|Chronic caffeine intake increases androgenic stimuli, epithelial cell proliferation and hyperplasia in rat ventral prostate. Coffee intake has been associated with a low risk of developing cancer, including prostate cancer, which is one of the most commonly diagnosed cancer in men. However, few studies have evaluated the chronic effects of caffeine, which is the most abundant methylxanthine in coffee, on prostate morphology and physiology. In the present study, we investigated the effects of chronic, low-dose caffeine intake on rat prostate morphology from puberty to adulthood. Five-week-old male Wistar rats were randomized into two experimental groups: caffeine-treated (20 ppm in drinking water, n = 12) and control (n = 12). The ventral and dorsolateral prostates were dissected, weighted and submitted to morphological, morphometrical and immunohistochemical analysis of cellular proliferation, apoptosis and androgen receptor (AR) tissue expression. The testosterone (T) and dihydrotestosterone (DHT) concentrations were measured in the plasma. Our results show that caffeine intake increased the concentrations of T and DHT, organ weight, epithelial cell proliferation and AR tissue expression in the ventral prostatic lobe. All the ventral prostates from the caffeine-treated animals presented various degrees of epithelial and stromal hyperplasia. Our results suggest that chronic caffeine intake from puberty increases androgenic signalling and cell proliferation in the rat prostate gland and can be related to the development of benign prostatic hyperplasia.
|Diffuse alopecia areata is associated with intense inflammatory infiltration and CD8+ T cells in hair loss regions and an increase in serum IgE level. Background: Mechanism leading to an abrupt hair loss in diffuse alopecia areata (AA) remains unclear. Aims: To explore the characteristics of diffuse AA and possible factors involved in its pathogenesis. Methods: Clinical and laboratory data of 17 diffuse AA patients and 37 patchy AA patients were analyzed retrospectively. Serum IgE level was evaluated in all diffuse and patchy AA patients, as well as 27 healthy subjects without hair loss to serve as normal control. Univariate analysis was performed using Fisher's exact test and Wilcoxon rank-sum test. Associations between inflammatory cell infiltration and laboratory values were analyzed using Spearman rank correlation test. Results: The mean age of patients with diffuse AA was 27 years with a mean disease duration of 1.77 months. All of them presented in spring or summer with an acute onset of diffuse hair loss preceded by higher incidence of scalp pruritus. Although no statistically significant difference on the incidence of atopic disease among three groups has been found, serum IgE level in diffuse AA was higher than that in healthy controls, but was comparable to that in patchy AA group. Histopathology of lesional scalp biopsies showed more intense infiltration comprising of mononuclear cells, eosinophils, CD3 + , and CD8 + T cells around hair bulbs in diffuse AA group than in patchy AA group. Moreover, IgE level in diffuse AA patients positively correlated with intensity of infiltration by mononuclear cells, eosinophils, and CD8 + T cells. Conclusions: Hypersensitivity may be involved in pathogenesis of diffuse AA. The acute onset of diffuse AA may be related to intense local inflammatory infiltration of hair loss region and an increase in serum IgE level.
|The prostamide-related glaucoma therapy, bimatoprost, offers a novel approach for treating scalp alopecias. Balding causes widespread psychological distress but is poorly controlled. The commonest treatment, minoxidil, was originally an antihypertensive drug that promoted unwanted hair. We hypothesized that another serendipitous discovery, increased eyelash growth side-effects of prostamide F(2α)-related eyedrops for glaucoma, may be relevant for scalp alopecias. Eyelash hairs and follicles are highly specialized and remain unaffected by androgens that inhibit scalp follicles and stimulate many others. Therefore, we investigated whether non-eyelash follicles could respond to bimatoprost, a prostamide F(2α) analog recently licensed for eyelash hypotrichosis. Bimatoprost, at pharmacologically selective concentrations, increased hair synthesis in scalp follicle organ culture and advanced mouse pelage hair regrowth in vivo compared to vehicle alone. A prostamide receptor antagonist blocked isolated follicle growth, confirming a direct, receptor-mediated mechanism within follicles; RT-PCR analysis identified 3 relevant receptor genes in scalp follicles in vivo. Receptors were located in the key follicle regulator, the dermal papilla, by analyzing individual follicular structures and immunohistochemistry. Thus, bimatoprost stimulates human scalp follicles in culture and rodent pelage follicles in vivo, mirroring eyelash behavior, and scalp follicles contain bimatoprost-sensitive prostamide receptors in vivo. This highlights a new follicular signaling system and confirms that bimatoprost offers a novel, low-risk therapeutic approach for scalp alopecias.
