Premature Greying of Hair (PGH): What Conditions Do I Consider? What tests do I order?

Premature Greying of Hair (PGH): A Short Primer for Hair Specialists

Introduction

Age and racial background strongly influence when a person will start greying. Typically, Caucasians begin greying in their mid-30s; Asians in the late 30s; African-Americans in the mid-40s. The average age of the onset of graying in Caucasians is 34 ± 9.6 years, and in Blacks, it is 43.9 ± 10.3 years. Overall, 6-23 % of the world’s population has 50 % of the scalp grey by age 50.

The term "premature greying" or early canities refers to hair greying that occurs before the age of 20 in Caucasians, before 25 in Asian individuals and before 30 in black men and women. Premature graying of hair (PGH) can have an adverse effect on the self-esteem of the individual.

The cause of grey hair is not fully worked out but it appears that oxidative stress may have a role in many cases.

 

Causes and Associations of Premature Grey Hair

I occasionally evaluate patients in my clinic who start greying in the teens or twenties. Many, many factors influence hair greying especially genetics. Let’s take a look at some of the underlying issues that may be involved:

a)    Genetics

Genetics has a key role in PGH. PGH may occur in an autosomal dominant manner.  About 39 % of patients with PGH have a strong family history. This may come from mom’s side and dad’s side although a small study suggested a greater role from dad’s side.

b)    B12 deficiency 

B12 deficiency is seen in some patients. In 1970, Dawber reported that about 55% of patients with pernicious anemia had greying before 50 years as compared to 30% in the control group.

c)    Thyroid Abnormalities.

Some patients with early greying have thyroid abnormalities. Thyroid hormones T3 and T4 act on hair follicles directly to increase melanogenesis. It’s critically important to check thyroid function in those with PGH.

 d)    Smoking

Patients with PGH sometimes have a smoking history. Not all of course,  A 1996 study in the British Medical Journal showed that smokers are about two to four times more likely to have grey hair. It appears that smoking increases reactive oxygen species (ROS) and this damages hair follicle melanocytes. Several studies over the years have linked smoking to early greying of hair.  Smokers with PGH may be even more likely to be at risk for cardiovascular disease. We’ll discuss this more in one moment.

e)    Vitamin and Mineral Deficiencies

Various studies suggest various deficiencies. For example, a recent study supports a possible link between low iron, calcium, zinc, copper and vitamin D. A study by Bhat et al  Indian population reported lower serum levels of ferritin, calcium, and Vitamin D3 levels in subjects prone to PGH.

It’s the meta-analyses that carry a bit more weight as to what findings are probably more relevant. A recent meta-analysis of mineral showed that copper and calcium were the two most consistently altered minerals in PGH based on 5 studies. Iron and zinc did not seem to be clearly associated when all data is analyzed.

f)      Autoimmune conditions

Autoimmune conditions like alopecia areata, atopic dermatitis and vitiligo can cause PGH.

Alopecia areata can cause grey hair. A condition known as canities subita or the overnight greying of hair can rarely be seen with alopecia areata and can also be seen with vitiligo.

Vitiligo can be associated with premature greying of hair. It appears that melanocytes in patients with vitiligo are more sensitive to oxidative stress. ROS damage to melanocytes leads to ectopic differentiation of stem cells and apoptosis of differentiated melanocytes

g)    Various Syndromes

Premature aging syndromes (like a condition called Werner's and a second called Progeria) can cause early greying of hair.  These are conditions of defective DNA repair and it appears such conditions promote oxidative stress. Other syndromes such as Book’s syndrome, Rothmund Thompson, Ataxia telangiectasia, Fisch syndrome, Down syndrome, cri due chat, dystrophia myotonica may be associated with PGH (Pandhi and Khanna 2013)

h)    High stress

High stress levels may cause greying in animal models but it's not yet clear if stress contributes to greying in humans. Likely, it’s related to at least some degree.

i)      Drugs

Drugs may cause PGH. Chemotherapy drugs and chloroquine are known to do it for example.

Key Studies Highlighting Important Associations with Grey Hair and Premature Greying of Hair

STUDIES ON CARDIOVASCULAR DISEASE

Schnor et al, 1995

In 1995, Schnor et al set out to evaluate the possible relation between aging signs such as graying of the hair, baldness, and facial wrinkling and myocardial infarction (also known as heart attacks). They analyzed data from The Copenhagen City Heart Study which had 12 years of follow up data.

