Will you go bald? Genetics and baldness

Male pattern baldness, or androgenic alopecia, is a condition that will affect the majority of men of European descent by the age of 50.  So the question of “Will you go bald” should be… “Will you be the one who keeps your hair?”

What causes male pattern baldness?

A combination of genetics, nutrition, and environmental toxins come together to form the risk factors for baldness.  But genetics really seems to rule the roost here.

It is estimated that approximately 80% of men and up to 50% of women will be affected by androgenic alopecia. [ref] Other estimates put the percentage a little lower, but in general, most estimates show that 50% or more of men are losing their hair by age 50.

In pre-menopausal women, androgenic alopecia is found more frequently in women with PCOS who have higher androgen hormone levels.

Twin studies from the early 2000s found that 80% of baldness is due to genetic risk factors, leaving the other 20% to be blamed on nutrition and toxicant exposure. [ref]  More recent studies on the genes involved in balding put the heritability at over 90%, leaving little to be blamed on the environment. It is considered to be a complex trait, with many genetic variants involved in the risk for balding (or protection against balding).[ref]

So the question is: Can you do anything about going bald?

The answer for many is that there are diet and lifestyle factors that may delay balding. There are medications that may work for some, but the risk of side effects needs to be carefully considered.

Terminology: Most studies refer to androgenic alopecia or male pattern baldness. Some of the most recent studies call it just ‘pattern baldness’, which is an indication that this is a problem that affects women as well as men.  Whatever you call it, this type of balding usually begins as a receding hairline at the temples and a thinning of hair at the top, rear of the head (vertex).

Can you blame mom for your baldness?

A lot of the genes that increase the risk for baldness are found on the X chromosome.  The androgen receptor (AR) and ectodysplasin A2 receptor (EDA2R), along with a region in between those two genes, have all been linked in multiple studies to an increased risk of baldness.

Being on the X chromosome, males only have one copy of the genes, which they inherited from their mom.

Hair follicle. Image source: Public domain

Another way of looking at this is that the default is to go bald, and the people who don’t go bald usually carry a genetic variant that protects against it.

Not all of the genes involved in baldness, though, are on the X chromosome. So mom may be only partially to blame.

Androgen Receptors (AR)

The androgen receptor binds to the androgen hormones, testosterone or dihydrotestosterone.  When an androgen hormone binds to the receptor, it causes a reaction within the cell that results eventually in the transcription of certain genes in the nuclear DNA. One product that is produced by androgens binding to the receptor is IGF-1R, which is the insulin-like growth factor 1 receptor.

IGF1, which binds to IFG-1R (receptor), is responsible for growth in childhood and muscle growth as an adult. So testosterone binds to the androgen receptor causing an increase in IGF1 receptors, triggering muscle growth.

Two androgens bind to AR: testosterone and dihydrotestosterone (DHT). DHT binds more preferentially to the receptor than testosterone. And DHT is the focus for male pattern baldness…

DHT is found in high levels in the scalp of men who are balding.  It is thought that the high levels of DHT are causing microinflammation in the hair follicles, which then results in the miniaturization of the follicles and hair loss.

A study of 178 young men with male pattern baldness looked at their androgen hormone levels, compared with a control group. The study found that the men who were balding had higher total testosterone, higher free testosterone, and higher DHT levels than controls.  But their sex-hormone binding globulin, follicle stimulating hormone, and luteinizing hormone levels were similar to control. The 178 patients were treated with finasteride, and 136 of them had a decrease in DHT, testosterone, and free testosterone — along with a reversal of hair loss. (Note that not all men reacted the same to finasteride).  The study noted that a greater reduction in androgens did not necessarily correlate to more hair growth. Also, there were some men for whom the decrease in androgens did not bring about hair improvements. [ref] More was not better and too much finasteride has adverse effects (more on that in the finasteride section).

The reasons that high DHT levels cause pattern baldness are not completely known. When males go through puberty and testosterone and DHT levels rise, this is what triggers hair growth all over the body. So why does it decrease hair growth on the head?

Diet and lifestyle factors:

Early male pattern baldness is more frequent in men with metabolic syndrome than in a control group.[ref]  This has been shown in a couple of small studies, but none of them really prove that metabolic syndrome causes baldness — vs. just the two conditions being more likely to coincide together.

A meta-analysis of seven studies found that men with early balding had a slightly worse glycolipid profile on average. The conclusion was that this may be similar to the insulin-resistance found in women with PCOS. [ref]

A study showed that post-menopausal women with hyperinsulinemia (insulin >10 mU/l – which is still in the normal range?) are at a higher risk for hair thinning. [ref]

Other theories of balding:

One theory, proposed by Dr. Ustuner, and explained ina 2013 paper theorizes that the tightness of the skin across the top of the head is what causes the miniaturization of the hair follicles, resulting in male pattern baldness. [ref] It is an interesting theory and attempts to explain why high levels of DHT are linked to balding only in certain areas of the scalp.

Does baldness cause prostate cancer risk?

The androgen hormones promote prostate cancer and finasteride (Propecia) is a medication used both for prostate enlargement and preventing hair loss…

So it makes sense to investigate whether prostate cancer is linked to baldness.

A meta-analysis investigated 15 different studies on the topic and concluded that no, prostate cancer is not linked to baldness in general.

