The science of treating hair loss with Shapiro MD

Understanding Hair

 Hair is a protein filament with biological functions in sense, heat regulation, and ultraviolet radiation protection. Its complex multicellular filament structures allow it to adaptively regulate heat; insulating via goosebumps, and cooling via sweat evaporation; and transmit mechanical forces perceived as the sense of touch. While these functions are not critical for human survival, they remain critical for other mammals. Follicle defects can lead to loss of fur or faulty coloration, quickly leading to death from cold or predation. Proper hair growth can only occur from correctly functioning follicles.

In human beings, hair plays important roles in human communication, in both social and sexual contexts. This is evidenced by the significant amounts of time and money devoted to hair care, in the form of shaving, hairdresser appointments, and hair care products. Hair growth disorders have been recognized to cause substantial psychological distress.

 

Hair growth is typically diminished by age and strongly diminished by the elevation of DHT levels. In particular, elevation of DHT levels in hair follicles negatively affects the growth environment and consequently the hair growth cycle, which results in thinning or hair loss.

 

The Hair Growth Cycle

There are approximately 100,000 hair follicles on the scalp alone. Hair follicles can be considered the root from which hair grows and serve a critical role in the development of hair and hair loss. In order to understand how hair loss occurs, the hair growth cycle must first be understood. We note that each hair follicle on the human body must be in one of the three stages of the hair growth cycle: Anagen, Catagen, and Telogen.

 

Anagen (The Growth Phase)

The anagen phase is the most critical stage where all hair growth occurs. The anagen phase is composed of six distinct subphases in which new hair cells are formed, undergo mitosis or cell division rapidly, acquire pigmentation (hair color), visibly emerge from the follicle, and continue increasing in length.

This phase represents the longest stage of the hair growth cycle, typically lasting 2-8 years for healthy individuals. The average span of time a strand of hair will remain in this phase is largely determined by genetics. Hair strands in the anagen phase remain connected to the blood supply, which nourishes the strand and allow for the continuation of growth. On average, hair typically grows at a rate of approximately 1.25cm every 4 weeks, or roughly 6 inches per year. In a normal hair growth cycle, 85-90% of the hairs growing on the scalp are in the anagen phase at any given time.

 

Catagen (The Transition Phase)

The catagen phase represents the transition phase. During this phase, hair follicles will shrink, effectively detaching strands of hair from their blood supply. This not only leads to the cessation of hair growth for the strand, but also serves to slowly squeeze the hair shaft upwards. This transitional stage typically takes two weeks to complete and is critical for the hair follicle’s continued ability to grow hair. It is largely hypothesized that the catagen phase allows for the recovery or renewal of hair follicles before the growth of new hair.

Hair follicles move from the anagen phase to the catagen phase from signals sent out from the body, with normal signaling putting 1-3% of all hair follicles in catagen at any given time.

Telogen (The Recovery Phase)

The telogen phase represents the resting period for hair follicles. During this phase, follicles remain dormant for one to four months. The telogen phase is evidenced by the recovery of hair follicles, seen through the growth of epidermal cells lining the follicle channel. The growth of epidermal cells may also play a role in holding disconnected hair strands in place until new growth is able to take its place. Generally, 10-15% of hair follicles on the scalp are in this phase of the cycle at any given time.

 

Exogen (The Shedding Phase)

The exogen phase marks the return to the anagen growth phase. After hair follicles recover sufficiently in the telogen phase, they begin growing back to their normal size. This simultaneously allows for the growth of new strands as described in the anagen phase and also allows for the release of old hair strands. Commonly referred to as shedding, the release of hair from hair follicles in the exogen phase results from the relaxation of mechanical forces responsible for holding detached strands in place. New strands emerge within two weeks of the completion of the telogen phase.

On average, 50-150 strands of hair are shed daily.

A Better Understanding of Hair Loss

Proper hair growth relies on the delicate ratio follicles spend in their respective anagen, catagen and telogen phases. Despite the average shedding of 50-150 strands of hair per day, this amount often goes visibly unnoticed due to the substantial amount of hair growth occurring at the same time. It is only when new hair growth is being matched or surpassed by shedding that the phenomenon of hair loss becomes noticeable.

Hair loss typically stems from a disruption in the hair growth cycle, with follicles spending significantly less time in the anagen phase. This results in not only shorter hair, but also a drastic shift in the ratio follicles spend in each phase. When follicles reach the catagen and telogen phases faster than normal, excess shedding begins, quickly progressing into thinning and baldness. In fact, hair loss could really be understood as inadequate hair growth due to its progressive, non-acute nature.

