Study More Accurately Predicts Severe Balding Risk Using New Genetic Profile

Study More Accurately Predicts Severe Balding Risk Using New Genetic Profile

What are the chances that I will go bald? How bald will I be? Can I know for sure? These are among the most common questions we get from patients in our hair loss consultations. Despite extensive knowledge about the mechanisms and causes of androgenetic alopecia (common baldness), the answers to these questions have been a bit hazy. New research has sharpened the focus on the genetic mix that results in hair loss and has enabled more accurate predictions. A study published in February 2017 in the journal PLoS Genetics identified over 250 gene locations newly linked to hair loss. Using this information, researchers more accurately predicted severe balding compared to previous methods.

Background

We know that susceptibility to hair loss is driven by genetics. One in two men in their 50s experience some degree of balding, with that proportion increasing to over 60% of men aged 60 and over. We also know that one of the most important genes in hair loss, called the androgen receptor (AR) gene, is located on the X chromosome. Outside of that, knowledge of the precise genetic makeup resulting in baldness is sparse and there is wide variation in balding patterns. Some genetic tests, such as the HairDx test, have been developed to predict a patient’s risk of balding, but lack the ability to determine its severity. To date, the best method for predicting the extent of future hair loss is to have an experienced physician take a personal and family history and perform a physical examination that includes an assessment of miniaturization of scalp hair.

Developing a more thorough understanding of the complex genetic relationships that result in hair loss will be important in clinical practice as these relationships may help predict future hair loss and guide methods of treatment.

The Study

Researchers selected a pool of more than 52,000 men with male pattern baldness from UK Biobank. This is a massive database of over half a million people aged 40-69 years with information accumulated from 2006 to 2010. This pool was over four times the size of the previously largest hair loss study. Researchers applied a genome-wide association study (GWAS) to a cohort of about 40,000 men and identified 287 statistically important gene locations (loci) linked to varying degrees of baldness — more than 35 times the eight genetic signals found in the previous largest study.

Using this set of 247 loci on non-sex, or autosomal, chromosomes and 40 loci on the X chromosome, the researchers analyzed the remaining 12,000 men for predictive patterns. The results indicated that the predictive value of using this set of gene loci was 0.78 for severe hair loss, 0.68 for moderate hair loss, and 0.61 for slight hair loss. When the subject’s age was added, the predictive score improved to 0.79 for severe hair loss, 0.70 for moderate hair loss, and 0.61 for slight hair loss. Subjects whose individual scores, based on their genetic makeup, were below the mid-point of the range of scores were significantly more likely to have no hair loss than severe hair loss. By contrast, almost 60% of subjects whose individual scores were in the top 10% of the range of scores were moderate to severely bald.

While the predictions were not extraordinarily accurate – the authors characterized the accuracy as “still relatively crude” – they did show a distinct improvement in predictive accuracy over prior studies.

Summary

Hair loss is a serious concern for many people. Research shows that men with extensive hair loss may experience significant psychosocial impacts such as reduced self-image and reduced social interactions. Some studies have associated baldness with increased risk of prostate cancer and heart disease.

Understanding the complex factors that comprise the genetics of hair loss can help physicians potentially customize treatments based on a patient’s genetic profile and their risk of balding. Beyond that, diagnosing the potential severity of hair loss may help doctors get a head start on treating what could be related life-threatening conditions.

With large databases like UK Biobank, researchers can now drill down into this information and develop increasingly clear, highly granular data sets that can identify complex systems and potentially lead to improved treatments.

References

Hagenaars SP, Hill WD, Harris SE, Ritchie SJ, Davies G, Liewald DC, et al. (2017) Genetic prediction of male pattern baldness. PLoS Genet 13(2): e1006594. doi:10.1371/journal.pgen.1006594

Posted by Robert M. Bernstein M.D.

