EADV Fostering Training Course in Hair & Scalp
Bologna, Italy - 18-20 November 2011
Telogen Effluvium
(Old Myths and New Insights into Hair Loss in Women)
Professor Ralph M. Trüeb, M.D.
Center for Dermatology and Hair Diseases
Zentrum Wallisellen
Bahnhofplatz 1a
CH-8304 Wallisellen (Zurich)
Switzerland
A Definition of Myth
1. A traditional sacred story, typically
revolving around the activities of gods and
heroes, which purports to explain a natural
phenomenon or cultural practice.
2. A fiction or half-truth, especially one that
forms part of an ideology:




Religious myth
Historical myth
Popular (layman„s) myths
Physician„s myths
Religious Myth: The „Hair Miracle“ of St. Agnes of Rome
According to tradition, St. Agnes was a member of
the Roman nobility and raised in a Christian
family. She suffered martyrdom at the age of 12
during the reign of Roman Emperor Diocletian in
304.
The Prefect Sempronius wished Agnes to marry
his son, and on Agnes' refusal he condemned her
to death.
As Roman law did not permit the execution of
virgins, Sempronius had a naked Agnes dragged
through the streets to a brothel. Various versions
of the legend give different methods of escape
from this predicament. In one, as she prayed,
her hair grew and covered her body.
Trüeb RM. St. Agnes of Rome: Patron Saint for women with hair loss?
Dermatology 2009;219:97-8
Historical Myths: Experiments on Hair Loss Cures
Hair loss cures have been experimented
for centuries:
The great Greek doctor Hippocrates
handled his patients‟ yearning for hair loss
cures by applying pigeon droppings on their
head.
Renowned bald philosopher Aristotle used
goat‟s urine to cure baldness.
Cleopatra applied a mixture of ground horse
teeth and deer marrow to help out Julius
Caesar‟s receding hairline. She did this to
save her beloved from being ridiculed since
his name “Caesar” means “abundant hair” in
Latin.
Age Old Myths: Popular or Layman„s Myths
Wearing hats causes hair loss
Frequent washing and blow drying can lead
to hair loss
Hair styling products and dyes cause hair
loss
Brushing your hair can make it stronger and
more resistant to hair loss
Cutting your hair will make it grow back
thicker
Hair loss can't be stopped or helped
Don‘t Believe Everything You Hear About Hair: Physician‘s Myths
The majority of women complaining of hair loss are
suffering of imaginary hair loss
Losing 100 strands of hair per day is normal
The most frequent disorder associated with hair loss in
women is iron deficiency
The first line treatment for androgenetic alopecia in
women are antiandrogens
Nutritional supplements have no significant effect on
hair growth
Ageing of hair and androgenetic alopecia are basically
the same
Starting Position
Hair loss is frequent
Norwood. South Med J 1975;68:1359-1365
Norwood. Dermatol Surg 2001;27:53-54
Hair loss causes considerable distress
Cash. Br J Dermatol 1999 141:398-405
Treament options are available, though limited, both in
terms of indications and of efficacy
Ross and Shapiro. Dermatol Clin 2005;23:227-43
Success depends on unpatronizing sympathy from the side
of the physician and comprehension of the underlying
pathology
Treatment must meet patients‘ expectations, otherwise
patients must be informed on what to expect
Psychocutaneous Disorders Related to the Hair
Imaginary Hair Loss
(Psychogenic Pseudoeffluvium)
Adjustment Disorders
Feeling of Disfigurement
(Body Dysmorphic Syndrome)
Abnormal Scalp Sensations
(Cutaneous Sensory Disorder)
Self-Induced Injury
(Trichotillomania, Factitious Disorder)
Trüeb RM, Gieler U. Psychocutaneous disorders of hair and scalp. In: Blume-Peytavi U, Tosti A, Whiting DA, Trüeb
RM (eds.) Hair Growth and Disorders, Springer Berlin Heidelberg 2008: pp. 407-426
Adjustment Disorders to Hair Loss
 Prolonged depressive reaction
(ICD-10 F43.21)
 Mixed anxiety and depressive reaction
(ICD-10 F43.22)
 With predominant disturbance of conduct
(ICD-10 F43.24)
 With mixed disturbance of emotions and conduct
(ICD-10 F43.25)
Cash TF. J Am Acad Dermatol 1992;26:926-931
Cash et al. J Am Acad Dermatol 1993;29:569-575
Maffei C et al. Arch Dermatol 1994;130:868-872
Panconesi E et al. Dermatol Clin 1996;14:399-422
The best way to treat the adjustment disorder is to effectively treat the
underlying hair disorder!