The effects of DHT on the hair growth cycle…

A complex biochemical system exists in the regulation of hair follicle physiology and activity. It is a source and target of various neurohormones, neuropeptides, and neurotransmitters. While many of the complex interactions have yet to be identified or understood, dihydrotestosterone, a neurohormone has been identified to play a pivotal role in the overwhelming majority of hair loss.

The effects of DHT reduction can be clearly seen in the clinical results of finasteride, a drug that is a competitive and specific inhibitor of the Type II- isozyme of 5α-reductase, an enzyme responsible for the conversion of testosterone into 5α-DHT. In a 48 week study conducted by Van Neste et al, 212 men age 18-40 were randomized into placebo or daily treatment with 1mg finasteride. The results were particularly striking.

Compared to the baseline where 62% of hair were in the anagen phase, the finasteride group saw net improvement compared with placebo of both total and anagen hair counts of 8.3% (+/- 1.4%) and 26% (+/- 3.1%) respectively (P<0.001). The finasteride treatment group also saw net improvement in the anagen to telogen ratio of 47%.

In other words, reduction of DHT levels leads to increased total hair counts, lengthened anagen growth phase relative to telogen rest phase, and increased percentage of hair follicles in the anagen phase. The increase in the total hair count compared to baseline reveals that reduction of DHT promotes the re-entry of resting telogen follicles into the anagen phase, including follicles exhibiting abnormally prolonged telogen phase. Abnormally prolonged telogen phase follicles typically shed their telogen hair shaft before the production of a new hair shaft, contributing to thinning and balding.

Based upon the highly selective nature of the finasteride drug, these results can be used to infer the effects of DHT on the hair growth cycle.

•     DHT shortens the anagen growth phase and lengthens the telogen rest phase.
•     DHT reduces the percentage of hair follicles in the anagen phase relative to catagen and telogen phases.
•     DHT can eventually prevent hair follicles from entering the anagen phase altogether.

DHT, a potent neurohormone, has been shown to stimulate TGF-β1, TGF-β2, DKK1 and Interleukin 6, all of which are powerful neuropeptides or proteins which contribute to the miniaturization of hair follicles. It has been proposed that the hair loss in pattern hair loss is the consequence of repeated miniaturization of the hair follicles through shortened hair growth cycles. Additionally, the diameter or thickness of hair and pigmentation or color has been shown to diminish in tandem with the reduction of follicle size.

Miniaturization of hair follicle size may contribute the shortening of the anagen phase. The duration of the anagen phase is the primary determinant of hair length, and progressive hair follicle miniaturization has been shown to reduce the anagen to telogen ratio from 12:1 to 5:1. Through this disruption in the hair growth cycle, the average anagen phase can shorten to the point where new hairs will no longer be able to grow enough to reach the skin surface, leading to the visible phenomena of hair loss.

SAW PALMETTO, EPIGALLOCATECHIN-3-GALLATE, AND CAFFEINE : THREE NATURAL POTENT DHT BLOCKERS

Saw Palmetto Berry

Saw Palmetto Berry, also known as serenoa repens, has been studied extensively for its DHT blocking activity. Used since the 1700s as folk medicine for urinary and prostate conditions, Saw Palmetto’s activity as a competitive, non-selective inhibitor for Type I and II isozymes of 5α-reductase was later characterized in the 1900s. Following the success of finasteride in the treatment of hair loss through 5α-reductase inhibition, studies were run to explore Saw Palmetto’s potential in treating androgenetic alopecia.

In a two-year study, male patients treated with an oral saw palmetto extract exhibited a significant increase in hair growth. Participants in the study included 100 men from the age of twenty to forty. 38% of participants saw an increase in hair count and over 52% grew or maintained hair density, recorded at study start baseline. No adverse events were reported.

Saw Palmetto’s Anti-inflammatory effects may contribute to follicle health

Additionally, Saw Palmetto has been shown to contain the antioxidants epicatechin and methyl gallate, which have been shown to reduce oxidative damage to cells and reduce inflammation. These effects may support hair growth through the reduction of inflammation and follicular damage. Increased inflammation has long been recorded in patients with androgenetic alopecia, this may be a result from DHT, which has been shown to stimulate TGF and Interleukin-6, which play pivotal roles in inflammatory processes. Inflammation often leads to cell damage, and chronic inflammation often results in fibrosis or scar tissue. It has been suggested that fibrosis contributes to follicle miniaturization by reducing oxygen and nutrient flow, diminishing tissue integrity. Female patients with androgenetic alopecia responded positively to combined modality therapy based upon their immunoreactant profile.