Study Identifies A Possible Cause of Age-Induced Hair Loss

Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

Researchers show how the normal hair cycle (left) is disrupted by DNA damage (center),
resulting in age-induced hair follicle miniaturization (right)

We have known for decades that the incidence of male pattern baldness increases with age. New research published in the February 2016 edition of the journal Science has shed light on why this is the case. Researchers examining the role of hair follicle stem cells (HFSC) in the hair growth cycle have found that accumulated DNA damage in these cells results in the depletion of a key signaling protein and the progressive miniaturization of the hair follicle (and eventual hair loss). ((Matsumura H, Mohri Y, Binh NT, et al. Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science. 2016 Feb: Vol. 351, Issue 6273, p. 613.)) The study represents a breakthrough in our understanding of the cell aging process and could open new pathways for the treatment of not only hair loss but other age-related conditions as well.

Background: The Hair Growth Cycle

At any point in time, a hair follicle exists in one of three phases:

Anagen Phase – this is the “growth” phase in which the hair follicle is actively producing living hair. Anagen can last from two to seven years.
Catagen Phase – this is a short transitional phase in which hair growth stops, the middle of the follicle constricts, and the bottom of the follicle begins to form the “club.” The follicle also separates from the bloodstream. Catagen lasts two to three weeks.
Telogen Phase – this is the “resting” phase in which the clubbed hair detaches from the dermal papilla and is susceptible to falling out. Telogen lasts three to four months before hair follicle stem cells initiate a new anagen (growth) phase and the cycle repeats.

Stem Cells and the Hair Cycle

Normally, hair follicle stem cells (HFSC) perpetuate the hair cycle by initiating a new anagen (growth) phase after the telogen (resting) phase. But HFSC, like all cells, age over time. Included in this aging process is damage to DNA strands inside these cells due to spontaneous errors in DNA replication or those due to exposure to sunlight and other insults. While it has been well understood that hair follicle miniaturization occurs as a person ages and that damage to genetic material contributes to the process, the exact mechanism that ties cell aging to the disruption of the normal hair cycle was unknown. The recent study examines miniaturization from cell aging and distinguishes it from miniaturization caused by the effects of DHT.

Results of the Study

The key finding in this new research is that as hair follicle stem cells (HFSC) accumulate genetic damage over time, their store of a signaling protein called COL17A1 is depleted. The depletion of this key protein forces HFSC to differentiate into a common type of skin cell called a keratinocyte. By differentiating into keratinocytes, the population of HFSC gradually shrinks, there are fewer HFSC to initiate the anagen (growth) phase, and the telogen (resting) phase is extended. With a gradually longer telogen phase and shorter anagen phase, the follicle progressively miniaturizes. Eventually, the hair-producing follicle disappears leaving a bald scalp and the keratinocytes, which no longer serve a purpose in the hair growth cycle, are ejected from the skin.¹ Click here to view the graphic that illustrates this process.

The authors of the study suggest that restoring COL17A1 levels, or halting their depletion, may prevent this aging-induced hair follicle miniaturization from occurring.¹

With perhaps much broader significance, the study confirms the tight linkage between the instability of genetic material in stem cells (that can be due to environmental factors) and the shrinkage and functional decline seen in many organs as they age.

Conclusion

Progressive hair loss is a pervasive problem for males as they age. However, current treatments deal, exclusively, with hormone-induced miniaturization. The discovery of the mechanism behind age-induced miniaturization may result in a new avenue for the treatment of hair loss. More research into methods of boosting levels, or preventing the depletion, of COL17A1 may yield a hair loss therapy that targets this cause of hair loss.

Further, developing a better understanding of the cell aging process may open up new avenues of research into the causes of, and potential solutions to, the age-induced decline of major organs in the body.

Image c/o Science

Posted by Robert M. Bernstein M.D.

Treatments for Hair Loss in Women Detailed in Article Featuring Dr. Bernstein

Dr. Bernstein was interviewed for an article in NYCityWoman.com that ran the gamut of available treatments for hair loss in women. Read below for some select quotes on a wide range of topics related to hair loss in women and treatments for female patients with androgenetic alopecia (common genetic hair loss).

