Hair Loss and Hair Regrowth

Tohoku J Exp Med. 1977;121(1):1

Histochemical quantification of glucose-6-phosphate dehydrogenase activity in human hair follicles.

Sasai Y, et al

Glucose-6-phosphate dehydrogenase activity was studied in hair follicles from both the bald and hairy regions of the scalp of 5 patients with male pattern alopecia by the application of the method of Lineweaver-Burk to the histochemistry and by the fluorometric method of Lowry. In vitro experiment showed that the incubation time necessary for yielding a certain amount of formazan is related to the amount of enzyme present. In the case of section experiment, the time required for the first appearance of formazan deposition in the tissue at various substrate concentrations was plotted against the reciprocal of the substrate concentration. The data obtained by this method seem to be consistent with the data by the fluorometric method.

Br J Dermatol. 1997 Oct;137(4):491-7.

Topical FK506: a potent immunotherapy for alopecia areata?

McElwee KJ, et al

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 hair loss 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.

Science. 1965 Jun 11;148(3676):1471
Hereditary Absence of Sebaceous Glands in the Mouse.
Gates AH, Karasek M.

An autosomal recessive mutation, characterized by an absence of sebaceous glands, and by hyperkeratosis, alopecia (hair loss), and single (rather than the usual multiple) hair-follicle units, has occurred spontaneously in the BALB/c strain of mouse. Studies in which reciprocal transplantations of skin were made between normal and mutant mice suggest that some diffusible substance(s) synthesized by normal skin can stimulate hair regrowth and alleviate the hyperkeratosis characteristic of the skin syndrome.

Int J Dermatol. 1992 Dec;31(12):858-9.
Hormonal status in postmenopausal androgenetic alopecia.Georgala S, et al

The development of androgenetic alopecia is thought to be caused by increased androgen action on hair follicles with menopause. Testosterone, estradiol and sex hormone binding globulin (SHBG) serum levels were determined in ten postmenopausal women with androgenetic alopecia and in ten sex and age matched healthy controls. No statistically significant differences were found in the hormone levels between the patients and the controls. These findings suggest that a genetically determined functional alteration of androgen receptors and/or a metabolic disturbance may exist in the hair follicle keratinocytes in androgenetic alopecia or pattern hair loss.

PMID: 1478763

Ann N Y Acad Sci. 1991 Dec 26;642:376-83; discussion 383-4.

Steroid chemistry and hormone controls during the hair follicle cycle.
Sawaya ME.

Human hair follicles contain several steroid enzymes capable of transforming weak androgens, such as dehydroepiandrosterone, into more potent target tissue androgens, such as testosterone and dihydrotestosterone. Kinetic constants have been evaluated for the 3-alpha, 3-beta, and 17-beta hydroxysteroid dehydrogenase enzymes, 5a-reductase, and the aromatase enzyme in isolated human HF from scalp of men and women with androgenetic alopecia or pattern hair loss. The apparent Km values did not differ for each enzyme whether present in bald, receded HF or thick, anagen HF of men or women. However, levels of specific activity varied greatly in the frontal versus occipital HF analyzed. The androgen receptor content and activation factors also differ between men and women. The steroid mechanisms influencing AGA in men and women may be similar, but differences in the specific activity/amounts of enzymes, receptors, and activation factors differ between men and women. These findings may explain the varied clinical presentations of men and women with AGA, and may shape treatment options for the future.

Development. 2003 Nov;130(21):5241-55.

Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis.

Braun KM, et al

Mammalian epidermis is maintained by stem cells that have the ability to self-renew and generate daughter cells that differentiate along the lineages of the hair follicles, interfollicular epidermis and sebaceous gland. As stem cells divide infrequently in adult mouse epidermis, they can be visualised as DNA label-retaining cells (LRC). With whole-mount labelling, we can examine large areas of interfollicular epidermis and many hair follicles simultaneously, enabling us to evaluate stem cell markers and examine the effects of different stimuli on the LRC population. LRC are not confined to the hair follicle, but also lie in sebaceous glands and interfollicular epidermis. LRC reside throughout the permanent region of the hair follicle, where they express keratin 15 and lie in a region of high alpha6beta4 integrin expression. LRC are not significantly depleted by successive hair regrowth cycles. They can, nevertheless, be stimulated to divide by treatment with phorbol ester, resulting in near complete loss of LRC within 12 days. Activation of Myc stimulates epidermal proliferation without depleting LRC and induces differentiation of sebocytes within the interfollicular epidermis. Expression of N-terminally truncated Lef1 to block beta-catenin signalling induces transdifferentiation of hair follicles into interfollicular epidermis and sebocytes and causes loss of LRC primarily through proliferation. We conclude that LRC are more sensitive to some proliferative stimuli than others and that changes in lineage can occur with or without recruitment of LRC into cycle.