Topical Application of Saw Palmetto Increased Hair Density

The benefit seen from Saw Palmetto is supported by its DHT-blocking activity. In a study from 2001 conducted by Marks et al and published in the journal Urology, it was published that administration of a saw palmetto herbal blend can lead to a reduction of DHT levels by 32%. Saw palmetto may also act upon the hair follicles; its ability in reducing DHT’s ability to bind to androgen receptors in the hair follicles was demonstrated in 2009. This same study demonstrated saw palmetto’s ability to work topically, where topical application in 62 adults for three months led to an increase in hair density by 35%.

Green Tea Extract

Epigallocatechin-3-Gallate, or EGCG, is one of the active constituents of green tea. In the February 2003 issue of The Journal of Nutrition, researchers from Harvard Medical School reported that green tea significantly reduced the concentration of DHT in the blood. Subsequent research has revealed that EGCG works to inhibit the metabolism of testosterone into DHT and suppresses androgen activity by repressing the transcription of the androgen receptor gene.

EGCG, as part of the family of catechins, also demonstrates potent antioxidant properties, which may help stop the progression of hair loss by mitigating follicular damage. EGCG also belongs to the structural class of polyphenols, which are reputed to hold a number of positive health benefits including the modulation of inflammatory factors. EGCG’s role as a polyphenol may be responsible for the promotion of hair growth seen in a study conducted on hair follicles ex vivo and cultured dermal papilla cells (DPC).

DPCs have been an area of substantial research interest for the treatment of hair loss. DPCs play a pivotal role in the development and growth of hair follicles and the interactions that govern the production of hair. EGCG has been shown to stimulate the growth of DPCs in vitro with the proposed mechanisms of upregulating phosphorylated Erk and Akt and increasing the Bcl-2/Bax ratio. In combination with EGCG’s role in the inhibition of DHT production, EGCG from green tea appears to contribute to hair growth through two distinct pathways.

Caffeine

Caffeine is primarily known for its global use as a stimulant in coffee and energy drinks. Lately, it has been increasingly utilized in cosmetic products due to its high biological activity and ability to easily penetrate the skin barrier. Caffeine has been noted for its rare characteristic to be both soluble in water and hydrophobic enough to pass through biological membranes. This allows for caffeine to be well suited for topical applications.

It has been shown to have powerful antioxidant properties, prevent the excess buildup of fat in cells, and protect against UV radiation. UV radiation has been noted to play a role in reducing pigmentation and the thickness of hair shafts. In addition to these effects, it is used in cosmetic formulations for its ability to increase the microcirculation of blood in the skin.

The anagen phase is characterized by the hair shaft’s continued connection to the blood supply. It is only after hair shaft is disconnected from the blood supply by catagen processes that the shaft ceases growth. Reduced oxygen flow stemming from diminished blood flow has the direct consequence of diminishing tissue integrity, which results in follicular miniaturization when localized to the scalp.

Caffeine exhibits a multi-modal effect resulting from its ability to act upon various biological processes. While it is best known for its antagonism of adenosine receptors responsible for its stimulant and wakefulness effects, caffeine also acts an inhibitor of certain enzymes such as phosphodiesterase (leading to reduction of inflammatory activity, degradation of fats via lipolysis, and improved circulation) and 5α-reductase.

These properties demonstrate caffeine’s triple-threat ability in addressing the factors contributing to hair loss. Notably, caffeine’s mechanistic properties are remarkably similar to minoxidil, an FDA approved treatment for hair loss that works by improving blood flow to the scalp. A study conducted by Fischer et al, published in 2014 by the British Journal of Dermatology, appears to confirm this, with differential effects of caffeine noticed on hair shaft elongation, [hair] matrix and outer root sheath keratinocyte proliferation, and IGF 1/TGF activity regulation in both male and female hair follicles in vitro. Caffeine’s effect in male hair follicles is particularly pronounced, where evidence of caffeine’s ability to interfere with testosterone activity in hair follicles was reported by Fischer et al in the International Journal of Dermatology. The same study demonstrated the promise of topical solution where caffeine was shown to have a fast and high penetration through hair follicles. An open label study conducted in 2017 found that a 0.2% caffeine solution saw comparable results to a 5% minoxidil solution in men, where the caffeine saw an improvement in the anagen ratio of 10.59% compared to the minoxidil arm’s 11.68% in a 6 month period.

