenetic alopecia (AGA) in men, occurs with varying severity and age of onset. Two new treatments widely available as alternatives to 2% minoxidil are 1 mg finasteride and topical 5% minoxidil. Finasteride is a 5 alpha-reductase inhibitor available by prescription only; 5% minoxidil is available over the counter. METHODS: We searched MEDLINE to identify all articles on AGA and its pharmacologic therapies. RESULTS: We found limited information on AGA in peer review medical journals. Associated diseases include psychologic disorders and coronary heart disease. Hair growth is unpredictable and limited for all pharmacologic therapies, with the vast majority of treatment studies being industry sponsored. CONCLUSION: AGA is not easy to treat. Finasteride and 5% minoxidil offer new therapeutic options to the balding man. Treatment options may improve as new drugs are further investigated.

Hautarzt. 1989 Nov;40(11):669-78.

Androgenetic alopecia in the male. Recent developments

Braun-Falco O, Bergner T.

In this review ,male-pattern hair loss or androgenetic alopoecia (AA) (pattern balding) is discussed. AA is characterized as a physiological process. Some of the reactions that take place in its pathogenesis and many of the substrates involved in androgen metabolism are now known, but the question as to the androgen stimulus leads to retrograde transformation of the hair follicles only in skin of the parieto-occipital scalp can still not be answered. Specific antiandrogens for the treatment of AA are not available for either topical application or systemic administration. Minoxidil seems to have a positive effect in the treatment of pattern hair loss but in most cases the cosmetic result is not satisfactory.

Scand J Plast Reconstr Surg Suppl. 1976;14:1-37.

Hair transplantation. The use of hairbearing compound grafts for correction of alopecia due to chronic discoid lupus erythematosus, traumatic alopecia, and male pattern baldness.

Nordström RE.

In this study 8 patients with alopecia due to chronic discoid lupus erythematosus (CDLE), 10 patients with traumatic alopecia (TA), and 12 patients with male pattern baldness (MP were treated with the punch graft method (PGM). Stastistical evaluations of the results and factors influencing the results were careied out. The mean survival rate of hairs was 72% in CDLE, 97% in TA, and 104% in MPB. The mean number of hairs in a 4 mm graft before transplantation in 30 patients and 752 grafts was found to be 18.2. This is far more than the number reported in previous publications concerning PGM owing probably to the difficulties of counting several hairs simultaneously emerging from the same pilary canal when the hair is cut to a length of 1–2mm preoperatively. For this purpose the author has developed a special photographical magnifying system. The number of hairs surviving transplantation in MPB in a 4 mm graft was about 19 hairs per graft, which is superior to previous reports. This is possibly due to some modifications of the procedure made by the author. In a control series done with the same technique as that often seen in the literature, about 50% inferior results were obtained. These results were however similar to those reported in the literature. Consequently the modifications of the procedure have been successful. Only one article with a series of 12 patients with TA treated with PGM was found in the literature. The hair survival results of the author exeeded the reported results by about 100%. The size, hardness, and elevation of the scars of the donor holes were checked statistically after various treatments. It was found that the diameter of the scar is the same regardless of type of treatment but that a signifcantly greater risk of hard and elevated scars is taken if the bald grafts are put back in the donor holes. No complications were seen in this series. PGM is a safe method that gives good hair survival results on transplanted hairs in MPB and TA, but the results vary in CDLE. In spite of the good results with PGM the author emphasizes that, although the therory of the method is simple, both the preoperative judement and the performance with its practical difficulties and many cosmetic problems is complex and requires a lot of psychological insight, practice and experience before correct preoperative judgement and a maximally good cosmetic result can be achieved.

An early paper on the use of hair transplantation for male pattern hair loss and traumatic alopecia

Eur J Dermatol. 2002 Jul-Aug;12(4):327-34. Diphencyprone immunotherapy alters anti-hair follicle antibody status in patients with alopecia areata.

