Gender differences in scalp hair growth rates are maintained but reduced in pattern hair loss compared to controls.

BACKGROUND: Hair loss is related to follicular density, programmed regrowth and hair productivity. OBJECTIVE: The dissatisfaction with hair growth in patients experiencing hair loss might be due to slower linear hair growth rate (LHGR). METHODS: LHGR and hair diameter was evaluated in Caucasian controls and patients with patterned hair loss employing the validated non-invasive, contrast-enhanced-phototrichogram with exogen collection. RESULTS: We evaluated 59,765 anagen hairs (controls 24,609, patients 35,156) and found thinner hairs grew slower than thicker hairs. LHGR in normal women was generally higher than in normal men. LHGR correlates with hair diameter (P < 0.006) and global thinning is associated with slower growth rates. Compared with hair of equal thickness in controls, subjects affected with patterned hair loss showed reduced hair growth rates, an observation found in both male and female patients. Males with pattern hair loss showed further reduction in growth rates as clinical severity worsened. However, sample size limitations prevented statistical evaluation of LHGR in severely affected females. LIMITATIONS: Caucasian ethnicity. CONCLUSION: In pattern hair loss, LHGR significantly contributes to the apparent decrease in hair volume in affected areas. In early onset, LHRG might have a prognostic value in females but not in males.

Nutritional factors and hair loss.

The literature reveals what little is known about nutritional factors and hair loss. What we do know emanates from studies in protein-energy malnutrition, starvation, and eating disorders. In otherwise healthy individuals, nutritional factors appear to play a role in subjects with persistent increased hair shedding. Hård, 40 years ago, demonstrated the importance of iron supplements in nonanaemic, iron-deficient women with hair loss. Serum ferritin concentrations provide a good assessment of an individual's iron status. Rushton et al. first published data showing that serum ferritin concentrations were a factor in female hair loss and, 10 years later, Kantor et al. confirmed this association. What level of serum ferritin to employ in subjects with increased hair shedding is yet to be definitively established but 70 micro g/L, with a normal erythrocyte sedimentation rate (< 10 mm/h), is recommended. The role of the essential amino acid, l-lysine in hair loss also appears to be important. Double-blind data confirmed the findings of an open study in women with increased hair shedding, where a significant proportion responded to l-lysine and iron therapy. There is no evidence to support the popular view that low serum zinc concentrations cause hair loss. Excessive intakes of nutritional supplements may actually cause hair loss and are not recommended in the absence of a proven deficiency. While nutritional factors affect the hair directly, one should not forget that they also affect the skin. In the management of subjects with hair loss, eliminating scaling problems is important as is good hair care advice and the need to explain fully the hair cycle. Many individuals reduced their shampooing frequency due to fear of losing more hair but this increases the amount seen in subsequent shampoos fuelling their fear of going bald and adversely affecting their quality of life.

Causes of hair loss and the developments in hair rejuvenation.

Hair is considered to be a major component of an individual's general appearance. The psychological impact of hair loss results in a measurably detrimental change in self-esteem and is associated with images of reduced worth. It is not surprising that both men and women find hair loss a stressful experience. Genetic hair loss is the major problem affecting men and by the age of 50, up to 50% will be affected. Initial attempts to regenerate the lost hair have centred on applying a topical solution of between 2% to 5% minoxidil; however, the results proved disappointing. Recently, finasteride, a type II 5alpha reductase inhibitor has been found to regrow a noticeable amount of hair in about 40% of balding men. Further developments in treatments have lead to the use of a dual type I and type II inhibitor where 90% of those treated regrow a noticeable amount of hair. In women the major cause of hair loss before the age of 50 is nutritional, with 30% affected. Increased and persistent hair shedding (chronic telogen effluvium) and reduced hair volume are the principle changes occurring. The main cause appears to be depleted iron stores, compromised by a suboptimal intake of the essential amino acid l-lysine. Correction of these imbalances stops the excessive hair loss and returns the hair back to its former glory. However, it can take many months to redress the situation.

Androgenetic alopecia in men: the scale of the problem and prospects for treatment.

While the precise incidence of androgenetic alopecia is unknown, it is universally acknowledged to be the most common hair problem in men. Balding is generally associated with ageing; consequently, the desire to prolong a youthful appearance inevitably leads to demands for effective treatments. Further, changing attitudes in modern society have resulted in people becoming concerned about their appearance and less tolerant about conditions that might be alleviated by medical intervention. The importance of hair loss upon quality of life has been underestimated by the medical profession. Clinicians failing to accept hair loss as an important medical problem ignore the real distress suffered by a significant proportion of those affected. New options for treatment that selectively target the metabolic pathways involved in the balding process are showing promise. The first generation of such drugs, Propecia, is now available in some countries and other molecules are currently under development.

Topical FK506: a potent immunotherapy for alopecia areata? Studies using the Dundee experimental bald rat model.

