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Dr Proctor's Hair Loss Blog



A new formulation of minoxidil


Lee HJ1, et al, Preparation and in vivo evaluation of lecithin-based microparticles for topical delivery of minoxidil. Arch Pharm Res. 2017 Aug 2. doi: 10.1007/s12272-017-0934-x

Abstract: Minoxidil is widely used for treatment of male pattern hair loss. Commercial products containing minoxidil are usually in solution form. Repeated applications of minoxidil solution can lead to adverse effects such as skin irritation and horniness. The aims of this study were to prepare lecithin-based microparticle in minoxidil solution for enhancement of minoxidil topical delivery and skin protection and evaluate the ability of lecithin on in vitro delivery, in vivo hair growth, and skin trouble improvement compared to commercial minoxidil solution. In in vitro skin permeation study, minoxidil solution containing lecithin microparticle showed higher skin penetration rate and higher retention of drug inside the skin compared to minoxidil solution without lecithin. After topical application of minoxidil solutions with or without lecithin to C57BL/6 mice, minoxidil 5% solution containing lecithin microparticle showed hair re-growth as efficient as commercial product of minoxidil 5% solution. It also significantly improved skin troubles while commercial product presented horny substance and crust formation. Therefore, the lecithin-based microparticle in minoxidil 5% solution has good ability to promote hair growth without adverse effects.



A review of some hair loss treatment methods.

Adil A1, Godwin M2.The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis. J Am Acad Dermatol. 2017 Apr 7. pii: S0190-9622(17)30306-7. doi: 10.1016/j.jaad.2017.02.054.

Abstract: Androgenetic alopecia, or male pattern hair loss, is a hair loss disorder mediated by dihydrotestosterone, the potent form of testosterone. Currently, minoxidil and finasteride are Food and Drug Administration (FDA)-approved, and HairMax LaserComb, which is FDA-cleared, are the only treatments recognized by the FDA as treatments of androgenetic alopecia.

This systematic review and meta-analysis assesses the efficacy of nonsurgical treatments of androgenetic alopecia in comparison to placebo for improving hair density, thickness, growth (defined by an increased anagen:telogen ratio), or subjective global assessments done by patients and investigators.

A systematic review of randomized controlled trials was conducted. PubMed, Embase, and Cochrane were searched up to December 2016, with no lower limit on the year. We included only randomized controlled trials of good or fair quality based on the US Preventive Services Task Force quality assessment process.

A meta-analysis was conducted separately for 5 groups of studies that tested the following hair loss treatments: low-level laser light therapy in men, 5% minoxidil in men, 2% minoxidil in men, 1 mg finasteride in men, and 2% minoxidil in women. All treatments were superior to placebo in the 5 meta-analyses

CONCLUSIONS: This meta-analysis strongly suggests that minoxidil, finasteride, and low-level laser light therapy are effective for promoting hair growth in men with androgenetic alopecia and that minoxidil is effective in women with androgenetic alopecia.


Another paper on possible sexual dysfunction with Finasteride (Propecia).

"Persistent Sexual Side Effects of Finasteride (Propecia) for Male Pattern Hair Loss," Irwig, Michael S. et al. The Journal of Sexual Medicine , Volume 8 , Issue 6 , 1747 - 1753

ABSTRACT: Finasteride has been associated with reversible adverse sexual side effects in multiple randomized, controlled trials for the treatment of male pattern hair loss (MPHL). The Medicines and Healthcare Products Regulatory Agency of the United Kingdom and the Swedish Medical Products Agency have both updated their patient information leaflets to note that “persistence of erectile dysfunction after discontinuation of treatment with Propecia has been reported in post-marketing use.”

Aim: We sought to characterize the types and duration of persistent sexual side effects in otherwise healthy men who took finasteride for MPHL (Male Pattern Hair Loss).

Methods: We conducted standardized interviews with 71 otherwise healthy men aged 21–46 years who reported the new onset of sexual side effects associated with the temporal use of finasteride, in which the symptoms persisted for at least 3 months despite the discontinuation of finasteride.

Main Outcome Measures: The types and duration of sexual dysfunction and the changes in perceived sexual frequency and sexual dysfunction score between pre- and post-finasteride use.

Results: Subjects reported new-onset persistent sexual dysfunction associated with the use of finasteride: 94% developed low libido, 92% developed erectile dysfunction, 92% developed decreased arousal, and 69% developed problems with orgasm. The mean number of sexual episodes per month dropped and the total sexual dysfunction score increased for before and after finasteride use according to the Arizona Sexual Experience Scale. The mean duration of finasteride use was 28 months and the mean duration of persistent sexual side effects was 40 months from the time of finasteride cessation to the interview date. Study limitations include a post hoc approach, selection bias, recall bias for before finasteride data, and no serum hormone levels.

Conclusion: Physicians treating MPHL should discuss the potential risk of persistent sexual side effects associated with finasteride.

Slightly-edited for Blog use


Dr P notes-- more on ATK-activation and hair regrowth.

Effect of sinapic acid on hair regrowth in human hair follicle dermal papilla cells via Akt activation. Woo H1, et al.Arch Dermatol Res. 2017 Mar 20. doi: 10.1007/s00403-017-1732-5

Hair loss also or alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth. We investigated whether the function of sinapic acid (SA) is able to promote hair growth in human hair follicle dermal papilla cells (hHFDPC). We showed that treatment of SA in hHFDPC could induce proliferation and the activation of Akt signaling in HFDPC. In addition, SA could stimulate the expressions of the several growth factors, insulin-like growth factor 1, and vascular endothelial growth factor for hair growth. We showed that SA led to an increased level of phospho-GSK-3β and β-catenin accumulation in HFDPC. Finally, the promoting effect of SA in hHFDPC cell growth occurred by the induction of cell cycle progression. These results suggest that SA could be one of the potential candidate compounds for the treatment of alopecia by inducing hair regrowth through triggering the expressions of growth factors via activation of Akt and subsequent inactivation of GSK-3β /β-catenin pathway.


Dr Proctor sez: Intersting paper on using low-level red light to treat hair loss.