Tobin DJ,

Alopecia areata (AA) is a relatively common reversible hair loss disorder usually manifesting as patchy areas of complete hair loss on the scalp and other body parts that can progress to complete loss of all body hair. This condition is now generally assumed to be an autoimmune disease with the hair follicle (HF) as the principal target tissue. AA may be passively transferred by T cells and there is some evidence that serum IgG may also disturb hair cycling. Here, we examine whether the status of anti-HF antibody reactivity is altered during hair regrowth associated with topical immunotherapy using the contact sensitizer diphencyprone. Eleven patients with severe AA of the scalp were treated with diphencyprone on one side of the scalp and serum was obtained from each patient before the start of therapy, after unilateral hair regrowth, during continuing hair regrowth and in some cases after complete and sustained regrowth. The presence and titer of circulating antibodies to HF was assessed by indirect immunofluorescence and immunoblotting analysis. A striking reduction was detected in both the titer and range of HF components/antigens targeted by anti-hair follicle IgG antibodies in those patients that exhibited complete and sustained hair regrowth after DCP-treatment. By contrast, unilateral hair regrowth was associated with no change, or even an increase, in anti-HF antibody titer and reactivity. Therefore we can conclude that the down-regulation of antibody reactivity is likely to be a result rather than the cause of hair regrowth induction by topical immunotherapy. As this immunotherapy is associated with a reduction in the titer/pattern of anti-HF antibodies, these may hold the key to the identity of the HF antigen targets in AA. Moreover, the presence/titer of anti-HF antibodies may be a marker of clinical disease activity or opportunity for spontaneous regrowth.

hair loss treatment balding

J Cutan Med Surg. 2002 Jan-Feb;6(1):1-9. Epub 2002 Jan 9. Effects of finasteride on apoptosis and regulation of the human hair cycle.

Sawaya ME,et al

BACKGROUND: A number of studies have provided evidence that apoptosis is a central element in the regulation of hair follicle regression. In androgenetic alopecia (AGA), the exact location and control of key players in the apoptotic pathways remains obscure. OBJECTIVE: In the present study, we used a panel of antibodies and investigated the spatial and cellular pattern of expression of caspases and inhibitors of apoptosis (IAPs), such as XIAP and FLIP, in men with normal scalp and in men with AGA before and after 6 months of treatment with 1 mg oral finasteride treatment. METHODS AND RESULTS: Constitutive expression of caspases-1, -3, -8, and -9 and XIAP was detected predominantly within the isthmic and infundibular hair follicle area, basilar layer of the epidermis, and eccrine and sebaceous glands. AGA-affected tissues showed an increase in caspase (-1, -3, -6, -9) immunoreactivity with a concomitant decrease in XIAP staining. After 6 months of finasteride treatment, both caspases and XIAP were similar to levels exhibited by normal subjects. Immunoblot analysis was performed to determine antibody specificity and cellular expression of caspases. Purified populations of keratinocytes, melanocytes, dermal papilla, and dermal fibroblasts derived from human hair follicles were cultured in vitro and treated with 0.5 mm staurosporin. Time-course experiments revealed that processing of caspase-3 is a principal event during apoptosis of these hair cell types. CONCLUSION: These data suggest that alterations in levels of caspases and IAPs regulate hair follicle homeostasis. Moreover, finasteride appears to influence caspase and XIAP expression in hair follicle cells thus signaling anagen, active growth in the hair cycle.

Support Care Cancer. 2009 Feb;17(2):181-9. Epub 2008 Jun 17. Links
Scalp cooling to prevent chemotherapy-induced hair loss: practical and clinical considerations.Mols F, van den Hurk CJ, Vingerhoets AJ, Breed WP.

