Hair Loss and hair loss treatment

BJU Int. 2002 Nov;90(7):682-5.

Hormonal treatment for male-pattern hair loss: implications for cancer of the prostate?

Anderson WR, Harris NM, Holmes SA.

Solent Department of Urology, St Mary’s Hospital, Portsmouth, UK.

Int J Clin Pract. 1999 Jan-Feb;53(1):50-3.

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

While the precise incidence of androgenetic alopecia ( male pattern hair loss ) 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.

Pharmacotherapy. 1993 Jul-Aug;13(4):309-25; discussion 325-9.

Finasteride: the first 5 alpha-reductase inhibitor
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Sudduth SL, Koronkowski MJ.
Program on Aging, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.

Finasteride is a synthetic 4-azasteroid that is a specific competitive inhibitor of 5 alpha-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone (DHT). It has no binding affinity for androgen receptor sites and itself possesses no androgenic, antiandrogenic, or other steroid hormone-related properties. It is well absorbed after oral administration, with absolute bioavailability in humans of 63% (range 34-108%). The mean time to maximum concentration is 1-2 hours, and it is approximately 90% plasma protein bound. The elimination half-life averages 6-8 hours. The agent is metabolized to a series of five metabolites, of which two are active and possess less than 20% of the 5 alpha-reductase activity of finasteride. Little is known about potential drug interactions, although they appear to be minimal and not clinically relevant. The drug is indicated for the treatment of symptomatic benign prostatic hyperplasia. Its efficacy in regression of prostate gland enlargement is rapid and predictable, although correlation with subsequent improvement in urinary flow and symptoms is highly variable. Dosages of 0.5-100 mg/day regress prostate enlargement; the recommended dosage is 5 mg once/day. Finasteride may hold promise for other DHT-mediated disorders such as acne, facial hirsutism, frontal lobe alopecia, and prostate cancer, but its use in these conditions remains investigational. The frequency of adverse drug events is low, with the most common side effects being impotence, decreased libido, and decreased volume of ejaculate. No reports of intentional overdose have been reported, and dosages of up to 80 mg/day for 3 months have been taken without adverse effect.

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hair loss and hair loss treatment

Dermatology. 1996;193(3):177-84.

The 5 alpha-reductase system and its inhibitors. Recent development and its perspective in treating androgen-dependent skin disorders.
Chen W, Zouboulis CC, Orfanos CE.

5 alpha-Reductase, the enzyme system that metabolizes testosterone into dihydrotestosterone, occurs in two isoforms. The type 1 isozyme is composed of 259 amino acids, has an optimal pH of 6-9 and represents the ‘cutaneous type’; it is located mainly in sebocytes but also in epidermal and follicular keratinocytes, dermal papilla cells and sweat glands as well as in fibroblasts from genital and non-genital skin. The type 2 isozyme is composed of 254 amino acids, has an optimal pH of about 5.5 and is located mainly in the epididymis, seminal vesicles, prostate and fetal genital skin as well as in the inner root sheath of the hair follicle and in fibroblasts from normal adult genital skin. The genes encoding type 1 and type 2 isozymes are found in chromosomes 5p and 2p, respectively, and each consists of 5 exons and 4 introns. During the last decade, several steroid analogues and non-steroid agents have been developed to interfere with 5 alpha-reductase activity. Finasteride, which has a higher affinity for the type 2 isozyme, is the first 5 alpha-reductase antagonist clinically introduced for treatment of benign prostate hyperplasia. The clinical evaluation of finasteride or other 5 alpha-reductase inhibitors in the field of dermatology has been very limited; in particular, those that selectively bind to type 1 isozyme (e.g. MK-386, LY191704) may be regarded as candidates for treatment of androgen-dependent skin disorders such as seborrhoea, acne, hirsutism and/or androgenetic alopecia.

J Androl. 1996 Sep-Oct;17(5):516-21.

Effect of finasteride on human testicular steroidogenesis.
Castro-Magana M, Angulo M, Fuentes B, Canas A, Sarrantonio M, Arguello R, Vitollo P.

We studied the testicular function and some androgen-mediated events in 22 males (16-30 years of age) with male pattern baldness that was treated with finasteride (10 mg once daily) for 2 years. Patients were evaluated every 3 months. Prostatic volume was determined in six subjects by endorectal ultrasound scans. Serum gonadotropin, prostate-specific antigen (PSA), and sex hormone levels were determined basally and periodically during the treatment period. Fourteen subjects underwent gonadal stimulation with human chorionic gonadotropin (hCG), and the gonadotropin response to gonadotropin releasing hormone (GnRH) was determined in eight subjects, prior to and after 2 years of therapy. Finasteride treatment resulted in an improvement in the male pattern baldness and prostatic shrinkage that was associated with an increase in serum testosterone levels (17.2 +/- 2.5 vs. 26.3 +/- 1.7 nmol/L) and a decrease in dihydrotestosterone (DHT) levels (1.45 +/- 0.41 vs. 0.38 +/- 0.10 nmol/L), causing a marked increase in that testosterone/DHT ratio. A significant increase in the serum levels of androstenedione (3.67 +/- 0.49 vs. 7.05 +/- 0.70 nmol/L) and estradiol (132 +/- 44 vs. 187 +/- 26 pmol/L) was also noted, whereas androstanediol glucoronide (33.3 +/- 6.4 vs. 10.7 +/- 4.5 pmol) and PSA (1.6 +/- 0.6 vs. 0.4 +/- 0.1 ng/ml) were significantly decreased. No changes in basal or stimulated levels of gonadotropin were observed. There was a significant increase in the testosterone response to hCG during finasteride therapy (delta: 16.7 vs. 35.5 nmol/L) that could be explained, at least in part, by the reduction of testosterone metabolism resulting from the blockage induced by finasteride. The decrease in the androstenedione to testosterone and estrone to estradiol ratios observed after hCG treatment, however, strongly suggests increased activity of the 17-ketosteroid reductase enzyme and an improvement of the testicular capacity for testosterone production.

