Hair Retention and Regrowth Using Minoxidil, Rogaine, Propecia, Folligen, Tricomin and Other Hair Factors

Scientific clinical proof requires independent clinical investigators who publish the study results regardless of the outcome (positive or negative). For publication of results in a reputable journal, the clinical results are sent to a medical journal. The journal editors then have the manuscript review by two or more experts in the field. Only after their review is the article accepted for publication. Even this does not imply acceptance of the claims. Only after other medical researchers confirm these results are the results accepted as valid.

The FDA has estimated that 300,000 hair growth remedies have been marketed in the United States. Yet only a handful of these have rigorous, published scientific proof that they help hair growth, or hair health or scalp health.

Many hair products are sold say they are "clinically proven" - yet there is no evidence that there ever have been any clinical studies. We have often asked sellers of such products for copies of such studies but have never received a reply to this request. It is more likely that there are no studies.

First, all the studies minoxidil found a high level of hair growth in the placebo group which was about 55% of the effect with minoxidil. The power of the human mind is such that placebo pills often cures diseases nearly as well as an effective pharmaceutical drug. This is why placebo controls are so important.

Second, since men increase hair growth from winter to summer in the Northern hemisphere, virtually any inactive factor tested in this time period, without placebo controls, will give even more "evidence" of hair growth. Just the action of applying a placebo to the hair every day often produces measurable hair growth. Finally, skin irritants such as dinitrobenzene, or just plucking our hair, can induce significant hair growth but produce serious skin damage.

(On the other hand, some scientists are of the opinion that there is no true placebo effect with minoxidil if all variables are carefully accounted for. They find that better measurements eliminate any placebo effect for minoxidil. See James and Rushton 1986, Rushton et al 1989)

Many marketing groups have been selling "hair stimulating" products for years. Yet, they never fund any independent tests of their product. And no papers are on their product are ever published in respectable, peer-reviewed journals. In reality, they have no "hair stimulating" product.

There are only three major types of products that help reverse pattern baldness which are supported by independent scientific research: These are:

             1. Minoxidil (Rogaine) and minoxidil-like agents
             2. DHT blockers such as finasteride (Propecia) and anti- androgens
             3. Skin repair and hair growth agents based on copper-peptides or retinoic acid

A number of other drugs and natural products are sold with hair growth claims but lack evidence of efficacy. These include:

Note: Please thoroughly research all precautions on Minoxidil before purchasing this product.

Minoxidil, developed by the Upjohn Company as Rogaine, works in part by partially enlarging miniaturized follicles and reversing the miniaturization process. This prolongs the growth phase of the hair cycle, allowing the hair to become longer and thicker. With more follicles in the growth phase at the same time, it is possible to see improved coverage of the scalp. Although the growth phase may be prolonged, the follicle will continue to cycle. Several cycles may be necessary before maximum potential hair regrowth can be achieved.

Minoxidil works best for adults experiencing gradually thinning hair or gradual hair loss on top of the head. Rogaine is for men or women with hair loss or thinning that begins at the top of the scalp (Vertex) and where there is a family history of gradual thinning hair or gradual hair loss.

Minoxidil is applied before going to bed and again in the morning. It takes about 4 months of twice-daily treatment before initial results are noticeable. Initial results can include less hair shedding and some new hair growth. The newly regrown hairs may be finer and substantially less pigmented than other full size hairs, however many of these hairs will enlarge and darken as they grow out. After about 12 months of minoxidil use, the maximum benefit is usually achieved, and hair regrowth tends to stabilize.

If minoxidil treatment is discontinued for several months, the regrown hairs will probably be shed, and hair loss will resume. Minoxidil is sold in a solution of water, alcohol, and propylene glycol.

For hair counts in minoxidil studies, marks are made on a specific area on the scalp and all of the non-vellus hairs (hairs thicker and darker than "peach fuzz") were counted at the start of the trial, and then again after a period of time. Pinpoint tattoos are made on the scalp of the subjects to mark the measurement areas and assure that they are exactly the same for both counts.

Male subject hair count increases
(1" diameter circle)
4 months of placebo	4 months of Rogaine	12 months of Rogaine
New hairs = 39 (p<.0005)	New hairs = 72 (p<.0005)	New hairs = 112 (p<.0005)

Female subject vellus hair count increases (1 square centimeter)
Study 1 - USA 8 months of placebo	8 months of Rogaine
New hairs = 11.0 (p<.0004)	New hairs = 22.7 (p<.0004)
Study 2 - International 8 months of placebo	8 months of Rogaine
New hairs = 19.1 (p<.0001)	New hairs = 19.1 (p<.0001)

Comment on placebo effect and hair studies: Although the subjects being studied knew that they had only a 50% chance of receiving the real minoxidil, many believed that they are the ones who are getting the real thing, and they expect results. And, they grew more hair! The placebo effect demonstrates the remarkable power of the human mind, even for such seemingly uncontrollable conditions as stopping hair loss and regrowing hair.

Other clinical studies of minoxidil (Rogaine brand) used 4 categories of hair regrowth to describe observed effectiveness of minoxidil when compared to the placebo lotion:

   1. None: No visible regrowth.
   2. Minimal: Barely discernible regrowth.
   3. Moderate: Readily discernible regrowth.
   4. Dense: Full regrowth similar to non-thinning areas.

Other clinical studies at 27 US medical centers involving over 2,300 patients concluded that minoxidil increases hair growth in both men and women.

Male subject self-evaluation of hair regrowth
4 months of placebo	4 months of Rogaine	4 months of Rogaine
None = 68%	None = 42%	None = 16%
Minimal = 31%	Minimal = 32%	Minimal = 36%
Moderate = 9%	Moderate = 24%	Moderate = 40%
Dense = 2%	Dense = 2%	Dense = 8%
Total = 100%	Total = 100%	Total = 100% (p<.0005)

Upjohn has continued its minoxidil development and tested a 5% minoxidil solution (Rogaine Extra Strength) which is approved by the FDA for treating hair loss. Ronald Trancik, Ph.D, from Pharmacia & Upjohn presented data on 5% Minoxidil at the American Association of Dermatology in March, 1998. In a 120 week study of 5% Minoxidil, hair growth continued until the end of the study. In two other studies using hair count and photographic assessment, the following results were shown:

These results are on the crown area of the head where Minoxidil has the best effect and not on the front. The most common side effects of 5% minoxidil are scalp itch and irritation. It is available over the counter at about $18 to $29 per month. Some report improved results with the simultaneous use of Propecia and/or 0.025% retinoic acid (Retin-A).

Pharmacia & Upjohn 1998 Minoxidil Study - Hair Growth Results
	Moderate/Dense	Minimal	No Change	Loss Of Hair	Unknown
5% Minoxidil	30%	24%	29%	6%	11%
2% Minoxidil	15%	23%	47%	1%	13%
Placebo	7%	22%	61%	N/A	N/A

Some people get benefit from minoxidil, others don't. It seems to work better in women than in men. Minoxidil is much better at helping people retain and improve the hair they still have than in growing new hair.

In people with fine hair, the combination of regrowth plus "deminiaturization" of the existing hair can provide an acceptable cosmetic result about 40-50% of the time. As a bonus, most of these people stop getting balder.

Common cutaneous adverse reactions included erythema, scaling, pruritus, and dermatitis.

Cutaneous blood flow is decreased in pattern baldness and minoxidil increases cutaneous blood flow to the scalp, possibly promoting hair growth by this mechanism. However, other vasodilators do not grow hair.

The stump tailed macaque is a superior animal model for studying pattern baldness (Uno 1987a) They have balding patterns similar to that in humans. Balding begins shortly after puberty occurs in nearly all macaques including females. Uno et al. demonstrated that minoxidil activated resting follicles in the balding scalp inducing follicular enlargement and preventing progression of balding. When treatment was discontinued, all beneficial effects were reversed, and balding progressed. (Uno 1985a, 1985b)

The figure to the left was developed from Uno's meticulous research on the effect of minoxidil through various phases of the hair cell cycle in rat models. Both sets of figures start at T or teleogen. The minoxidil treated skin produces larger hair follicles. It should be emphasized that effects in humans are not this dramatic.

