Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.

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FASEB J 2002 Dec;16(14):1967-9

Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.

We attempted establishing an in vitro coculture system by using human dermal papilla cells (DPCs) from androgenetic alopecia (AGA) and keratinocytes (KCs) to explore the role of androgens in hair growth regulation. Androgen showed no significant effect on the growth of KCs when they were cocultured with DPCs from AGA. Because the expressions of mRNA of androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this modified coculture, androgen significantly suppressed the growth of KCs by approximately 50%, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen stimulated the expression of TGF-beta1 mRNA in the cocultured DPCs. ELISA assays demonstrated that androgen treatment increased the secretion of both total and active TGF-beta1 in the conditioned medium. Moreover, the neutralizing anti-TGF-beta1 antibody reversed the androgen-elicited growth inhibition of KCs in a dose-dependent manner. These findings suggest that androgen-inducible TGF-beta1 derived from DPCs of AGA is involved in epithelial cell growth suppression in our coculture system, providing the clue to understand the paradoxical effects of androgens for human hair growth.

Ann Dermatol Venereol 2002 May;129(5 Pt 2):801-3

Androgenetic alopecia

Androgenetic alopecia (AGA) is the combined result of an androgen-dependent process and genetic transmission. These characteristics have mainly, if not exclusively, been demonstrated in men and perhaps improperly extended to women. When considering the androgen-dependent process, AGA must only be limited to the androgen receptor areas. In the scalp, these receptors have only been detected in the frontal and vertex areas but never in the temporal or the occipital areas. Male AGA exhibits these clinical features, whereas in women hair loss is rarely limited to this localization, even when large areas of hair loss often appear with age. It is now commonly accepted that male AGA is associated with an increase in 5 alpha reductase activity leading to an increase in local production of dihydrotestosterone. The mechanism by which the local dihydrotestosterone increase leads to hair follicle loss is not clearly demonstrated. Inhibition of cell proliferation in the dermal papilla and a vascular process based on the inhibition in local production of vascular endothelial growth factor (VEGF) have been proposed. The increase in 5 alpha reductase activity is genetic and depends on androgen receptor polymorphism, characterized by a decrease in the number of CAG sequences on the exon 1. Male AGA is associated with an insulin-resistant process and to a higher risk of polycystic ovary in the lineage. Therapeutically, this hormone-dependent process explains the well demonstrated efficacy of 5 alpha reductase inhibitors. In women, except in some rare cases, alopecia is diffuse and the mechanisms are different. Their origin is unknown, and probably ambiguous. Based on an association with Hashimoto's thyroiditis, an auto-immune origin could be suggested in some cases. Alopecia is unaffected by thyroid substitution. Pharmacological doses of oestrogens (pregnancy, contraception) have a beneficial effect on such alopecia, probably through different mechanisms: anti-androgen effect, increased VEGF, proliferative effect of dermal papilla cells. However, it is important to mention that the dermal papilla has an aromatase, particularly in the occipital area, the activity of which has not been assessed in female alopecia. In practice 5 alpha reductase inhibitors are ineffective in women. It is likely that the predominance observed in the frontal and vertex areas, occasionally in elderly women, is a result of the two combined disorders, the almost physiological androgen-dependent hair loss combined with diffuse loss. Pharmacological doses of oestrogens associated with anti-androgen progesterone-like agents are widely used with positive results, but not demonstrated by clinical trials.

Eur J Dermatol 2002 Jan-Feb;12(1):38-49

Long-term (5-year) multinational experience with finasteride 1 mg in the treatment of men with androgenetic alopecia.

BACKGROUND: Finasteride 1 mg (Propecia) is indicated for the treatment of men with androgenetic alopecia (male pattern hair loss, MPHL). However, the long-term (> 2 years) efficacy and safety of finasteride in this population has not been previously reported. Objectives. To assess the efficacy and safety of finasteride in men with MPHL compared to treatment with placebo over five years. METHODS: In two 1-year, Phase III trials, 1,553 men with MPHL were randomized to receive finasteride 1 mg/day or placebo, and 1,215 men continued in up to four 1-year, placebo-controlled extension studies. Efficacy was evaluated by hair counts, patient and investigator assessments, and panel review of clinical photographs. RESULTS: Treatment with finasteride led to durable improvements in scalp hair over five years (p 3/4 0.001 versus placebo, all endpoints), while treatment with placebo led to progressive hair loss. Finasteride was generally well tolerated and no new safety concerns were identified during long-term use. CONCLUSIONS: In men with MPHL, long-term treatment with finasteride 1 mg/day over five years was well tolerated, led to durable improvements in scalp hair growth, and slowed the further progression of hair loss that occurred without treatment.

Support Care Cancer. 2003 Jun;11(6):371-7. Epub 2003 Mar 21.

Scalp hypothermia to prevent chemotherapy-induced alopecia is effective and safe: A pilot study of a new digitized scalp-cooling system used in 74 patients.

GOALS. The aim of this study was to examine the efficacy and safety of a new digitized, controlled, scalp-cooling system to prevent chemotherapy-induced alopecia. METHOD. Seventy-four female cancer patients who received 13 varying chemotherapy regimens were included in a nonrandomized pilot study. The Digni 2-3 with Dignicap system consists of a refrigerator unit and a control unit integrated into a mobile cabinet and connected to a tight-fitting cooling cap. This system maintains a constant scalp temperature of +5 degrees C for many hours. In this study, 60 patients were treated for ovarian cancer with either taxane or epirubicin combination chemotherapy. Eight patients with Hodgkin's lymphoma, three with breast cancer, two with endometrial cancer, and one with sarcoma were also included. Photo documentation and patient assessment of hair loss and discomfort were performed. RESULTS. In anthracycline-treated patients, total prevention of hair loss was observed, whereas hair loss in paclitaxel/docetaxel-treated patients was minimal to none. The combination of anthracycline and taxane resulted in more hair loss, but only three of six patients used a wig. Scalp cooling was generally very well tolerated; only two of 74 patients discontinued use of the cold cap due to discomfort. No scalp metastases occurred over a median follow-up period of 15 months. CONCLUSIONS. The digitized, controlled, scalp-cooling system represents an effective and safe device that should be clinically evaluated in a randomized trial and in studies using other chemotherapy regimens to determine optimal temperatures and durations of cooling for maximal efficacy.

Natural Herbal Supplement: Hair Million

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DHEA has been suggested to provide numerous potential benefits. DHEA (or dehydroepiandrosterone) is converted into androgens (male hormones) or estrogens (female hormones) in the cells.

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