CNS Drug Rev. 2006 Spring;12(1):53-76.

A new look at the 5alpha-reductase inhibitor finasteride.
Finn DA, Beadles-Bohling AS, Beckley EH, Ford MM, Gililland KR, Gorin-Meyer RE, Wiren KM.

Finasteride is the first 5alpha-reductase inhibitor that received clinical approval for the treatment of human benign prostatic hyperplasia (BPH) and androgenetic alopecia (male pattern hair loss). These clinical applications are based on the ability of finasteride to inhibit the Type II isoform of the 5alpha-reductase enzyme, which is the predominant form in human prostate and hair follicles, and the concomitant reduction of testosterone to dihydrotestosterone (DHT). In addition to catalyzing the rate-limiting step in the reduction of testosterone, both isoforms of the 5alpha-reductase enzyme are responsible for the reduction of progesterone and deoxycorticosterone to dihydroprogesterone (DHP) and dihydrodeoxycorticosterone (DHDOC), respectively. Recent preclinical data indicate that the subsequent 3alpha-reduction of DHT, DHP and DHDOC produces steroid metabolites with rapid non-genomic effects on brain function and behavior, primarily via an enhancement of gamma-aminobutyric acid (GABA)ergic inhibitory neurotransmission. Consistent with their ability to enhance the action of GABA at GABA(A) receptors, these steroid derivatives (termed neuroactive steroids) possess anticonvulsant, antidepressant and anxiolytic effects in addition to altering aspects of sexual- and alcohol-related behaviors. Thus, finasteride, which inhibits both isoforms of 5alpha-reductase in rodents, has been used as a tool to manipulate neuroactive steroid levels and determine the impact on behavior. Results of some preclinical studies and clinical observations with finasteride are described in this review article. The data suggest that endogenous neuroactive steroid levels may be inversely related to symptoms of premenstrual and postpartum dysphoric disorder, catamenial epilepsy, depression, and alcohol withdrawal.

Am Fam Physician. 1999 Apr 15;59(8):2189-94, 2196.

Scow DT, Nolte RS, Shaughnessy AF.

Harrisburg Family Practice Residency, PA 17105-8700, USA.

Two drugs are available for the treatment of balding in men. Minoxidil, a topical product, is available without a prescription in two strengths. Finasteride is a prescription drug taken orally once daily. Both agents are modestly effective in maintaining (and sometimes regrowing) hair that is lost as a result of androgenic alopecia. The vertex of the scalp is the area that is most likely to respond to treatment, with little or no hair regrowth occurring on the anterior scalp or at the hairline. Side effects of these medications are minimal, making them suitable treatments for this benign but psychologically disruptive condition.

Clin Dermatol. 1988 Oct-Dec;6(4):159-62.

Animal models of alopecia.

Holland JM.

Section on Pathology and Toxicology Research, Upjohn Company, Kalamazoo, Michigan.

A genetic model of androchronogenic alopecia has yet to be described in the rat or mouse, two of the better characterized species. It may be relevant that the best current animal model of androchronogenic alopecia, the stumptailed macaque, is a primate. The age of onset and the pattern of hair loss closely resemble human male-pattern baldness and morphologically, as well as mechanistically, may be analogous to the corresponding process in humans. Since genetically controlled regional hairlessness is a phenomenon relatively unique to Homo sapiens, it may be too much to expect to find an analogous process among rodents.

Br J Dermatol. 2005 Mar;152(3):466-73.

Treatment of female pattern hair loss with oral antiandrogens.

Sinclair R, Wewerinke M, Jolley D.

BACKGROUND: It has not been conclusively established that female pattern hair loss (FPHL) is either due to androgens or responsive to oral antiandrogen therapy. OBJECTIVES: To evaluate the efficacy of oral antiandrogen therapy in the management of women with FPHL using standardized photographic techniques (Canfield Scientific), and to identify clinical and histological parameters predictive of clinical response. METHODS: For this single-centre, before-after, open intervention study, 80 women aged between 12 and 79 years, with FPHL and biopsy-confirmed hair follicle miniaturization were photographed at baseline and again after receiving a minimum of 12 months of oral antiandrogen therapy. Forty women received spironolactone 200 mg daily and 40 women received cyproterone acetate, either 50 mg daily or 100 mg for 10 days per month if premenopausal. Women using topical minoxidil were excluded. Standardized photographs of the midfrontal and vertex scalp were taken with the head positioned in a stereotactic device. Images were evaluated by a panel of three clinicians experienced in the assessment of FPHL, blinded to patient details and treatment and using a three-point scale.