Friedman S, Schnoor P.,Novel Approach to Treating Androgenetic Alopecia in Females With Photobiomodulation (Low-Level Laser Therapy). Dermatol Surg. 2017 Mar 21. doi: 10.1097/DSS.0000000000001114.

Abstract

BACKGROUND: Photobiomodulation, also referred to as low-level laser therapy (LLLT),is used for the promotion of hair regrowth.

To better clarify the effects on the human hair follicle and surrounding tissue structures of laser light at 650 nm. ow-level laser treatment of the scalp every other day for 17 weeks is a safe and effective treatment for androgenetic alopecia in healthy females with Ludwig-Savin Baldness Scale I-2 to II-2 baldness patterns. Subjects receiving LLLT at 650 nm achieved an increase in hair counts compared with sham-treated control patients in this multicenter randomized controlled trial.

Thus, low-level laser therapy may play a potentially significant role in health care providers' armamentarium for androgenic alopecia or male pattern hairloss.. (edited for blog use)


Arif T1, et al, Dutasteride in androgenetic alopecia: An update. Curr Clin Pharmacol. 2017 Mar 10. doi: 10.2174/1574884712666170310111125.

Abstract

BACKGROUND:Androgenetic alopecia is a common condition characterized by thinning of scalp hair. Conversion of testosterone to dihydrotestosterone, a more potent androgen, by the enzyme 5-a-reductase is responsible for underlying pathogenesis. Dutasteride, a synthetic 4-azasteroid, is a selective and competitive inhibitor of both type-1 and type-2 isoenzymes of 5-alpha-reductase. Finasteride and minoxidil are the only approved drugs for androgenetic alopecia. Dutasteride has been demonstrated to be effective in several randomized, double-blind, placebo controlled trials in androgenetic alopecia. In this review, after the pharmacology of dutasteride, the authors have discussed the status of dutasteride in androgenetic alopecia and has compared its efficacy with that of finasteride.

OBJECTIVE:This article aims to review the current status of dutasteride in androgenetic alopecia. The structure, mechanism of action, pharmacokinetic and side effects are discussed along with its comparission with finasteride in androgenetic alopecia.


One of our agents, Tempol, inhibits JAK-STAT signaling. This may account for at least some of its effectiveness in hair loss treatment.

McCormick J1, et al, "Free radical scavenging inhibits STAT phosphorylation following in vivo ischemia/reperfusion injury.", FASEB J. 2006 Oct;20(12):2115-7.

The signal transducer and activator of transcription (STAT family are latent transcription factors involved in a variety of signal transduction pathways, including cell death cascades. STAT1 has been shown to have a crucial role in regulating cardiac cell apoptosis in the myocardium exposed to ischemia/reperfusion (I/R) injury. The free radical scavenger, tempol, is known to have cardioprotective properties, although little is known about the molecular mechanism(s) by which it acts. In the present study, we assessed the levels of phosphorylated STAT1 and STAT3 and examined whether tempol was able to affect STAT activation after in vivo cardiac I/R injury. We observed a reperfusion time-dependent increase in the tyrosine phosphorylation of STAT1 and STAT3 at residues 701 and 705, respectively. Here we show for the first time that tempol dramatically reduced STAT1 and 3 phosphorylation. The reduction in STAT1 and 3 phosphorylation was accompanied by a concomitant decrease in cellular malondialdehyde (MDA) levels. To verify the role of STAT1 in modulating the cardioprotective effect of tempol, rats were injected with the STAT1 activator, IFN-gamma, and tempol during I/R injury. We found that the presence of IFN-gamma abrogated the protective effects of tempol, suggesting that the protective effects of tempol may partly operate by decreasing the phosphorylation of STAT1. This study demonstrates that careful dissection of the molecular mechanisms that underpin I/R injury may reveal cardioprotective targets for future therapy.


Harel, S. et al, "Pharmacologic inhibition of JAK-STAT signaling promotes hair growth." Sci Adv. 2015 Oct 23;1(9):e1500973. doi: 10.1126/sciadv.1500973

Abstract: Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells.


Dr Proctor sez-- Papers on on PRP (Platelet-Rich Plasma) Treatment of Hair loss.

By Moustafa A. et al, "Platelets Rich Plasma Versus Minoxidil 5% in Treatment of Alopecia Areata: A Trichoscopic Evaluation", October 28, 2016

Abstract: Alopecia areata is a common cause of nonscarring alopecia that occurs in a patchy, confluent, or diffuse pattern. Dermoscopy is a noninvasive technique for the clinical diagnosis of many skin diseases. Topical minoxidil solution 5% and platelet rich plasma are important modalities used in treatment of alopecia areata. We aimed to evaluate the efficacy of PRP versus topical minoxidil 5% in the treatment of AA by clinical evaluation and trichoscopic examination. Ninety patients were allocated into three groups; the first was treated with topical minoxidil 5% solution, the second with platelets rich plasma injections, and the third with placebo. Diagnosis and follow up were done by serial digital camera photography of lesions and dermoscopic scan before and every 1 month after treatment for 3 months. Patients treated with minoxidil 5% and platelets rich plasma both have significant hair growth than placebo. Patients treated with platelets rich plasma had an earlier response in the form of hair regrowth, reduction in short vellus hair and dystrophic hair unlike patients treated with minoxidil and control In conclusion, platelets rich plasma is more effective in the treatment of alopecia areata than topical minoxidil 5% as evaluated by clinical and trichoscopic examination.

Gupta AK, Carviel J., A Mechanistic Model of Platelet-Rich Plasma Treatment for Androgenetic Alopecia.Dermatol Surg. 2016 Sep 14.

BACKGROUND: Platelet-rich plasma (PRP) therapy is a novel procedure used to treat androgenetic alopecia (AGA).

OBJECTIVE: Propose a mechanism of action of PRP therapy for AGA.

METHODS AND MATERIALS: A thorough literature search including PRP research for AGA therapy as well as PRP research in other areas of medicine was conducted.

RESULTS: A mechanistic model for the action of PRP on the hair follicle was created.

