Having discussed the anatomy and physiology of hair growth, let’s take on the issue that everyone cares about most – hair loss – something that affects nearly all men at some time in their lives, and a surprisingly large number of women. Because of the greater role hair plays in the public persona of women, they may suffer greater psychological impact although men and women both invest heavily in treatments to restore lost hair.
Most men eventually develop a receding M-shaped hairline and thinning hair on the top of the head – classic male pattern baldness, also referred to as androgenetic alopecia. It’s caused by the male hormone, dihydrotestosterone (DHT). DHT is five times as potent as testosterone and is vital for development of male genitalia in utero. It is also responsible for adult male body characteristics. Hair follicles in parts of the male scalp are particularly susceptible to the effects of DHT and miniaturize in response. DHT results from the action of the enzyme 5-alpha reductase on testosterone.
For men, the percentage experiencing hair loss tracks their age decade by decade. In their 20s approximately 20% of men experience noticeable hair loss. In their 30s, the number is 30% and so on. So in their 50s, half of men have noticeable hair loss. For women, the numbers are not as great but large nonetheless. Noticeable hair loss affects 40% of women by age 70. Each sex also has a particular pattern distribution of hair loss.
Although there is considerable crossover in pathophysiology with the effects of androgenic (male) hormones playing a major role in both sexes, the conditions are now referred to separately: MPHL (male pattern hair loss) and FPHL (female pattern hair loss.) Treatments for both are similar as is the morphological characteristics of the hair changes. It basically is a permanent return of terminal hair into vellus hair, those tiny, wispy, colorless, almost invisible hairs found on children’s bodies. The same thing happens in aging men and women. Hair follicles get smaller. The anagen stage of hair growth gets shorter, and the resting (telogen) stage gets longer. The result: Thin, very short hairs — and many follicles empty of hair shafts.
The good news is the follicle is still alive which makes it potentially possible for it to transition back into producing actively growing, longer, terminal hair.
TRIGGERS of FEMALE HAIR LOSS
Each day we lose about 50 to 100 hairs. When all is well an equal number is growing back. Severe stress (death in the family, divorce, job loss) and changes in diet (crash programs, lack of protein) can cause hair to shed more rapidly. Antidepressants, beta blockers, anti-acne prescriptions and medications with testosterone, which women may take to increase their sex drive, can cause hair loss. So can iron deficiency and an overactive or underactive thyroid gland. When women go through menopause and their estrogen levels fall, their hair often begins to thin. Many women also lose some hair a few months after giving birth because of the hormonal changes the body experiences.
OTHER LESS COMMON TYPES OF HAIR LOSS
Chemotherapy-induced alopecia is an expected and associated side-effect of chemotherapeutic agents used to treat malignancies. Because the target of these agents is rapidly growing tissue, i.e. where cells have high turnover rates, some normal cells are adversely affected, most notably cells in the gastrointestinal tract and hair follicles.
Alopecia areata is an autoimmune inflammatory condition which may affect the hair of the head, face, and body. Although most commonly thought of as an acquired disorder, congenital cases have been described. It has an incidence of 0.1–0.2%, and affects 1–2% of men and women. Hair involvement in AA is often patchy. Two variants of AA are alopecia totalis, a total loss of scalp hair, and alopecia universalis, total loss of scalp and body hair.
Alopecia mucinosa, often referred to as follicular mucinosis, is dermatologic condition where follicles accumulate a mucus-like material that causes an inflammatory condition that causes follicular death. The face, the neck, and the scalp are the most frequently affected sites, although lesions may appear on any part of the body.
Trichotillomania (also known as trichotillosis or hair pulling disorder) is an obsessive compulsive disorder characterized by the compulsive urge to pull out one’s hair, leading to hair loss and balding, distress, and social or functional impairment. It appears in the ICD chapter 5 on mental and behavioral disorders, and is often chronic and difficult to treat. Common areas for hair to be pulled out are the scalp, eyelashes, eyebrows, legs, arms, hands, nose and the pubic areas.
TREATMENTS for HAIR LOSS
Minoxidil (Rogaine) is used topically to treat hair loss in men and women. Products are a 2% lotion and 5% foam. Minoxidil was originally marketed as an effective oral anti-hypertensive drug that reduced blood pressure through vasodilatation. The observed side-effect of hair growth has been known for decades and related to the local increase in blood flow to hair follicles.
Finasteride (Propecia) is a Type II 5-alpha reductase inhibitor that prevents the conversion of testosterone into much more potent DHT. 5-alpha reductase is found predominantly in the prostate gland and in hair follicles. It has long been used to treat MPHL but studies show it is also effective in treating FPHL. Topical finasteride is available but without FDA approval. Side effects of oral finasteride in men include loss of libido, reduced ejaculate, and orgasmic inhibition. Pregnant women should not take finasteride.