In a 1996 paper Uno (Uno 1996) reported that that topical minoxidil induced an increased rate of DNA synthesis in follicular cells in early anagen but not in nonfollicular cells such as fibrocytes or epidermal keratinocytes. Minoxidil induced a significant increase in DNA synthesis in all follicle cells in a dose-specific manner. They suggest that minoxidil has a specific affinity to hair follicular cells and induced their cell proliferation. Recently, researchers at L'Oreal suggested that minoxidil works by activating PGHS 1 (prostaglandin endoperoxide synthase-1) which helps promote hair growth.

Aminexil (Dercap) is an antifibrosis molecule that is related to minoxidil. This treatment, developed by L'Oreal's Vichy labs, was tested on 130 men and 160 women. It was reported that the daily use of Aminexil for 6 weeks increased hair growth in men by 8%. In clinical study of the women, 66% of women experienced a decrease of hair loss and over 80% reported stronger, thicker hair. The L'Oreal groups posits that hair loss is linked to the accelerated aging of the roots, characterized by fibrosis, which stiffens the roots and compresses the blood vessels that nourish the follicles and deprives them of adequate nourishment. This causes the roots to weaken and damages the follicle. Aminexil is felt to counter the aging process. The cost is about about $42 for a 6 week supply and $11 for Aminexil containing-shampoo and available from www.pharmaworld.com.

If the L'Oreal theory is correct, it may also explain the hair promoting actions of copper-peptides (see below) which have angiogenic properties which stimulate new blood vessel formation which may restore hair follicle nutrition.

At Skin Biology, a significant number of our customers have reported exceptionally strong hair growth when using both copper-peptides and Aminexil. These people report that this gives much better hair growth than does minoxidil.

Cromakalim / BRL 34915 is a potassium (K+) channel opener used in the treatment of heart conditions. Research indicates that works similarly to minoxidil. Upjohn has patented it for potential treatment of hair loss. It stimulates potassium channel conductance and stimulates DNA synthesis in mouse epidermal keratinocyte and whole hair follicle cultures.

Diazoxide (Hyperstat IV, Proglycem) is an anti-hypertensive, potassium channel blocker, that has a positive effect on hair loss. It is reported to produces minimal to moderate hair growth and is FDA approved for lowering blood pressure. It is expensive and must be specially formulated for topical use.

Pinacidil and a close analog PC-1075 are anti-hypertensive drugs and potassium channel blockers similar to minoxidil. They have been reported to stimulate hair growth when applied topically. It is in clinical testing.

The primary sexual hormones are the feminizing estrogens and the masculinizing androgens - testosterone and its derivatives. Sexual hormones do not specifically stimulate or inhibit hair growth. Rather, they act in concert with pre-existing genetic instructions in hair follicles cells in various regions of the body. For example, the estrogens act to stimulate hair growth on the head in women but inhibit facial hair growth. Excessive facial hair growth in women, hirsutism, is stopped by antiandrogenic drugs that act to block the actions of testosterone in women. Conversely, the testosterone hormones inhibit head hair growth in men and women but stimulate hair growth on the face and the generally hair-free body areas. Thus, when considering various hormones and drugs, one must keep in mind that the effects on hair growth depend on the specific area of the body under consideration.

Anti-androgens: Anti-androgens are prescription medications that decrease the action of androgen hormones that occur naturally in the body. Androgen hormones play key roles in triggering hair loss in people with a genetic predisposition to androgens, a condition known as androgenetic hair loss. In men, androgenetic hair loss is commonly referred to as "male pattern baldness" and in women it is "female pattern baldness". Anti-androgens act in a variety of ways, including reducing androgen production, and blocking androgens from attaching to androgen receptor sites on hair follicle cells.

Many hair growth therapies focus on either reducing testosterone or DHT effects in the body. Many men worry about the potential effects of reducing testosterone effects. There is actually very little to worry over.

Blood Testosterone and Employment Status
Occupation	Blood Testosterone Level and Standard Deviation nanograms/deciliter
Unemployed	720 + 12
Production Workers and Assembly Line	705 + 8
Operator and Laborer	695 + 11
Service Industries	690 + 21
Technical and Sales	668 + 9
Professional or Manager	640 + 10
Farmer	626 + 22

An excellent book on testosterone and behavior is James McBride Dabbs "Heroes, Rogues, and Lovers: Testosterone and Behavior" ( McGraw Hill, 2000). The above data is from Hill's studies.

In modern advanced cultures, somewhat lower testosterone appear to be of great benefit. Men with highest testosterone levels have lower incomes, lower social status, more unstable relationships, and more difficulty in life. For our ancestors 20,000 years ago, individual strength and aggression were critical to survival. But obtaining rewards in modern cultures usually require patience, cunning, and interpersonal skills.

The use of anti-androgens and DHT blockers may improve male health. Testosterone has often been suspected as a cause of the increased heart disease in men. Studies of men who were castrated in the 1920's in the USA found that they lived an average of 13.6 years longer than comparable men. In contrast, smoking one pack of cigarettes daily reduces one's life span by an average of 4.9 years. (Hamilton & Mesler 1969)

Effects of Testosterone Levels on Behavior
	Negatives	Positive
High Testosterone	More Unemployment More violent Less stable relationships More Interpersonal conflict Lower social status More arrests and imprisonment	Better at armed combat More muscular Better at concentrating on single project More direct approach to problems Better as trial lawyers Would have an advantage in a more primitive, less civilized society
Moderate	In modern, advanced societies there are few negatives	Higher Income More Stable Relationships More Social Status Higher education Better verbal skills Better as corporate lawyers
Very Low	Little interest in sex Little interest in domination of others	No male pattern baldness Live 13.6 years longer than average men

Finasteride (Propecia and Proscar): Finasteride is a prescription anti-androgen medication developed by Merck Pharmaceuticals and first prescribed for men with enlarged prostrate glands, sold under the brand name Proscar, and used at the 5 milligram per day level. It inhibits the enzyme 5-alpha-reductase that converts testosterone into DHT.

Finasteride as Propecia can stop further hair loss, and may be combined with other medications such as minoxidil to promote hair growth. Propecia is a one-milligram tablet form of finasteride. It is an oral treatment - taken once daily - for hair loss in men. In a two-year clinical studies in men between the ages of 18-41 with mild to moderate hair loss at the top of their heads, Propecia was shown to maintain or increase the amount of hair in 83% of men vs. 28% taking the placebo. A panel of dermatologists evaluating patient photographs found 37 percent of the patients treated with Propecia increased their hair growth, while 7 percent of those taking a placebo showed improvement. 53 percent of the men with frontal hair loss said Propecia treatments improved the appearance of their hair. This is interesting because minoxidil works best at the top of the scalp but more poorly in the frontal area.

Propecia works within about 3 months. Hair grows very slowly, about half an inch a month. Most men begin to see the first benefit of Propecia, slowing of hair loss, as easily as 3 months, and after 6 months begin to experience regrowth.

The side effect among the 1,879 men participating in Propecia clinical trials was decreased libido in 1.8 percent and erectile dysfunction in 1.3 percent. Some young men tell us that they view this decrease in libido drive as calming influence on their mental state.

Propecia is for use by men only and it may cause a birth defect known as hypospadias in a male fetus if used by pregnant women. Merck also studied Propecia in 136 postmenopausal women suffering hair loss. Despite a year of therapy, the women who took Propecia had no more hair than women who got a placebo pill.

Male pattern hair loss is characterized by progressive miniaturization of hair follicles. Finasteride inhibits a key factor responsible for this miniaturization. This leads to a reversal of the process of scalp hair loss in many men. In a recent, double-blind clinical study of men using Propecia for one year presented by Dr. David Whiting and based on microscopic analysis of 4 millimeter punch biopsies from the scalp in 26 patients (14 on finasteride, 12 on placebo pill), found that the drug increase the number of follicles growing terminal hairs by 29% and reduced the follicles growing vellus hair by 6.9% when compared to the placebo group. In normal non-balding men, the ratio of terminal hairs to vellus hairs male head is 6-8 terminal hairs to 1 vellus hair, but in balding men, the ratio ranges between 0.1 to 3.9 terminal hairs to 1 vellus hair. Balding persons on Propecia changed from a starting ratio of 1 terminal hair to 1.7 vellus hairs to final ratio of 1 terminal hair to 1.1 vellus hairs. This data demonstrates that Propecia helped to partially reverse the hair follicle miniaturization process.

A similar study by Dr. Whiting 127 postmenopausal females on Propecia failed to demonstrate a hair stimulating effect of propecia.