J Am Acad Dermatol. 1987 Feb;16(2 Pt 1):392-4

Effect of time on male pattern baldness.

Epstein E.
PMID: 3819080

hair loss blog

J Dermatol Surg Oncol. 1979 May;5(5):407-11.

Epilation by electrocoagulation: factors that result in regrowth of hair.

McKinstry CT, Inaba M, Anthony JN.

From our experience, the most important requirement for permanent epilation by electrocoagulation is not only to destroy hair bulbs, but also to destroy the isthmal regions of hair follicles and the sebaceous glands.

J Cutan Pathol. 1975;2(5):240-5.

Cellular activity in the dermis surrounding the hair bulb in alopecia areata.

Pierard GE, De la Brassinne M.

The metabolic activity of the cells in the connective tissue surrounding the hair bulb has been studied by radioautography in alopecia areata and in normal scalp, using in vitro incorporation of tritiated thymidine, uridine, histidine, leucine and proline. In alopecia areata, the hair bulbs are blocked in the anagen IV stage and DNA, RNA and protein synthesis are restrained. Cells in the papilla, as well as the cellular infiltrate, display a very low rate of metabolic activity. During regrowth in alopecia areata, the activity of endothelial cells is increased in the papillary and peribulbar layers before DNA, RNA and protein synthesis are restored in the epithelial cells of the hair bulb. The dermal and epithelial labelling patterns eventually reach levels comparable to those observed in an induced anagen IV state of a normal scalp. It is concluded that the progression from anagen IV to a further stage represents a critical period in the growth of hair that would closely depend upon an adequate metabolic function of the connective tissue. It is impaired in alopecia areata.

J Drugs Dermatol. 2004 Jul-Aug;3(4):363-4.Links
5 alpha-reductase and finasteride in pattern alopecia and acne.Burkhart CG, Burkhart CN.
PMID: 15303779

Pattern hair loss treatment with finasteride

J Drugs Dermatol. 2004 Jul-Aug;3(4):363-4.Links
5 alpha-reductase and finasteride in pattern alopecia and acne.Burkhart CG, Burkhart CN.
PMID: 15303779

Pattern hair loss treatment with finasteride

Kaohsiung J Med Sci. 2002 Aug;18(8):379-85.

Finasteride in the treatment of Taiwanese men with androgenetic alopecia: a 12-month open-label study.
Lin JH, Chen WC.

Finasteride 1 mg/day is effective in the treatment of androgenetic alopecia (AGA) or male pattern hair loss. Our open-label study assessed the efficacy and safety of finasteride for the treatment of Taiwanese men with hair loss. We enrolled 34 Taiwanese men (aged 18-40 yr) with AGA of modified Norwood/Hamilton scale (MNHS) grade II-V. In investigator assessments at 12 months, five of 21 subjects (23.8%) had two-grade improvement in MNHS grade and 12 of 21 subjects (57.1%) had one-grade improvement; the others remained at the same grade. In global photographic evaluation, five of 31 subjects (15.1%) had observable hair growth at 6 months and 11 of 21 subjects (52.4%) had observable hair growth at 12 months. Patient self-assessment of hair growth was favorable across all questions in the treatment course, more significantly at 12 months than at 6 months; nine of 21 subjects (42.9%) were satisfied with their overall appearance at 12 months. Serum prostate specific antigen levels had decreased by 23.4% at 12 months. Adverse effects, including abnormal liver function (5/34), were minimal, and the causal relationship with finasteride could not be established. Thus, in Taiwanese men with AGA, finasteride 1 mg/day for 1 year slowed the progression of hair loss and increased hair regrowth.

Am Fam Physician. 2003 Jul 1;68(1):93-102.

Common hair loss disorders.