On the fading stigma of hair loss in women:

“Women today are more comfortable talking about their hair loss.”

On indicators of hormone-driven female hair loss:

“It is typical to have a positive family history of hair loss and the presence of miniaturization (short, fine hairs) in the thinning areas.”

On minoxidil for regrowth of thinning hair:

“Rogaine (minoxidil) can increase the quality (length and diameter) of hair that is just starting to thin.”

On the different strengths of Rogaine (minoxidil):

“I generally recommend the 5 percent for women and men. Although it’s sold in separate packages for men and women, the basic ingredients are essentially the same.”

On Rogaine Foam:

“It is an elegant mixture, made for compliance,” says Dr. Bernstein. “It is an aerosolized foam, so it is less irritating than liquid Rogaine, but can be more difficult to get directly on the scalp.”

On LaserComb vs. cap-based Low Level Laser Therapy (LLLT) devices:

“The cap is both easier to use and more effective for very thin hair, due to the greater number of lasers. But for higher-density hair, a laser comb or the LaserBand82 may be more effective, as it’s probably better at getting the laser therapy beam to the scalp.”

On Platelet-Rich Plasma (PRP) therapy for hair loss:

“Platelet-rich plasma therapy involves spinning the patient’s own blood (preferably twice) in a centrifuge to separate out the growth factors.”

On Follicular Unit Transplant (FUT) surgery:

“FUT hair transplants allow many women to have a completely natural hair restoration, producing a dramatic change in their appearance.”

On Robotic FUE hair transplants:

“Robotic FUE allows for unparalleled precision, without any line scars in the donor area and no post-operative limitations on physical activity.”

See before and after photos of some of our female hair transplant patients
Read about the causes, classification, diagnosis and treatment of hair loss in women

Posted by Robert M. Bernstein M.D.

Dr. Christiano Discovers JAK Inhibitors as Potential New Topical Treatment for Hair Loss

Dr. Angela Christiano and her team of researchers at Columbia University studying the autoimmune disease alopecia areata, have shed new light on how to move hair follicles from their resting stage (telogen) into the growth stage (anagen) in which they can produce normal hairs. The study, published in the October issue of Science Advances, introduces the possibility of a new topical medication for hair growth stemming from a class of chemicals that block enzymes in the Janus kinase (JAK) family. ((Harel S, Higgins CA, Cerise JE, Dai Z, Chen JC, Clynes R, Christiano AM. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci Adv. 2015 Oct; 1(9): e1500973.)) The findings on the topical application of JAK inhibitors have implications in the treatment of common hair loss as well as alopecia areata, which causes a non-scarring form of localized hair loss.

Scientists had, until now, tried unsuccessfully to use drugs to induce follicles en masse into the anagen phase. The two FDA-approved medications currently used to treat hair loss each use a different approach. Finasteride (Propecia) blocks the conversion of testosterone to dihydrotestosterone (DHT) – the hormone that causes genetically susceptible hair follicles to progressively shrink or miniaturize. Minoxidil (Rogaine) extends the anagen phase, thereby delaying the onset of hair follicle miniaturization. JAK inhibitors could develop into a third major medical option for the treatment of hair loss.

Background: Research Investigating Alopecia Areata

Dr. Christiano, herself diagnosed with alopecia areata, has made several significant breakthroughs involving hair loss and its treatment in the past. Bernstein Medical has written extensively about her study of alopecia areata, hair loss genetics, and hair cloning.