Hair Follicle Cycle
Hair cycling in a random
catagen
mosaic pattern
(2 weeks)
Mildred Trotter
(1899-1991)
Control of hair cycling within
the hair follicle itself
anagen
(2-6 years)
Anagen
(2-6 years)
teloptosis
Influence of systemic and
external factors:
• hormones
telogen
• cytokines
(3 months)
• toxins
• deficiencies (nutrients,
vitamins, energy)
empty hair
follicle
Teloptosis
Daily telogen shedding: 35-100 depending on amount of
hair on the head!
Catagen
(2 weeks)
Telogen
(3 months)
Diffuse Alopecia: Dystrophic Anagen Effluvium
catagen
(2 weeks)
Direct insult to the rapidly dividing bulb matrix cells
anagen
(2-6 years)
telogen
(3 months)
LM: Tapered proximal end and lack of root sheath
teloptosis
empty hair follicle
Within days to few weeks loss of 90% of scalp hair
 antineoplastic drugs: chemotherapy-induced alopecia
 x-ray: radiation-induced alopecia:
temporary > 3-4 Gy
Krasovec, Trüeb. Hautarzt 1998;49:307-309
permanent > 30 Gy deep x-rays,
> 50 Gy soft x-rays
 environmental or occupational toxin exposure:
toxic alopecia
 immunologic injury: alopecia areata
Alopecia Areata
Most frequent cause of hair loss in childhood. Before age 2 <2%,
before age 20 32,5-63 %, and after age 40 20% of cases
May cause diffuse hair loss (2% of patients, women > 40 years)!
Organ specific autoimmune disease of hair follicle with usually
focal alopecia and unpredictable course with tendency to
recurrence or chronicity, depending on age of onset, disease
associations, duration of disease, and extent of hair loss
Diagnosis:
• Non-cicatrizing alopecia with dystrophic hairs and empty follicles:
typical dermascopic findings
• Nail changes in 20-40% (more frequent in children)
• Trichogram: telogen or dystrophic anagen effluvium
• Histology: peribulbar lymphocytic infiltration
• Immune serology: Frequently circulating
autoantibodies (thyroid, intrinsic factor)
Telogen Effluvium
catagen
(2 weeks)
anagen
(2-6 years)
telogen
(3 months)
teloptosis
Definition:
Disruption of the hair cycle resulting in increased
proportion (> 20%) and shedding of telogen hair
empty hair follicle
Hair loss < 50% of scalp hair: Diffuse thinning of hair,
most conspicuous at the temples
Positive pull test of telogen club hairs
< 6 months: acute telogen effluvium:
 Fever: postfebrile telogen effluvium
 Childbirth: postpartum telogen effluvium
 etc.
> 6 months: chronic telogen effluvium:
 Primary disorder
 Secondary to a variety of systemic disorders
Kligman. Arch Dermatol 1961;83:175-198
Headington. Arch Dermatol 1993;129:356-363
Whiting. J Am Acad Dermatol 1996;35:899-906
Pathologic Dynamics of Telogen Effluvium
With synchronization:
catagen
(2 weeks)
anagen
(2-6 years)
telogen
(3 months)
- Diffuse Telogen effluvium:
 Immediate anagen release
 Delayed anagen release
 Immediate telogen release
 Delayed telogen release
teloptosis
empty hair follicle
Without synchronization:
 Short anagen:
- Androgenetic alopecia
- Senescent alopecia
Headington JT. Telogen effluvium. New concepts and review.
Arch Dermatol 1993;129:356-363
Seasonality of Hair Growth and Shedding
Reports 3 women in New York who experienced
maximum hair loss in November
Orentreich N. Scalp replacement in man. In: Advances
in Biology of Skin. Vol IX: Hair Growth. (Montagna W,
Bobson RL., eds.). Oxford: Pergamon. 1969:99-108
Demonstrate in 14 men over a period of 18
months that the proportion of telogen hair and of
hair shedding were maximal in September
Randall VA, Ebling FJG. Seasonal changes in
human hair growth. Br J Dermatol 1991;124:146-51
Demonstrate in 10 men with or without alopecia
during a period of 8-14years a maximal
proportion of telogen hairs at the end of summer
Courtois M, Loussouarn G, Hourseau S,
Grollier JF. Periodicity in the growth and
shedding of hair. Br J Dermatol 1996;134:47-54
Seasonality of Hair Growth and Shedding in Women
Fluctuations in frontal telogen rates
(n = 823) in relation to the day of the
year:
Telogen rates showed an overall
annual periodicity, manifested by a
maximal proportion of telogen hair
in July.
A second telogen peak seems to
exist, although less pronounced, in
April.
From: Kunz M, Seifert B, Trüeb RM. Dermatology 2009;219(2):105-10.