Experts estimate that cosmetically significant regrowth will probably be observed in about a quarter of the Propecia users. The reason for the relatively moderate effectiveness of Propecia in reversing baldness is that it counteracts only one (albeit important) factor involved in hair loss, a hormone dihydrotestosterone (DHT) and, of the two types of 5-alpha reductase (both type 1 and type 2) that produce DHT, it only blocks type 2 DHT. Propecia comes in a 1 mg pill form, available by prescription only, and costs about $40-50 per month.

Recent research indicates that the DHT that harms hair follicles comes from the the skin's sebocytes and sweat glands (sebaceous glands) (Chen et al 1996). 5 alpha-Reductase, the enzyme system that converts testosterone into DHT occurs in two enzyme forms. The type 1 represents the 'cutaneous type'; it is located primarily in the skin's sebocytes but also in epidermal and follicular keratinocytes, dermal papilla cells and sweat glands as well as in fibroblasts. The type 2 is located mainly in the seminal vesicles, prostate and in the inner root sheath of the hair follicle.

Propecia® (Finasteride), which has a higher affinity for the type 2 form, is best suited for for controlling prostate enlargement. It also must be administered by pills that spread the drug throughout the body.

Copper ion in the skin is more effective in inhibiting the type 1 form which is primarily producing the DHT that damages follicles and can be administered locally to the skin. Sugimoto et al (Sugimito 1995) found that copper ion is a potent inhibitor of 5-alpha reductase, inhibiting both types of 5-alpha reductase (both type 1 and type 2) that produce DHT and is the only metal to do so. Copper ion inhibits (50% reduction in activity) type 1 alpha reductase at 1.9 micromolar (0.12 micrograms copper ion per milliliter) and type 2 alpha reductase at 19.2 micromolar (1.2 micrograms copper ion per milliliter). No other metal has these effects.

The application of copper-peptides may provide sufficient copper ion into the hair follicle area to block DHT production in the scalp. Metabolically active copper ion (that is, copper ion free to block 5-alpha reductase) in the human body exists at about 1 microgram per milliliter in the blood and less in the skin. While the uptake of ionic copper from copper-peptides applied to the scalp is very low, human experiments by Prof. John Sorenson (University of Arkansas) have found that they can raise copper ion levels in the skin to the effective level of 1 microgram per milliliter.

The red saw palmetto berries of a small palm native to the south east US, or serenoa repens, possess activities that inhibit 5-alpha reductase and the binding of DHT to androgen receptors. In Europe the extract is called Permixon, and is extensively to treat benign prostatic hypertrophy. Numerous European studies have demonstrated its efficacy in reducing prostate hyperplasia in a manner similar to finasteride. It is both a 5-alpha reductase inhibitor and blocks 50% of the uptake of DHT at its target tissue receptor sites. Saw palmetto is very safe, being used by local Native Americans as a food and as a herbal treatment for enuresis, nocturia, atrophy of the testes, impotence, inflammation of the prostate and low libido in men. Many herbalists consider saw palmetto a mild aphrodisiac for men. Women used the berries to treat infertility, painful periods and problems with lactation.

Saw palmetto berries contain an oil with several fatty acids, including capric, caprylic, caproic, lauric, oleic and palmitic and acid, and their ethyl esters plus high amounts of phytosterols (beta-sitosterol, cycloartenol, stigmasterol, lupeol, lupenone and 24-methyl-cycloartenol), as well as other oils, resins, and tannins.

Saw palmetto is a "multi-site" inhibitor of the formation and actions of DHT. It inhibits 50% of the binding of DHT to receptor sites in the prostate, blocks the uptake of DHT into the nucleus of prostate cells, and inhibits the action of testosterone 5-alpha-reductase, which converts testosterone to DHT.

Because of its use is not patentable, it has not been developed by pharmaceutical companies and there are no published studies evaluating its effects on balding. Dr. James Duke in his book The Green Pharmacy lists Serenoa repens as his first choice for hair loss treatment He writes that the biochemistry certainly supports the use of serenoa repens. The herb blocks the formation of DHT much like Propecia. Serenoa repens has also been shown to reduce inflammation, a common factor seen in tissues involved in androgenic alopecia.

Like finasteride (Propecia), saw palmetto shrinks enlarged prostates and improves the rate of urine flow and the voiding of urine. Thirteen clinical studies, six of which have been double blinded vs. a placebo control, have found statistically significant positive effects on prostate function. Dr. Michael Murray analyzed the effects of saw palmetto oil vs. finasteride (Proscar and Propecia) in published placebo-controlled studies (Healthy Talk, July/August 1998, Vitamin Shoppe Publication).

** Many saw palmetto studies were 90 days or less, final measurements were calculated as 90 day measurements.

Urine flow (ml/sec)
	Saw Palmetto Extract	Finasteride
Initial measurement	9.53	9.6
3 months	13.15	10.4
12 months	**	11.2
Improvement in urine flow	+38% in 3 months	+16% in 12 months

Johan Braeckman of the Department of Urology, University of Brussels in Belgium reported (The Extract of Serenoa Repens in the Treatment of Benign Prostatic Hyperplasia: A Multicenter Open Study." in Cur Ther Res. 1994;55:776-785) that urologists studied 305 patients with BPH in a 90-day study to evaluate the efficacy of a standardized saw palmetto extract. On average prostatic volume was significantly decreased during the study - averaging 9 percent after 45 days and 10 percent after 90 days. Patients subjectively said that saw palmetto helped - 83 percent said it was effective after 45 days.

Paubert-Braquet et al ("Effect of Serenoa repens extract (Permixon) on estradiol/testosterone-induced experimental prostate enlargement in the rat." Pharmacological Research, Vol. 34, pages 71-179,1996) treated rats treated with estradiol and testosterone in order to induce prostate enlargement and then determined the degree of effect on reducing this enlargement by use of saw palmetto extract. After 90 days of treatment, a statistically significant decrease (45.5%) in weight of the dorsal lobe of the prostate was observed.

Champault G., Patel J.C., and Bonnard A.M. ("A double-blind trial of an extract of the plant Serenoa repens in benign prostatic hyperplasia." Br. J. Clin. Pharmac. Vol.18, pp. 461-462,1984.) reported a double-blind, placebo-controlled trial involving 110 outpatients with established signs and symptoms of benign prostate hyperplasia receiving saw palmetto extract and 55 receiving placebo. Patients received 320 mg per day of saw palmetto extract or placebo. Nocuria, intensity of dysuria, flow rate, post-micturition residue, self-rating by patients and global physician rating were assessed before treatment and after 30 days of therapy. Ninety-four (94) patients (44 placebo, 50 saw palmetto) completed the study and were evaluated at the end of 30 days. Patients receiving saw palmetto extract were significantly (compared to placebo) improved in each of the objective criteria as well as in the subjective patient and physician evaluations. The extract was very well-tolerated, with less patients reporting side effects (mild, e.g. headaches) with saw palmetto than with the inert placebo.

Saw palmetto is often combined with zinc and vitamin B6 which add to the anti-DHT activity and can be purchased from most health stores.

Like saw palmetto described above, extracts of two plants, pygeum bark (Pygeum africanum) and nettle root (Urtica dioica) are widely used for the treatment of prostate hyperplasia. The two extracts block the body's production of DHT and estrogen. Both extracts inhibit enzymes critical for DHT production (5-alpha reductase and aromatase), but a combination of the two has a synergistic action that increases their effects when combined. The combination is sold in Europe as "Prostatin" and may have similar positive actions on hair growth. (RW Hartman, M Mark and F Soldati, Phytomedicine Vol. 3, 121-128, 1996).

Anti-androgens and DHT Blockers - Cancer-Inhibiting Phytoestrogens - Genistein and Daidzien

Isoflavonoids, such as genistein and daidzein are weak estrogens and may lessen the risk of osteoporosis and heart disease. These compounds are found in soy foods, flax seeds, and some herbs. The phytoestrogenic compounds are called isoflavones and lignans. One of the first phytoestrogens to be studied was found in red clover. It was noted that when female sheep ate a diet high in red clover, their menstrual cycles became irregular.

Several studies have found a protective effect of soybean products against the development of breast cancer. The protective effect may be due to the fact that phytoestrogens can act both as weak estrogens and weak anti-estrogens. It is presumed the anti-estrogen effect on the breast confers protection against breast cancer.