Building on initial research in 1998 implicating a type of white blood cell known as “T lymphocytes” in the development of alopecia areata, ((Gilhar A, Ullmann Y, Berkutzki T, Assy B, Kalish RS. Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice. J Clin Invest. 1998 Jan 1; 101(1):62-7.)) Dr. Christiano and her team set out to find ways to modulate them. In research published in the September 2014 issue of Nature Medicine, they looked at two different FDA-approved chemicals, ruxolitinib and tofacitinib, and how they act as inhibitors of enzymes in the family Janus kinase (JAK). Inhibiting JAK cut off communication to the T cells. Without an accumulation of T cells, alopecia areata could not progress. ((Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L, Singh P, Petukhova L, Mackay-Wiggan J, Christiano AM, Clynes R. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014 Sep; 20(9):1043-9.)) The JAK inhibitors both prevented the onset of the disease, and reversed the condition where it was already established.

The most surprising finding of this study concerned the effect of topically applying the inhibitors.

“We found that topical ruxolitinib and topical tofacitinib were both highly effective in reversing disease in treated lesions (applied to back skin). A full coat of hair emerged in the ruxolitinib- or tofacitinib-treated mice by 7 weeks of treatment, and we observed complete hair regrowth within 12 weeks following topical therapy.”²

Findings: JAK Inhibitors and Hair Growth in Normal Subjects

Having successfully tested JAK inhibitors against alopecia areata, Dr. Christiano and her team sought to investigate JAK inhibition on normal mice and humans.

The researchers applied solutions of tofacitinib and ruxolitinib to one side of the backs of mice with hair in the telogen phase, while the other side was treated with a control solution. Within seven days of treatment, each mouse saw robust hair growth on the treated side, while the control side did not. This indicates a rapid transition of the hair cycle from telogen (resting) to anagen (growth). Furthermore, they found that treatment with JAK inhibitors resulted in “significant proliferation” of hair follicle stem cells, indicating that the inhibitors activated progenitor stem cells within the follicles. The topical application of JAK inhibitors in mice unmistakably resulted in rapid onset of hair growth.

Next, the team looked at the effects of JAK inhibitors on cultured dermal papilla (DP) spheres. In 2013, Dr. Christiano achieved a breakthrough in using an ingenious technique, called a “hanging drop culture.” Using this process, her team caused dermal papilla cells to clump together in a spherical (tear drop) shaped configuration. They found that DP cells in this three-dimensional mass more easily communicate with one another and are then capable of forming new hair follicles. When cultured in a solution containing the JAK inhibitor, tofacitnib, the DP spheres showed an enhanced ability to induce hair follicle development in larger sizes and in significantly greater numbers.

Conclusion/Summary

Topical application of JAK inhibitors leads to the activation and proliferation of hair follicle stem cells and a rapid transition to the anagen phase of the hair growth cycle. This research could be the catalyst for the development of a new topical treatment for hair loss that could potentially benefit individuals who are not indicated for, or who have not seen a positive response from, traditional hair loss medications or are not candidates for hair transplantation. Additionally, JAK inhibitors may be developed into a topical treatment for alopecia areata and potentially other autoimmune conditions that cause localized hair loss or other skin problems. JAK inhibitors might even aid in the development of hair cloning techniques, which could effectively cure hair loss.

Posted by Robert M. Bernstein M.D.

Caffeine Reverses Androgenetic Alopecia, Promotes Hair Growth in Cell-Cultured Hair Follicles

Androgenetic Alopecia and Limited Medicated Treatment Options

Androgenetic alopecia (AGA) is the most common cause of hair loss in men and women. Over half of all men by the age of 50, and the same proportion of women by the age of 80, will experience some degree of permanent hair loss due to AGA.

Much is known about how AGA causes hair loss. Normally, hair follicles repeatedly cycle through growth (anagen) and rest (telogen) stages, but in individuals with AGA, hair follicles in genetically predetermined areas of the scalp gradually spend more and more time in the resting stage. Additionally, each growth stage produces a smaller and smaller hair shaft caused by a progressive miniaturization of the hair follicle. Eventually, the follicle stops producing hair ((Alonso L and Fuchs E. “The Hair Cycle,” February 1, 2006 J Cell Sci 119, 391-393.)).