CONCLUSION: Platelet-rich plasma therapy stimulates hair growth through the promotion of vascularization and angiogenesis, as well as encourages hair follicles to enter and extend the duration of the anagen phase of the growth cycle. The process is accomplished through growth factor-mediated increased activation of wingless (Wnt)/β-catenin, extracellular signaling regulated kinase (ERK), and protein kinase B (Akt) signaling pathways, which leads to the necessary cellular proliferation and differentiation.


Tempol and JAK kinases

Recently, medical researchers discovered that JAK kinase inhibitors such as Ruxolitinib and Tofacitinib are hair growth stimulators. As this paper shows, Tempol likewise modulates the action of JAK kinases. Tempol is in all our products and is a much safer agent.


Banday AA1, Lokhandwala MF. Oxidative stress causes renal angiotensin II type 1 receptor upregulation, Na+/H+ exchanger 3 overstimulation, and hypertension. Hypertension. 2011 Mar;57(3):452-9. doi: 10.1161/HYPERTENSIONAHA.110.162339. Epub 2011 Jan 31.

Abstract Oxidative stress modulates angiotensin (Ang) II type 1 receptor (AT(1)R) expression and function. Ang II activates renal Na(+)/H(+) exchanger 3 (NHE3) to increase sodium reabsorption, but the mechanisms are still elusive. In addition, the upregulation of AT(1)R during oxidative stress could promote sodium retention and lead to an increase in blood pressure. Herein, we investigated the mechanism of Ang II-mediated, AT(1)R-dependent renal NHE3 regulation and effect of oxidative stress on AT(1)R signaling and development of hypertension. Male Sprague-Dawley rats received tap water (control) or 30 mmol/L of l-buthionine-sulfoximine, an oxidant, with and without 1 mmol/L of Tempol, an antioxidant, for 3 weeks. l-Buthionine-sulfoximine-treated rats exhibited oxidative stress and high blood pressure. Incubation of renal proximal tubules with Ang II caused significantly higher NHE3 activation in l-buthionine-sulfoximine-treated rats compared with control. The activation of NHE3 was sensitive to AT(1)R blocker and inhibitors of phospholipase C, tyrosine kinase, janus kinase 2 (Jak2), Ca(2+)-dependent calmodulin (CaM), and Ca(2+) chelator. Also, incubation of proximal tubules with Ang II caused Jak2-dependent CaM phosphorylation, which led to Jak2-CaM complex formation and increased Jak2-CaM interaction with NHE3. The activation of these signaling molecules was exaggerated in l-buthionine-sulfoximine-treated rats, whereas Tempol normalized the AT(1)R signaling. In conclusion, Ang II activates renal proximal tubular NHE3 through novel pathways that involve phospholipase C and an increase in intracellular Ca(2+), Jak2, and CaM. In addition, oxidative stress exaggerates Ang II signaling, which leads to overstimulation of renal NHE3 and contributes to an increase in blood pressure.




DR P sez: Note how TEMPOL, used in our hair loss treatment formulation, "restored hair cycle"

Liu N, et al, Chronic Restraint Stress Inhibits Hair Growth via Substance P Mediated by Reactive Oxygen Species in Mice. PLoS One. 2013 Apr 26;8(4):e61574. doi: 10.1371/journal.pone.0061574. Print 2013.

BACKGROUNDS: Solid evidence has demonstrated that psychoemotional stress induced alteration of hair cycle through neuropeptide substance P (SP) mediated immune response, the role of reactive oxygen species (ROS) in brain-skin-axis regulation system remains unknown.

OBJECTIVES: The present study aims to investigate possible mechanisms of ROS in regulation of SP-mast cell signal pathway in chronic restraint stress (CRS, a model of chronic psychoemotional stress) which induced abnormal of hair cycle.

METHODS AND RESULTS:Our results have demonstrated that CRS actually altered hair cycle by inhibiting hair follicle growth in vivo, prolonging the telogen stage and delaying subsequent anagen and catagen stage. Up-regulation of SP protein expression in cutaneous peripheral nerve fibers and activation of mast cell were observed accompanied with increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in CRS mice skin. In addition, SP receptor antagonist (RP67580) reduced mast cell activations and lipid peroxidation levels as well as increased GSH-Px activity and normalized hair cycle. Furthermore, antioxidant Tempol (a free radical scavenger) also restored hair cycle, reduced SP protein expression and mast cell activation.

CONCLUSIONS: Our study provides the first solid evidence for how ROS play a role in regulation of psychoemotional stress induced SP-Mast cell pathway which may provide a convincing rationale for antioxidant application in clinical treatment with psychological stress induced hair loss.




G. Douauda, et al, Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment, PNAS, vol. 110 no. 23, 9523–9528

Abstract: Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer's disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.




Catalase and graying hair

We are getting questions about recent media reports of the use of catalase and pseudocatalase to prevent hair from greying. Briefly: Hydrogen peroxide produced in metabolism prevents the production of the pigment melanin and make hair turn grey. Agents such as catalase itself or with catalase-like activity (pseudocatalase) such as PC-KUS destroy hydrogen peroxide and thus prevent hair from turning gray.

This is not exactly new information. Dr Proctor is a world-recognized expert on melanin pigment and on catalase. In fact, Dr Proctor published papers on the experimental use of catalase as medical treatment nearly three decades ago and is a pioneer in this field. Similarly, part of our experimental apparatus in melanin research is in the Smithsonian Institution's American Museum of History collection of pioneering items in semiconductor science. See: Organic Semiconductors.

Thus, we have long added agents which block the inhibitory action of hydrogen peroxide and other "active oxygen species" on hair pigmentation and hair graying. This includes "pseudocatalases". And yes, our agents do inhibit graying of hair. However, if gray hair and not hair loss is your only consideration, arguably, the best thing is just to dye it.