RESULTS: As there was no significant difference in the results or the trend between spironolactone and cyproterone acetate the results were combined. Thirty-five (44%) women had hair regrowth, 35 (44%) had no clear change in hair density before and after treatment, and 10 (12%) experienced continuing hair loss during the treatment period. Ordinal logistic regression analysis to identify predictors of response revealed no influence of patient age, menopause status, serum ferritin, serum hormone levels, clinical stage (Ludwig) or histological parameters such as T/V ratio or fibrosis. The only significant predictor was midscalp clinical grade, with higher-scale values associated with a greater response.

CONCLUSION: Eighty-eight percent of women receiving oral antiandrogens could expect to see no progression of their FPHL or improvement. High midscalp clinical grade was the only predictor of response identified. A placebo-controlled study is required to compare this outcome to the natural history of FPHL.

Hair loss and hair loss treatment blog

J Dermatol. 2002 Aug;29(8):489-98.

Comparative efficacy of various treatment regimens for androgenetic alopecia in men.

Khandpur S, Suman M, Reddy BS.

Department of Dermatology and S.T.D., Maulana Azad Meical College and Associated Lok Nayak Hospital, New Delhi, India.

Our understanding of the aetiology of androgenetic alopecia (AGA) has substantially increased in recent years. As a result, several treatment modalities have been tried with promising results especially in early stages of AGA. However, as far as has been ascertained, there is no comprehensive study comparing the efficacy of these agents alone and in combination with each other. One hundered male patients with AGA of Hamilton grades II to IV were enrolled in an open, randomized, parallel-group study, designed to evaluate and compare the efficacy of oral finasteride (1 mg per day), topical 2% minoxidil solution and topical 2% ketoconazole shampoo alone and in combination. They were randomized into four groups. Group I (30 patients) was administered oral finasteride, Group II (36 patients) was given a combination of finasteride and topical minoxidil, Group III (24 patients) applied minoxidil alone and Group IV (10 patients) was administered finasteride with topical ketoconazole. Treatment efficacy was assessed on the basis of patient and physician assessment scores and global photographic review during the study period of one year. At the end of one year, hair regrowth was observed in all the groups with best results recorded with a combination of finasteride and minoxidil (Group II) followed by groups IV, I and III. Subjects receiving finasteride alone or in combination with minoxidil or ketoconazole showed statistically significant improvement over minoxidil only recipients. No signifcant side-effects related to the drugs were observed. In conclusion, it is inferred that the therapeutic efficacy is enhanced by combining the two drugs acting on different aetiological aspects of AGA.

Br J Dermatol. 2003 Aug;149(2):354-62.

The effects of minoxidil, 1% pyrithione zinc and a combination of both on hair density: a randomized controlled trial.

Berger RS, et al

BACKGROUND: Recent studies of antidandruff shampoos or tonics containing antifungal or antibacterial agents produced effects suggestive of a potential hair growth benefit. OBJECTIVES: The purpose of this 6-month, 200-patient, randomized, investigator-blinded, parallel-group clinical study was to assess the hair growth benefits of a 1% pyrithione zinc shampoo. The efficacy of a 1% pyrithione zinc shampoo (used daily), was compared with that of a 5% minoxidil topical solution (applied twice daily), a placebo shampoo and a combination of the 1% pyrithione zinc shampoo and the 5% minoxidil topical solution. METHODS: Two hundred healthy men between the ages of 18 and 49 years (inclusive) exhibiting Hamilton-Norwood type III vertex or type IV baldness were enrolled. Total hair counts, the primary efficacy measure, were obtained using fibre-optic microscopy and a computer-assisted, manual hair count method. Secondary measures of efficacy included assessments of hair diameter, as well as patient and investigator global assessments of improvement in hair regrowth. These were based on photographs of the scalp using both midline and vertex views. RESULTS: Hair count results showed a significant net increase in total visible hair counts for the 1% pyrithione zinc shampoo, the 5% minoxidil topical solution, and the combination treatment groups relative to the placebo shampoo after 9 weeks of treatment. The relative increase in hair count for the 1% pyrithione zinc shampoo was slightly less than half that for the minoxidil topical solution and was essentially maintained throughout the 26-week treatment period. No advantage was seen in using both the 5% minoxidil topical solution and the 1% pyrithione zinc shampoo. A small increase in hair diameter was observed for the minoxidil-containing treatment groups at week 17. Assessments of global improvements by the patients and investigator generally showed the benefit of 5% minoxidil. The benefit of the 1% pyrithione zinc shampoo used alone tended to be apparent only to the investigator. CONCLUSIONS: Hair count results show a modest and sustained improvement in hair regrowth with daily use of a 1% pyrithione zinc shampoo over a 26-week treatment period.