Hair loss caused by AGA can be stopped by existing medications, but to date, only two FDA-approved drugs are available for treatment of AGA: finasteride (Proscar ®) and topical minoxidil (Rogaine®). Unfortunately, up to 3 out of 10 individuals will not respond to one or more of these drugs ((Fischer TW, Hipler UC, Elsner P. “Effect of Caffeine and Testosterone on the Proliferation of Human Hair Follicles in vitro.” Int J Dermatol 2007; 46: 27-35.)). Because of this, researchers have searched for alternate treatments, especially for women since finasteride is not approved for use in female patients.

Caffeine: A Possible Alternative Treatment?

One possible alternative substance is caffeine. This is because as a phosphodiesterase-inhibitor, caffeine increases cellular metabolic activity ((Green H. “Cyclic AMP in relation to proliferation of the epidermal cell: a new view.” Cell 1978;15: 801-11.)). Researchers theorize that this could counteract the miniaturization of the hair follicle ((Fischer TW, Hipler UC, Elsner P. “Effect of Caffeine and Testosterone on the Proliferation of Human Hair Follicles in vitro.” Int J Dermatol 2007; 46: 27-35.)).

Indeed, using cell-cultured (i.e., in vitro or “test tube”) male human hair follicles, researchers have demonstrated that caffeine reverses testosterone’s inhibitory effect on keratinocyte proliferation, which could lead to increased hair shaft cell production. Researchers have also demonstrated that caffeine normalizes testosterone’s inhibition of hair shaft elongation ((Fischer TW, Hipler UC, Elsner P. “Effect of Caffeine and Testosterone on the Proliferation of Human Hair Follicles in vitro.” Int J Dermatol 2007; 46: 27-35.)).

Evidence that Caffeine can Stimulate Hair Follicle Growth in Cell-Cultures and Protect those Hair Follicles from the Effects of AGA

A 2014 paper in the British Journal of Dermatology ((Fischer TW, Herczeg-Lisztes E, Funk W, Zillikens D, Bíró T, Paus R. “Differential effects of caffeine on hair shaft elongation, matrix and outer root sheath keratinocyte proliferation, and TGF-β2-/IGF-1-mediated regulation of hair cycle in male and female human hair follicles in vitro.” Br J Dermatol. 2014 May 16)). reported that caffeine stimulated hair growth in cell-cultured follicles in three ways:

It enhanced hair shaft elongation in both male and female cell-cultured follicles.
It increased the number of hair matrix keratinocytes, i.e., cells that create the hair shaft and its surrounding protective structure (the inner and outer root sheath), in both male and female cell-cultured hair follicles.
It increased the stimulation of a hair growth factor called IGF-1 in both male and female cell-cultured hair follicles.

The paper also reported that caffeine may protect cell-cultured hair follicles against the effects of AGA in two ways:

It reversed testosterone’s suppressive effects on the anagen (growth) stage of both male and female cell-cultured hair follicles, one of the primary mechanisms of hair loss in AGA.
It protected both male and female cell-cultured hair follicle against apoptosis, a process that leads to the end of the anagen (growth) stage of hair follicles. This is significant because premature exit from anagen is another mechanism of hair loss in AGA.

In sum, this 2014 research not only replicates a past finding that caffeine counteracts some of the hair growth suppression mechanisms of AGA but also, for the first time, shows that caffeine stimulates hair growth in both male and female cell-cultured hair follicles. Its beneficial effects have yet to be shown in humans.

Posted by Robert M. Bernstein M.D.

Why Does A Hair Transplant Work?

Q: Why does a hair transplant grow – why doesn’t the transplanted hair fall out? — J.F., Redding, C.T.

A: Hair transplants work because hair removed from the permanent zone in the back and sides of the scalp continues to grow when transplanted to the balding area in the front or top of one’s head. The reason is that the genetic predisposition for hair to fall out resides in the hair follicle itself, rather than in the scalp — this idea is called Donor Dominance. This predisposition is an inherited sensitivity to the effects of DHT, which causes affected hair to decrease in diameter and in length and eventually disappear — a process called “miniaturization.” When DHT resistant hair from the back of the scalp is transplanted to the top, it will continue to be resistant to DHT in its new location and grow normally.