Shah AA, Sinha AA., Oxidative stress and autoimmune skin disease. Eur J Dermatol. 2013 Feb 1;23(1):5-13. doi: 10.1684/ejd.2012.1884. antioxidants play the important role in our body of neutralizing free radicals and peroxides that are formed during normal physiologic events. While these reactive oxygen species are necessary for numerous biological processes, when created in excess they can have deleterious effects. The skin as an organ is constantly under attack by reactive oxygen species from both endogenous and exogenous sources. The pathophysiology of many autoimmune diseases is unknown and recently oxidative stress has come to light as a possible triggering mechanism. Recent investigations attempting to link autoimmune skin diseases and oxidative stress have had varying degrees of success. In this article, we review the current literature regarding antioxidants in hair loss due to alopecia areata, pemphigus vulgaris and other blistering diseases, vitiligo, and psoriasis, and suggest possible future studies and treatment options.

KEYWORDS: alopecia areata, antioxidant, autoimmune, free radicals, catalase, psudocatalase,oxidative stress, pemphigus vulgaris, reactive oxygen species, organic semiconductors, vitiligo,gray, grey, graying, PC-KUS


Rasheed H,et al, Serum Ferritin and Vitamin D in Female Hair Loss: Do They Play a Role?. Skin Pharmacol Physiol. 2013 Feb 20;26(2):101-107.

Abstract

Evaluation of serum ferritin and vitamin D levels in females with chronic telogen effluvium (TE) or female pattern hair loss (FPHL), in order to validate their role in these common hair loss diseases. Methods: Eighty females (18 to 45 years old) with hair loss, in the form of TE or FPHL, and 40 age-matched females with no hair loss were included in the study. Diagnosis was based upon clinical examination as well as trichogram and dermoscopy. Serum ferritin and vitamin D(2) levels were determined for each participant. Results: Serum ferritin levels in the TE (14.7 ± 22.1 μg/l) and FPHL (23.9 ± 38.5 μg/l) candidates were significantly lower than in controls (43.5 ± 20.4 μg/l). Serum vitamin D(2) levels in females with TE (28.8 ± 10.5 nmol/l) and FPHL (29.1 ± 8.5 nmol/l) were significantly lower than in controls (118.2 ± 68.1 nmol/l; p < 0.001). These levels decreased with increased disease severity. Serum ferritin cut-off values for TE and FPHL were 27.5 and 29.4 μg/l, respectively, and those for vitamin D were 40.9 and 67.9 nmol/l. Conclusion: Low serum ferritin and vitamin D(2) are associated with hair loss in females with TE and FPHL. Screening to establish these levels in cases of hair loss and supplementing with them when they are deficient may be beneficial in the treatment of disease.


Dr Proctor comments on the following paper: We hold the primary patents for TEMPOL and use it in our hair loss treatment formulations. As the abstract below reports, part of its efficacy may be that it prevents pathological increases in the numbers of androgen receptors and thus makes antiandrogens work longer and better. We long-ago discovered that TEMPOL works in hair loss treatment. Preventing tissue reflex hyperandrogenicity is an unexpected bonus that may partially explian why TEMPOL seems to work so well as part of combination treatment:

Thomas R, Sharifi N., SOD mimetics: a novel class of androgen receptor inhibitors that suppresses castration-resistant growth of prostate cancer, Mol Cancer Ther. 2012 Jan;11(1):87-97. Epub 2011 Dec 15

Abstract: Advanced prostate cancer is the second leading cause of cancer-related deaths among American men. The androgen receptor (AR) is vital for prostate cancer progression, even in the face of castrate levels of serum testosterone following androgen ablation therapy, a mainstay therapy for advanced prostate cancer. Downregulation of superoxide dismutase 2 (SOD2), a major intracellular antioxidant enzyme, occurs progressively during prostate cancer progression to advanced states and is known to promote AR activity in prostate cancer. Therefore, this study investigated the effects of SOD mimetics on AR expression and function in AR-dependent LNCaP, CWR22Rv1, and LAPC-4AD prostate cancer cells. Treatment with Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a SOD mimetic, not only lowered cellular superoxide levels but also concomitantly attenuated AR transcriptional activity and AR target gene expression in a dose- and time-dependent manner, in the presence and absence of dihydrotestosterone, the major endogenous AR agonist. Inhibition of AR by Tempol was mediated, in large part, by its ability to decrease AR protein via increased degradation, in the absence of any inhibitory effects on other nuclear receptors. Inhibitory effects of Tempol on AR were also reproducible with other SOD mimetics, MnTBAP and MnTMPyP. Importantly, effects of Tempol on AR function were accompanied by significant in vitro and in vivo reduction in castration-resistant prostate cancer (CRPC) survival and growth. Collectively, this study has shown for the first time that SOD mimetics, by virtue of their ability to suppress AR function, may be beneficial in treating the currently incurable CRPC, in which SOD2 expression is highly suppressed.



The role of inflammation and immunity in the pathogenesis of androgenetic alopecia.

Magro CM, Rossi A, Poe J, Manhas-Bhutani S, Sadick N.

Abstract

Background: Female pattern hair loss affects many women; its pathogenetic basis has been held to be similar to men with common baldness. Objective: The objective of this study was to determine the role of immunity and inflammation in androgenetic alopecia in women and modulate therapy according to inflammatory and immunoreactant profiles. Materials and Methods: 52 women with pattern hair loss (AA) underwent scalp biopsies for microscopic assessment and immunofluroescent studies. In 18 patients, serologic assessment for antibodies to androgen receptor, estrogen receptor and cytokeratin 15 was conducted. Results: A lymphocytic folliculitis targeting the bulge epithelium was observed in many cases. Thirty-three of 52 female patients had significant deposits of IgM within the epidermal basement membrane zone typically accompanied by components of complement activation. The severity of changes light microscopically were more apparent in the positive immunoreactant group. Biopsies from men with male pattern hair loss showed a similar pattern of inflammation and immunoreactant deposition. Serologic assessment for antibodies to androgen receptor, estrogen receptor or cytokeratin 15 were negative. Combined modality therapy with minocycline and topical steroids along with red light produced consistent good results in the positive immunoreactant group compared to the negative immunoreactant group. Conclusion: A lymphocytic microfolliculitis targeting the bulge epithelium along with deposits of epithelial basement membrane zone immunoreactants are frequent findings in male pattern hairloss and could point toward an immunologically driven trigger. Cases showing a positive immunoreactant profile respond well to combined modality therapy compared to those with a negative result. J Drugs Dermatol. 2011;10(12):1404-1411.