Arch Dermatol. 1999 Oct;135(10):1223-6.

Acquired progressive kinking of the hair: clinical features, pathological study, and follow-up of 7 patients.

Tosti A, Piraccini BM, Pazzaglia M, Misciali C.

BACKGROUND: Acquired progressive kinking of the hair (APKH) is a relatively rare condition, with fewer than 20 cases reported in the literature. Whether APKH is a separate entity or a variety of androgenetic alopecia is still controversial. This study reviews the clinical and pathological features and long-term follow-up of 7 patients with APKH. OBSERVATIONS: Since January 1989, we have diagnosed APKH in 7 males aged 15 to 22 years. All patients had strong family history for androgenetic alopecia. Hair kinking affected the frontotemporal region and/or the vertex where the hair appeared curly, frizzy, and lusterless. The pathological features of the affected scalp were consistent with the diagnosis of the early stages of androgenetic alopecia. In all patients, APKH evolved into androgenetic alopecia during the follow-up period. Mean follow-up was 4.5 years (range, 2-9 years). Treatment with topical minoxidil did not prevent development of hair thinning in the scalp areas affected by hair kinking. CONCLUSIONS: The term acquired progressive kinking of the hair encompasses a number of conditions characterized by acquired curling of the scalp hair. Acquired hair kinking on the androgen-dependent areas of the scalp represents a modality of onset of androgenetic alopecia associated with poor prognosis.

Dermatol Surg. 2000;26(6):555-61.

male and female androgenetic alopecia.

Bouhanna P.

edited

Hair Loss Blogs

BACKGROUND: Various classifications of male androgenetic alopecia or “pattern hair loss” are known….. A more objective, accurate, and detailed approach to classifying baldness is needed. OBJECTIVE: To propose a dynamic multifactorial classification of certain parameters that can be quantitated and computerized. METHODS: A multifactorial classification has been developed to study parameters such as fixed distances of the face, scalp mobility and thickness, and covering power of hair. This includes density, caliber, shape, length, growth rate, and hair color.

RESULTS: Classification proved to be efficient during the fluctuations of different parameters in hormonal and minoxidil treatments. It also helps to determine surgical indications of hair transplant and the stage of baldness. CONCLUSION: This approach will lead to a better evaluation of the evolution of androgenetic alopecia in both sexes, either spontaneously or under treatment.

Psychol Rep. 1989 Aug;65(1):323-30.

Why men with hair loss go to the doctor.

Passchier J, Rijpma SE, Dutrée-Meulenberg RO, Verhage F, Stolz E.

Consultations, motives, experience, and attitudes were explored in 201 men with alopecia androgenetica who had two years before shown interest in hair loss treatment using minoxidil. During the past two years, one-third consulted a professional on account of hair loss. General practitioners were consulted by 60% and other professionals by about 75%. The main motive for the consultation was hair treatment, which was offered to half of the consulting subjects. Medical professionals were generally considered to be more suitable than other professionals for consultation on minoxidil treatment. The perceived chance of the treatment being successful and the amount of hair problems experienced seemed more important factors for consulting than the views on the suitability of a professional or the extent of baldness. There were indications that subjects who consulted both general practitioners and other professionals had also more general problems.

Hair Loss Blog

Hair Loss Blog

Clin Exp Dermatol. 1989 Jan;14(1):40-6.

Quantitative assessment of 2% topical minoxidil in the treatment of male pattern baldness.

Rushton DH, Unger WP, Cotterill PC, Kingsley P, James KC.