We elected to examine the efficacy of the topically applied immunosuppressive agent FK506 (Prograf) in the treatment of alopecia areata (AA) using the Dundee experimental bald rat (DEBR) model. Thirty lesional DEBR rats were allocated to five groups of six. Group 1 rats received 0.1 mL of a 0.25% solution of FK506 within a 2 x 2 cm marked area on one bald flank twice a week (125 micrograms FK506/cm2 per week) for 8 weeks, while the contralateral flank was left untreated. In group II, 0.05 mL of a 0.1% solution of FK 506 was applied 5 days per week on one flank (62.5 micrograms FK506/ cm2 per week) and control vehicle to the opposite flank for 8 weeks. Group III rats were treated as in group II except that drug and vehicle were applied twice a week (25 micrograms FK506/cm2 per week) for 4 weeks. A positive control group received orally administered cyclosporin A (CsA) (10 mg/kg daily) for 8 weeks and a further group was left untreated. Rats were regularly examined and photographed with skin biopsies taken from groups II and III. All FK 506-treated rats regrew hair at the site of drug application within 14-21 days. Growth continued for 3 weeks beyond termination of treatment after which gradual hair loss was observed. No hair growth was seen as a result of vehicle application and hair loss continued on untreated areas and in the untreated control group. Immunohistology revealed a drastic reduction in the follicular inflammatory infiltrate at the site of the FK506 application. The oral CsA group responded by simultaneous regrowth of hair over the whole body. Our findings suggest that FK506 may have considerable potential as a topical treatment for AA.

Comparative evaluation of scalp hair by phototrichogram and unit area trichogram analysis within the same subjects.

Quantitative evaluation of scalp hair requires techniques that are reproducible. The unit area trichogram is such a method but is unsuitable for large-scale clinical trials. An alternative may be the phototrichogram--a non-plucking, non-invasive method. Hair variables were evaluated in 12 Caucasian subjects employing both methods. The mean value for total hair density was significantly underestimated by the phototrichogram (181 versus 237 hairs/cm2); however, no significant difference was found between this phototrichogram value and the number of non-vellus hairs/cm2. Estimates for the percentage of anagen hairs were similar with both methods. Hair diameters from the phototrichogram were too unreliable to be of any practical use. Analysis of the individual hair data revealed that light hair was much more difficult to evaluate than dark hair. Consequently, Caucasian subjects with light hair or dark skin subjects with dark hair should be excluded from studies employing phototrichograms.

Management of hair loss in women.

Hair loss in otherwise healthy women presents several challenges for the clinician. The first is to identify the cause, which may be complicated by two or more secondary factors; the second is to find effective treatments; and the third is to establish requirements for long-term management. An optimal hair growth potential is considered to exist when specific parameters for biochemical variables are operating. These include red blood cell and serum folate concentrations within the normal range, serum vitamin B12 levels between 300 and 1000 ng/L, hemoglobin levels greater than 13.0 g/dL, and serum ferritin concentrations of 70 ng/mL or greater. The two predominant disturbances, diffuse androgen-dependent alopecia and chronic telogen effluvium, both require months of treatment before the benefits can be seen. During this time several follow-up investigations and reassuring consultations must occur. Current systemic antiandrogen regimens are highly effective, but the prospect of long-term therapy, possibly for life, is daunting. For some patients there is no systemic choice and topical treatment is the only option. Minoxidil is the only topical preparation currently licensed, but with no quantitative long-term data available, assessing its value in the long-term treatment of androgen-dependent alopecia is difficult.

The importance of adequate serum ferritin levels during oral cyproterone acetate and ethinyl oestradiol treatment of diffuse androgen-dependent alopecia in women.

OBJECT: To evaluate the treatment with cyproterone acetate and ethinyl oestradiol of diffuse androgen-dependent alopecia in women. DESIGN: Twenty women were treated for a period of 12 months in a reverse sequential regimen employing cyproterone acetate (CPA, 50 mg once daily from Day 5 to Day 15) and ethinyl oestradiol (EE2, 30 micrograms once daily from Day 5 to Day 24 of the menstrual cycle), and 20 were left untreated and acted as controls. Half of each group had serum ferritin concentrations above or below 40 micrograms/l. PATIENTS: Forty Caucasian premenopausal women aged between 18 and 47 years, presenting with diffuse androgen-dependent alopecia, were enrolled into this study. MEASUREMENTS: Hair variables were assessed initially by the unit area trichogram and again in the same sites 12 months later. Biochemical investigations were performed before treatment and after 3, 6, and 12 months. RESULTS: In the treated group, a significant (P less than 0.01) mean increase in total hair density (hair/cm2) and meaningful hair density (non-vellus hair/cm2) was found in patients in whom the serum ferritin was above, but not below 40 micrograms/l. However, in the control group a significant (P less than 0.05) mean decrease in total hair density and meaningful hair density was observed after 12 months. No correlation between serum ferritin levels and the degree of hair loss within this group could be established. CONCLUSION: Patients treated with the anti-androgen cyproterone acetate and ethinyl oestradiol respond best when serum ferritin is above 40 micrograms/l.