Posted by Robert M. Bernstein M.D.

After a Hair Transplant What are the Effects of DHT on Donor Hair?

Q: Hi! I wanted to ask if after hair restoration surgery the transplanted hair will eventually fall out? Because the surgery is to restore hair mainly for people with genetic hair loss which results from DHT, won’t the DHT make the new follicles implanted fall out as well? — B.C., Stamford, C.T.

A: Hair loss is due to the action of DHT (a byproduct of testosterone) on hair follicles that cause them to shrink and eventually disappear (the process is called miniaturization). The follicles on the back and sides of the scalp are not sensitive to DHT and therefore don’t bald (miniaturize).

When you transplant hair from the back and sides to the bald area on the front or top of the scalp the hair follicles maintain their original characteristics (their resistance to DHT) and therefore they will continue to grow.

Read about Miniaturization

Posted by Robert M. Bernstein M.D.

Hair Loss Causes: What is Miniaturization and What is Effect of DHT on Hair Follicles?

Q: I have read that in the evaluation of a patient for hair restoration surgery some doctors use a densitometer to measure miniaturization – the decrease in size of hair diameters. I read that miniaturization is a sign of genetic hair loss, but when there is miniaturization of greater than 20% in the donor area, a person may not be a good candidate for hair transplants. Is this correct and does 20% miniaturization mean that 20% of the population of terminal hairs have become fine vellus-like hairs or that there is a 20% decrease in the actual diameter of each of the terminal hairs? — B.A., New Albany, Ohio

A: Miniaturization is the decrease in hair shaft length and diameter that results from the action of DHT on healthy, full thickness terminal hairs. The hairs eventually become so small that they resemble the fine, vellus hair normally present in small numbers on the scalp and body. Miniaturized hairs have little cosmetic value. Eventually miniaturized hairs will totally disappear. Twenty percent miniaturization refers to the observation, under densitometry, that 20% of the hairs in an area show some degree of decreased diameter.

In the evaluation of candidates for hair transplantation, we use the 20% as a rough guide to include all hairs that are not full thickness terminal hairs. Of course we are most interested in the presence of intermediate diameter hairs — i.e. those whose diameters are somewhere between terminal and vellus and are clearly the result of DHT. I don’t know if one can tell the difference on densitometry between vellus hairs, fully miniaturized hairs and senile alopecia. The partially miniaturized population is most revealing.

Miniaturization in the recipient scalp (i.e. the balding areas on the front top and crown that we perform hair transplants into) is present in everyone with androgenetic hair loss. Miniaturization in the donor area, however, is less common (in men). It means that the donor area is not stable and will not be permanent. Men with more than 20% of the hair in the donor area showing miniaturization are generally not good candidates for hair transplant surgery.

Read about Miniaturization
Read about Candidacy for Hair Transplant Surgery

Posted by Robert M. Bernstein M.D.

Browse Hair Restoration Answers by topic:

▲ Top of Page

Hair Follicle Miniaturization

Study More Accurately Predicts Severe Balding Risk Using New Genetic Profile

Study Identifies A Possible Cause of Age-Induced Hair Loss

Treatments for Hair Loss in Women Detailed in Article Featuring Dr. Bernstein

Dr. Christiano Discovers JAK Inhibitors as Potential New Topical Treatment for Hair Loss

Caffeine Reverses Androgenetic Alopecia, Promotes Hair Growth in Cell-Cultured Hair Follicles

Why Does A Hair Transplant Work?

After a Hair Transplant What are the Effects of DHT on Donor Hair?

Hair Loss Causes: What is Miniaturization and What is Effect of DHT on Hair Follicles?

Address

Phone

Clinic Hours

Services

Contact Us

Address

Phone

Clinic Hours

Services

Contact Us

Directions