Springer K, Brown M, Stulberg DL.

Hair loss (alopecia) affects men and women of all ages and often significantly affects social and psychologic well-being. Although alopecia has several causes, a careful history, dose attention to the appearance of the hair loss, and a few simple studies can quickly narrow the potential diagnoses. Androgenetic alopecia, one of the most common forms of hair loss, usually has a specific pattern of temporal-frontal loss in men and central thinning in women. The U.S. Food and Drug Administration has approved topical minoxidil to treat men and women, with the addition of finasteride for men. Telogen effluvium is characterized by the loss of "handfuls" of hair, often following emotional or physical stressors. Alopecia areata, trichotillomania, traction alopecia, and tinea capitis have unique features on examination that aid in diagnosis. Treatment for these disorders and telogen effluvium focuses on resolution of the underlying cause.

J Am Acad Dermatol. 1999 Jun;40(6 Pt 1):930-7

Finasteride in the treatment of men with frontal male pattern hair loss.

Leyden J, et al

BACKGROUND: Finasteride, a specific inhibitor of type II 5alpha-reductase, decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss. OBJECTIVE: This study evaluated the efficacy of finasteride 1 mg/day in men with frontal (anterior/mid) scalp hair thinning. METHODS: This was a 1-year, double-blind, placebo-controlled study followed by a 1-year open extension. Efficacy was assessed by hair counts (1 cm2 circular area), patient and investigator assessments, and global photographic review. RESULTS: There was a significant increase in hair count in the frontal scalp of finasteride-treated patients, as well as significant improvements in patient, investigator, and global photographic assessments. Efficacy was maintained or improved throughout the second year of the study. Finasteride was generally well tolerated. CONCLUSION: In men with hair loss in the anterior/mid area of the scalp, finasteride 1 mg/day slowed hair loss and increased hair regrowth.

Postgrad Med. 1989 May 1;85(6):52-8, 67-73, 77.

Hair loss. What causes it and what can be done about it.
Burke KE.
Department of Medicine, Cabrini Medical Center, New York City.

Although both men and women throughout history have seen hair as an important aspect of appearance, it is especially important today, in light of the great emphasis on youthfulness. A new interest in preventing baldness has been stimulated recently by the publicity given to certain products now under investigation that have shown an ability to retard or reverse male pattern baldness in certain individuals. Hair loss has many possible causes, such as systemic diseases, infections, toxic agents, and hormone imbalances. Treatment of the underlying disorder alleviates the shedding of hair. Balding may also be a normal physiologic occurrence in women taking oral contraceptives or after parturition and in men with male pattern baldness. The latter can be treated topically with progesterone or minoxidil. Minoxidil has been studied extensively and has been shown to improve balding at the vertex of the scalp, particularly in young men who have only begun to lose hair. Cases of more extensive male pattern baldness and baldness secondary to scarring can be treated effectively with surgical procedures.

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Dermatol Surg. 2000 Aug;26(8):801-5.

Hair-grafting in between existing follicles in patients with early pattern baldness.

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Brandy DA.

University of Pittsburgh Medical Center, PA, USA.

BACKGROUND: When using follicular hair transplantation on patients with early male or female pattern baldness, there can be significant trauma to preexisting hair follicles. This becomes especially important in view of the fact that finasteride and minoxidil can stop or slow hair loss. OBJECTIVE: To develop a system that averts damage to preexisting hair follicles in patients with early male or female pattern baldness. METHODS: A Lutex headlight (2.5-3.5x loupe magnification system) is used to make 1.0-1.5 mm spear incisions in between the hair follicles in patients with early male or female pattern balding. Magnification is also utilized during the graft cutting and placement phases of the operation. RESULTS: This headlight-loupe magnification system has dramatically decreased the amount of permanent hair loss and anagen effluvium on 144 patients with early male and female pattern baldness. With less permanent hair loss there is greater density observed with each progressive session. CONCLUSION: Hair surgeons now have a method to consistently and significantly minimize the amount of damage to preexisting hair follicles in patients in the early stages of male and female pattern baldness. This becomes even more important in light of the fact that more and more patients are using finasteride or minoxidil to stop the thinning process. Existing hairs can therefore be preserved.

Exp Gerontol. 2002 Aug-Sep;37(8-9):981-90

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Molecular mechanisms of androgenetic alopecia.