|Secondary infertility due to use of low-dose finasteride. Herein, we present an unusual case of secondary infertility after prolonged use of low-dose finasteride for androgenetic alopecia in a 40-year-old man. We detected sperm DNA damage in the patient. Despite such a long-term use, we observed that impairment in semen parameters and sperm DNA fragmentation index regressed after the drug was discontinued. Consequently, pregnancy occurred and resulted in live birth.
|Clinical and histological challenge in the differential diagnosis of diffuse alopecia: female androgenetic alopecia, telogen effluvium and alopecia areata - part I. Diffuse androgenetic alopecia (female pattern hair loss), telogen effluvium, and diffuse alopecia areata may have similar clinical manifestations. Subtle details on physical examination and dermoscopy of the scalp may help to identify those disorders. The authors present a practical discussion on how to approach the patient with diffuse alopecia, considering clinical history, physical examination, and dermoscopic findings. If the diagnosis remains unclear after a careful analysis of the clinical signs, a scalp biopsy may help to distinguish between the three diseases. In this first part of our study, an objective review of female androgenetic alopecia is presented and the most important histological changes are discussed.
|Age dependent associations between androgenetic alopecia and prostate cancer risk. BACKGROUND: Both prostate cancer and androgenetic alopecia (AA) are strongly age related conditions that are considered to be androgen dependent, but studies of the relationship between them have yielded inconsistent results. We aimed to assess whether AA at ages 20 and 40 are associated with risk of prostate cancer. METHODS: At a follow up of the Melbourne Collaborative Cohort Study men were asked to assess their hair pattern at ages 20 and 40 relative to eight categories in showcards. Cases were men notified to the Victorian Cancer Registry with prostate cancer diagnosed between cohort enrolment (1990-1994) and follow-up attendance (2003-2009). Flexible parametric survival models were used to estimate age varying hazard ratios and predicted cumulative probabilities of prostate cancer by AA categories. RESULTS: Of 9,448 men that attended follow-up and provided data on AA we identified 476 prostate cancer cases during a median follow up of 11 years 4 months. Cumulative probability of prostate cancer was greater at all ages up to 76 years for men with vertex versus no AA at age 40. At age 76 the estimated probabilities converged to 0.15. Vertex AA at 40 was also associated with younger age of diagnosis for prostate cancer cases. CONCLUSIONS: Vertex AA at age 40 might be a marker of increased risk of early onset prostate cancer. Impact: If confirmed, these results suggest that the apparently conflicting findings of previous studies might be explained by failure to adequately model the age-varying nature of the association between AA and prostate cancer.
|Androgen actions on the human hair follicle: perspectives. Androgens stimulate beard growth but suppress hair growth in androgenetic alopecia (AGA). This condition is known as 'androgen paradox'. Human pilosebaceous units possess enough enzymes to form the active androgens testosterone and dihydrotestosterone. In hair follicles, 5α-reductase type 1 and 2, androgen receptors (AR) and AR coactivators can regulate androgen sensitivity of dermal papillae (DP). To regulate hair growth, androgens stimulate production of IGF-1 as positive mediators from beard DP cells and of TGF-β1, TGF-β2, dickkopf1 and IL-6 as negative mediators from balding DP cells. In addition, androgens enhance inducible nitric oxide synthase from occipital DP cells and stem cell factor for positive regulation of hair growth in beard and negative regulation of balding DP cells. Moreover, AGA involves crosstalk between androgen and Wnt/β-catenin signalling. Finally, recent data on susceptibility genes have provided us with the impetus to investigate the molecular pathogenesis of AGA.
Hair regrowth in a male patient with extensive androgenetic alopecia on estrogen therapy
Estrogen therapy provided almost complete regrowth on male patient.
Fig 1. A, Extensive frontal and vertex hair loss. B, Improved regrowth of vertex hair. C, Continued regrowth of terminal hair on vertex. D, Significant regrowth of terminal hair with appreciable coverage on vertex. E, Almost full regrowth of terminal hair on scalp with some vertex thinning noted. Photographs taken approximately January 1989 (A), August 1990 (B), November 1990 (C), April 1991 (D), and September 1991 (E).
|Drug-induced gynecomastia: an evidence-based review. INTRODUCTION: Drugs are estimated to cause about 10 - 25% of all cases of gynecomastia. Over the course of several decades, multiple medications have been implicated in the development of gynecomastia mostly in the form of case reports and case series. However, these reports suffer from a multitude of deficiencies, including poor quality of evidence. AREAS COVERED: Studies were selected for this review by performing an extensive electronic and hand-search using BIOSIS, EMBASE and Medline, from 1940 to present, for all reported drug associations of gynecomastia and their possible pathophysiology. Quality of evidence was assessed on a three-point scale: good, fair and poor, and each of the drugs reported to cause gynecomastia was assigned a level of strength. The pathophysiology of gynecomastia is also discussed in detail for each of the drugs found to have a good or fair evidence of association with gynecomastia. EXPERT OPINION: Most of the reported drug-gynecomastia associations were based on poor quality evidence. The drugs definitely associated with the onset of gynecomastia are spironolactone, cimetidine, ketoconazole, hGH, estrogens, hCG, anti-androgens, GnRH analogs and 5-α reductase inhibitors. Medications probably associated with gynecomastia include risperidone, verapamil, nifedipine, omeprazole, alkylating agents, HIV medications (efavirenz), anabolic steroids, alcohol and opioids.