Gensing extract for Hair Loss treatment

November 14th, 2011

Dr Proctor notes: There have long been reports that gensing extract has some hair loss treatment efficacy.

J Ethnopharmacol. 2011 Sep 21. [Epub ahead of print]

Fructus panax ginseng extract promotes hair regeneration in C57BL/6 mice.

Park S, Shin WS, Ho J.

Radix panax ginseng (Panax ginseng C.A. Meyer, Araliaceae, RPG) has been documented to possess hair growth activity and widely used to treat alopecia, while no report has been issued to date on the effect of Fructus panax ginseng (FPG) on hair regeneration.

MATERIALS AND METHODS:

To investigate the effects of FPG extract on the proliferation of human hair dermal papilla cells (DPCs) and on the promotion of hair regeneration in C57BL6 mice, cell proliferation was evaluated in cultured DPC by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of Bcl-2 and Bax by immunoblot assay. We also compared the effects of topical FPG extract (1 and 10mg/ml, 100ìl/d) with the effects of minoxidil as a positive control (5%, 100ìl/d) or vehicle control (30% ethanol) on the depilation-induced hair cycling in 7 week-old-C57BL/6 mice.

RESULTS:

FPG extract significantly increased the proliferation of DPCs in dose and time dependent manners . FPG extract also enhanced Bcl-
2 expression and decreased Bax expression compared with control. Moreover, significant elongations of anagen phase during hair cycle after application of FPG were evaluated by photographical and histological observations.

CONCLUSIONS:

FPG extract improves the cell proliferation of human DPCs through anti apoptotic activation. Topical administration of FPG extract might have hair regeneration activity for the treatment of hair loss.

Slightly edited for hair loss blog use

Dr Proctor's Hair loss treatment website.


Wnt- and Follistatin Containing Treatment for Hair Loss
November
9th, 2011
Dr Proctor sez: Some of our agents may work thru some of the these same pathways.

J Drugs Dermatol.
2011 Nov 1;10(11):1308-12.

Hair Regrowth Following a Wnt- and Follistatin Containing Treatment: Safety and Efficacy in a First-in-Man Phase
1 Clinical Trial.

Zimber MP, et al

Abstract

Research has shown the importance of follistatin, Wnt
7a, and wound healing growth factors on the stimulation of bulge cells and inter-follicular stem cells to induce hair growth. We have studied the effects of a bioengineered, non-recombinant, human cell-derived formulation, termed Hair Stimulating Complex (HSC), containing these factors to assess its hair growth activity in male pattern baldness. HSC showed in vitro Wnt activity and contained follistatin, KGF, and VEGF. The clinical study was a double-blind, placebo-controlled, randomized single site trial and was designed to evaluate safety of the HSC product and assess efficacy in stimulating hair growth. All 26 subjects tolerated the single, intradermal injection of HSC procedures well, and no signs of an adverse reaction were reported. Histopathological evaluation of the treatment site biopsies taken at 22 and 52 weeks post-treatment revealed no abnormal morphology, hamartomas, or other pathological responses. Trichoscan image analysis of HSC-treated sites at 12 and 52 weeks showed significant improvements in hair growth over the placebo. At the initial 12-week evaluation period, HSC-treated sites demonstrated an increase in hair shaft thickness (6.32.5% vs. -0.632.1%; P=0.046), thickness density (12.84.5% vs. -0.22.9%; P=0.028), and terminal hair density (20.6±4.9% vs. 4.4±4.9%; P=0.029). At one year, a statistically significant increase in total hair count (P=0.032) continued to be seen. These results demonstrate that a single intradermal administration of HSC improved hair growth in subjects with androgenetic alopecia and is a clinical substantiation of previous preclinical research with Wnts, follistatin, and other growth factors associated with wound healing and regeneration. J Drugs Dermatol. 2011;10(11):1308-1312.

Slightly edited for hair loss blog use.



Minoxidil associated with eye changes ?
September
28th, 2011

Dr Proctor sez: To my knowledge, this potentially-serious eye problem does not happen when minoxidil is taken orally. So most likely, it is just coincidental. But I will keep my eye on it....

Cutan Ocul Toxicol.
2011 Sep 23

Central chorioretinopathy associated with topical use of minoxidil
2% for treatment of baldness.

Scarinci F, et al

Abstract

Purpose: Minoxidil is one of the drugs approved for the treatment of androgenetic alopecia or male pattern hair loss. This article presents a case of central serous chorioretinopathy after application of topical minoxidil solution. Methods: We examined a
37-year-old man who complained of a positive relative scotoma, metamorphopsia and impaired dark adaptation involving the right eye. The patient reported an 8 month history of daily topical use but denied previous treatment with other drugs. Dilated fundus examination of right eye revealed central swelling located over the macula. Optical coherence tomography showed the presence of subretinal fluid. Fluorescein angiography disclosed one focal hyperfluorescent spot in the foveal area with minimal pigmentary changes limitated to that area. The patient was diagnosed with central serous chorioretinopathy (CSC) potentially related to an 8 month topical minoxidil solution administration. One month after the drug was discontinued, normal findings were found upon reexamination. The patient reported no previous episode of CSC. Conclusion: Major systemic side effects from topical solution of minoxidil are rare. To our knowledge, this is the first reported case of a central serous chorioretinopathy associated with long-term use of this drug.

Hair loss hair loss treatment and hair regrowth

Dr Proctor's Hair loss treatment website.