J Dermatol Sci. 2001 Sep;27(1):7-13.

Topical application of cyclosporin A induces rapid-remodeling of damaged anagen hair follicles produced in cyclophosphamide administered mice.

Shirai A, Tsunoda H, Tamaoki T, Kamiya T.

Kyowa Hakko Kogyo Co., Ltd., Tokyo Research Laboratories

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Adult C3H mice which had either anagen IV or anagen VI hair follicles were given the anti-tumor drug cyclophosphamide, and cyclosporin A or minoxidil were topically applied to the mice daily from the 4th day after cyclophosphamide administration. In the mice that had anagen IV-hair follicles, 0.5% cyclosporin A induced very thick and long hairs after 21 days of cyclophosphamide administration, while vehicle and 1% minoxidil induced sparsely visible, short hairs. In the mice which received cyclosporin A, the injured hair follicles seemed to remodel themselves into intact anagen hair follicles and restart the production of hairs, instead of shifting to telogen. In the mice that had anagen VI-hair follicles at the time of cyclophosphamide administration, complete alopecia occurred within the first 7 days in all groups. After 14 days of cyclophosphamide administration, hair regrowth was observed in both the 0.5% cyclosporin A-group and the 1% minoxidil- group with the predominant effect over the vehicle. This study shows that anagen hair follicles respond to cyclophosphamide in different ways depending on their stages (IV and VI), and that the damaged anagen IV hair follicles have the potential of remodeling themselves, which is promoted by topical cyclosporin A administration.

Am J Clin Dermatol. 2000 May-Jun;1(3):151-8.

Management of androgenetic alopecia.

Bolduc C, Shapiro J.
Division of Dermatology, Health Sciences Centre, Vancouver Hospital, Vancouver, Canada.

Androgenetic alopecia is by far the most common cause of hair loss. It affects approximately 50% of men by the age of 50 and 20 to 53% of women by the age 50. Although it is a medically benign condition, it is a significant psychosocial issue for many patients. Various different treatment options are now available for androgenetic alopecia. The best treatment option for women with androgenetic alopecia Ludwig stage I and II is minoxidil 5% solution. If it is not effective after 1 year, antiandrogens can be tried, but there are no large studies showing their efficacy and they have considerable adverse effects. Also, for patients with alopecia that is unresponsive to treatment or with Ludwig stage III, hair transplantation can be offered if the occipital donor area is sufficient. For men, we always offer minoxidil or finasteride therapy and leave the choice of therapy to the patient. Some patients may prefer a systemic agent, whereas others may favor a topical agent. If the condition is not stabilized after 1 year or if the patient wants greater hair density, hair transplantation can be discussed. There have been tremendous advances in the treatment of hair loss in recent years and the future is very encouraging. As our knowledge of androgenetic alopecia pathophysiology increases, novel targeted treatments will potentially be developed.

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J Am Acad Dermatol. 1998 Oct;39(4 Pt 1):578-89.

Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group.

Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, Bergfeld W, Price VH, Van Neste D, Roberts JL, Hordinsky M, Shapiro J, Binkowitz B, Gormley GJ.
Department of Clinical Research, Merck Research Laboratories, Rahway, NJ 07065, USA.

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 5alpha-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 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. Treatment with placebo resulted in progressive hair loss. Patients’ self-assessment demonstrated that finasteride treatment slowed hair loss, increased hair regrowth, 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 Dermatol Surg Oncol. 1989 Jan;15(1):50-3.

Topical minoxidil used before and after hair transplantation.

Bouhanna P.

A 2% solution of topical minoxidil was applied on the recipient bald scalp of 16 patients aged 25 to 52 years with Hamilton classifications of androgenetic alopecia from III to VI. Therapy was begun 4 weeks before surgery, was interrupted for 3 weeks, and was started again and continued for 3 months. Four-millimeter donor grafts were inserted into 3.5-mm recipient sites. Follow-up utilizing macrophotography was done for 3 months on 4 grafts near a tattooed area. In 71% of the 64 grafts, partial or total hair is still growing without the shedding that usually occurs 2-4 weeks after transplantation. Topical minoxidil seems to be an adjunct for a better evolution of grafts after hair transplantation surgery.

Br J Dermatol. 1999 Sep;141(3):398-405.

The psychosocial consequences of androgenetic alopecia: a review of the research literature.
Cash TF.

Androgenetic alopecia is a common dermatological condition, with potentially adverse psychosocial sequelae. The present review critically examines scientific evidence concerning the effects of androgenetic hair loss on social processes and psychological functioning, as well as the psychosocial outcomes of medical treatments. Research confirms a negative but modest effect of visible hair loss on social perceptions. More importantly, androgenetic alopecia is typically experienced as a moderately stressful condition that diminishes body image satisfaction. Deleterious effects on self-esteem and certain facets of psychological adjustment are more apparent among women than men and among treatment-seeking patients. Various ‘risk factors’ vis-à-vis the psychological adversity of androgenetic alopecia are identified. Medical treatments, i.e. minoxidil and finasteride, appear to have some psychological efficacy. A conceptual model is delineated to explain the psychological effects of hair loss and its treatment. Directions for needed research are discussed. Strategies are presented for the clinical management of psychological issues among these patients.