|The role of androgen and androgen receptor in skin-related disorders. Androgen and androgen receptor (AR) may play important roles in several skin-related diseases, such as androgenetic alopecia and acne vulgaris. Current treatments for these androgen/AR-involved diseases, which target the synthesis of androgens or prevent its binding to AR, can cause significant adverse side effects. Based on the recent studies using AR knockout mice, it has been suggested that AR and androgens play distinct roles in the skin pathogenesis, and AR seems to be a better target than androgens for the treatment of these skin diseases. Here, we review recent studies of androgen/AR roles in several skin-related disorders, including acne vulgaris, androgenetic alopecia and hirsutism, as well as cutaneous wound healing.
|Current status of hair restoration surgery. Hair restoration has emerged as a subspecialty of aesthetic plastic surgery practiced by a wide range of doctors including plastic surgeons, general surgeons, dermatologists, and even general practitioners. As a current trend, most doctors practice "Ultrarefined follicular unit hair transplantation" in which the entire procedure is done precisely with minimal donor scar. In selected cases, Mega or even Giga sessions are now done with natural appearance and almost undetectable scar, in a single session with good density. This article is an attempt to review the history of hair restoration surgery, describe a novel technique currently practiced in our center, and summarize possible future innovations.
|Successful treatment of alopecia areata with topical calcipotriol. Alopecia areata (AA) is an inflammatory hair loss of unknown etiology. AA is chronic and relapsing, and no effective cure or preventive treatment has been established. Vitamin D was recently reported to be important in cutaneous immune modulation as well as calcium regulation and bone metabolism. It is well known that areata is common clinical finding in patients with vitamin D deficiency, vitamin D-resistant rickets, or vitamin D receptor (VDR) mutation. The biological actions of vitamin D3 derivatives include regulation of epidermal cell proliferation and differentiation and modulation of cytokine production. These effects might explain the efficacy of vitamin D3 derivatives for treating AA. In this study, we report a 7-year-old boy with reduced VDR expression in AA, recovery of whom was observed by topical application of calcipotriol, a strong vitamin D analog.
|5α-Reductases in Human Physiology: An Unfolding Story. Objective: 5α-reductases are a family of isozymes expressed in a wide host of tissues including the central nervous system and play a pivotal role in male sexual differentiation, development and physiology.Methods: A comprehensive literature search from 1970-2011 was made via PubMed and the relevant information was summarized.Results: 5α reductases convert testosterone, progesterone, deoxycorticosterone, aldosterone and corticosterone into their respective 5α -dihydro-derivatives, which serve as substrates for 3α - hydroxysteroid dehydrogenase (3α-HSD) enzymes. The latter transforms these 5α-reduced metabolites into a subclass of neuro-active steroid hormones with distinct physiological function. The neuro-active steroid hormones modulate multitude of functions in human physiology encompassing regulation of sexual differentiation, neuro-protection, memory enhancement, anxiety, sleep and stress, among others. In addition, 5α -reductase type 3 is also implicated in the N-glycosylation of proteins via formation of dolichol phosphate. The family of 5α-reductases was targeted for drug development to treat pathophysiological conditions, such as benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). While the clinical use of 5α-reductases inhibitors was well established, the scope and the magnitude of the adverse side effects of such drugs especially on the central nervous systems is still unrecognized, due to lack of knowledge of the various physiological function of this family of enzymes, especially in the central nervous system.Conclusion: There is an urgent need to better understand the function of 5α-reductases and the role of neuro-active steroids in human physiology in order to minimize the potential adverse side effects of inhibitors targeting 5α-reductases to treat BPH and AGA.
|Promising therapies for treating and/or preventing androgenic alopecia. Androgenetic alopecia (AGA) may affect up to 70% of men and 40% of women at some point in their lifetime. While men typically present with a distinctive alopecia pattern involving hairline recession and vertex balding, women normally exhibit a diffuse hair thinning over the top of their scalps. The treatment standard in dermatology clinics continues to be minoxidil and finasteride with hair transplantation as a surgical option. Here we briefly review current therapeutic options and treatments under active investigation. Dutasteride and ketoconazole are also employed for AGA, while prostaglandin analogues latanoprost and bimatoprost are being investigated for their hair growth promoting potential. Laser treatment products available for home use and from cosmetic clinics are becoming popular. In the future, new cell mediated treatment approaches may be available for AGA. While there are a number of potential treatment options, good clinical trial data proving hair growth efficacy is limited.