Libido Decrease, Erectile Dysfunction, and Depression with Propecia
March
21st, 2011
Traish, A. M., Hassani, J., Guay, A. T., Zitzmann, M. and Hansen, M. L. (
2011), Adverse Side Effects of 5á-Reductase Inhibitors Therapy: Persistent Diminished Libido and Erectile Dysfunction and Depression in a Subset of Patients. The Journal of Sexual Medicine, 8: 872884. doi: 10.1111/j.1743-6109.2010.02157.x

Introduction.
5á-reductase inhibitors (5á-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
5á-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
5á-RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia.
Traish AM, Hassani J, Guay AT, Zitzmann M, and Hansen M. Adverse side effects of
5á-reductase inhibitors therapy: Persistent diminished libido and erectile dysfunction and depression in a subset of patients. J Sex Med 2011;8:872844.


5á-Reductase inhibitor treatment for hair loss-- potential side-effects
November
12th, 2010
Dr Proctor sez: This is an interesting review on the potential side-effects of (e.g.) finasteride and dutasteride used for hair loss treatment


5á-Reductase inhibitor therapy: Should physicians be concerned with persistent diminished libido, erectile dysfunction and depression in a subset of patients?

Background:
5á-reductase inhibitors have been approved for treatment of androgenetic alopecia and benign prostatic hypertrophy (BPH) with marked clinical efficacy. The magnitude of adverse effects of these agents on sexual function and quality of life varies considerably among patients and remains in question. However, to what extent 5á-redctase inhibitor therapy adversely affects sexual function, depression and quality of life is yet to be addressed? More importantly, should physicians be concerned regarding these adverse effects, especially when treating benign conditions of androgenetic alopecia and BPH?


Abdulmaged M. Traish, John Hassani, Andre T. Guay, Michael Zitzmann, Michael L. Hansen
journal of men's health
October
2010 (Vol. 7, Issue 3, Page 307)

Dr Proctor's Hair loss treatment website.
Review of Finasteride ( Propecia ) in the treatment of male pattern hair loss
October
22nd, 2010

Dr Proctor sez: The following paper is a very good general review of the literature on hair loss treatment with finasteride ( Propecia )


Evidence-Based Dermatology: Review Efficacy and Safety of Finasteride Therapy for Androgenetic Alopecia A Systematic Review

José Manuel Mella, MD; María Clara Perret, MD; Matías Manzotti, MD; Hugo Norberto Catalano, MD, PhD; Gordon Guyatt, MD, PhD

Arch Dermatol.
2010;146(10):1141-1150. doi:10.1001/archdermatol.2010.256

Context Androgenetic alopecia is the most common form of alopecia in men.

Objective To determine the efficacy and safety of finasteride therapy for patients with androgenetic alopecia.

Data Sources: MEDLINE, EMBASE, CINAHL, Cochrane Registers, and LILACS were searched for randomized controlled trials reported in any language that evaluated the efficacy and safety of finasteride therapy in comparison to treatment with placebo in adults with androgenetic alopecia.

Study Selection and Data Extraction: Two reviewers independently evaluated eligibility and collected the data, including assessment of methodological quality (Jadad score). Outcome measures included patient self-assessment, hair count, investigator clinical assessment, global photographic assessment, and adverse effects at short term (
12 months) and long term (24 months). Heterogeneity was explored by testing a priori hypotheses.

Data Synthesis: Twelve studies fulfilled the eligibility criteria (
3927 male patients), 10 of which demonstrated a Jadad score of 3 or more. The proportion of patients reporting an improvement in scalp hair was greater with finasteride therapy than with placebo treatment in the short term (relative risk [RR], 1.81 [95% confidence interval (CI), 1.42-2.32]; I2, 64%) and in the long term (RR, 1.71 [95% CI, 1.15-2.53]; I2, 16%); both results were considered to have moderate-quality evidence. The number needed to treat for 1 patient to perceive himself as improved was 5.6 (95% CI, 4.6-7.0) in the short term and 3.4 (95% CI, 2.6-5.1) in the long term. Moderate-quality evidence suggested that finasteride therapy increased the mean hair count from baseline in comparison to placebo treatment, expressed as a percentage of the initial count in each individual, at short term (mean difference [MD], 9.42% [95% CI, 7.95%-10.90%]; I2, 50%) and at long term (MD, 24.3% [95% CI, 17.92%-30.60%]; I2, 0%). Also, the proportion of patients reported as improved by investigator assessment was greater in the short term (RR, 1.80 [95% CI, 1.43-2.26]; number needed to treat, 3.7 [95% CI, 3.2-4.3]; I2, 82%) (moderate-quality evidence). Moderate-quality evidence suggested an increase in erectile dysfunction (RR, 2.22 [95% CI, 1.03-4.78]; I2, 1%; number needed to harm, 82.1 [95% CI, 56-231]) and a possible increase in the risk of any sexual disturbances (RR, 1.39 [95% CI, 0.99-1.95]; I2, 0%). The risk of discontinuing treatment because of sexual adverse effects was similar to that of placebo (RR, 0.88 [95% CI, 0.51-1.49]; I2, 5%) (moderate-quality evidence).

Conclusion: Moderate-quality evidence suggests that daily use of oral finasteride increases hair count and improves patient and investigator assessment of hair appearance, while increasing the risk of sexual dysfunction.

Iron deficiency and diffuse nonscarring scalp alopecia in women
October
15th, 2010

Dr Proctor notes: The relationship between iron deficiency and hair loss in women is still not very well worked out.

J Am Acad Dermatol.
2010 Sep 29.

Iron deficiency and diffuse nonscarring scalp alopecia in women: More pieces to the puzzle.
St Pierre SA, et al

Abstract
The relationship between nonscarring scalp alopecia ( hair loss ) in women and iron deficiency continues to be a subject of debate. We review the literature regarding the relationship between iron deficiency and nonscarring scalp alopecia and describe iron-dependent genes in the hair follicle bulge region that may be affected by iron deficiency. We conclude with a description of our approach to the diagnosis and treatment of nonscarring alopecia in women with low iron stores. Limitations include published studies with small numbers of patients, different study designs, and absence of randomized, controlled treatment protocols. Additional research regarding the potential role of iron during the normal hair cycle is needed, as is a well-designed clinical trial evaluating the effect of iron supplementation in iron-deficient women with nonscarring alopecia.