Isoflavones are chemically similar to the drug tamoxifen. They reduce the risk of breast cancer by binding to the estrogen receptor sites on the chromosomal material in mammary gland cells and preventing the dangerous C-16-hydroxyestrogen form of estrogen from binding to DNA. Soy products (soybeans or tofu) are particularly abundant in isoflavones, and they have been observed to reduce the incidence of tumors in experimental mammals.

A clue to soybean plant's estrogen-like compounds was that women in Asia, where the diet is high in soy foods, reported less menopausal symptoms and had a lower incidence of breast cancer. However when Asian women come to America and adopt the traditional American diet, their postmenopausal symptoms increased as did their incidence of breast cancer. Asian women usually consume more than 35 grams of soybeans or soy-derived food per day as in contrast to American woman who only get 1-2 grams per day. This observation generated interest and further studies were undertaken. A 1990 study of 23 women showed that a diet high in soy food and flax or linseed meal reversed the atrophic changes seen in the vagina after menopause.

Genistein, from soybeans, has been shown to have significant 5-alpha reductase blocking activity and androgen modulating properties. Genistein is a potent phytoestrogen and non-drug supplement which currently under intense research for its cancer fighting activity. This substance not only inhibits two enzymes necessary for tumor growth, but there is recent evidence that it reduces the blood supply to tumors.

Daidzien, also from soybeans, is a potent phytoestrogen is reported to have vasodilation activity as well as 5-alpha reductase blocking activity. It has been approved and used as a cardiovascular drug in the People's Republic of China. It was approved in 1986 by the Health Bureau of Liao Ning Province, Approval Number (86)772-2-2. The Chinese report that daidzien exhibits hair growth and hair color promoting activity.

Ginkgo Biloba is a popular herb used world wide to improve cerebral blood flow and general blood circulation. It was recently reported by the Journal of the American Medical Association to slow the progression of Alzheimer's disease. It has been reported to inhibit 5-alpha reductase activity. With Ginkgo, you may be able to keep your hair and keep your brain!

Spironolactone is a prescription anti-androgen medication prescribed for high blood pressure, and is sold under the brand name Aldactone. It is a very powerful antiandrogen and decreases adrenal gland production of testosterone and also interferes with DHT binding at hormone receptor sites on hair follicle cells. It has been used to normalize body hair form in women with elevated androgen levels and hair loss.

Spironolactone may cause irregular menstruation and mood swings. It may feminize a male fetus in pregnant women. In men, it causes decreased libido and gynecomastia (larger-than-normal breasts). It does not decrease levels of serum testosterone but it does compete with DHT for cytosolic receptors. For pattern baldness, some subjective improvement has been noted with oral doses of 50-200 mg/day. No placebo-controlled studies on topically applied spironolactone have been reported. It costs about $5 to $20 per month, depending on the prescription strength.

Cimetidine is a histamine H2-receptor antagonist used to treat peptic ulcers and reduces the secretion of acid in the stomach, and treat reflux esophagitis (inflammation of the esophagus), and duodenal ulcers. It also has antiandrogenic side effects in men including gynecomastia, impotence, and loss of libido. Cimetidine is sold under the brand name Tagamet. It inhibits DHT and increases estrogen hormone activity. It has been used as a hair loss treatment for women with elevated androgen levels and a genetic predisposition to androgenetic alopecia. In one study of ten women treated with 300 mg orally five times a day, seven reportedly had good to excellent regrowth of hair. Conversely, it also has been used to reduce excessive facial hair in women. Cimetidine may cause women to experience breast milk production not related to pregnancy or nursing. When used by men, cimetidine may cause of enlarged breasts, loss of sex drive, and impotence.

Cyproterone is a prescription anti-androgen medication that stops the activity of the ovaries and testes, including the production of both androgens and estrogens. Cyproterone acetate reduces sex drive in men who have an excessive sex drive and is used to treat men with pronounced sexual aggression.

Like cimitedine and other similar type drugs, cyproterone acetate exerts its effects by blocking the binding of DHT to its receptors and interferes with DHT binding at hormone receptor sites on hair follicle cells. When used to treat androgenetic hair loss in women, it is combined with a powerful estrogen hormone called ethinyl estradiol. It is also prescribed for women of childbearing age to treat severe hirsuitism.

Estrogens are feminizing hormones that counterbalance and help regulate androgens. Estrogens compete with androgens at receptor sites on hair follicle cells, but do not trigger hair loss. Women have much higher proportions of estrogens than androgens when compared to men. Estrogens protect women from androgenetic hair loss until menopause. Treatments for hair loss often attempt to elevate estrogen levels. One study found women treated with topical estrogen halted loss of head hair in 89% of those treated, but conversely, estrogen reduces facial hair at the same time. Estrogen and leuporide are used together in the treatment of hirsutism. Estrogen treatment may cause irregular menstrual cycles, and possibly increased or decreased risk of cancer in women, depending on the dosage used. Men report decreased sex drive (libido loss) and breast enlargement (gynocomnestia).

Researchers Robert C. Smart and Hye-Sun Oh (1996) discovered that an estrogen blocker called ICI 182,780 designed to block the production of estrogen also had the surprising side effect of awakening sleeping (dormant) hair follicles. "Our findings indicate that an estrogen-receptor pathway in specific cells of the mice's hair follicles somehow acts as a switch, essentially turning on and off hair growth," Smart explained, adding that the study sheds new light on the role of estrogens in regulating the normal cycle of hair growth. "

Progesterone is a hormone that supports uterine function and also is a precursor for estrogen and testosterone synthesis. Progestins are a class of progesterone-like drugs and natural products. Progesterone and progestins have been used as either oral pills or topical creams since the 1970's to reduce head hair loss both men and women. Some physicians use a progesterone cream precombined with minoxidil for the treatment of hair loss. Progestins are often used with estrogen for reducing hair loss and other conditions.

The compounds are also used to help regulation the menstrual cycle, for the lessening of cramps, for the lessening of menopausal symptoms, and the prevention of estrogen side effects. Topical creams cost about $10 per month and are available from www.life-enhancement.com/displayprod.asp?ID=114

Anti-androgens and DHT Blockers - Diane 35 (Cyproterone Acetate with Ethinyloestradiol)

Diane 35 is a contraceptive pill prescribed for women with severe acne and hirsuitism, female pattern baldness, and androgenetic alopecia. Diane 35 is designed to block the peripheral action of male hormones present in the female body. Diane 35 has been reported to stop hair loss and increase hair thickness within about a year but the treatment must be continued to maintain the positive effects. Side effects include breast tenderness, headaches and decreased libido. Diane 35 helps prevent osteoporosis.

Simvastin is a cholesterol lowering drug with weak antiandrogen properties. Simvastin is prescribed to lower cholesterol and lipid levels in men and women with hypercholesterolemia. Some of it's antiandrogen properties are enhanced when taking other antiandrogens. Since men experience both excessive lipid levels during aging - which affects the cardiovascular system - and more pronounced deleterious effects of DHT - which produces prostate hyperplasia and possibly prostate cancer in addition to hair loss - this drug has possibilities of reversing to aging problems in men with one drug.

GI198745 is a dual 5-alpha reductase inhibitor in clinical testing. Propecia (Finasteride) inhibits only one of the two types of 5-alpha reductase, so it only blocks only a portion of the DHT being created in the body. GI198745 will inhibit both types and may produce DHT levels close to that of men who have been castrated.

Clinical tests will determine whether the medication is more effective than Propecia and whether it is as safe or safer than Propecia. Another question is whether further inhibiting DHT will cause more side effects. Glaxo Wellcome has initiated hair loss studies before the new drug. The product is said to be on track for FDA approval in 2003.

Flutamide is a very powerful antiandrogens that blocks the androgen receptor so completely that androgens virtually have no effect in the body. Generally, it is not recommended for men. However, some physicians use it in small doses mixed into topically-applied minoxidil. They report that in men there is some hair growth and a reduction of facial hair in women. Potentially adverse effects include diarrhea, impotence, liver problems, and high blood pressure.

Casodex is a new derivative of flutamide, and a powerful antiandrogens that blocks the androgen receptors. It has fewer side-effects than flutamide. Because of its anti-androgen effects it has more serious side-effects in men than women. It is not yet available for marketing.