|Combination therapy with finasteride and low-dose dutasteride in the treatment of androgenetic alopecia. We report on a 47-year-old man who was initially treated with finasteride for androgenetic alopecia. Despite continuous treatment, after year 4 his hair density was not as good as at year 2, and low-dose dutasteride at 0.5mg/week was added to the finasteride therapy. This resulted in a dramatic increase in his hair density, demonstrating that combined therapy with finasteride and dutasteride can improve hair density in patients already taking finasteride.
|Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial. CONTEXT: Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and androgenic alopecia, but the role of 5α-dihydrotestosterone (DHT) in mediating testosterone's effects on muscle, sexual function, erythropoiesis, and other androgen-dependent processes remains poorly understood. OBJECTIVE: To determine whether testosterone's effects on muscle mass, strength, sexual function, hematocrit level, prostate volume, sebum production, and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride (an inhibitor of 5α-reductase type 1 and 2). DESIGN, SETTING, AND PATIENTS: The 5α-Reductase Trial was a randomized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010. INTERVENTIONS: Eight treatment groups received 50, 125, 300, or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups). MAIN OUTCOME MEASURES: The primary outcome was change in fat-free mass; secondary outcomes: changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels. RESULTS: A total of 139 men were randomized; 102 completed the 20-week intervention. Men assigned to dutasteride were similar at baseline to those assigned to placebo. The mean fat-free mass gained by the dutasteride groups was 0.6 kg (95% CI, -0.1 to 1.2 kg) when receiving 50 mg/wk of testosterone enanthate, 2.6 kg (95% CI, 0.9 to 4.3 kg) for 125 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9 kg) for 300 mg/wk, and 7.1 kg (95% CI, 6.0 to 8.2 kg) for 600 mg/wk. The mean fat-free mass gained by the placebo groups was 0.8 kg (95% CI, -0.1 to 1.7 kg) when receiving 50 mg/wk of testosterone enanthate, 3.5 kg (95% CI, 2.1 to 4.8 kg) for 125 mg/wk, 5.7 kg (95% CI, 4.8 to 6.5 kg) for 300 mg/wk, and 8.1 kg (95% CI, 6.7 to 9.5 kg) for 600 mg/wk. The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant (P = .18). Changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels did not differ between groups. CONCLUSION: Changes in fat-free mass in response to graded testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo, indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle.
|Treatment of female pattern hair loss with the androgen receptor antagonist flutamide Female pattern hair loss is a common but difficult to manage condition. Commonly used treatments include oral antiandrogens such as spironolactone and topical minoxidil. The response to treatment is variable. We report a woman whose hair loss progressed while using spironolactone and topical minoxidil in combination, but reversed with flutamide, a potent androgen receptor antagonist.
|Pilot Study of 15 Patients Receiving a New Treatment Regimen for Androgenic Alopecia: The Effects of Atopy on AGA. Background. We examined the efficacy of a new regimen to treat AGA, with attention to male patients who are atopic. Objective. To assess the efficacy of a four-part regimen for the treatment of AGA in atopic and nonatopic patients. NuH Hair is a novel topical combination of finasteride, dutasteride, and minoxidil, which is blended in a hypoallergenic lotion. The other three components included Rogaine foam, Propecia, and ketoconazole shampoo. Methods. A prospective pilot study was conducted in 15 patients. All patients were assessed for the presence of atopy. Each patient served as their own control. All patients were treated specifically with NuH Hair and were given the option to add any of the other components of the protocol to their regimen. Photographs were taken of each patient's scalp at months 0, 1, 3, 6, and 9. Results. All 15 patients demonstrated significant growth of hair. In those patients who utilized all 4 components, significant growth was achieved in as little as 30 days. In those patients who choose only to utilize NuH Hair, significant growth was demonstrated after 3 months. Conclusion. Aggressively treating AGA achieves significant and rapid growth of new hair. This is effective in atopic and nonatopic male patients.