OBJECTIVE: The objective of this prospective multicenter study was to obtain insight into the severity and burden of hair loss among cancer patients treated with chemotherapy. In addition, we described the effectiveness and burden of scalp cooling and the satisfaction with wigs, with hair regrowth, and with body image. MATERIALS AND METHODS: Breast cancer patients treated with (n = 98) and without (n = 168) scalp cooling completed questionnaires before chemotherapy and 3 weeks and 6 months after completion of chemotherapy. RESULTS: Scalp cooling was effective in preventing chemotherapy-induced hair loss in 32 of 62 available patients (52%). Even though patients knew hair loss was temporary, it was a burden to 54% of them (n = 100). Scalp cooling was a burden for only 17 out of 51 patients (33%). Most patients who used a wig or head cover were satisfied with it (82%, n = 126). Patients were moderately satisfied with the regrowth of their hair after chemotherapy (mean 11.6; SD 2.53; range 0-20). Successfully cooled patients rated their hair as less important for their body image compared to patients who did experience hair loss (p = 0.014). DISCUSSION: Chemotherapy-induced hair loss is perceived as burdensome. It may be prevented by offering scalp cooling which is often an effective method to prevent this form of hair loss and is tolerated well by patients. However, if possible, scalp-cooling techniques should be improved and their effectiveness should be increased because if scalp cooling is unsuccessful, patients’ rate their hair loss as more burdensome compared to noncooled patients.

Potential treatments for hair loss.Med Hypotheses. 2009

The most efficient follicular regenerating unit and the smallest follicular regenerating unit: Potential treatments for hair loss.

Wang S, Li Y, Ji YC, Lin CM, Man C, Zheng XX.

Tissue Engineering Lab, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou 515041, PR China.

Hair loss affects many people, especially adult males. An effective treatment is hair transplantation which involves harvesting hair grafts from a donor site and relocating them to a bald site. However, this traditional method, equivalent to one-to-one transplantation, simply redistributes hair rather than increases the number of existing hairs. Although hair transplantation is actually the transplantation of hair follicle (HF), it has been confirmed that whole HFs could be reformed from parts of HFs containing different constituents, implying the existence of more efficient and smaller HF regenerating units in a whole HF. Thus we hypothesize that the most efficient follicular regenerating unit (EFRU) and the smallest follicular regenerating unit (SFRU) could be found in whole HFs. As a result, the one-to-many hair transplantation would be achieved in clinic. One-to-many means to double or triple the number of hairs. In order to test and verify the hypothesis, we design a method called hair follicle micro-dissection (HFM) which aims to help find the regenerating units and increase the number ofhair for transplantation. The postulation may provide a more mature and realistic treatment for hair loss if it proved to be practical.

Treatments for Alopecia Areata Cochrane Database Syst Rev. 2008 Apr 16;(2):CD004413.

Delamere FM, et al

BACKGROUND: Alopecia areata is a disorder in which there is loss of hair causing patches of baldness but with no scarring of the affected area. It can affect the entire scalp (alopecia totalis) or cause loss of all body hair (alopecia universalis). It is a relatively common condition affecting 0.15% of the population. Although in many cases it can be a self-limiting condition, nevertheless hair loss can often have a severe social and emotional impact. OBJECTIVES: To assess the effects of interventions used in the management of alopecia areata, alopecia totalis and alopecia universalis. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register

DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and extracted the data. We contacted trial authors for more information. We collected adverse effects information from the included trials. MAIN RESULTS: Seventeen trials were included with a total of 540 participants. Each trial included from 6 to 85 participants and they assessed a range of interventions that included topical and oral corticosteroids, topical ciclosporin, photodynamic therapy and topical minoxidil. Overall, none of the interventions showed significant treatment benefit in terms of hair growth when compared with placebo. We did not find any studies where the participants self-assessed their hair growth or quality of life.

CONCLUSIONS: We found no RCTs on the use of diphencyprone, dinitrochlorobenzene, intralesional corticosteroids or dithranol although they are commonly used for the treatment of alopecia areata. Similarly although topical steroids and minoxidil are widely prescribed and appear to be safe, there is no convincing evidence that they are beneficial in the long-term. There is a desperate need for large well conducted studies that evaluate long-term effects of therapies on quality of life. Considering the possibility of spontaneous remission especially for those in the early stages of the disease, the options of not being treated therapeutically or, depending on individual preference wearing a wig may be alternative ways of dealing with this condition.

Biol Pharm Bull. 2008 Mar;31(3):449-53.

trans-3,4Œ-Dimethyl-3-hydroxyflavanone, a hair growth enhancing active component,decreases active transforming growth factor beta2 (TGF-beta2) through control of urokinase-type plasminogen activator (uPA) on the surface of keratinocytes.