Inocoterone is a new antiandrogen that binds to androgen receptors and prevents androgens hormones from binding and exerting their actions. It is in clinical studies.

When you are young, your scalp is thick and your hair follicles have a rich blood supply. However, as you age and also because of DHT effects, your scalp thins, its blood supply is diminished, and it provides less support and nutrition for your hair follicles. This produces smaller follicles that produce thin hair shafts.

Skin repair and hair growth enhancement effects are closely linked. New skin appears to arise from the hair follicle. Certain products based on skin repairing copper-peptides can be used to both repair skin, increase hair follicle size, and stimulate hair growth.

Skin regenerating copper peptides may help reverse or minimize many of these effects. Studies by Prof. Hideo Uno (who wrote UpJohn's textbook for physicians when Rogaine first was marketed) have found that, in animal studies, skin repairing copper-peptides often convert thin, vellus hairs into thick, terminal hairs. (Uno and Kurata 1993, Uno, Packard, Patt 1996)

A major cause of hair follicle miniaturization appears to due to the development of striking changes in capillaries surrounding the hair follicles. Comprehensive surveys of the male scalp from birth to senescence find that very significant changes in the structure of the blood vessels of the scalp. The number of the blood capillary loops supplying the hair follicle is greatly diminished. The inadequate subepidermal circulation that can develop as males age does not provide a rich nutrition for the follicle. Strong hair growth requires a large flow of nutrients such as such as vitamins, minerals and amino acids so that the follicle can actively synthesize new hair.

Blood flow impairments to the follicle, and their reversal, may explain why the administration of copper peptides (such as Folligen and Tricomin) to the scalp increase hair growth and increase the size of hair shafts. It has long been known that certain copper-peptide complexes strongly stimulate angiogenesis or new blood vessel formation. The increase in hair follicle size and the rate of hair growth caused by the administration of copper-peptides may be due to their causing blood flow changes that provide adequate nutrients to the follicle, producing faster growing hair with thicker hair shafts.

In the microscopic images to the left, the magnifications are identical. The top photo is mouse skin untreated with copper- peptides. The bottom photo is mouse skin treated with copper-peptides. Note the larger hair follicles (the elongated purple columns) in the lower photo, the increased content of subcutaneous fat in the skin (the white material in the center of the skin), and the increased thickness of the skin. When we are young, we have a layer of fat under the skin (part of "baby fat") which is greatly reduced as we age. Hair researchers have noted the accumulation of this fat around healthy follicles that are vigorously growing hair, and its relative lack in around dormant follicles, and have postulated that these cells serve a supportive function for the hair follicle. In animal studies, copper peptides have reduced or stopped the hair loss associated with chemotherapy for cancer. It must be emphasized that effects in in humans on hair follicle health are not as dramatic.

In addition, copper ion in the skin is a potent inhibitor of both type I and Type II 5-alpha reductase which produces the hair-follicle-damaging DHT. Copper-peptide products may deliver sufficient copper ion into the skin to reduce DHT around the hair follicle. See above Is Copper Better Than Propecia® for Blocking DHT Production?


How Biologically Effective Copper Peptides Appear to Help Hair Growth. Left Diagram: At age 15, your scalp is thick and your hair follicles have a rich blood supply (red and blue) and are surrounded by many subcutaneous fat cells (yellow balls) that are felt to enhance the health of the hair follicles. This produces large hair follicles that produce thick shafts of hair. Center Diagram: As you age and DHT effects set in, your scalp thins, its blood supply is diminished, and the layer of fat cells narrows. This provide less support and nutrition for your hair follicles. This produces smaller follicles that produce thin hair shafts. Right Diagram: Biologically effective copper peptides help reverse many of these effects. They help re-thicken your scalp, improve the scalp's blood supply, and rebuild subcutaneous fat. This produces a larger follicle that produces thicker hair shafts.

Iamin-based hair products include Folligen by Skin Biology and the GraftCyte hair restoration system to improve hair transplant success (sold by ProCyte Corporation) and the Tricomin products to improve thinning hair (sold development by ProCyte Corporation).

Folligen® is a non-drug product designed by Dr. Loren Pickart to improve scalp and hair follicle health and hair vitality. Folligen is especially useful in helping to reduce scalp irritation caused by other hair growth products such as Rogaine® (minoxidil), Retin-A® (retinoic acid) and Propecia®. Compare Folligen Cream, Folligen Lotion, and Folligen Solution Therapy Spray for to Tricomin Solution Follicle Therapy Spray® sold by ProCyte for and GraftCyte Solution® which are products based on Dr. Pickart's earlier hair health inventions. Folligen Solution has more than 31.8 times more copper-peptide per ounce than Tricomin and 9.0 times more copper peptide than Graftcyte per ounce (Source - Evergreen Analytical Labs, Redmond, WA).

All Folligen products contain a high concentration of blue-colored copper-peptide complexes and do not contain any blue dyes. Tricomin contains blue dyes to give the impression of copper-peptide complexes. The Folligen Cream is used for hairlines, the Folligen Lotion for use areas of thicker hair, and the Folligen Solution Therapy Spray is an aqueous mixture applied with a fine-mist sprayer. Folligen Solution Therapy Spray uses small amounts of polysorbate 20 and propylene glycol to enhance the uptake of copper-peptide around the hair follicle .

Folligen is contains copper-complexes plus saw palmetto oil. It strongly stimulates hair growth in standard mouse models. In humans, the active copper-peptide complex in Folligen has been shown to strongly stimulate skin repair and possess anti-inflammatory properties. (Zhai et al 1998a, 1998b, 1998c, Zhai et al 1999) Folligen products may be purchased at www.folligen.com.

Folligen Lotion to restore scalp health after dyes, permanent waving and hair straighteners

Folligen Lotion is also used to restore scalp health after dyes, permanent waving and hair straighteners. The chemicals used for these purposes can be very damaging to the scalp and hair follicle. If damage is not repaired, eventually, these procedures can cause hair thinning and hair loss. Many women have reported that the use of Folligen Lotion after these procedures results in a much healthier looking hair and there is less hair shedding. Rub Folligen Lotion into your scalp at nighttime for the next 3 - 4 days to help restore scalp health.

Natural Multiple Stimulators - Folligen is an extension of this Iamin-based work but uses a more biological method to renew the scalp and follicles. Research on skin and hair follicle renewal indicates that optimal regeneration is obtained only when there are multiple signals for renewal. Folligen contains copper ion plus a mixture of numerous different peptides fragments that are generated by natural proteolytic enzymes (as happens after follicle or scalp damage). This produces numerous copper-peptide complexes in a more natural manner to assist the hair's natural regenerative processes.

Rebuilds Protective Acid Mantle - Folligen rebuilds the protective acid mantle of the scalp that shampoos and conditioners remove. The acid mantle is the combination of sebum (oils) and perspiration, on the skin's surface that protects the skin and renders the skin less vulnerable to damage and attack by environmental factors such as sun and wind and less prone to dehydration. The mantle also has strong anti-oxidant properties and is itself oxidized to protect the skin from oxidation. Sebum is naturally white but air oxidation turns it black (this is why "whitehead comedos" turn into "blackhead comedos").

Normal skin and scalp pH is somewhat acid and in the range of 4.2. to 5.6. It varies from one part of the body to another and, in general, the pH of a man's skin is lower (more acid) than that of a woman's. The acid mantle inhibits the growth of foreign bacteria and fungi and the skin remains healthier, and has fewer blemishes. Acne, allergies and other skin problems become more severe when the skin become more alkaline.

Folligen adjusts the scalp pH into the acid range of optimal scalp health at about pH 5.0. Folligen also contains high levels of lipids such as squalane, cetyl alcohol, glyceryl stearate and stearic acid that closely resembles the fats of the acid mantle. Furthermore, Folligen contains antioxidants such as allantoin, aloe, vitamin E and retinol to aid the mantles protective anti-oxidant properties.

In this manner, Folligen improves scalp health and aids hair growth. Folligen works well with Minoxidil or the Minoxidil and Retinoic Acid combination. Will Brinks, a noted nutritional writer, has recommended for hair growth, a combination of Folligen, Propecia, Minoxidil and Nizoral (a shampoo sold by Jannsen Pharmaceuticals) in a article in Muscle Magazine International (page 252, May, 1997).