Copyright ©
2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Edited for hair loss blog



Azathioprene in treatment of hair loss in alopecia areata
October
6th, 2010
Could azathioprine be considered as a therapeutic alternative in the treatment of alopecia areata? A pilot study

International Journal of Dermatology,
10/05/2010

Farshi S et al. – No significant statistical difference was observed with respect to gender before and after azathioprine treatment. Treatment with azathioprine as a systemic monotherapy clinically produces relevant improvement in moderate–to–severe hair loss due to alopecia areata. Generally azathioprine is a low–cost and well–tolerated drug and with controlled studies on larger number of patients, long–term efficacy and safety of this treatment should be investigated.

Edited for hair loss treatment blog

Dr Proctor's Hair loss treatment website.
Posted in Welcome

Hair Follicle Regrowth and Regeneration
September
13th, 2010

Dr Proctor: Being able to regrow and multiply hair follicles is an important step in the treatment of hair loss.

Regen Med.
2009;4:667

Hair follicle neogenesis induced by cultured human scalp dermal papilla cells.
Qiao J,-et al

AIM: To develop a method by which human hair follicle dermal papilla cells can be expanded in vitro while preserving their hair-regrowth potential for use in follicular cell implantation, a cellular therapy for the treatment of hair loss. ...snip..

RESULTS: ....( Hair follicle ) cultures from numerous donors reproducibly resulted in an expansion that averaged approximately five population doublings per passage. Furthermore, the cells consistently induced hair formation in an in vivo graft assay. Grafted DP cells appeared in DP structures of newly formed hairs, as well as in the dermal sheath and in the dermis surrounding follicles. Induced hair follicles persisted and regrew after being plucked
11 months after grafting. A process for the propagation of human DP cells has been developed that provides significant expansion of cells and maintenance of their hair-regrowth inductive capability, overcoming a major technical obstacle in the development of follicular cell implantation as a treatment for hair loss.

Edited for hair loss treatment blog use.



Hair loss treatment
September
11th, 2010
J Proteome Res.
2010 Aug 19.

Trichohyalin is a Potential Major Autoantigen in Human Alopecia Areata.

Leung MC, et al

Abstract
Several lines of evidence support an autoimmune basis for hair loss due to alopecia areata (AA), a common putative autoimmune hair loss disorder. However, definitive support is lacking largely because the identity of hair follicle (HF) autoantigen(s) involved in its pathogenesis remains unknown. Here, we isolated AA-reactive HF-specific antigens from normal human scalp anagen HF extracts by immunoprecipitation using serum antibodies from
10 AA patients. Samples were analyzed by LC-MALDI-TOF/TOF mass spectrometry, which indicated strong reactivity to the hair growth phase-specific structural protein trichohyalin in all AA sera. Keratin 16 (K16) was also identified as another potential AA-relevant target HF antigen. Double immunofluorescence studies using AA (and control sera) together with a monoclonal antibody to trichohyalin revealed that AA sera contained immunoreactivity that colocalized with trichohyalin in the growth phase-specific inner root sheath of HF. Furthermore, a partial colocalization of AA serum reactivity with anti-K16 antibody was observed in the outer root sheath of the HF. In summary, this study supports the involvement of an immune response to anagen-specific HFs antigens in AA and specifically suggests that an immune response to trichohyalin and K16 may have a role in the pathogenesis of the enigmatic disorder.

Prolactin and Hair loss
August
23rd, 2010
Am J Pathol.
2006 March; 168(3): 748756.
doi:
10.2353/ajpath.2006.050468. PMCID: PMC1606541


Title: Human Scalp Hair Follicles Are Both a Target and a Source of Prolactin, which Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven Hair Follicle Regression