Spironolactone (a type of potassium sparing diuretic) has androgen blocking properties and has been used with success in treating FPHL, particularly when combined with minoxidil.
Americans spend $800 million a year on hair restoration surgery. Great strides in hair transplant technology now make it possible to transplant hair in such a fashion that it is essentially undetectable. Early techniques often resulted in esthetically unpleasing results with tufts of hair placed into rows similar to the planting of crops. The effect was similar to how hair is placed into the heads of plastic dolls.
There are three advanced techniques in use now. The third actually increases the number of total follicles.
- Follicular Unit Hair Transplantation (FUT): Hair units are removed from a donor strip that has been excised from the donor area. This leaves a noticeable scar which can be visible if hair is not worn appropriately long.
- Follicular Unit Extraction (FUE): Individual hair units are removed directly from the donor area by a micro-punch individually, follicle by follicle, and transplanted to thinning areas. Now robotic machine use sophisticated software to identify and extract donor follicles.
- Hair Stem Cell Transplant (HST): Advanced surgical methods make it possible to transplant only part of a given follicle from which multiple hairs emerge. This enable part of the donor follicle, with its component stem cells, to remain in place making it possible for both the donor and transplanted parts of the same follicle to produce hair. The number of hair producing follicles increases because the donor follicle continues to function as a separate unit.
Low-level laser therapy (LLLT) is proved to stimulate hair re-growth. A review of randomized controlled trials (RCT) that investigated benefits of LLLT in patients with hair loss (male pattern hair loss (MPHL), female pattern hair loss (FPHL), alopecia areata (AA), and chemotherapy-induced alopecia (CIA)) demonstrated significant effect. 21 relevant studies were summarized in the review including 2 in vitro, 7 animal, and 12 clinical studies. The RCTs were critically appraised and found that FDA-cleared LLLT devices are both safe and effective in patients with MPHL and FPHL who did not respond or were not tolerant to standard treatments.
Low level laser therapy and hair regrowth: an evidence-based review. Lasers in Medical Science February 2016, Volume 31, Issue 2, pp 363-371
The growth of human scalp hair in females using visible red light laser and LED sources. Lasers in Surgery and Medicine;13 Aug 2014
Patients undergoing chemotherapy to treat malignancies almost always develop alopecia, which is usually universal and includes all hairy surfaces. In response, many patients resort to wearing wigs to replace lost hair. There is another choice.
Cooling caps worn during periods of relatively high blood levels of cytotoxic drugs can help. Designed to acutely lower the scalp temperature during drug administration, blood vessels constrict in response, thereby reducing exposure of the follicle to drugs that cause acute hair loss by inducing catagen.
Laboratory culture of follicular stem cells along with dermal papilla cell may one day lead to the ability to expand the number of follicles making it possible to create an unlimited number of transplantable hair follicles.
Researchers found that hair follicles in adult mice regenerate by re-awakening genes once active only in developing embryos. These findings provide unequivocal evidence that, like other animals such as newts and salamanders, mammals have the power to regenerate. These findings are published in the May 17 issue of Nature.
A gene called “sonic hedgehog” can convert resting hair into growing hair. It controls follicle size and growth.
Finding a method to upregulate this gene holds promise as a potential treatment. Sonic hedgehog is just one of several key genes scientists are tinkering with in labs.
Certain signaling molecules have direct influence on hair-follicle development. Prime examples are the “wnt” proteins. Wnt proteins can influence wound healing in a way that has less scarring and includes normal structures of the skin, such as hair follicles and oil glands. Researchers found that early wound healing in mice triggered an “embryonic-like” state in which dormant molecular pathways are awakened, sending stem cells to the area of injury. Unexpectedly, the regenerated hair follicles originated from non-hair-follicle stem cells.
By introducing more wnt proteins to the wound, the researchers found that they could take advantage of the embryonic genes to promote hair-follicle growth, thus making skin regenerate instead of just repair. Conversely by blocking wnt proteins, they also found that they could stop the production of hair follicles in healed skin.
Increased wnt signaling doubled the number of new hair follicles. This suggests that the embryonic window created by the wound-healing process can be used to manipulate hair-follicle regeneration, leading to novel ways to treat hair loss and hair overgrowth.
Cytokine and Growth Factor Manipulation
Platelet rich plasma (PRP) injections of the scalp have been shown to be of benefit in instigating hair re-growth. This is often performed in conjunction with microneedling, and may be part of transplant surgery protocols. PRP contains several cytokines and growth factors known to enhance hair growth.