Natural progression of male pattern baldness in young men.

Twenty-six men who presented with male pattern baldness (androgen-dependent alopecia), were quantitatively evaluated for scalp hair variables and compared with 13 age-matched controls. Compared to controls, significant mean differences for hair variables were found in the frontal-vertex area, while in the occipital area, a reduction in total hair density (hairs/cm2) was the only significant (P less than 0.05) finding. A large proportion (48.5%) of meaningful hair (non-vellus hair) was less than or equal to 40 mm in length, yet had diameters similar to hairs growing much longer. In controls, these hairs accounted for only 12.2% of the total population. Compared to baseline, mean values from the frontal-vertex area of subjects with androgen-dependent alopecia were significantly lower for total hair density, meaningful hair density (non-vellus hairs/cm2) and percentage of hair in the anagen growth phase, 12 and 24 months later. During this time, total hair density decreased by 6.5% after 12 months and by 11.9% after 24 months. Similarly, meaningful hair density declined at 12 months by 10.8% and by 22.7% after 24 months. No change in any hair variable was detected in controls after 12 or 24 months. Our findings suggest that medications capable of maintaining the existing hair population should be regarded as effective treatments for this condition. Left untreated androgen-dependent alopecia progressively deteriorates. The induction of non-vellus hairs less than or equal to 40 mm in length to grow longer, would substantially improve the aesthetic profile without the need to generate new hair.

Biochemical and trichological characterization of diffuse alopecia in women.

One hundred women who presented with diffuse alopecia, were quantitatively evaluated for hair variables and compared with 20 controls. Fifty were selected for biochemical and haematological investigations, 44 of whom also underwent endocrine evaluation. Compared to controls, significant changes in hair values were found in the frontal area of all subjects, while 84% had significant changes in the occipital area. A biphasic distribution of hair diameter was evident in subjects who had percentages of vellus hair and telogen hair less than or equal to 30 mm in length that were above the control ranges. No significant difference between the mean hormonal values of women with diffuse alopecia and controls could be found. No correlation between hair values and individual or combined hormonal levels could be established. In 18 subjects (40.9%) hormonal values were within the control ranges and these apparently normal findings were often associated with adverse hair profiles. A raised dihydrotestosterone was found in 13 subjects (29.5%) and was the most frequently elevated androgenic finding. Seventeen (34.0%) had changes in iron metabolism, while in 36 (72.0%) serum ferritin levels were below the lowest control value. All had a decrease in the percentage of hair in the anagen growth phase compared to controls. The hair changes were similar to those observed in genetic hair loss in men, a proven androgen-dependent condition. We propose that diffuse androgen-dependent alopecia is the appropriate name to describe this condition in these women.

Reduced serum vitamin B12 levels during oral cyproterone-acetate and ethinyl-oestradiol therapy in women with diffuse androgen-dependent alopecia.

In a group of healthy, non-vegetarian females currently being treated for diffuse androgen-dependent alopecia with 50 or 100 mg of oral cyproterone acetate for 11 days and 30 or 40 micrograms of ethinyl oestradiol for 20 days of the menstrual cycle, significant decreases in mean serum vitamin B12 (P less than 0.0001), haemoglobin (P less than 0.003) and haematocrit (P less than 0.004) values, were observed after 6 months. Serum folic acid, red-cell folate and mean cell volume remained unchanged within the normal range during this time. All patients responded to oral cyanocobalamin, or intramuscular injections of hydroxocobalamin. In patients with baseline serum vitamin B12 levels below 350 ng/l, we would suggest prophylactic cyanocobalamin concurrent with cyproterone-acetate-ethinyl-oestradiol (CPA EE2) therapy. Studies involving other dose regimens of CPA EE2 (Dianette) or cyproterone acetate alone (Androcur, Cyprostat), may require evaluation of the vitamin B12 status if treatment is to be given for periods of longer than 3 months.

Amino-acid composition in trichorrhexis nodosa.

Trichorrhexis nodosa is a common shaft defect affecting scalp hair. Two-hundred scalp hairs exhibiting trichorrhexis nodosa were obtained from two normal females; samples were prepared from proximal shaft, pre-nodule, nodule and post-nodule sections and analysed for their respective amino-acid compositions. Significant reductions in cystine (P less than 0.001) of the pre-nodule, nodule and post-nodule sections, which decreased by 17.2%, 19.8% and 14.3%, respectively, and an increase in the acidic amino acids (P less than 0.03) were found, compared to values obtained from proximal shaft of the same hairs. The majority of nodules occurred within the last 10% of the shaft, and the similarity in amino-acid compositions between pre-nodule, nodule and post-nodule sections suggests that 'weathering' is the major factor influencing nodule occurrence. It is postulated that nodule formation requires a specific degree of exposure to 'weathering' together with a reduction in cuticle cell coverage. It is suggested that an initial structural defect, created by a change in the DNA coding for a cuticle polypeptide fraction, could be responsible for the selective and isolated presentation of the nodule within a 'weathered' section of hair shaft.

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

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.