|Development and characterization of dutasteride bearing liposomal systems for topical use. Dutasteride loaded liposomal system were developed for topical application in order to avoid the side effects associated with the oral administration of the drug. Drug-loaded multilamellar liposomes were prepared using thin-film hydration method followed by sonication and optimized with respect to entrapment efficiency, drug payload, size and lamellarity. The vesicular systems consisting of egg phosphatidylcholine (100 mg), cholesterol (50 mg), and dutasteride (5 mg) showed highest drug entrapment efficiency (94.6%) and drug payload (31.5 µg/mg of total lipids). Mean vesicle size of these liposomes was noted to be 1.82 ± 0.15 µm. Significantly higher skin permeation of dutasteride through excised abdominal mouse skin was achieved via the developed liposomal formulations as compared to hydro-alcoholic solution and conventional gels. The formulation exhibited about seven fold higher deposition of drug in skin. Stability studies indicated that the liposomal formulations were quite stable in the refrigerated conditions for 10 weeks with negligible drug leakage or vesicle size alteration. Results of the current studies exhibited improved and localized drug action in the skin and thus could be formulated as a better option to cure androgenetic alopecia.
|Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. INTRODUCTION: 5α-reductase inhibitors (5α-RIs), finasteride and dutasteride, have been approved for treatment of lower urinary tract symptoms, due to benign prostatic hyperplasia, with marked clinical efficacy. Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia, depression, and quality of life remains ill-defined. AIM: The goal of this review is to discuss 5α-RIs therapy, the potential persistent side effects, and the possible mechanisms responsible for these undesirable effects. METHODS: We examined data reported in various clinical studies from the available literature concerning the side effects of finasteride and dutasteride. MAIN OUTCOME MEASURES: Data reported in the literature were reviewed and discussed. Results. Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship. CONCLUSIONS: We suggest discussion with patients on the potential sexual side effects of 5α-RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia.
|Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: a randomized, double-blind, placebo-controlled, phase III study. BACKGROUND: Dutasteride (Avodart) is a dual inhibitor of both type I and type II 5 alpha reductases, and thus inhibits conversion of testosterone to dihydrotestosterone, a key mediator of male pattern hair loss. OBJECTIVES: The aim of this randomized double-blind phase III study was to compare the efficacy, safety, and tolerability of dutasteride (0.5 mg) and placebo for 6 months of treatment in male patients with male pattern hair loss. METHODS: A total of 153 men, 18 to 49 years old, were randomized to receive 0.5 mg of dutasteride or placebo daily for 6 months. Efficacy was evaluated by the change of hair counts, subject assessment, and photographic assessment by investigators and panels. RESULTS: Mean change of hair counts from baseline to 6 months after treatment start was an increase of 12.2/cm(2) in dutasteride group and 4.7/cm(2) in placebo group and this difference was statistically significant (P = .0319). Dutasteride showed significantly higher efficacy than placebo group by subject self-assessment and by investigator and panel photographic assessment. There was no major difference in adverse events between two groups. LIMITATIONS: The study was limited to 6 months. CONCLUSIONS: This study clearly showed that 0.5 mg of dutasteride improved hair growth and was relatively well tolerated for the treatment of male pattern hair loss.
|Big head? Bald head! Skull expansion: alternative model for the primary mechanism of AGA. Currently, the predominant hypothesis explains androgenetic alopecia (AGA) as a process reliant upon affected follicles being individually programmed to accumulate dihydrotestosterone (DHT), which then causes progressive follicular miniaturisation. The goal of this paper is to suggest that such miniaturisation may result from an exaggeration of the bone remodelling process causing a reduction in blood supply to the capillary network within the affected region. The bones of the human skull continue to grow during adulthood and observations made of those with AGA suggest that such growth may be responsible for the development of this condition. Studies of human cranial anatomy indicate that frontal and parietal bone growth can account for the development of the male pattern baldness (MPB) profile and the variations that can occur in the rate and location of hair loss. Steroid hormones such as DHT promote facial and body hair growth. Logically, this suggests that DHT should stimulate hair growth within the MPB region and not hair loss. However, DHT also has an anabolic effect on bone formation, and it is hypothesised that this stimulation of bone growth will overwhelm the hair growth promoting effects of DHT. Androgen receptor sites, 5-alpha-reductase (5alpha-R) and DHT have all been associated with AGA, but they also exist within numerous types of bone cells. DHT will stimulate the proliferation of osteoblast cells and the formation of new bone. Verification of this hypothesis would imply that DHT is primarily involved with AGA through its stimulation of the skull expansion process rather than through interaction with individual follicles. Also, increased androgen receptor gene expression, 5alpha-R activity and subsequent production of DHT within the MPB region of balding individuals, may simply represent the body's attempt to compensate for the skull expansion expression of hair follicle miniaturisation. Furthermore, it suggests that MPB region follicles are not individually programmed for hair loss. A redirection of genetic research towards the identification of those genes responsible for skull shape and development would be appropriate, and may reveal the genetic connection to AGA including its paternal link.