Chronic Telogen Effluvium
Diffuse shedding of telogen hair > 6 months
Secondary to a variety of systemic disorders:
 iron deficiency, other dietary deficiencies
 thyroid disease, other metabolic diseases
 systemic lupus erythematosus, other connective tissue
disorders
 syphilis, HIV
 drug-induced hair loss
Primary disorder:
 First described 1960 as „Diffuse cyclic hair loss in women“
Guy and Edmundson. Arch Dermatol 1960;81:205-227
 Revived in 1996, since then focus of interest again
Whiting. J Am Acad Dermatol 1996;35:899-906
 Diagnosis of exclusion!
Differential diagnosis:
 Diffuse alopecia areata („alopecia areata incognita“)
 Androgenetic alopecia/Female pattern hair loss (FPHL)
Androgenetic Alopecia
Genetically determined, androgen induced, age-dependent progressive
loss of hair with sex-dependent differences in pattern of alopecia
Men:
Hamilton-Norwood I-VII
18 - 29: 12%
Women:
20 - 29:
3%
30 - 39: 38%
30 - 39: 17%
40 - 49: 45%
40 - 49: 16%
50 - 59: 52%
50 - 59: 23%
60 - 69: 65%
60 - 69: 25%
70 - 79: 64%
70 - 79: 28%
> 80:
80 - 89: 32%
70%
Ludwig I-III
Norwood. South Med J 1975;68:1359-1365
Norwood. Dermatol Surg 2001;27:53-54
Androgens
+
Androgen metabolism
Genetics
Progressive shortening of anagen phase
+
Reduction of volume of dermal papilla
Follicular microinflammation
catagen
(2 weeks)
anagen
(2-6 years)
telogen
(3 months)
teloptosis
empty hair follicle
Perifollicular fibrosis
Hair follicle miniaturization/hair growth arrest
Increased shedding of hair:
Telogen effluvium
Decreased hair growth:
Terminal-to-vellus hair
transformation
Value of Scalp Dermoscopy (Trichoscopy)
Normal finding
Diversity of hair shaft diameter > 20% in androgenetic
alopecia
de Lacharrière O, Deloche C, Misciali C, Piraccini BM, Vincenzi C,
Bastien P, Tardy I, Bernard BA, Tosti A. Hair diameter diversity: a
clinical sign reflecting the follicle miniaturization.
Arch Dermatol 2001;137:641-6
Yellow dots typical for alopecia areata
Lacarrubba F,Dall’Oglio F,Nasca MR, Micali G. Videodermoscopy
enhances diagnostic capability in some forms of hair loss.
Am J Clin Dermatol 2004;5:205-8
Dermoscopy of Scalp (Trichoscopy)
Tosti A. Dermoscopy of Hair and Scalp Disorders with clinical and
pathological correlations. Informa healthcare UK 2007
de Lacharrière et al. Hair diameter diversity: a clinical sign reflecting the
follicle miniaturization. Arch Dermatol 2001;137:641-6
Zinkernagel MS, Trüeb RM. Fibrosing alopecia in a pattern distribution:
patterned lichen planopilaris or androgenetic alopecia with a lichenoid
tissue reaction pattern? Arch Dermatol 2000;136:205-11
Inflammatory Phenomena and Fibrosis
Follicular microinflammation and fibrosis:
Whiting D. Diagnostic and predictive value of horizontal
sections of scalp biopsy specimens in male pattern
androgenetic alopecia.
JAAD 1993;28:755-763
microscopic
Kossard S. Postmenopausal frontal fibrosing alopecia.
Scarring alopecia in a pattern distribution.
Arch Dermatol. 1994;130:770-4
Kossard S, Lee MS, Wilkinson B. Postmenopausal frontal
fibrosing alopecia: a frontal variant of lichen planopilaris.
J Am Acad Dermatol 1997;36:59-66
Zinkernagel MS, Trüeb RM. Fibrosing alopecia in a pattern
distribution: patterned lichen planopilaris or androgenetic
alopecia with a lichenoid tissue reaction pattern?
Arch Dermatol 2000;136:205-11
localized
generalized
Follicular inflammation
and fibrosis
Investigating Diffuse Hair Loss
Family history of hair loss
Personal history:
• of hair loss
• of medical problems and drug intake
• of diet habits
Clinical examination:
• hair loss pattern
• hair loss activity (pull test)
• dermoscopy
Biochemical investigations:
• for hematinic deficiencies (CRP, ferritin, vitamin B12, folic acid)
• thyroid stimulating hormone
• estradiol (in menopausal), extended hormonal studies as indicated
• extended biochemical studies as indicated
Trichogram and scalp biopsy as indicated:
• CTE versus FPHL (trichogram)
• Loss of follicular orifices (biopsy)
Managing Diffuse Hair Loss
Trichological and biochemical characterization of hair loss
Quantitating hair loss:
• Daily count
• Wash test
• Combining epiluminiscence microscopy with digital imaging (TrichoScan)
Causal treatment, wherever possible!