The authors found a correlation between graying of the hair, facial wrinkling, and frontoparietal baldness and crown-top baldness and the risk of heart attacks in men. The relative risk was 1.4 (95% CI, 0.9 to 2.0) for men with moderately gray hair compared with men with no gray hair and 1.9 (1.2 to 2.8) for men with completely gray hair (p < 0.001). For women, there was no statistically significant trend between grey hair and heart attacks.  

All in all, the authors concluded that, in addition to established coronary risk factors, aging signs like graying of the hair and male baldness may be linked to an increased risk for heart attacks.

Schnor et al 1998

In 1998, Schonor et al  published another study using data from the Copenhagen City Heart Study. This was a study  comprising a random sample of 20,000 men and women. Authors evaluated cardiovascular risk factors, data on signs of aging: extent of gray hair, baldness, facial wrinkles, and arcus senilis (corneal arcus). They had 16 years of follow-up this time. Authors  found no correlation between the mortality and the extent of graying of the hair. They concluded that the degrees of graying of the hair, was not predictive of a shorter life span in men and women in the Copenhagen City Heart Study.

Data overall on premature greying and heart disease have been inconsistent. Studies by Eistenstein et al 1982 and Gould et al. 1978  also reported an association between PGH and cardiovascular disease. However  there was no association between the two in a study by Glasser et al, 1991. A 2015 study by Aggarwal et al. found that PGH was a significant risk factor for cardiovascular disease among smokers.  In 2012 Kocaman SA et al found that the degree of premature hair graying as an independent risk marker for coronary artery disease -  independent of age and other traditional risk factors in a cohort of 213 men undergoing coronary angiography.

Paik et al, 2018: Blood Pressure, Blood Sugars, Waist Circumference Higher in Individuals with Premature Greying of Hair.

In 2018, Paik et al  from Korea set out to perform a cross-sectional study to identify potential associations between premature hair greying and metabolic risk factors. The authors studied 1,929 young healthy subjects including 1,067 men and 862 women. Of these, 704 (36.4%) were categorized in the premature hair greying group.

Waist circumference was higher in the premature greying group compared to the non premature greying group (76.3 cm vs 74.3 vs. ; p < 0.001), systolic blood pressure was higher (111.7 vs 109.2; p<0.001) and diastolic blood pressure was higher (66.2 vs 65.0 mmHg p = 0.003). In addition, fasting blood sugar was higher in those with premature greying group (91.6 mg/dL vs 90.8; p = 0.013). Serum high-density lipoprotein cholesterol was lower (65.4 mg/dL vs 68.1 p < 0.001). This large study revealed an association between premature hair greying and metabolic risk factors.

BONE MINERAL DENSITY

PGH was reported as a risk factor for low bone mineral density by some studies including Rosen et al 1995 and Orr-Walker 1997.  Morton et al, 2007 did not find any such association. Other new studies conflict this association.   

HEARING LOSS

A newer study by Ozbay et al, in 2015 examined the relationship between hearing loss and PGH. Patients with premature hair graying had hearing impairment at extended high frequencies.

RECENT SYSTEMATIC REVIEWS AND META-ANALYSES

Mahindiratta et al 2020

In 2020, Mahendiratta et al performed a systematic review to address factors associated with premature greying of hair (PGH). Factors associated with PGH were : smoking, vitamin deficiency (B12, folic acid, and B7), mineral deficiency (low serum calcium and serum ferritin). Other important risk factors are family history of PGH, obesity, high B.P, lack of exercise, drugs, genetic syndromes, dyslipidemia, thyroid disorders, hyperuricemia, and alteration in liver function. PGH was found to be an important marker of CAD, and this was increased further in the case of smokers.

Chang and Sun, 2020: Meta-Analysis highlights Lower Levels of Copper and Calcium in Patients with PGH

In 2020, Chang and Sun set out to evaluated the studies addressing the association between serum minerals and premature greying of hair. The used five case–control studies involving a total of 285 patients with PHG and 255 controls  in their analysis.

All in all, patients with premature greying of hair were found to have lower levels of calcium and copper  compared to controls. Levels of iron and zinc were not found to be different.

This study is interesting. It’s not clear if copper and calcium are truly implicated in the pathogenesis of premature greying or not. It’s plausible that they are. Copper helps in the process of melanogenesis. Specifically, tyrosinase is a copper-dependent enzyme that catalyzes the conversion of L-tyrosine into levodopa. This is said to be the rate-limiting step of melanogenesis. In addition, calcium also plays a role in melanogenesis. Calcium is an important cofactor for various protein kinase C isoforms which have a critical role in melanogenesis through the phosphorylation and activation of tyrosinase.  It’s theoretically possible that deficiency of these minerals may adversely influence the physiology of melanogenesis in hair and contribute to premature greying.