Folligen Lotion to Restore Scalp Health After Permanent Waving and Hair Straighteners

Permanents and hair straighteners are very damaging to the scalp and hair follicle. If damage is not repaired, eventually, these procedures can cause hair thinning and hair loss. Many women have reported that the use of Folligen Lotion after these procedures results in a much healthier looking hair and there is less hair shedding. Rub Folligen Lotion into your scalp at nighttime for the next 3 - 4 days to restore scalp health. More information is at Folligen.

Tricomin Solution Follicle Therapy Spray is sold by ProCyte Corporation (See www.procyte.com). It is another copper-peptide complex that stimulates hair growth and was invented by Dr. Loren Pickart in 1987 and, in a sense, is an earlier version of the approach used in Folligen. Tricomin had its genesis in attempts to create Iamin molecules with an increased solubility in, and retention by, wounds and other tissues. To achieve this purpose, the non-polar or "fatty" character of the molecule was synthetically increased by either chemically linking fatty acids to Iamin or adding amino acid residues to Iamin which had a more "fat-like" nature. While such "fatty" Iamins worked well for wound-healing, they also markedly increased hair growth around experimental wounds.

Tricomin has demonstrated effectiveness for hair growth stimulation in placebo-controlled clinical trials and in direct comparisons with minoxidil. Tricomin produces slightly more hair growth than minoxidil and produces thicker hair shafts than minoxidil. Unfortunately, the solution into which Tricomin has been recently formulated gives evidence of inhibiting hair growth. Users often report scalp irritation, itching and flaking. Tricomin Solution contains high levels of ethyl alcohol, detergent and also contains blue dye, all of which may irritate the scalp. This may reduce its overall hair growth effects.

Tricomin vs. Minoxidil - Change in number of terminal hairs in tested area
Type of Treatment	Treatment Group	Placebo Control Group
Minoxidil 2% after 4 months (non vellus hair count)	+73	+31
Tricomin 2.5% after 3 months (non vellus hair count)	+97	-51 (inhibition of hair growth)

Tretinoin (Retin-A): Tretinoin is medication for reducing skin wrinkles, and is sold under the brand name Retin-A. It increases collagen production and causes inflammation on the skin when applied topically. Tretinoin is not approved for use as a hair loss treatment, however when used on the scalp in combination with minoxidil, it has been shown to increase hair growth more than minoxidil used alone. One theory is that retinoic acid works by reducing sebum production from the sebaceous glands. The idea is that sebum which contains DHT is secreted on the scalp, then reabsorbed into the hair follicles to do further damage.

In one study, retinoic acid alone and in combination with 0.5% minoxidil has been tested for the promotion of hair growth in 56 subjects with androgenetic alopecia. After 1 year, the combination of topical retinoic acid with 0.5% minoxidil resulted in terminal hair regrowth in 66% of the subjects studied. Retinoic acid alone was shown to stimulate some hair regrowth in approximately 58% of the subjects studied. One female subject with pronounced alopecia for more than 20 years had regrowth of hair using only retinoic acid for a period of 18 months. (Bazzano 1986) Some dermatologists claim that the combination of 2% minoxidil and retinoic acid works better than 5% minoxidil alone.

While minoxidil works best on the vertex of the scalp, the combination of retinoic acid (Tretinoin, Retin-A) and minoxidil results in improved hair growth in all regions of the scalp. The combination treatment of topical minoxidil and retinoic acid is said to be very effective in women.

The main problem with retinoic acid is the skin irritation include blistering, altered pigmentation, and increased sensitivity to light. Because of this irritation, a lower strength of retinoic acid (0.025%) is recommended. Folligen users report that it works well with retinoic acid and markedly reduces scalp irritation.

Retinoic acid and/or higher strength minoxidil may be purchased from www.gen.com/smallworld or www.hairback.com or www.martinavenue.com. Retinoic acid works on men and women and costs about about $20 - 30 for a normal tube in the USA but is much cheaper in many other countries.

There are claims that retinol (vitamin A or retinyl alcohol) and retinolaldehyde are as effective as retinoic acid but without the irritation. However, these claims are disputed. To achieve the skin and hair effects of retinoic acid with these compounds may require levels of these compounds that produce vitamin A toxicity.

Copper-peptide (in products such as Folligen, Iamin, and Protect & Restore) may be used to reduce minoxidil/retinoic acid irritation. During irritation and inflammation, the skin is damaged by immune cells that release toxic oxygen radicals into the damaged area. The purpose of these oxygen radicals is to kill invading bacteria after wounding but often the oxygen radicals are released in the absence of any bacteria.

The use of cortisone and corticosteroids to reduce skin irritation is not recommended. Corticosteroids act by killing the immune cells to stop oxygen radical release but this also kills the immune cells that release the skin repair growth factors and hence stops skin repair which ultimately leads to a thinned and damaged skin.

Copper-peptides, on the other hand, directly detoxify the oxygen radicals. They also transfer copper to superoxide dismutase (SOD), the skin's primary anti-oxidant protein, which activates the skin's SOD which further increases the removal of oxygen radicals. Also, the copper-complexes have been shown to strongly stimulate the skin's repair systems and improve healing and skin renewal. The above mentioned nickel allergy study demonstrated both the anti-inflammatory and skin repair properties of copper-peptides. (Zhai et al 1999).

Comparison: Effect of Copper Peptide vs Corticosteroids
for Skin Repair and Anti-inflammation
	Stops Inflammation by	Effect on Skin Repair and Renewal
Protect & Restore - Copper-Peptide	1. Detoxifying oxygen radicals 2. Activating the skin's superoxide dismutase	Strongly stimulates skin repair and renewal
Cortisone & Other Corticosteroids	1. Killing immune cell macrophages and neutrophils which secrete oxygen radicals	Stops skin repair and renewal by killing macrophages which secrete skin repair growth factors

Azelaic acid is used in the treatment of acne and other skin conditions. Studies in France found that the combination of zinc sulfate and azelaic acid could inhibit 5-alpha reductase activity in human skin at concentrations as low as 0.2 mmol/l and there was complete 5-alpha reductase inhibition at 3 mmol/l. The combination of zinc, vitamin B6 and azelaic acid was found to be even more effective in the inhibition of DHT production.

While there are no studies on hair growth with azelaic acid, but its anti-acne properties suggest that it may be useful as a topical antiandrogen. It is considered safe and FDA approved for skin treatment uses. It costs between $20 to $30 per tube.

Corticosteroids are used for the the treatment for alopecia areata. In mild cases of alopecia areata, a corticosteroid cream is applied only to the regions of hair loss. An alternative treatment is the intralesional injection of corticosteroids into the inflamed patches of scalp. A corticosteroid such as triamcinolone or kenelog is injected, approximately once per month, below the skin near the hair follicle. This treatment is often used for eyebrow hair loss.

Systemic corticosteroids are often prescribed if the hair loss is widespread. The drugs are administered by injection into the muscle of the buttock or arm once every four to six weeks. Sometimes this treatment brings a spontaneous recovery and the treatment is stopped as the hair returns. Oral cortisone is sometimes given by tablets but has all the side effects of injections.

Corticosteroids, with short term use, cause weight gain, mood changes and acne. Long term treatment with corticosteroids causes thinning of the skin and scalp damage, immune system suppression, increased cancer, bone degeneration, and cataracts. Folligen (see above) may be tried as an alternative to steroid use. Folligen is very safe and has anti-inflammatory actions as well a scalp repair properties.

Cyclosporin is an immunosuppressive drug used in organ transplants to to prevent the body from rejecting the new organ. It is used topically in the treatment of immune-associated severe skin conditions. In humans, cyclosporin is very effective orally (80% positive hair growth response) but only marginally effective (20%) when used topically for aiding hair growth. It promotes hair growth in animal models and promotes human hair growth in vitro.

Like corticosteroids, it has toxic side effects such as renal toxicity when used long term and a generally poor choice for as a hair treatment.

FK506 is an new immunosuppressant, like cyclosporin, used to prevent organ rejection. It is in a class of drugs similar to cyclosporin. When applied in a topical ointment, it is more effective in stimulating hair growth than cyclosporin. It is a strong immunosuppressant and its safety in long term use for hair growth is questionable. It may produce neural damage.

The following materials are widely used in hair products. They may stimulate hair growth in humans but controlled studies are lacking.