Drjohn and Drgeorge, your humble BFT authors, are busy at work developing hair restoration products that incorporate cytokine and growth factor strategies. We have already learned to manipulated our beloved bone marrow mesenchymal stem cells to modulate their bio-signal outputs to accentuate wnt proteins. Our first product, a serum for use with dermal needling of the scalp is showing promising results. While we perform additional clinical studies on that formula, we are busy at work creating a complementary lotion for daily home use.
Photos of patient below provided by Dr. Diane Duncan of Fort Collins, Colorado. Patient received three dermal needling treatments of scalp, each a month apart, using hair serum developed by BFT authors. Device used provided by ProCell Therapies.
What is the best product to use with micro needling for hair loss
Large randomized, double-blind control trials have not been yet performed assessing the value of medical microneedling in promoting hair growth in androgenetic alopecia (male and female pattern baldness). Anecdotal evidence, however, does show substantial promise. Microneedling not only creates localized trauma, it produces thousands of microchannels that can be exploited to allow greatly enhanced penetration of topically applied substances. These fall into two general categories: pharmaceuticals and growth factors.
The drugs minoxidil (Rogaine), finasteride (Propecia) and bimatopros (Latisse) are each used to promote hair growth. All were originally created to address other medical issues – minoxidil for blood pressure; finasteride for benign prostatic hypertrophy; bimatopros for glaucoma – and their benefit in hair regrowth was an “accidental” finding. The results with all are less than stellar, their benefit being more in helping slow hair loss than promoting hair regrowth. A study using topical minoxidil with microneedling is referenced below.
Topical growth factors may prove more efficacious since they address the physiologic bio-signaling that is in control of hair follicle function – a more natural and physiologic approach.
The oldest and most used (thus far) topical bio-signal is PRP (platelet rich plasma). PRP is used as both an injectable and as a topical. Results in published studies about PRP in hair regrowth are mixed. Hair microneedling serums based on cell cultures of fibroblasts, adipose and bone marrow stem cells, are currently available. We currently produce a hair product available carrying our and our private label brands.
Efforts are underway by us to create second-generation topical hair regrowth biosignal products that are based on the ever growing body of published science that addresses the myriad of biosignal pathways involved in follicle physiology. Our approach is to use our experience in laboratory culture of bone marrow mesenchymal stem cells to accentuate the Wnt / catenin pathway (instrumental in follicle stimulation) combined with synthetic versions of other human growth factors, including the major ones considered of benefit found in PRP. Because there is abundant published literature attesting the value of botanicals, we are exploring use of topical plant extracts also, although because they are foreign, i.e. not human substances, we will not use them in conjunction with microneedling. Clinical tests are now getting underway. Stay tuned.
Because hair growth is a slow motion process, clinical studies are time consuming with results many weeks into the future.
So…what’s the best product to use? As you know, we are partial to bone marrow stem cells and a rather large number of clinicians are reordering our products based on positive patient responses in their practices. As far as large, controlled, double-blind clinical studies are concerned, they don’t yet exist. Hopefully, they will before too long.
I read that the PRP protocol for hair loss has changed. A year or more ago the protocol called for 40+ injections of PRP. The protocol now is 14-16 deeper injections of PRP, the theory being that the deeper injections allow for a greater spread of plasma, thus needing fewer (painful) injections. I have done both and saw more improvement with the larger number of injections. That makes me wonder if it was the numerous injections that stimulated the growth – not the PRP. After reading the article on Microneedling and Hair Loss in the International Journal of Trichology, I am even more convinced. In the study, they microneedled only to the point of erythema once a week. The dermatologists and other medical offices tend to needle more aggressively but less often. Do you see a benefit to one approach over another for hair loss? What about if using in conjunction with the AnteAGE mircroneedling solution?
The major reason the protocol for PRP injections for hair regrowth changes is this is an active area of research and no one yet knows the magic number of treatments, the optimal interval between injection sessions, or the best depth of injection. To be more precise, no one yet knows that PRP is, in fact, the best way to provide the bio-signals that encourage hair follicle to become active, enlarge, and begin to grow visible hair. There are many efforts underway to find the best and most effective way to stimulate hair re-growth in androgenetic alopecia, or other types of alopecia. We are busy in that field ourselves and are conducting a pilot study as this is written.
The physiologic control of hair growth is extremely complex, much more so than skin healing and regeneration. Just think about it, both sexes are covered in fine short colorless velus hair as children except for colored, more coarse hair (called terminal hair) on our scalp, eyebrows and eye lashes. With puberty we develop the adult hair distribution pattern of male or female (with a lot of cross over based on ethnicity.) With age, areas of hair sensitive to 2-3 dihyrotestosterone begin to have their follicle become smaller and smaller (miniaturization) with each cycle of hair growth, to the point that the hair becomes invisible to the naked eye. Those are areas where restoration of terminal hair growth can improve the appearance of balding. If follicles have essentially disappeared, causing them to regenerate is an even bigger challenge.