|Value of hormonal levels in patients with male androgenetic alopecia treated with finasteride: better response in patients under 26 years old. BACKGROUND: Finasteride is a 5alpha-reductase inhibitor that has proved to be an effective treatment for men with androgenetic alopecia. OBJECTIVES: To investigate the hormonal influence of finasteride 1 mg daily on hormonal levels and hair growth in men of different ages and with different degrees of alopecia according to the Hamilton-Norwood scale. METHODS: Two hundred and seventy men aged 14-58 years with male androgenetic alopecia III-VI Hamilton-Norwood score (II-III Ebling score) were treated with finasteride 1 mg daily. Steroid hormone (free testosterone, 5alpha-dihydrotestosterone, dehydroepiandrosterone-sulphate, delta4-androstenedione, 17-hydroxyprogesterone), prostate-specific antigen (PSA) and sebum levels, and trichogram changes were determined at baseline, and at 6 and 12 months of treatment. RESULTS: According to significant hormonal statistical analysis, the patients were divided by age (up to or over 26 years). In the group of patients < = 26 years, higher levels of 5alpha-dihydrotestosterone were found at the beginning of the treatment, but there was a 50% decrease between the onset of treatment and month 12, particularly noticeable at 6 months (P<0.05) of treatment, running parallel to an improvement of the alopecia and an increase of anagen hairs in the trichogram. At 1 year, PSA levels decreased 20%, particularly in patients>26 years. No variations in sebum levels were observed. CONCLUSIONS: High levels of 5alpha-dihydrotestosterone in patients < = 26 years at the beginning of treatment are a predictive factor of good response to treatment with finasteride 1 mg daily.
|Hormonal profile of men with premature balding. OBJECTIVE: Premature androgenic alopecia has been suggested as a feature of the male equivalent of the syndrome of polycystic ovary. However, the hormonal pattern of men with premature balding has been investigated in only a few studies with inconsistent results. MATERIAL AND METHODS: We examined 37 men with premature balding (defined as frontoparietal and vertex hair loss before the age of 30 years with alopecia defined as grade 3 vertex or more on the alopecia classification scale of Hamilton with Norwood modification). The plasma concentrations of total testosterone, dihydrotestosterone, epitestosterone, androstenedione, cortisol, 17-OH-progesterone (17OHP), estradiol, LH, FSH, prolactin, SHBG and TSH and free thyroxine were measured. RESULTS: The frequency of subnormal values in SHBG, FSH, testosterone and epitestosterone (but not in free androgen index) was significant in the balding men. A borderline significant trend was recorded with respect to increased levels in 17OH-P and prolactin. CONCLUSIONS: The hormonal pattern of a substantial number of men with premature balding resembles in some respects the hormonal pattern of women with polycystic ovary syndrome.
|The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride. BACKGROUND: Male pattern hair loss (MPHL) is a potentially reversible condition in which dihydrotestosterone is an important etiologic factor. OBJECTIVE: Our aim was to evaluate the efficacy of the type 1 and 2 5alpha-reductase inhibitor dutasteride in men with MPHL. METHODS: Four hundred sixteen men, 21 to 45 years old, were randomized to receive dutasteride 0.05, 0.1, 0.5 or 2.5 mg, finasteride 5 mg, or placebo daily for 24 weeks. RESULTS: Dutasteride increased target area hair count versus placebo in a dose-dependent fashion and dutasteride 2.5 mg was superior to finasteride at 12 and 24 weeks. Expert panel photographic review and investigator assessment of hair growth confirmed these results. Scalp and serum dihydrotestosterone levels decreased, and testosterone levels increased, in a dose-dependent fashion with dutasteride. LIMITATIONS: The study was limited to 24 weeks. CONCLUSION: Dutasteride increases scalp hair growth in men with MPHL. Type 1 and type 2 5alpha-reductase may be important in the pathogenesis and treatment of MPHL.
|A role for 5alpha-reductase activity in the development of male homosexuality? Higher body hair with lower mesmorphism ratings were observed in Caucasian homosexual men compared with the general male population, reflecting elevated 5alpha-reductase (5alphaR) activity, and higher dihydrotestosterone-to-testosterone (DHT-to-T) ratio, in sharp contrast to 46,XY 5alphaR 2 deficiency subjects, who are often born with ambiguous, or female genitalia, but tend to grow up to be muscular, heterosexual men with very little body hair, or beard. One study also showed them scoring around dull normal IQs. A greater prevalence of liberal body hair growth in men with higher IQs and/or educational levels was also observed in several samples. The exceptions to this statistical trend are too unsettling, however. Nevertheless, the results of a number of published studies, including one showing higher DHT-to-T ratio in homosexual men, done with different objectives over a span of 80 years, together strongly support these findings. Furthermore, in an animal model, "cognitive-enhancing effects" of "5alpha-reduced androgen [metabolites]" were recently demonstrated.