SYNERGISTIC EFFECTS BETWEEN VARIOUS DHT BLOCKERS

Inspired by the current body of work on finasteride and DHT’s role on hair follicles, a formulation containing Saw Palmetto, Green Tea EGCG and Caffeine was created. This formulation was refined then tested as a topical solution in a dermatology clinic for its patients experiencing androgenetic hair loss. The trial was performed under informed consent in compliance with legal and ethical rules of the United States of America. Patients were asked to try this topical combination for 6 months with the aim of improving the thickness, appearance, and growth rate of hair.

The combination was conceived to treat the underlying factors upregulating hair loss through DHT.

In the initial trial run, several patients at varying stages of hair loss used the topical application daily. In the majority of patients, surprising results were noticed, potentially revealing that the combination of the three DHT-blocking ingredients worked synergistically in the treatment of hair loss. Treatment with the formulation typically led to visible results after some weeks to few months of daily use. The formulation was well tolerated without occurrence of local or systemic adverse effects.

In response to the promising results seen from the topical formulation, the formulation was adapted as a shampoo, conditioner, and foamer to promote frequent ease of use. This stemmed from patient reports correlating frequent daily applications with improved results. This theory seemed highly plausible due to the constant formation of DHT through natural biological processes.

Hair loss is generally a progressive condition. The results from the topical solution demonstrated the effectiveness of the formulation in improving the thickness, growth, and coloration of hair over a period of time.

 SHAPIRO MD: A HAIR LOSS SOLUTION

The original topical solution and its later shampoo, conditioner, foamer formulations were developed at the Gardens Dermatology Clinic in Palm Beach, Florida based on an exhaustive understanding of both the nutritive needs of hair and the role of DHT in hair loss. The shampoo, conditioner, and foamer was later named Shapiro MD after one of the two co-creators: Dr. Steven Shapiro who runsfounded the Gardens Dermatology Clinic alongside Dr. Michael Borenstein.

The Shapiro MD System is the only hair loss system with products containing the unique combination of three different DHT blockers: Saw Palmetto, EGCG, and Caffeine. These ingredients individually confer additional benefits on the multifactorial system that governs hair loss and growth. The unique formulation provides the scalp, hair follicles and hair with the optimal balance of nutrients, moisture, and DHT blocking activity to halt the primary factor for hair loss and improve the quality of hair.

DHT must be treated at the hair follicle level to restore vitality to hair growth.

 

Composition of Shampoo, Conditioner, and Foamer

Each Shapiro MD product includes our patented combination of the three DHT-blocking active ingredients. All three products are free of sulfates, phthalates, and parabens.

 All Ingredients for each product in the Shapiro MD Product Line is as follows:

 

Shampoo: DI Water, Sodium c14-16 Olefin Sulfonate, Cocamidopropyl Betaine, Cocamide DEA, Dimethiconol, dodecylbenzensulfonate, TEA-dodecylbenzensulfonate, Glycol Distearate, Sodium Chloride, Fragrance, Hydrolyzed Wheat Protein, Guar Hydroxypropyltrimonium Chloride, Epigallocatechin Gallate, Panthenol, Methylchloroisothiazolinone, Methylisothiazolinone, Caffeine, Serenoa Serrulata Fruit Extract, Citric Acid.

Conditioner: Water (Aqua, Propylene Glycol, Dimethicone, Behenamidopropyl Dimethylamine, PPG-3 Benzyl Ether Myristate, Cocos Nucifera (Coconut) Oil, Argania Spinosa Kernel Oil, Aloe Barbadensis Leaf Juice, Hydrolyzed Wheat Protein, Caffeine, Saw palmetto Extract, Glyceryl Stereate, PEG-100 Stereate, Cetearyl Alcohol, Stearalkonium Chloride, Behentrimonium Methosulfate, Cetyl Alcohol, Butylene Glycol, Benzyl Alcohol, Potassium Sorbate, Epigallocatechin Gallate, Sodium Benzoate, Ethyllhexyl Methoxycinnamate, Xanthan Gum, Panthenol, Lactic Acid, Fragrance, Tocopheryl Acetate

 Foamer: Water, Capryl/Capramidopropyl Betain, Epigallocatechin Gallate, Caffeine, Serenoa Serrulata Fruit Extract, Sodium Lactate, Sodium PCA, Creatine, Panthenol, Fructose, Niacinamide, Glycine, Fragrance, Urea, Polysorbate 20, Potassium sorbate, Sodium Benzoate, Benzyl alcohol, Inositol, Dimethyl Isosorbide, Xanthan Gum, Lactic Acid, Citric Acid.