PRP (platelet rich plasma) contains lots and lots of cytokines and growth factors. PRP might be considered a “shot gun” approach. There is no way to control what is in PRP to select those bio-signals most favorable to restore hair growth. Our efforts are to hopefully be more precise and develop products with selected biosignals with proven efficacy – more of a “rifle” approach. We are also exploring the value of certain botanical extract that science indicates may have value. This puzzle is far from solved.
Microneedling is showing benefit in hair regrowth even when no topical products are used. This may be because the trauma of microneedling itself will release bio-signals from platelets and other cells. We are far from fully understanding how best to stimulate hair re-growth and many companies are investing time and research dollars trying to unravel this mystery. We’ll keep you posted as progress is made.
Below are research articles that demonstrate just how complex this challenge is.
Int J Trichology. 2015 Apr-Jun; 7(2): 54–63.
Platelet-rich Plasma as a Potential Treatment for Noncicatricial Alopecias
Androgenetic alopecia (AGA) and alopecia areata (AA) are common hair loss disorders affecting both men and women. Despite available therapeutic options, search for new, more effective treatment is constant. Platelet-rich plasma (PRP) could be effective in promoting hair growth: (1) To present PRP and its mechanism of action in promoting hair growth and (2) to evaluate its preparation methods and its therapeutic potential in noncicatrial alopecias in a systematic review. An international bibliography search, through five databases, was conducted to find articles regarding PRP’s action on hair loss. Growth factors in platelets’ granules of PRP bind in the bulge area of hair follicle, promoting hair growth. PRP is a potential useful therapeutic tool for alopecias, without major adverse effects. Nevertheless, due to the small number of conducted trials, further studies are required to investigate its efficacy.
The value of PRP and a whole variety of other approaches to hair re-growth is underway. Time will tell what works best and why.
It’s difficult to attribute the improvement you saw to the number of needle sticks. Both 40 and 14-16 injections are minuscule numbers compared to the many thousands that occur during microneedling. Also, microneedling is done at much shallower depths than with PRP injections. As you likely know, the use of PRP is intended to deliver concentrated growth factors and cytokines to help stimulate follicle activity. Because the AnteAGE hair products contain many of the same pro-growth bio-signals (without the anti-growth ones) we have seen good results. The system also incorporates many botanicals and other molecules proven to help stimulate hair follicles, which PRP does not contain. Nationally recognized hair transplant specialists are no using the AnteAGE system in their practices.
I have a question about low molecular weight and high molecular weight (hyaluronic acid). With both powder types do I mix an eighth of a teaspoon with 2 ounces of distilled water and do I store in the fridge?
HA, regardless of molecular weight, takes very little powder to create a rather viscous gel. Trial and error are appropriate to get a consistency you like. Applied to intact skin, there is very limited absorption into the skin so molecular weight is of minimal importance compared to when one is using microneedling or other traumatic modalities. If given a choice, we would opt for the higher molecular weight. It will help hydrate the upper layers of the skin. Too much may create a dried “film” so again, trial and error will help sort this out. Distilled water is fine as is storing in the refrigerator.
What about using DMSO with Minoxidil instead of micro needing?
Studies of relative minoxidil uptake into appendages (hair follicles) and stratum corneum and permeation through human skin using ethanol, propylene glycol and water as vehicles showed best penetration by ethanol, then propylene glycol, then water. This was true during the early period (30 min and 2 h). At 12 hours, uptake was similar for all. Demonstrated was that the appendageal route is likely the key determinant of hair growth promotion by minoxidil. It is prescribed for oral use for hypertension, but only topical minoxidil is used for hair re-growth and the dosage schedule is twice a day or every 12 hours.
DMSO, dimethyl sulfoxide, is an industrial solvent with recognized anti-inflammatory potency. It has limited approved uses in medicine ( e.g. interstitial cystitis) and is a recognized effective enhancer of cutaneous permeation of medications applied to the skin. We find no use of DMSO in enhancing penetration of minoxidil with internet searches, although that may well occur. The question, however, may be moot insofar as penetration into appendages of the skin is where minoxidil exerts its mechanism of action, and the study mentioned suggests that by 12 hours, even water borne minoxidil has full penetration.
Microneedling has demonstrated efficacy in treating alopecia with and without minoxidil, although microneedling alone was as “cosmetically significant” as a combined therapy.
Relative uptake of minoxidil into appendages and stratum corneum and permeation through human skin in vitro. J Pharm Sci. 2010 Feb;99(2):712-8
A Randomized Controlled, Single-Observer Blinded Study to Determine the Efficacy of Topical Minoxidil plus Microneedling versus Topical Minoxidil Alone in the Treatment of Androgenetic Alopecia. J Cutan Aesthet Surg. Oct-Dec 2018;11(4):211-216