|Comparative studies on level of androgens in hair and plasma with premature male-pattern baldness. BACKGROUND: It is well known that male-pattern baldness (MPB) is not started from occipital, but frontal or scalp of head. We can assume that distribution of androgenic steroids is different for each region of the head. OBJECTIVE: We hypothesize that the levels of androgenic steroids are different not only between vertex hair with MPB and controls but also between occipital hair with MPB and controls. Moreover, we want to search for the biochemical indicator in plasma and hair sample (baldness: 22, non-baldness: 13) obtained from dermatology of medical center. After then, we desire to present fundamental data regarding diagnosis, medical cure, and prevention for premature MPB. METHODS: After hair and plasma were hydrolyzed, and then extracted with organic solvent. To assess androgenic steroids levels, we used gas chromatography-mass spectrometry (GC-MS) system in selected ion monitoring mode. RESULTS: The level of dihydrotestosterone (DHT) and the ratio of testosterone to epitestosterone (T/E ratio) in vertex hair from premature baldness subjects were higher than in the sample of non-baldness subjects (P < 0.001, 0.001), whereas the levels of androgens in occipital hair from the same baldness group were not different. In addition, we discovered the levels of DHT, testosterone, and DHT/T ratio in plasma from premature MPB were higher than in those of control subjects (P < 0.001, 0.001, 0.005). CONCLUSION: We verified that the distribution of androgenic steroids is unlike in various regions of individual subjects. Moreover, the increased DHT/T ratio in balding plasma indirectly confirms the high activity of 5alpha-reductase type II.
|Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. Dihydrotestosterone (DHT), a potent androgen, is converted from testosterone by 5alpha-reductase isozymes. There are two 5alpha-reductase isozymes, type 1 and type 2 in humans and animals. These two isozymes have differential biochemical and molecular features. Mutations in type 2 isozyme cause male pseudohermaphroditism, and many mutations have been reported from various ethnic groups. The affected 46XY individuals have high normal to elevated plasma testosterone levels with decreased DHT levels and elevated testosterone/DHT ratios. They have ambiguous external genitalia at birth so that they are believed to be girls and are often raised as such. However, Wolffian differentiation occurs normally and they have epididymides, vas deferens and seminal vesicles. Virilization occurs at puberty frequently with a gender role change. The prostate in adulthood is small and rudimentary, and facial and body hair is absent or decreased. Balding has not been reported. Spermatogenesis is normal if the testes are descended. The clinical, biochemical and molecular genetic analyses of 5alpha-reductase-2 deficiency highlight the significance of DHT in male sexual differentiation and male pathophysiology.
|Androgens and alopecia. Androgens have profound effects on scalp and body hair in humans. Scalp hair grows constitutively in the absence of androgens, while body hair growth is dependent on the action of androgens. Androgenetic alopecia, referred to as male pattern hair loss (MPHL) in men and female pattern hair loss (FPHL) in women, is due to the progressive miniaturization of scalp hair. Observations in both eunuchs, who have low levels of testicular androgens, and males with genetic 5alpha-reductase (5alphaR) deficiency, who have low levels of dihydrotestosterone (DHT), implicate DHT as a key androgen in the pathogenesis of MPHL in men. The development of finasteride, a type 2-selective 5alphaR inhibitor, further advanced our understanding of the role of DHT in the pathophysiology of scalp alopecia. Controlled clinical trials with finasteride demonstrated improvements in scalp hair growth in treated men associated with reductions in scalp DHT content, and a trend towards reversal of scalp hair miniaturization was evident by histopathologic evaluation of scalp biopsies. In contrast to its beneficial effects in men, finasteride did not improve hair growth in postmenopausal women with FPHL. Histopathological evaluation of scalp biopsies confirmed that finasteride treatment produced no benefit on scalp hair in these women. These findings suggest that MPHL and FPHL are distinct clinical entities, with disparate pathophysiologies. Studies that elucidate the molecular mechanisms by which androgens regulate hair growth would provide greater understanding of these differences.
|Cutting edge: agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2. Indomethacin is a widely used nonsteroidal anti-inflammatory drug and is generally known to exhibit its multiple biological functions by inhibiting cyclooxygenases or activating peroxisome proliferator-activated receptors. In this study, we present evidence demonstrating that the novel PGD(2) receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) is another functional target for indomethacin. Indomethacin induced Ca(2+) mobilization in CRTH2-transfected K562 cells at submicromolar concentrations (approximate EC(50), 50 nM) in a G(alphai)-dependent manner as PGD(2) did. Other nonsteroidal anti-inflammatory drugs (aspirin, sulindac, diclofenac, and acemetacin) had no such effect even at micromolar concentrations. In chemotaxis assay, three CRTH2-expressing cell types, Th2 cells, eosinophils, and basophils, were all significantly attracted by indomethacin (EC(50), 50-500 nM) as well as by PGD(2) (EC(50), 2-20 nM), and the effects of indomethacin were blocked by anti-CRTH2 mAb. These results suggest the involvement of CRTH2 in mediating some of therapeutic and/or unwanted side effects of indomethacin, independently of cyclooxygenases and peroxisome proliferator-activated receptors.
