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J Am Acad Dermatol 2002 Nov;47(5):795
Female pattern hair loss.
In this issue of the Journal (pages 733-9), Shum et al1 describe 4 female patients with increased androgens whose central scalp hair loss responded to finasteride. This is an important observation and one that highlights why the term androgenetic or androgenic alopecia, as used to describe the hereditary pattern balding of men, should be replaced with the term female pattern hair loss when applied to women.2 It is clear that only a small but distinct subset of women with central scalp pattern hair loss, such as the patients presented in the report by Shum et al, has signs of hyperandrogenism such as acne, hirsutism, and irregular periods with or without elevation of serum androgens. Therefore these women may have hair loss resulting from a different mechanism and may respond differently to treatments targeted at androgen blockade than women with a similar type of hair loss but without evidence of hyperandrogenism. Certainly these women with hyperandrogenemia may develop, in contradistinction to those without hyperandrogenemia, a Hamilton pattern of hair loss (male pattern baldness). Many of these women may, on more careful evaluation, have polycystic ovarian syndrome.
It is not surprising that a 5-reductase inhibitor such as finasteride, which has documented efficacy in men with androgenetic alopecia3,4 and has been shown to advantageously affect hirsutism,5,6 may cause hair growth in women with female pattern hair loss and hyperandrogenism. The fact that finasteride has not previously been shown to induce hair growth in postmenopausal women with “androgenetic alopecia”7 speaks for (1) adoption of different terminology for this type of hair loss in women and (2) separate evaluation of the different subgroups of women with female pattern hair loss as recently described,2 that is, early onset with and without hyperandrogenemia and late onset/postmenopausal with and without hyperandrogenemia. We should not be too quick to rule out efficacy of a potential therapeutic agent in all women with female pattern hair loss without first testing it in all the various subsets of women.
Clearly, finasteride may be an effective treatment for women with early-onset female pattern hair loss and hyperandrogenemia, but definitive results would require a large, well-controlled trial. Such a trial would likely necessitate inclusion of a “placebo” run-in phase with an oral contraceptive, both to protect these women of child-bearing potential from getting pregnant while taking a drug known to cause genital abnormalities in male fetuses and to rule out any effect from the oral contraceptive alone on female pattern hair loss (a study that needs to be conducted in any case). Anecdotal reports, such as that presented by Shum et al,1 should ignite interest in evaluating finasteride and other 5-reductase inhibitors, either type II or combination type I/II, in women with female pattern hair loss, a group of patients whose current treatment options are extremely limited.
J Dermatol Sci 2002 Aug;29(2):85-90
Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata.
Alopecia areata (AA) is an autoimmune inflammatory disease. However, little is known about the alterations in lipid peroxidation and antioxidant enzymes in the scalp of patients with AA. Therefore, the aim of this study was to investigate the status of oxidative stress in the scalp of patients with AA. We measured the levels of thiobarbituric acid reactive substances (TBARS) as lipid peroxidation status, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as antioxidant enzymes in the scalp of ten patients with AA and ten control subjects. The levels of TBARS in scalp of patients with AA (3654.1+/-621.2 nmol/g tissue) were significantly higher than those of controls (1210.2+/-188.8 nmol/g tissue) (P=0.002). The levels of SOD (134.8+/-23.8 U/g tissue) and GSH-Px (332.7+/-66.2 U/g tissue) in scalp of patients with AA were also significantly higher than those of controls (63.2+/-8.8 U/g tissue, 112.0+/-18.4 U/g tissue, respectively) (P=0.019, P=0.002, respectively). The mean levels of TBARS, SOD and GSH-Px in early phase of disease were increased 2-fold as compared with late phase of the disease. These results indicate that oxidative status is affected in AA. Lipid peroxidation and antioxidant enzymes may be involved in the pathogenesis of AA. Furthermore, we found high SOD and GSH-Px activities in the scalp of patient with AA. These high levels could not protect the patients against the reactive oxygen species, because lipid peroxidation could not be lowered in AA patients.
J Cutan Med Surg 2002 Jan-Feb;6(1):1-9
Effects of finasteride on apoptosis and regulation of the human hair cycle.
BACKGROUND: A number of studies have provided evidence that apoptosis is a central element in the regulation of hair follicle regression. In androgenetic alopecia (AGA), the exact location and control of key players in the apoptotic pathways remains obscure. OBJECTIVE: In the present study, we used a panel of antibodies and investigated the spatial and cellular pattern of expression of caspases and inhibitors of apoptosis (IAPs), such as XIAP and FLIP, in men with normal scalp and in men with AGA before and after 6 months of treatment with 1 mg oral finasteride treatment. METHODS AND RESULTS: Constitutive expression of caspases-1, -3, -8, and -9 and XIAP was detected predominantly within the isthmic and infundibular hair follicle area, basilar layer of the epidermis, and eccrine and sebaceous glands. AGA-affected tissues showed an increase in caspase (-1, -3, -6, -9) immunoreactivity with a concomitant decrease in XIAP staining. After 6 months of finasteride treatment, both caspases and XIAP were similar to levels exhibited by normal subjects. Immunoblot analysis was performed to determine antibody specificity and cellular expression of caspases. Purified populations of keratinocytes, melanocytes, dermal papilla, and dermal fibroblasts derived from human hair follicles were cultured in vitro and treated with 0.5 mm staurosporin. Time-course experiments revealed that processing of caspase-3 is a principal event during apoptosis of these hair cell types. CONCLUSION: These data suggest that alterations in levels of caspases and IAPs regulate hair follicle homeostasis. Moreover, finasteride appears to influence caspase and XIAP expression in hair follicle cells thus signaling anagen, active growth in the hair cycle.
Br J Dermatol. 2003 Jun;148(6):1205-11.
Female alopecia: the mediating effect of attachment patterns on changes in subjective health indicators.
Background The interrelationship between female alopecia and psychological disorders is complex, with a range of psychosocial consequences, but also antecedents. Psychosocial antecedents are to a large extent interpersonal and can be assumed to have a mediating effect on health care utilization and subjective health. Objectives To analyse whether changes in health-related quality of life (QoL) are mediated by relational or attachment styles and whether these styles are associated with a particular, dysmorphophobic type of alopecia. Methods Seventy-four women with androgenetic and diffuse alopecia underwent psychological assessment at the first consultation at a university clinic and at 2 months' follow-up. Attachment styles were evaluated by an observer rating scale. As a primary endpoint a disease-specific QoL instrument was employed. Results Findings indicated an association between patients with nonvisible hair loss and the ambivalent attachment style. Global clinical impressions and attachment indicators, e.g. attachment security and coping strategies, showed significant contributions in predicting changes in the QoL scales 'self-esteem' and 'emotions'. Conclusions These findings suggest that attachment security may be one of the underlying mechanisms mediating subjective health and that a specific attachment vulnerability can be identified in a subgroup of patients with female alopecia. Future studies will have to focus on the relevance of attachment patterns in the doctor-patient relationship and on psychotherapeutic interventions.
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