Trüeb RM.

Androgenetic alopecia (AGA) is hereditary and androgen-dependent, progressive thinning of the scalp hair that follows a defined pattern. While the genetic involvement is pronounced but poorly understood, major advances have been achieved in understanding principal elements of the androgen metabolism involved: androgen-dependent processes are predominantly due to the binding of dihydrotestosterone (DHT) to the androgen receptor (AR). DHT-dependent cell functions depend on the availability of weak androgens, their conversion to more potent androgens via the action of 5 alpha-reductase, low enzymatic activity of androgen inactivating enzymes, and functionally active AR present in high numbers. The predisposed scalp exhibits high levels of DHT, and increased expression of the AR. Conversion of testosterone to DHT within the dermal papilla plays a central role, while androgen-regulated factors deriving from dermal papilla cells are believed to influence growth of other components of the hair follicle. Current available treatment modalities with proven efficacy are oral finasteride, a competitive inhibitor of type 2 5 alpha-reductase, and topical minoxidil, an adenosine-triphosphate-sensitive potassium channel opener which has been reported to stimulate the production of vascular endothelial growth factor in cultured dermal papilla cells. Since the clinical success rate of treatment of AGA with modulators of androgen metabolism or hair growth promoters is limited, sustained microscopic follicular inflammation with connective tissue remodeling, eventually resulting in permanent hair loss, is considered a possible cofactor in the complex etiology of AGA.

Exp Gerontol. 2002 Aug-Sep;37(8-9):981-90

Molecular mechanisms of androgenetic alopecia.

Trüeb RM.

Androgenetic alopecia (AGA) is hereditary and androgen-dependent, progressive thinning of the scalp hair that follows a defined pattern. While the genetic involvement is pronounced but poorly understood, major advances have been achieved in understanding principal elements of the androgen metabolism involved: androgen-dependent processes are predominantly due to the binding of dihydrotestosterone (DHT) to the androgen receptor (AR). DHT-dependent cell functions depend on the availability of weak androgens, their conversion to more potent androgens via the action of 5 alpha-reductase, low enzymatic activity of androgen inactivating enzymes, and functionally active AR present in high numbers. The predisposed scalp exhibits high levels of DHT, and increased expression of the AR. Conversion of testosterone to DHT within the dermal papilla plays a central role, while androgen-regulated factors deriving from dermal papilla cells are believed to influence growth of other components of the hair follicle. Current available treatment modalities with proven efficacy are oral finasteride, a competitive inhibitor of type 2 5 alpha-reductase, and topical minoxidil, an adenosine-triphosphate-sensitive potassium channel opener which has been reported to stimulate the production of vascular endothelial growth factor in cultured dermal papilla cells. Since the clinical success rate of treatment of AGA with modulators of androgen metabolism or hair growth promoters is limited, sustained microscopic follicular inflammation with connective tissue remodeling, eventually resulting in permanent hair loss, is considered a possible cofactor in the complex etiology of AGA.

Eur J Dermatol. 2000 Jul-Aug;10(5):410-7.

Current understanding of androgenetic alopecia. Part II: clinical aspects and treatment.

Hoffmann R, Happle R.

The first signs of androgenetic alopecia (AGA) may start to develop with the onset of puberty. The prevalence of progressive AGA approaches 50% of Caucasian men and women beyond the age of 40; whereas in Asian, native American and African-American men the prevalence is lower and AGA is less severe. Only exceptionally laboratory tests or scalp biopsies are needed to confirm the diagnosis. Therefore the clinical assessment of AGA is largely a matter of common sense and practice. The loss of hair is often trivialised, but hair loss may have profound effects on a patient's well-being and quality of life. The treatment of AGA is obscured by myths. Many products or procedures are advertized for the treatment of AGA such as vitamins, trace elements, exotic herbs, amino acids, "soft laser", scalp massage, etc. Most of these techniques or substances have never been verified in sound clinical trials. Because of the psychosocial impact of hair loss, however, it is important to explain to patients what they may expect in terms of continuing hair loss, and that response to any therapy may be slow and may include hair regrowth or only retardation of further thinning. The aim of AGA treatment is to reverse or to stabilize the process of HF miniaturization and with this overview we summarize the present treatment modalities for both men and women.