 

Regimen and usage for Shapiro MD Hair Loss System

Many people with various hair types and conditions may benefit from the daily use of the Shapiro MD System in order to:

• Substantially reduce DHT, the primary agent leading to hair loss
• Nourish and hydrate damaged or aged scalp helping rejuvenation
• Improve the look and feel of their hair
• Improve the blood flow to follicles on the scalp
• Reduce or stop the formation of follicular inflammation
• Stimulate additional factors supporting scalp and hair health

 

Use of Shapiro MD Shampoo

The administration of Shapiro MD Shampoo is typically a three-step process.

Step 1: “Cleanse the skin”

Wash the skin and remove x or other external elements and irritants that may have been, water temp etxc.

 Step 2: Nourish and Restore

Apply a thin layer daily etc. and leave in continue daily use until results are visible which may take up to several weeks or months.

 Step 3:Rinse Out

Wet hair and then apply shampoo to hands to mix before applying to sclap. Leave for 2 to 5 minutes before rinsing off, and if possible, leave in for up to 20 minutes at most.

 

Use of Shapiro MD Conditioner

The Shapiro MD Conditioner has been designed for application after the use of the Shapiro MD Shampoo

REFERENCES:

1. Sawaya ME, Price VH. Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. J Invest Dermatol. 1997;109:296–300.
2. Schweikert HU, Wilson JD. Regulation of human hair growth by steroid hormones. I. Testerone metabolism in isolated hairs. J Clin Endocrinol Metab. 1974;38:811–819.
3. Dallob AL, Sadick NS, Unger W, et al. The effect of finasteride, a 5 alpha-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. J Clin Endocrinol Metab. 1994;79:703–706.
4. Hibberts NA, Howell AE, Randall VA. Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp. J Endocrinol. 1998;156:59–65.
5. Kaufman KD, Olsen EA, Whiting D, et al. Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol. 1998;39(4, Part 1):578–589.
6. Kaufman KD. Androgens and alopecia. Mol Cell Endocrinol. 2002;198:89–95.
7. Randall VA. Androgens and human hair growth. Clin Endocrinol (Oxf) 1994;40:439–457.
8. Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev. 2001;81:449–494.
9. Ustuner ET. Baldness may be caused by the weight of the scalp: gravity as a proposed mechanism for hair loss. Med Hypotheses. 2008;71:505–514.
10. Trüeb RM. Molecular mechanisms of androgenetic alopecia. Exp Gerontol. 2002;37:981–990.
11. Levakov A, Vucković N, Dolai M, et al. Age-related skin changes. Med Pregl. 2012;65:191–195.
12. Caso G, McNurlan MA, Mileva I, et al. Peripheral fat loss and decline in adipogenesis in older humans. Metabolism. 2013;62:337–340.
13. Xu XF, De Pergola G, Björntorp P. Testosterone increases lipolysis and the number of beta-adrenoceptors in male rat adipocytes. Endocrinology. 1991;128:379–382.
14. Frederiksen L, Højlund K, Hougaard DM, et al. Testosterone therapy decreases subcutaneous fat and adiponectin in aging men. Eur J Endocrinol. 2012;166:469–476.
15. Dieudonne MN, Pecquery R, Leneveu MC, et al. Opposite effects of androgens and estrogens on adipogenesis in rat preadipocytes: evidence for sex and site-related specificities and possible involvement of insulin-like growth factor 1 receptor and peroxisome proliferator-activated receptor gamma2. Endocrinology. 2000;141:649–656.
16. Corbould A. Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. J Endocrinol. 2007;192:585–594.
17. Shen W, Punyanitya M, Silva AM, et al. Sexual dimorphism of adipose tissue distribution across the lifespan: a cross-sectional whole-body magnetic resonance imaging study. Nutr Metab (Lond) 2009;6:17.
18. Enzi G, Gasparo M, Biondetti PR, et al. Subcutaneous and visceral fat distribution according to sex, age, and overweight, evaluated by computed tomography. Am J Clin Nutr. 1986;44:739–746.