Forty-seven men with male pattern baldness were treated in a double-blind clinical trial with topical 2% minoxidil or placebo. Twelve were randomly selected for quantitative hair measurement using the unit area trichogram and visual counting. There was no significant difference after 6 or 12 months of treatment with a 2% minoxidil solution for total hair density (THD; hair cm-2), meaningful hair density (MHD; hair greater than 40 microns in diameter greater than 30 mm in length cm-2), per cent of hair in the anagen growth phase, or the per cent of meaningful hair in the anagen growth phase. Significantly fewer hairs were recorded with the visual hair counting method, compared to values obtained from adjacent sites with the unit area trichogram. In addition, a significantly larger mean total hair count was recorded by an experienced observer, compared to an inexperienced observer. Increased pigmentation was observed within the vellus hair population of treated subjects. Our findings indicate that minoxidil appears unlikely to affect the long-term course of male pattern baldness. However, we found no significant deterioration in total hair density, or meaningful hair density in treated subjects, suggesting minoxidil may have a prophylactic effect. Further long-term studies employing the unit area trichogram are required to evaluate this finding.

Formation of hair structures suitable for implantation
Regen Med. 2008 Sep;3(5):683-92.

Hair morphogenesis in vitro: formation of hair structures suitable for implantation.

Qiao J, Turetsky A, Kemp P, Teumer J.

Intercytex, Innovation House, Crewe Road, Manchester, M23 9QR, UK.

AIM: To develop a construct through which implanted follicular cells will efficiently cause hair regeneration for the treatment of androgenetic alopecia.

MATERIALS & METHODS: Follicular dermal and epidermal cells isolated from embryonic mouse skin were formed into aggregates. The aggregates were incubated in culture for 5-7 days and then implanted intradermally into athymic mice. RESULTS: During culture, mixed cell aggregates developed into hair-like structures, termed ‘proto-hairs’. Proto-hairs contained structures that resembled normal hair components, such as dermal papillae, hair matrix and rudimentary hair
shafts. When implanted into mouse skin, they developed further into mature hair follicles capable of prolonged growth. CONCLUSION: Mixed aggregates of murine follicular cells have the ability to develop in culture into proto-hairs that
retain the ability to fully develop into hair follicles after implantation. Proto-hairs from human cells could provide a convenient and practical means by which follicular cells could be implanted for efficient hair regeneration to treat hair loss.

Minoxidil and Pyrithione zinc

Br J Dermatol. 2003 Aug;149(2):354-62.

The effects of minoxidil, 1% pyrithione zinc and a combination of both on hair density: a randomized controlled trial.

Berger RS, Fu JL, Smiles KA, Turner CB, Schnell BM, Werchowski KM, Lammers KM.

BACKGROUND: Recent studies of antidandruff shampoos or tonics containing antifungal or antibacterial agents produced effects suggestive of a potential hair growth benefit. OBJECTIVES: The purpose of this 6-month, 200-patient, randomized, investigator-blinded, parallel-group clinical study was to assess the hair growth benefits of a 1% pyrithione zinc shampoo. The efficacy of a 1% pyrithione zinc shampoo (used daily), was compared with that of a 5% minoxidil topical solution (applied twice daily), a placebo shampoo and a combination ofthe 1% pyrithione zinc shampoo and the 5% minoxidil topical solution.

METHODS: Two hundred healthy men between the ages of 18 and 49 years (inclusive) exhibiting Hamilton-Norwood type III vertex or type IV baldness were enrolled. Total hair counts, the primary efficacy measure, were obtained using fibre-optic microscopy and a computer-assisted, manual hair count method. Secondary measures of efficacy included assessments of hair diameter, as well as patient and investigator global assessments of improvement in hair growth. These were based on photographs of the scalp using both midline and vertex views. RESULTS: Hair count results showed a significant net increase in total visible hair counts for the 1% pyrithione zinc shampoo, the 5% minoxidil topical solution, and the combination treatment groups relative to the placebo shampoo after 9 weeks of treatment. The relative increase in hair count for the 1% pyrithione zinc shampoo was slightly less than half that for the minoxidil topical solution and was essentially maintained throughout the 26-week treatment period. No advantage was seen in using both the 5% minoxidil topical solution and the 1% pyrithione zinc shampoo. A small increase in hair diameter was observed for the minoxidil-containing treatment groups at week 17. Assessments of global improvements by the patients and investigator generally showed the benefit of 5% minoxidil. The benefit of the 1% pyrithione zinc shampoo used alone tended to be apparent only to the investigator. CONCLUSIONS: Hair count results show a modest and sustained improvement in hair growth with daily use of a 1% pyrithione zinc shampoo over a 26-week treatment period.