Kerstin Foitzik et al

From
"discussion" section

" Here, we provide the first evidence that human scalp HFs not only express functional PRL-R but also serve as an important extrapituitary site of PRL expression on the gene and protein level (Figure 1, A–D, and Figure 4). Given that human skin has been calculated to display ~5 million HFs, this calls attention to a very substantial, newly identified source of potential PRL synthesis in humans. This deserves further scrutiny and characterization, eg, in healthy versus inflamed human skin, and definition of the quantity of HF-derived PRL that is actually secreted systemically and thus exerts genuine endocrine, rather than autocrine or paracrine activities.Although our finding of intracutaneous transcription of the PRL gene in human skin in situ is well in line with the previous finding of PRL transcription in murine skin in vivo and in human cultured dermal fibroblasts, keratinocytes, and sweat glands in vitro,36,39 it conflicts with the report of Slominski and colleagues40 who could not detect PRL mRNA in human skin by RT-PCR. In our experiments, we detected PRL transcripts of the expected length both in human full-thickness skin and in isolated human HFs, using pituitary gland as positive control, and confirmed our data by sequencing the PRL RT-PCR product. The negative PRL expression data of Slominski and colleagues40 may be related to the fact that these investigators studied sun-exposed truncal skin (containing primarily vellus HFs, approximately half of which are in the telogen stage of the hair cycle), whereas we analyzed scalp skin, which is unusually rich in very large terminal HFs, 80 to 90% of which are in anagen VI HF. In addition, we used different primer sequences and PCR conditions than these investigators, who may well have identified an alternatively spliced PRL mRNA variant that could not be detected because of the exonal location of their primers. The sense primer used by Slominski and colleagues40 was located in exon 3, and the anti-sense primer contained both the end of exon 4 sequences and the initial part of exon 5 sequences. In contrast, our sense primer is in exon 2 and anti-sense primer is in exon 4.PRL mRNA as well as PRL and PRL-R immunoreactivity can be detected within the same epithelial human HF compartments (Figure 1, A–D, and Figure 4), and culture of microdissected, denervated, and avascular HFs in the presence of exogenous PRL exerts significant growth-modulatory effects (Figure 1, E–H, and Figure 2, a and b). This supports the hypothesis that PRL acts in an autocrine and/or paracrine manner on locally expressed high-affinity receptors and functions as a catagen-promoting signal in human HFs just as it does in mouse HFs. The strictly epithelial immunoreactivity pattern of PRL and PRL-R identified here for human scalp HFs corresponds well to the one previously described in mice. However, in ovine HFs, PRL-R expression has also been detected in the dermal papilla. Thus, expression of PRL-R seems to be differentially regulated in seasonally dependent HFs (ovine) compared to seasonally independent HFs (mouse, human).Steroid hormones stimulate cognate receptors in the HF epithelium and mesenchyme and change the secretion of potent hair growth modulators such as TGF-â, which then act back on the epithelium. In contrast, the polypeptide hormone PRL seems capable of signaling more directly within the HF epithelium as an autocrine and/or paracrine promoter of apoptosis-driven HF regression. However, our currently available data do not allow us to exclude that the observed HF effects of PRL were mediated at least in part also indirectly. This could happen via the recognized effects of PRL on peripheral androgen27 and estrogen metabolism, and/or via induction of changes in the intrafollicular expression of PRL-sensitive growth factors, cytokines, and enzymes with recognized hair growth-modulatory functions,21 such as TGF-â1,55 vascular endothelial growth factor,2 IGF-2, interferon-ã, and ornithine decarboxylase.58Treatment of isolated human HFs in culture with PRL results in apoptosis-driven HF regression (catagen), decreased proliferation, and increased apoptosis of follicular keratinocytes (Figure 3). These data correspond well to the rapid, premature induction of apoptosis-driven catagen development in murine anagen skin organ culture22 and to the reported catagen induction by PRL in sheep in vivo. However, PRL has also been shown to exert anti-apoptotic functions, eg, in cultured human breast cancer cell lines in vitro, to act as a larval growth hormone and to be required for limb regeneration in amphibians.61 Therefore, the anti-proliferative and proapoptotic properties of PRL in HF epithelium may not extend to all epithelial-mesenchymal interaction systems and may be developmentally controlled.Although it remains to be clarified how PRL exerts its activities on human HFs, we show that PRL is a potent catagen-promoter of human HFs in vitro, with efficacy comparable to that of TGF-â2, yet is lower than that of interferon-ã. We also show that the catagen-promoting activity of PRL is independent of the hypothalamus-pituitary-adrenal axis and systemic hormone levels. It applies to HFs of a mammalian species with mosaic and seasonally independent HF cycling (=human scalp HF). PRL has long been recognized to play a role in hair growth control in seasonally dependent coat changes, because both rising and falling daily plasma PRL levels can induce moulting. The current human data fit well with the previous reports that PRL induces premature catagen in the, also seasonally independent, murine hair cycle22 and that murine PRL-R-null mutants show longer and coarser hair as well as hair cycle perturbations.23 The present data, therefore, underscore the importance of PRL as a hair growth modulator for both seasonally dependent and independent HF cycling across different mammalian species.PRL has also been implicated in the pathogenesis of androgenetic alopecia25 by modulation of androgens, and hyperprolactemia is associated with an androgenetic alopecia-type hair loss pattern, along with hirsutism (in females). Usually, occipital scalp HFs are insensitive to hormones such as androgens. In our experiments we used mostly occipital scalp HFs and additionally frontal HFs. It is therefore particularly interesting that PRL was able to induce catagen in these hormone-insensitive HFs. It is important to mention that PRL may have distinct functions on distinct areas of scalp and body HFs and that this will be an interesting issue to investigate in the future. Recently, it has been shown that neuroendocrine factors mediate stress-induced acne. HFs and the sebaceous glands express functional receptors for stress-related hormones, which are able to modulate androgen metabolism in the sebaceous gland. These up-regulated androgens in the sebaceous gland could also be involved in stress-induced hair loss. Therefore, it will be interesting to investigate whether PRL is able to modulate androgen receptor expression and/or androgen metabolism in the human pilosebaceous unit. In summary, our study shows that human anagen scalp HFs are very sensitive for inhibitory PRL-R-mediated signals. This is clinically relevant, because it provides a reasonable mechanism to explain the, as yet ill-understood, telogen effluvium associated with hyperprolactinemia.25 It also points to novel therapeutic strategies for the management of stress-related and hormonal hair loss in men and women, by use of recently developed PRL-R antagonists...."

Modified for baldness blog


Keywords: hair loss treatment hair regrowth balding minoxidil nano shampoo Dr Droctor tempol hair loss regrowth propecia proxiphen (tm).

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Tags: hair, hair loss, hair loss treatment, hair regrowth, loss, propecia, proxiphen, regrowth, treatment


Prolactin and Hair loss
August
23rd, 2010

Interesting paper on the role of prolactin in the hair cycle. One more thing that seems to drive the hair loss process. Dr Proctor

Am J Pathol.
2006 Mar;168(3):748-56.

Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression.

Foitzik K, et al

Abstract
The prototypic pituitary hormone prolactin (PRL) exerts a wide variety of bioregulatory effects in mammals and is also found in extrapituitary sites, including murine skin. Here, we show by reverse transcriptase-polymerase chain reaction and immunohistology that, contrary to a previous report, human skin and normal human scalp hair follicles (HFs), in particular, express both PRL and PRL receptors (PRL-R) at the mRNA and protein level. PRL and PRL-R immunoreactivity can be detected in the epithelium of human anagen VI HFs, while the HF mesenchyme is negative. During the HF transformation from growth (anagen) to apoptosis-driven regression (catagen), PRL and PRL-R immunoreactivity appear up-regulated. Treatment of organ-cultured human scalp HFs with high-dose PRL (
400 ng/ml) results in a significant inhibition of hair shaft elongation and premature catagen development, along with reduced proliferation and increased apoptosis of hair bulb keratinocytes (Ki-67/terminal dUTP nick-end labeling immunohistomorphometry). This shows that PRL receptors, expressed in HFs, are functional and that human skin and human scalp HFs are both direct targets and sources of PRL. Our data suggest that PRL acts as an autocrine hair regrowth modulator with catagen-promoting functions and that the hair growth-inhibitory effects of PRL demonstrated here may underlie the as yet ill-understood hair loss in patients with hyper-prolactinemia.

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