|Androgen responsive genes as they affect hair growth. Finasteride has been shown to be an effective treatment for men with androgenetic alopecia (AGA) as it restores hair growth to miniaturized hair follicles on the top of the scalp . Caspases are regulators of programmed cell death, and very likely some specific caspases may function as mediators of the hair growth cycle. It is unclear whether finasteride influences the regulation of apoptosis via caspases in the hair follicle. Very little information is available regarding the role of caspases present in human hair follicles in normal scalp and in androgenetic alopecia. In this study we have analyzed the family of caspases, 1-10 along with usurpin, and XIAP, in men with normal scalp and in men with androgenetic alopecia before and after 6 months treatment with 1 mg oral finasteride treatment. Caspases 1, 3, 8 and 9 were detected predominantly within the isthmic and infundibular hair follicle area for both normal and AGA patients, however the expression of all factors, especially caspase 3 was greater in the AGA group than in the normal scalp group. AGA men had the same caspase factors but with greater expression. In the same AGA men treated with finasteride for 6 months, the expression of these factors was similar to levels in the normal group. Results from our study indicate caspase 3 to be of primary importance in normal hair homeostasis and that DHT may be signaling greater expression of caspases, inducing apoptosis in androgenetic alopecia. In conclusion, DHT may selectively regulate the caspase genes which play an important role in signaling programmed cell death, affecting the hair growth cycle.
|Finasteride increases anagen hair in men with androgenetic alopecia. BACKGROUND: The growth of scalp hair is a cyclical process of successive phases of growth (anagen) and rest (telogen). In previous clinical trials in men with androgenetic alopecia, treatment with finasteride increased scalp hair counts in a defined area (i.e. increased hair density). OBJECTIVES: The current study used a phototrichogram methodology to assess the effect of finasteride on the phases of the hair growth cycle. PATIENTS/METHODS: Two hundred and twelve men, age 18-40 years, with androgenetic alopecia were randomized to receive finasteride 1 mg daily or placebo for 48 weeks. At baseline and at 24 and 48 weeks, macrophotographs were taken to measure total and anagen hair count in a 1-cm(2) target area of the scalp. RESULTS: At baseline, mean total and anagen hair counts in the finasteride group were 200 and 124 hairs, respectively (% anagen = 62%) and the anagen to telogen ratio was 1.74 (geometric mean). In the placebo group, the respective values were 196 and 119 hairs (% anagen = 60%) and 1.57. At week 48, the finasteride group had a net improvement (mean +/- SE) compared with placebo in total and anagen hair counts of 17.3 +/- 2.5 hairs (8.3% +/- 1.4%) and 27.0 +/- 2.9 hairs (26% +/- 3.1%), respectively (P < 0.001). Furthermore, treatment with finasteride resulted in a net improvement in the anagen to telogen ratio of 47% (P < 0.001). In this study, treatment with finasteride 1 mg day(-1) for 48 weeks increased both total and anagen hair counts, and improved the anagen to telogen ratio. CONCLUSIONS: These data provide direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase. These data support that finasteride treatment results in favourable effects on hair quality that contribute to the visible improvements in hair growth observed in treated patients.
|Finasteride in the treatment of men with frontal male pattern hair loss. 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 (P < .001), 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 growth.
|Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating effect. ibuprofen, induce hair loss in vivo. These NSAIDs are well-known inhibitors of both the cytoprotective isoform of prostaglandin endoperoxide synthase-1 (PGHS-1) and of the inducible form (PGHS-2). By immunohistochemical staining, we found that PGHS-1 is the main isoform present in the dermal papilla from normal human hair follicle (either anagen or catagen), whereas PGHS-2 was only faintly and exclusively expressed in anagen dermal papilla. Thus, PGHS-1 might be the primary target of the hair growth-inhibitory effects of NSAIDs. We thus speculated that activation of PGHS-1 might be a mechanism by which minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxyde) stimulates hair growth in vivo. We demonstrate here that minoxidil is a potent activator of purified PGHS-1 (AC50 = 80 microM), as assayed by oxygen consumption and PGE2 production. This activation was also evidenced by increased PGE2 production by BALB/c 3T3 fibroblasts and by human dermal papilla fibroblasts in culture. Our findings suggest that minoxidil and its derivatives may have a cytoprotective activity in vivo and that more potent second-generation hair growth-promoting drugs might be designed, based on this mechanism.
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