Hair loss in women with hyperandrogenism: four cases responding to finasteride.

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J Am Acad Dermatol 2002 Nov;47(5):733-9

Hair loss in women with hyperandrogenism: four cases responding to finasteride.

Oral finasteride, a type II 5 alpha-reductase inhibitor, has been shown to increase hair growth and slow progression of thinning in men with androgenetic or male pattern balding (Hamiliton type) but has no affect on hair growth in postmenopausal women with female pattern hair loss (Ludwig type). We describe 4 cases of hair loss with characteristics of both male and female patterns in women with hyperandrogenism in which finasteride has improved or stabilized the alopecia. Improved hair growth was seen after 6 months, 1 year, 2 years, and 2.5 years, respectively. The finding that finasteride treatment improves pattern hair loss in women with hyperandrogenism but does not affect those postmenopausal women with female pattern hair loss without hyperandrogenism supports the concept that not all types of female hair loss have the same pathophysiology.

Ann Dermatol Venereol 2002 May;129(5 Pt 2):831-6

Alopecia areata: update on therapy

The management of patients with alopecia areata is obviously not restricted to the prescription of a treatment inducing hair growth. It requires thorough exploration (history of hair loss, treatments and concomitant pathologies), detailed clinical examination of the integument and palpation of the thyroid. The patient must, systematically, be given a simple explanation of his/her pathology, thus avoiding any feelings of mystery, hopelessness and guilt and hence paradoxically turning alopecia into "just another disease", even if flares are unpredictable and cannot always be treated. Innovations over the past few years have not met dermatologist's expectations: in particular immunosuppressors administered locally have not shown efficacy in human, as opposed to animal models of alopecia areata. Moreover, we must remain critical and rigorous with regard to "false" innovations: several recent publications are, methodologically, open to criticism. Older products provide clear descriptions of their indications and use, and relatively standardize the therapeutic approach to alopecia. Some of them lead to hair growth on the treated area: localized immuno-therapy that in certain cases induces hair growth where other treatments have failed. PUVA-therapy, however, because of frequent relapses on withdrawal and the characteristic recurrence of alopecia, rapidly leads to the use of high cumulative doses; balneo-PUVA therapy is effective with lower doses (PUVA-turban). Recently, UVB TL01 has shown efficacy in anecdotal studies. Local corticosteroids; notably injectable and anthralin, an old treatment which remains a useful therapeutic approach in alopecia areata plaques and in the ophiasic forms in children and adults. Finally, among the available treatment arms, systemic corticosteroids still have a place in recent extended forms: although still under experimentation, the bolus appears efficient during the primary episodes of alopecia areata, when administered within the first three months

Eur J Immunogenet 2002 Feb;29(1):25-30

Genetic analysis of the interleukin-1 receptor antagonist and its homologue IL-1L1 in alopecia areata: strong severity association and possible gene interaction.

Alopecia areata is an inflammatory hair loss disease with a major genetic component. The presence of focal inflammatory lesions with perifollicular T-cell infiltrates reflects the importance of local cytokine production in the pathogenesis. In addition to its fundamental pro-inflammatory role, the interleukin-1 (IL-1) system has major effects on hair growth regulation in vitro, with the inhibitory actions of IL-1alpha and IL-1beta being opposed by the receptor antagonist IL-1ra. The novel interleukin-1 like molecule 1 (IL-1L1) which has greatest gene sequence homology with IL1RN, the gene encoding IL-1ra, is another potential IL-1 antagonist. In view of previous studies suggesting a significant role for IL1RN polymorphisms in the pathogenesis of autoimmune/inflammatory disease, we have analysed polymorphisms of IL-1ra (IL1RN+2018) and its homologue IL-1L1 (IL1L1+4734) in a case-control association study on 165 patients and a large number of matched controls. Homozygosity for the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our previous findings of significant association with the IL1RN variable number tandem repeat (VNTR). The results also revealed a novel association involving a polymorphism of the interleukin-1 receptor antagonist homologue IL1L1 at position + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734 alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata.

J Dermatol Sci. 2003 Apr;31(2):91-8.

The extract of Thujae occidentalis semen inhibited 5alpha-reductase and androchronogenetic alopecia of B6CBAF1/j hybrid mouse.

BACKGROUND: The conversion of testosterone to dihydrotestosterone; 5alpha-androstan-17beta-ol-3-one by 5alpha-reductase plays a crucial role in hair baldness and prostatomegaly. Recent approach showed specific inhibitors for 5alpha-reductase type 2 such as finasteride promoted hair growth in male pattern alopecia. OBJECTIVE: In order to search for effective medicinal plant extracts applied topically for androgenetic alopecia, we screened natural plant extracts having inhibitory activities of 5alpha-reductase type 2 and demonstrated its biological function in androgen-related animal models. METHODS: We evaluated the inhibition activities of numerous plant extracts by contact cell based metabolic method using a stable HEK 293 cell line expressing human 5alpha-reductase (type 2). To elucidate the biological activity in vivo, the Thujae occidentalis semen (TOS) extract was topically applied to fuzzy rat and androchronogenetic alopecia (AGA) mouse, respectively. The secreted sebum and the size of sebaceous glands of fuzzy rat were measured after 6 weeks. Also, after the topical treatment with TOS extract and androgen receptor antagonist (cyproterone acetate) simultaneously with subcutaneous injection of testosterone (1 mg/mice/day), hair loss patterns of female B6CBAF1/j hybrid mouse were observed. RESULTS: TOS extract showed higher inhibition activity of 5alpha-reductase type 2(IC(50) value=2.6 microg/ml) than that of gamma-linolenic acid, but lower than that of finasteride. When applied to fuzzy rat, the amount of sebum and sebaceous gland size decreased remarkably. In AGA model, alopecia degrees of two groups, treated with TOS extract (P<0.015) or cyproterone acetate (P<0.01), were lower than that of vehicle (propylene glycol:ethanol=7:3) and there was no difference between above two groups. CONCLUSION: We have demonstrated the inhibitory activity of TOS extract for 5alpha-reductase type 2 and its biological action in two animal models, suggesting that TOS extract would be used as an effective agent for male pattern baldness by modifying androgen conversion.

Since hair growth is a complicated biological process, modern science has yet to grasp a complete picture. A number of traditional and alternative therapeutic methods that include drugs, surgery, and suppelements have been developed to help those who are losing hair. Unfortunately, none of these approaches are perfect for all hair loss problems due to the complexity of the phenomenon and diverse nature of the causes underlying hair loss. Also, most of chemical drugs and hair transplantation surgeries are accompanied by undesirable side effects.

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