A specific type of balding known as vertex balding (bald spot on the top, back of your head), though, slightly increased the likelihood of prostate cancer. [ref]

One study shows that baldness is also not linked to prostate size. But not all of the research agrees on this topic.  A second, smaller study did find a link to both prostate size and urine flow. [ref][ref]

Genetic Variants involved in  Pattern Baldness:

Since the majority of men (in most ethnicities) are likely to start balding at some point, these variants are listed to show the minority, which is usually those who are less likely to go bald.

What you are probably hoping for here is to carry several of the genetic variants that decrease the risk of balding…

Intergenetic locations:

Check your genetic data for rs1998076 (23andMe v4, v5)

  • AA: less than half the normal risk of going bald  [ref][ref][ref]
  • AG: decreased risk of going bald
  • GG: normal risk of going bald

Check your genetic data for rs2223841 (23andMe v4):

  • G/G (or G): much less likely to go bald [ref]
  • T/T (or T): normal risk of going bald

Check your genetic data for rs925391 (23andMe v4):

  • G/G (or G): normal risk for going bald
  • A/G: decreased risk of baldness
  • A/A (or A): much less likely to go bald early [ref]

Check your genetic data for rs6945541 (23andMe v4, v5):

  • C/C: increased risk of balding [ref][ref]
  • C/T: slightly increased risk of balding
  • T/T: normal risk of balding

AR gene (androgen receptor, X chromosome):

Check your genetic data for rs10521339 (23andMe v4):

  • A/A (or A): less likely to go bald [ref]
  • A/T: less likely to go bald
  • T/T (or T): normal risk of balding

Check your genetic data for rs6625163 (23andMe v4):

  • G/G (or G): less likely to go bald [ref]
  • A/G: less likely to go bald
  • A/A (or A): normal risk of balding

EDA2R gene (a type of tumor necrosis factor receptor, located on the X chromosome near AR gene):

Check your genetic data for rs1385699 (23andMe v4):

  • CC (or C): less likely to go bald [ref]
  • CT: less likely to go bald
  • T/T (or T): normal balding risk

Check your genetic data for rs1511061 (23andMe v4):

  • C/C (or C): less likely to go bald (strongest effect allele in GWAS) [ref]
  • C/T: less likely to go bald
  • T/T (or T): normal risk of balding

C1orf127 gene (unknown function):

Check your genetic data for rs12565727 (23andMe v5):

  • G/G: less likely to go bald [ref][ref]
  • A/G: somewhat less likely to go bald
  • A/A: normal balding risk

SLC14A2 gene (urea transport, metal ion transport):

Check your genetic data for rs10502861 (23andMe v4, v5):

  • T/T: decreased risk of balding [ref][ref]
  • C/T: slightly decreased risk of balding
  • C/C: normal risk of balding

MAPT-AS1 gene (non-coding RNA, regulates MAPT expression):

Check your genetic data for rs12373124 (23andMe v4):

  • C/C: decreased risk of balding[ref][ref]
  • C/T: slightly decreased risk of balding
  • T/T: normal risk of balding

LINC01432 gene (non-coding RNA):

Check your genetic data for rs1160312 (23andMe v4, v5):

  • A/A: normal risk of baldness [ref]
  • A/G: normal risk of baldness
  • G/G: decreased risk of baldness

IRF4 gene: (controls melanin, hair color)

Check your genetic data for rs12203592 (23andMe v4, v5):

  • C/C: normal
  • C/T: increased risk of earlier balding
  • T/T: increased risk of early balding [ref] more likely to have lighter skin and eye color[ref]

 

Lifehacks

Below are a few of the research-based options for delaying or reducing hair loss.

Hair loss medications:

I’ll let you all look into many studies on the sexual dysfunction side effects of finasteride… [ref][ref][ref]  And the side effects from minoxidil (hair loss, allergy)… [ref]

Stem cells:

Injections of adipose-derived stem cells into the scalp has been tested for hair regrowth.  The results are somewhat promising. [ref][ref][ref]

Platelet Rich Plasma (PrP):

Studies show that injections of platelet-rich plasma are beneficial for male pattern baldness. [ref][ref]

Red light therapy:

Animal studies show that photobiomodulation or light therapy should be effective for hair growth (in mice). Low-level laser light therapy has been shown in a couple of studies to be effective in humans.  One study (sponsored by a manufacturer) found that 655nm red LED light increased hair growth. [ref] Another small study found that a combo of 655nm and 808nm (infrared) laser scanner worked best. [ref]

Vitamins, Minerals, and Diet:

Riboflavin (vitamin B2) and biotin deficiency can cause hair loss. [ref] Both types of deficiency are rare in people eating a normal diet.

Low ferritin levels in women may cause hair loss. [ref] Always get a blood test done to check your iron levels before supplementing with iron. UltaLabs has inexpensive tests that you can order online without needing to go to the doctor.

Too much iron, as is the case with hemochromatosis, may also lead to alopecia. [ref] Check to see if you carry the genetic variants associated with iron overload.

A small study showed that eating fresh herbs and raw vegetables more than 3 times per week was associated with half the risk of baldness. [ref]  (Makes you wonder, though, what those guys who don’t eat vegetables three times a week are eating?)

Sudden weight loss and calorie restriction can cause hair loss, possibly due to micronutrient deficiency. [ref]

Being an overweight smoker increases the risk of balding by 6 fold. [ref]

Korean red ginseng has been shown in a study to increase hair density and thickness.[ref] The study didn’t really say whether the hair loss was due to male pattern baldness or an autoimmune alopecia cause.

 



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