Sasajima M, Moriwaki S, Hotta M, Kitahara T, Takema Y.

trans-3,4Œ-Dimethyl-3-hydroxyflavanone (t-flavanone) is a synthetic compound withhair growth enhancing activity that is effective against male pattern alopecia.t-Flavanone was designed as a derivative of astilbin, the active hair growth enhancing component of Hypericum perforatum extracts. This study was designed to elucidate the mechanism of hair growth enhancement by t-flavanone. We investigated the effects of t-flavanone on transforming growth factor beta (TGF-beta), a known catagen-inducing factor induced in hair papilla cells by male hormone. When t-flavanone was added to cocultures of human hair papilla cells and human keratinocytes, there was no change in the total level of TGF-beta2. However, levels of active TGF-beta2 were reduced, suggesting the involvement oft-flavanone in the activation pathway of TGF-beta2. In order to investigate the effects of t-flavanone on TGF-beta2 activation by human keratinocytes, we evaluated the level of active TGF-beta2 converted from the inactive form in t-flavanone-treated human keratinocytes. The amount of active TGF-beta2 was reduced compared with controls suggesting that t-flavanone suppresses the TGF-beta2 activation cascade in human keratinocytes. We then examined the activity of urokinase-type plasminogen activator (uPA), the rate-limiting enzyme in the TGF-beta2 activation cascade, in t-flavanone-treated human keratinocytes. We found that t-flavanone reduces uPA activity on the keratinocyte surface. t-Flavanone is a hair growth enhancing component that has a novel mechanism of action which suppresses TGF-beta2 activation, and thereby is expected to have therapeutic effects on other types of alopecia in addition to male pattern alopecia.

Facial Plast Surg. 2008 Nov;24(4):381-8

Follicular unit transplantation.

Rousso DE, Presti PM.

Follicular unit transplantation (FUT) is the culmination of decades of refinement and evolution of hair transplantation techniques. Hair naturally grows in groups of one to four individual follicles separated by intervening soft tissue. These clumps or groups of hairs are termed FOLLICULAR UNITS. FUT uses microscopic dissection to separate these units for transplantation in a fashion that mostclosely resembles naturally occurring hair. FUT has grown to become recognized by many prominent hair restoration surgeons as the state-of-the-art method of hairreplacement surgery for both male and female pattern alopecia. Although larger punch grafts, scalp flaps, and alopecia reductions may play a role in certaincases, FUT achieves results that are difficult to differentiate from naturallyoccurring hair. The central attributes of the technique are the provision of natural-appearing hairlines with reasonable density together with low morbidity and minimal “downtime.” Nevertheless, the technique is only as effective as the technician, and results are heavily dependent on the forethought of the architect.

Yun SJ, Kim SJ. Hair loss pattern due to chemotherapy-induced anagen effluvium: a cross-sectional
observation. Dermatology. 2007;215(1):36-40.

Anagen effluvium is a common side effect of chemotherapy, but few studies have examined its clinical characteristics. OBJECTIVE: This study was aimed at evaluating the hair loss caused by chemotherapeutic agents. METHODS: Sixty-four patients with anagen effluvium were evaluated in the study. Chemotherapeutic agents were classified into 5 different groups. The pattern of hair loss was analyzed when specific involvement of the hairline was obvious.

RESULTS: Forty-six (71.9%) of the 64 total patients maintained hairs along their hairline. Hairs were maintained with a total hairline in 20 (31.3%), frontal hairline in 13 (20.3%) and occipital hairline in 12 (18.8%) patients. Among the 20 males with patterned hair loss, the following hairlines were preserved: occipital in 10 (50%), total in 7 (35%) and frontal in 3 (15%). Among the 25 females with patterned hair loss, hairlines were preserved as total in 13 (52%), frontal in 10 (40%) and occipital in 2 (8%). However, no significant differences were detected in hair loss patterns according to age, associated symptoms, chemotherapeutic agent group or combination of chemotherapeutic agents.

Hair Loss

CONCLUSION: Our results suggest that anagen effluvium induced by chemotherapeutic agents represents patterned hair loss.