Arginine is an essential amino acid available in groceries and health stores. It is necessary for proper human health. More interestingly, it is the metabolic precursor of nitric acid or NO, which is biochemical messenger that is a potent vasodilator and which may stimulates hair growth by opening potassium transport channels into cells. Arginine, usually in combination with another amino acid called ornithine, increases the release of human growth hormone (HGH - see Chapter 8). Increased HGH has been observed to increase hair growth along with other aging reversal effects.

BioFolic H is a natural vitamin and mineral treatment developed over 25 years ago. It is sold for use "by persons all over the United States who have experienced or are currently experiencing thinning hair, hair loss, balding or weak, splitting fingernails". It is claimed to produce thicker and healthier hair. It can be obtained at the www.biofolic.com/.

Crinagen is a topical lotion, formulated by Dr. Nassar Razack (on the right) of Raztec Enterprises of New York and which contains DHT blockers saw palmetto extract and zinc. It is sold for use in the treatment of androgenetic alopecia. Raztec is located at www.rastec.com/.

Cysteine is an essential, sulfer-containing, amino acid available in groceries and health stores. Hair (and feathers which are thought to have arisen in an evolutionary sequence from hair) has very high levels of cysteine and an insufficient dietary intake could slow hair growth. It is known that significant modifications may be induced in wool growth patterns on sheep by the enrichment of the diet of sheep with cysteine or sulfur amino acids. In rats, the addition of a supplement of gelatin (from collagen digests such as Knox gelatin or Jello) and cysteine, caused an increase in the cysteine content of hair and produced thicker hair shafts. The content of the sulfer-rich hair proteins increased up over 50% and the content of cysteine in hair increased by 35%. (Gelatin-cystine, keratogenesis and structure of the hair, Boll Soc Ital Biol Sper (ITALY) Jan 31 1983, 59 )

Cytadren or aminoglutethimide is an adrenal cortex hormone suppressant, an antiestrogen, an aromatase inhibitor, and a anticortisol drug which is used to treat hyperactive adrenal cortexes. The adrenals produce female estrogens and estradiols, cortisol in response to stress, increases testosterone and precursor hormones such as DHEA. The drug is used by weight lifters to suppress female hormones and help build muscle. Some persons report moderate to dense regrowth with the drug.

Cytadren educes DHEA levels which may play a significant role in female hair loss and may explain its hair promoting properties in women. The drug is taken a doses up to 500 mgs per day and is FDA approved for non-hair uses. Since it is a very powerful drug, it should only be used under the close supervision of a physician. Side effects include depression, dark skin, drowsiness, dizziness, headache, deepening of voice in females, lack of energy, muscle pain, neck tenderness, vomiting, irregular menstruation, and vomiting. It costs around $60 per month at standard dosage.

Dilantin or phenytoin is an anticonvulsant long used for the treatment of epileptic seizures. It is considered one of the "smart drugs" said to increase human intelligence. It has wound healing properties but also causes side effects such as excessive gum growth around the teeth in users and more hair growth. It is well tested and reasonably safe.

Dithranol is a tar-like ointment used for the treatment of psoriasis. It is applied to the scalp and it reduces cell division. Its irritant action may cause some hair growth. Because of the carcinogenic properties of all coal tars, we do not recommend such treatments.

Electrotrichogenesis is the electrical stimulation of hair follicles and was developed by a company called Current Technologies. It is available in salons in Canada and Mexico. In the USA, the FDA has asked for long-term safety data - especially on potential effects on the brain and has effectively stopped its development. It is possible that it may work in a manner that electrical fields have been proven effective in stimulating bone regeneration in humans.

Fabao 101 is a herbal mixture from China. Its is claimed to be the "World's World's Leading Treatment for Hair Loss" and was developed by the dermatologist, Dr. Zhang-guang Zhao. It is claimed to be "the only safe and effective treatment proven to regrow normal hair and rapidly improve existing hair in 90% of patients". The potion is formulated with extract of plants such as sophera flavescens, radix astragali, capsicum, seu radix notopterygii, safflower oil, cortex dictamni radicis, rhizhoma gastroidia ginseng, notoginseng, heshouwu and peach kernel oil.

The marketers cite an article by A. G. H. Kessels, R. L. L. M. Cardynaals, R. L. L. Borger, M. J. T. H. Go, J. C. C. A. Lambers, J.A. Knottnerus and P. G. Knipschild, of the University of Limburg, in Maastricht, The Netherlands in the Journal of Clinical Epidemiology, Vol. 44, No. 4/5, pp 439-447, 1991, a 1988 report by Takashi Anzai of the Japan Red Cross, and an abstract by B. C. Qian, J. Chen and H. J. Xu, Pharmacological Action of 101 Hair Regeneration Extract On Skin and Hair In Experimental Animals in the Journal of Traditional and Modern Medicine, Vol. 14, No. 4, pp 227-229, 1994 claiming that the product stimulates hair growth in rats, guinea pigs and rabbit

It costs $30 to $60 per month and can be found at http://members.aol.com/~fabao/ and several other online websites.

Certain unsaturated fatty such as gamma linolenic acid significant inhibit 5-alpha reductase and DHT production in biochemical test-tube assays. Many products used for treatment of prostate hyperplasia included gamma linolenic acid in their formula. It has been speculated that such fats may be useful in the treatment of disorders related to DHT such as benign prostrate hyperplasia, acne, androgenetic alopecia and female hirsuitism.

Emu Oil has a high level of linolenic acid. Hair restoration products which contain emu oil have been patented. The application of emu oil to the skin causes an increased the synthesis of DNA in the epidermis and may increase the proliferative activity of the skin. Animals fed emu oil have an increased pigmentation and hair growth. The skin of the animals increases in thickness and the size of the hair follicle increases.

Green Tea is widely used as a herbal health promoting drink and many studies have associated green tea with decreased cancer rates and less degenerative disease. Green tea contains powerful antioxidants called polyphenols and caretenoids which are natural antioxidant which scavenge free radicals. There is evidence that green tea has been some anti-androgenic effect similar to saw palmetto. There are also shampoos available that contain green tea extract that are said to have beneficial effects on hair and skin.

Luftek claims to obtain full hair regrowth in men and women by teaching you special techniques to regrow hair. It costs $149.95 and can be found at the at the www.spanit.com/luftek.natural.hair/.

Nizoral is an antiandrogen, antimycotic, and antifungal prescription drug in the USA but an over-the-counter drug in most other countries. It is a shampoo designed for the treatment of seborrheic dermatitis. The active ingredient, ketoconazole, has antiandrogenic effects. Many report it is a very good shampoo, but can be mildly irritating. A month's supply cost between $12 to $30.

NANO shampoo contains pyrmidine N-Oxides and was invented by Peter Proctor (M.D. with Ph.D in Pharmacology), a physician-scientist with an early interest in human aging, and who also the resident guru of the hair loss chat group at alt.baldspot and is pictured below. NANO is claimed to stop hair fallout and stimulate hair growth. Proctor also has developed a NANO conditioner. It is claimed to be as effective as minoxidil. Some users report mild irritation at first. It costs $39.95 for a three month supply.

Proxiphen was also developed by Dr. Proctor and contains a variety of ingredients including minoxidil, retinoic acid, phenytoin, spironolactone, prezatide copper (similar to Iamin), lys-lys-his (a copper-binding peptide), NANO, arginine, allantoin, butylated hydroxytoluene and ascorbyl palmitate. Some people have reported loss of hairs gained with minoxidil when using Proxiphen which has a lower concentration of commercial minoxidil. Others have reported that it irritates the scalp. Dr. Proctor says that Proxiphen stops hair loss, thickens hair, and enlarges miniaturized hairs, and produces regrowth at the front of the hair line.

The product, in various formulations, costs about $59.95 for 2 months and $109.95 for 4 months. Dr. Proctor is a real scientist (in contrast to the sales organizations that promote various petro-chemical combinations as hair growth systems) and should be taken seriously. Proctor can be contacted at www.drproctor.com/.

Nioxin is heavily advertised as a "natural" treatment that feeds 100,000 hairs on your head. It is sold by mail order and in many salons. It is claimed to produce nearly normal hair growth. It costs between $30 and $125 per month.