19. Brincat MP, Baron YM, Galea R. Estrogens and the skin. Climacteric. 2005;8:110–123.
20. Hall G, Phillips TJ. Estrogen and skin: the effects of estrogen, menopause, and hormone replacement therapy on the skin. J Am Acad Dermatol. 2005;53:555–568. quiz 569–572.
21. Raine-Fenning NJ, Brincat MP, Muscat-Baron Y. Skin aging and menopause: implications for treatment. Am J Clin Dermatol. 2003;4:371–378.
22. Shu YY, Maibach HI. Estrogen and skin: therapeutic options. Am J Clin Dermatol. 2011;12:297–311.
23. Archer DF. Postmenopausal skin and estrogen. Gynecol Endocrinol. 2012;28(Suppl 2):2–6.
24. Van Pelt RE, Gozansky WS, Hickner RC, et al. Acute modulation of adipose tissue lipolysis by intravenous estrogens. Obesity (Silver Spring) 2006;14:2163–2172.
25. Magerl M, Tobin DJ, Müller-Röver S, et al. Patterns of proliferation and apoptosis during murine hair follicle morphogenesis. J Invest Dermatol. 2001;116:947–955.
26. Paus R, Müller-Röver S, Van Der Veen C, et al. A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. J Invest Dermatol. 1999;113:523–532.
27. Gupta V, Bhasin S, Guo W, et al. Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes. Mol Cell Endocrinol. 2008;296:32–40.
28. Xu X, De Pergola G, Björntorp P. The effects of androgens on the regulation of lipolysis in adipose precursor cells. Endocrinology. 1990;126:1229–1234.
29. Singh R, Artaza JN, Taylor WE, et al. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003;144:5081–5088.
30. Glaser RL, Dimitrakakis C, Messenger AG. Improvement in scalp hair growth in androgen-deficient women treated with testosterone: a questionnaire study. Br J Dermatol. 2012;166:274–278.
31. Jaworsky C, Kligman AM, Murphy GF. Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis. Br J Dermatol. 1992;127:239–246.
32. Mahé YF, Michelet JF, Billoni N, et al. Androgenetic alopecia and microinflammation. Int J Dermatol. 2000;39:576–584.
33. Ellis JA, Stebbing M, Harrap SB. Genetic analysis of male pattern baldness and the 5alpha-reductase genes. J Invest Dermatol. 1998;110:849–853.
34. Propecia (finasteride) prescribing information. Whitehouse Station (NJ): Merck & Co., Inc; 1997.
35. Hajheydari Z, Akbari J, Saeedi M and Shokoohi L. Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia. Indian J Dermatol Venereol Leprol. 2009 Jan;75(10):45-71.
36. P. Morganti, G. Fabrizi, B. James, C. Bruno. Effect of Gelatin-Cystine and Serenoa Repens Extract on Free Radicals Level and Hair Growth J. Appl. Cosmetol. 1998;16:57-64.
37. Ustuner E. Cause of Androgenic Alopecia: Crux of the Matter Plast Reconstr Surg Glob Open 2013 Oct;1(7):e64.
38. Herman A, Herman A.P. Caffeine’s Mechanisms of Action and Its Cosmetic Use Skin Pharmacol Physiol 2013;26:8-14.
39. Tobias F, Uta-Christina H, Peter E. Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro International Journal of Dermatology 2007;46(1):27-35.
40. C. Bussoletti, F. Mastropietro, M.V. Tolaini, L. Celleno Use of a Caffeine Shampoo for the Treatment of Male Androgenetic Alopecia J Appl Cosmetol 2010;28:153-162.
41. R. Dhurat, J. Chitallia, T. W. May, A. M. Jayaraamen, J. Madhukara, S. Anandan, P. Vaidya, A. Klenk An Open-Label Randomized Multicenter Study Assessing the Noninferiority of a Caffeine-Based Topical Liquid 0.2% versus Minoxidil 5% Solution in Male Androgenetic Alopecia Skin Pharmacol Physiol 2018;30(6):298-305.
42. C. Bussoletti, M.V. Tolaini, L. Celleno Efficacy of a cosmetic phyto-caffeine shampoo in female androgenetic alopecia G Ital Dermatol Venereol 2018 doi: 10.23736/S0392-0488.18.05499-8.
43. R. A. Hiipakka, HZ Zhang, W. Dai, Q. Dai, S. Liao Structure-activity relationships for inhibition of human 5α-reductases by polyphenols Biochem Pharmacol 2002;63:1165-1176.