Evaluation: How I evaluate patients

Patients, who present with PGH, should be assessed for syndromes and metabolic diseases. A family history of PGH, diabetes, and metabolic syndrome should be ascertained.

Medical conditions associated with PGH should be ruled out including alopecia areata, pernicious anemia, atopic dermatitis and vitiligo. A detailed family history and smoking history and medication history should be obtained. Genetic syndromes should be considered through a careful developmental history.  

I generally order blood tests for the following :

CBC

TSH

Ferritin

Zinc

25 hydroxy-vitamin D

Folic acid

Copper

Calcium

CRP

Fasting cholesterol

Hemoglobin A1c, fasting glucose

Insulin

AST, ALT

I measure blood pressure. Height and weight are measured to calculate the BMI.

Treatment

 Supplementation may be tried in the case of deficiencies. Hair dye is the main treatment although other treatments are being studied. Psychosocial issue need to be addressed to as  graying of hair  can have an adverse effect on the self-esteem of the individual.

Conclusion

A full workup is needed for individuals with premature greying. Evaluation of cardiovascular risk factors is also important in such situations.

 REFERENCES

Aggarwal A, Srivastava S, Agarwal MP, Dwivedi S. Premature graying of hair: An independent risk marker for coronary artery disease in smokers – A retrospective case control study. Ethiop J Health Sci. 2015;25:123–8. 

Beardsworth SA, Kearney CE, Steel SA, Newman J, Purdie DW. Premature greying of the hair is not associated with low bone mineral density. Osteoporos Int. 1999;10:290–4.

Bhat RM et al. Epidemiological and investigative study of premature graying of hair in higher secondary and pre-university school children. Int J Trichology. 2013;5:17–21.

Dawber RP. Integumentary associations of pernicious anaemia. Br J Dermatol . 1970 Mar;82(3):221-3.

Eisenstein I, Edelstein J. Gray hair in black males a possible risk factor in coronary artery disease. Angiology. 1982;33:652–4. 

Gould L, Reddy CV, Oh KC, Kim SG, Becker W. Premature hair graying: A probable coronary risk factor. Angiology. 1978;29:800–3. 

Glasser M. Is early onset of gray hair a risk factor? Med Hypotheses. 1991;36:404–11. 

Kocaman SA, Cetin M, Durakoðlugil ME, Erdoðan T, Canga A, Ciçek Y, et al . The degree of premature hair graying as an independent risk marker for coronary artery disease: A predictor of biological age rather than chronological age. Anadolu Kardiyol Derg 2012;12:457-63.

Morton DJ, Kritz-Silverstein D, Riley DJ, Barrett-Connor EL, Wingard DL. Premature graying, balding, and low bone mineral density in older women and men: The Rancho Bernardo study. J Aging Health 2007;19:275-85.

Orr-Walker BJ, Evans MC, Ames RW, Clearwater JM, Reid IR. Premature hair graying and bone mineral density. J Clin Endocrinol Metab 1997;82:3580-3.

Ozbay I, Kahraman C, Kucur C, Namdar ND, Oghan F. Is there a relationship between premature hair greying and hearing impairment? J Laryngol Otol. 2015;129:1097–100.

Paik S et al Association Between Premature Hair Greying and Metabolic Risk Factors: A Cross-sectional Study. Acta Derm Venereo. 2018 Aug 29;98(8):748-752.

Pandhi and Khanna. Premature graying of hair. Symposium-Hair Disorders 2013:79:5;641-653

Rosen CJ, Holick MF, Millard PS. Premature graying of hair is a risk marker for osteopenia. J Clin Endocrinol Metab 1994;79:854-7.

Saniya Mahendiratta et al. Premature graying of hair: Risk factors, co-morbid conditions, pharmacotherapy and reversal-A systematic review and meta-analysis. Dermatol Ther. 2020 Nov;33(6):e13990.

Schnohr P et al. Longevity and gray hair, baldness, facial wrinkles, and arcus senilis in 13,000 men and women: The Copenhagen city heart study. J Gerontol A Biol Sci Med Sci. 1998;53:M347–50. 

Schnohr P et al. Gray hair, baldness, and wrinkles in relation to myocardial infarction: the Copenhagen City Heart Study. Am Heart J  1995 Nov;130(5):1003-10.Vinay K, Yadav S, Handa S. Zinc deficiency and canities: An unusual manifestation. JAMA Dermatol. 2014;150:1116–7.