Nisim sells a herbal product designed to increase hair growth and another product to decrease hair growth. Nisim has an independent study that claiming Nisim stops hair loss and stimulates hair regrowth in men and women. The Nisim New Hair Biofactors Stimulating Extract and the Nisim New Hair Biofactors Shampoo contain mixtures of nutrients and vitamins such as such as the sulfur containing amino acids which are very high in hair, inositol, the B group vitamins, panthanthenol, and biotin plus a a herbal extract. It costs $50 to 60/month. There is a website at www.nisim.com/.

These polysorbates are commonly sold in three versions polysorbate 20, 60 and 80. They are cleansers that are found in many commercial hair products. Polysorbates are chemical emulsifying agents that are used to dissolve fat in water. Polysorbates were the main original ingredients in the Helsinki Formula. The polysorbates irritate the skin and break down mast cells which release of histamine. Histamine release will cause itching but also many stimulate some hair growth. However, a study concluded that polysorbate 60 is ineffective in treating hair loss. (Groveman HD et al , 1985, Arch Intern Med pp 1454-1458)

Because of polysorbate's functions as an emulsifier, many companies say they use polysorbates to "unclog" hair follicles from fatty substances such as cholesterol, DHT, and other secretions they feel detrimental to hair growth. However, there is no scientific support for the "clogged-pore" theory of hair loss.

Polysorbate - like propylene glycol or DMSO - can be used to increase the penetration of substances into the sebum around the hair follicle. Folligen Solution Therapy Spray uses small amounts of polysorbate 20 and propylene glycol to enhance the uptake of copper-peptide around the hair follicle and Crinagen uses polysorbate 80 to increase the uptake of zinc and saw palmetto oil around the follicle.

Thymuskin is reportedly an antiandrogen extract from calf thymus which is claimed to reverse male pattern hair loss and alopecia areata. It costs $39 to $108 per month and is available from Thymuskin's Web Page.

Viviscal is a with marine extracts and a silica compound taken as a food supplement that was developed by university researchers in Helsinki, Finland. It is claimed to stop hair loss. A study on Vivsical "A comparative study of a new food supplement, ViviScal, with fish extract for the treatment of hereditary androgenic alopecia in young males" appeared in J Int Med Res, 20: 6, 1992 Nov, 445-53. The study compared six months of treatment with Viviscal or fish oil and claimed a 36% increase in hair growth over the fish oil group (a true placebo control would have used the inert components of Viviscal).

The combination of zinc and vitamin B6 inhibits the conversion of testosterone to DHT in the skin. As B6 levels increase in cells, they are reported to become less responsive to less responsive to the hormones that can cause androgenetic alopecia and other disorders related to DHT.

One problem with high dosages of zinc is that it competes with copper for receptor sites. Too much zinc can drive out copper from the scalp. Without adequate copper, angiogenesis (new blood vessel formation) will not occur and ultimately this will produce scalp damage.

Xandrox is a product from Dr. Robert Lee who sells various mixtures of products for hair growth at www.minoxidil.com. Xandrox is consists of 5% to 12% Minoxidil and Azelaic Acid. Avoid the version of the product with Betamethasone Valerate. The latter is a corticosteroid included to counteract the effect of the Azelaic Acid which often causes skin irritation. Azelaic Acid, which is similar to retinoic acid, is normally used to treat acne and does have hair promoting properties in combination with minoxidil. Success rates on hair growth up to 70% are claimed. The versions without corticosteroids are basically OK.

The problem with the corticosteroid version is what happens with long term use? The long term use of corticosteroids on skin inflammations is usually causes a thinning of the scalp and this may hurt hair growth. If you want to use these types of azelaic/retinoic acid/minoxidil combinations, copper-peptides may help to control the scalp irritation.

Revivogen is promoted as a "clinically proven" product but there are no published studies on the product itself. The main problem with is product is the use of zinc. Zinc may promote hair growth when it acts as a skin irritant but skin irritation has long term negative consequences. Zinc can also drive out copper and this may damage your hair and speed aging in your body.

Copper deficiency in animals causes increased cellular oxidation, increased cancer, increased cardiovascular risk, more atherosclerosis, higher LDL-cholesterol, decreased HDL-cholesterol, more lipid oxidation, aortic aneurysms, osteoarthritis, rheumatoid arthritis, osteoporosis, chronic conditions involving bone and connective tissue, brain defects in newborn, obesity, graying of hair, increased sensitivity to pain, obesity, and reproductive problems. See more below.

In humans, copper deficiency is associated with all of the previous plus depression, impaired brain function, and general fatigue. For more information, please visit copper health.

Copper is usually in short supply in the body and high zinc usage drives copper from the body and can produce copper deficiency.

Expected effect of excessive zinc ingestion patterns
Regimen	Effect	Expected effects of lower copper
High zinc usage	Competes for with copper for binding sites and lowers copper in tissues	Lose main anti-oxidant defense, Less active Cu,Zn-superoxide dismutase Energy production drops, Immune system defects, More carcinogenesis, More cancer, Less endorphin - higher pain, Brain defects in newborns, More degenerative disease

Studies have found that ionic zinc can inhibit 5-alpha reductase (type I) but zinc has no effect on type II reductase. Some studies have found that the combination of B6, zinc salts and azelaic acid, even at low concentrations, caused a 90% inhibition of 5-alpha reductase activity - but this is still not hair growth. In some persons zinc salts are often used in disorders related to excess DHT such as acne and prostrate hyperplasia. The topical application of zinc has shown to reduce sebum production and acne. Some people suffering from acne have been found to have zinc deficiencies in their skin, despite of the fact that they have normal levels within their bloodstream.

The effects of topical zinc on hair growth may be due to skin irritation actions. In the 1970's, a number of severe skin irritants, such as nitrobenzene derivatives, were investigated for hair growth properties. While they initially stimulated hair growth, they ultimately produced unacceptable scalp damage and irritation and could not be continued for use.

Zinc salts can inhibit the action of the immune system macrophages on the skin. Since the macrophages are key cell responsible for skin repair, excessive use of zinc salts on the skin could inhibit skin and hair follicle repair. Mulhern et al 1986 reported that excessive dietary zinc in mice reduced plasma copper and induced alopecia. Lansdown 1991 (Westminster Medical School, Department of Comparative Biology, London, UK) examined the dermal irritancy of six zinc compounds was examined in three animal models. In open patch tests involving five daily applications, zinc chloride (1% aqueous solution) was severely irritant in rabbit, guinea-pig and mouse tests, inducing epidermal hyperplasia and ulceration; aqueous zinc acetate (20%) was slightly less irritant. Zinc oxide (20% suspension dilute Tween 80), zinc sulphate (1% aqueous solution) and zinc pyrithione (20% suspension) were not overtly irritant, but induced a marginal epidermal hyperplasia and increased hair growth. Thus, hair growth effects observed with zinc may be secondary to dermal irritation. (Lansdown AB, Interspecies variations in response to topical application of selected zinc compounds, Food Chem Toxicol 1991 Jan; 29 (1): 57-64)

Like zinc, topical cortisone has been used to promote hair growth and is often reasonable effective in persons with inflammatory scalp conditions. But cortisone stops skin repair and, if used for an extended period, ultimately thins the skin, damages hair follicles, and causes hair loss.

Bazzano 1986 - Bazzano GS, Terezakis N, Galen W; J Am Acad Dermatol, 15: 4 Pt 2, 1986 Oct, 880-3)

Chen et al 1996 - The 5 alpha-reductase system and its inhibitors. Recent development and its perspective in treating androgen-dependent skin disorders. Chen W; Zouboulis CC; Orfanos CE Dermatology 1996;193(3):177-84

Hamilton & Mesler 1969, Mortality and survival: comparison of eunuchs with intact men and women in a mentally retarded population, J. Gerontology 24:pp. 395-411

James K.C, Rushton D.H: Evaluation technic in male pattern baldness. J. Am. Acad. Dermatol. 1986; 14:
849-50.

Kevis references 1988-90 - La Medicina Estetica number 3, 1988, Editrice Salus Iternazionale Roma; La Medicina Estetica number 1, 1988, Editrice Salus Internazionale Roma; Les Nouvelles Dermatologiques 18-19 May. 1990, Marseille, France

Lansdown 1991 - Lansdown AB, Interspecies variations in response to topical application of selected zinc compounds, Food Chem Toxicol 1991 Jan;29(1):57-64

Mulhern 1986 - Mulhern SA; Stroube WB Jr; Jacobs RM, Alopecia induced in young mice by exposure to excess diet