J Dermatol. 1991 Dec;18(12):714-9.

Hair growth on nude mice due to cyclosporin A.

Watanabe S, Mochizuki A, Wagatsuma K, Kobayashi M, Kawa Y, Takahashi H.

One of the most common dermatological side effects of cyclosporin A (CsA) is dose-dependent hypertrichosis. Similar hair growth was noted in nude mice in an attempt to increase the acceptance of human xenografts with CsA in the T-cell-deficient congenitally athymic nude (nu/nu) mice. The aim of the present study was to further investigate the stimulation of hair growth on nude mice not only by oral administration of CsA but also by topical and subcutaneous administration of CsA. Young BALB/c female nude mice were treated for 3 or 4 weeks with topical, oral, or subcutaneous applications of CsA dissolved in olive oil at various doses. The hair of CsA-treated mice appeared to grow from 7 days after the treatment, even at low doses. Induced hair growth was dose-dependent and became clearly obvious 3 weeks after the treatment. The stimulation of hair growth was not restricted to the site of topical application. The distribution of the new hair depended on the natural pattern of hair growth in the mice. However, there was no hair growth in the control mice which were given only olive oil. Histological examination revealed that there were no differences in the structures of skin and hair between the control and the CsA-treated mice. Furthermore, the number of hair follicles did not remarkably increase after CsA treatment. The hair growth in the CsA-treated mice stopped after cessation of the treatment and returned to the level of the control mice on day 14 after the end of the treatment. Subsequent retreatment with CsA resulted in further regrowth of the hair.(ABSTRACT TRUNCATED AT 250 WORDS)

Przegl Lek. 1995;52(6):311-4.L

[Examination of the significance of psychological factors in the etiology of alopecia areata. I. Examining Type A behavior]

Wygledowska-Kania M, Bogdanowski T.
I Katedry i Kliniki Dermatologii Slaskiej Akademii Medycznej w Katowicach.

We tested the significance of psychic factors in the etiology of alopecia areata by means of the assessment of the Behaviour Pattern A (BPA)–a particular way of regulation of the relations between the individual and the environment, the basis of which is a great need for achievement in the individual who realizes this need by means of domination and aggressiveness. The testing was carried out by means of the Polish Questionnaire for the Assessment of the Behaviour Pattern A in adults. 60 patients were tested (31 women and 29 men). The results were compared with the normative groups described by Wrzeœniewski. The frequency of the occurrence of the Behaviour Pattern A in the tested patients may indicate the connection of this type of regulation of relations between the individual and the environment with the susceptibility to this disease.

Hair Loss and Hair Loss Treatment

Genet Test. 2007 Summer;11(2):179-82.

The value of MLPA in Waardenburg syndrome.

Milunsky JM, Maher TA, Ito M, Milunsky A.

Waardenburg syndrome (WS) is an autosomal-dominant neurocristopathy characterized by sensorineural hearing loss, pigmentary abnormalities of the iris, hair, and skin, and is responsible for about 3% of congenital hearing loss. Point mutations in PAX3 have been identified in more than 90% of affected individuals with WS Type 1/WS Type 3. MITF point mutations have been identified in 10-15% of individuals affected with WS Type 2 (lacking dystopia canthorum). Multiplex ligation-dependent probe amplification (MLPA) is now a standard technology in the molecular genetics laboratory to detect copy number changes in targeted genes. We employed MLPA for PAX3 and MITF in a cohort of patients submitted with a diagnosis of WS1, 2 or 3 who were sequence negative for PAX3 and/or MITF. All coding exons of PAX3 and exons 1, 2, 3, and 10 of MITF were included in the MLPA assay. MLPA on 48 patients with WS 1 or 3 revealed 3 PAX3 whole gene deletions (2 WS1; 1 WS3), 2 PAX3 partial gene deletions [WS1, exon 1 and promoter (1st report); WS1, exons 5-9], and 1 partial MITF deletion ("WS1″, exons 3-10) (6/48 approximately 12.5%). MLPA on 41 patients with WS2 and 20 patients submitted with a diagnosis of either WS1 or WS2 revealed no copy number changes. The detection of both partial and whole gene deletions of PAX3/MITF in this clinical cohort increases the mutation detection yield by at least 6% and supports integrating MLPA into clinical molecular testing primarily for patients with WS1 and 3.