Specific treatments for the scarring alopecias
Specific treatments for alopecia areata:
• Acute: Corticosteroids (pulse therapy, intralesional)
• Chronic: Topical immunotherapy
Specific treatments for androgenetic alopecia:
• Topical 2-5% minoxidil
• 5-alpha reductase inhibition
Role for hormonal and nutritional treatments?
Efficacy of Corticosteroid Pulse Therapy in Diffuse Alopecia Areata
3 x 500 mg i.v. methylprednisolone on 3 consecutive days
Sato-Kawamura M, Aiba S, Tagami H. Acute diffuse and total alopecia of the female scalp. A new subtype of
diffuse alopecia areata that has a favorable prognosis. Dermatology. 2002;205(4):367-73
Nakjima et al. Pulse corticosteroid therapy for alopecia areata: study of 139 patients.
Dermatology 2007;215:320-324
Efficacy of Topical Minoxidil in Androgenetic Alopecia/FPHL
Male
Female
Price et al. Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5%
and 2% topical minoxidil, placebo, or no treatment. J Am Acad Dermatol 1999;41:717-21
Role for Hormonal Treatments (in FPHL)
?
Effect of estrogen therapy on postmenopausal women?
Antiandrogen therapy not effective in normoandrogenic women
Vexiau et al. Br J Dermatol 2002;146:992-999
Gestagens with androgenic action may precipitate hair loss in
women: norethisterone, levonorgestrel, tibolone contraindicated!
DHEA may cause hair loss in women in a dose-dependent manner!
Finasteride in Postmenopausal Women
Randomized, double-blind, placebo-controlled study with 1 mg oral finasteride
during 12 months in137 postmenopausal age 41-60 Y.
Study endpoints:
 Hair count
 Global photographic assessment
 Biopsy (morphometric)
Results: For all endpoints no difference in comparison to placebo
Price et al. J Am Acad Dermatol 2000;43:768-776
5 normoandrogenic postmenopausal women
treated with 2.5 – 5 mg oral finasteride for up to
18 months showed improvement on global
photographic assessments.
Trüeb et al. Dermatology 2004;209:202-207
Iorizzo et al. Arch Dermatol 2006;142:298-302
Role for Nutritional Treatments in Diffuse Hair Loss
Pharmacy aisles and Internet drugstores are
full of nutrients promising full, thick, luscious
hair -- for prices that range from suspiciously
cheap to dishearteningly exorbitant.
What are the facts?
 Unless the hair is falling out due to a
nutritional deficiency, there's only so much
that nutrients can do to increase the size of
individual hairs. This is because hair
thickness is largely genetic.
 Nevertheless, there are external factors that
influence hair health to a great degree, and
nutritients can boost hair that's suffering
from these problems.
Role of Nutritional Deficiency: Iron
Iron deficiency most common nutritional deficiency: 12-16% prevalence in adolescent
girls and women of childbearing age (16-49 years of age) and 6-9% in women 50 years of age
and older in the USA
Most laboratories use 10 - 15 µg/l as lower limit of normal for menstruating women, and
30 µg/l for children, men and non-menstruating women. In women of childbearing age, a
cutoff of 10-15 µg/l yields a sensitivity of 75% and specificity of 98%, a cutoff of 30 µg/l yields
a sensitivity of 92% and a specificity of 98%
Most common causes of iron deficiency:
 in premenopausal women: menstrual blood loss, pregnancy and lactation
 in postmenopausal women: decreased absorption and gastrointestinal loss.
 Risk factors: heavy menstrual bleeding (> 80 ml per month), use of an IUD,
history of iron deficiency anemia,insufficient dietary iron intake.
From: Bregy and Trüeb.Dermatology 2008;217:1-6
Role for Iron Supplementation
Decreased serum ferritin is associated with alopecia in women
(“Rushtonians”):
Hard S. Acta DermVenereol 1963;43:562-569
Rushton et al.Br J Dermatol 1990;123:187-197
Rushton et al. Clin Endocrinol 1992;36:421-427
Kantor et al. J Invest Dermatol 2003;121:985-988
There is no clear association between low serum ferritin and chronic
diffuse telogen hair loss (“Sinclairians”):
Aydingoz et al.1999;13:65-7
Sinclair R. Br J Dermatol 2002;147:982-4
No association between serum ferritin levels >10 microg/L and hair
loss activity in women (trichogram).
From: Bregy and Trüeb. Dermatology 2008;217:1-6
Androgenetic alopecia
Senescent alopecia
Onset
Early (teens, twens)
Late (60 years +)
Distribution
Patterned
Diffuse
Pathophyisology
Increased activity of 5-
reductase (DHT) in men
Senescence
(decreased activity of 5- reductase )
Genetics
Polygenic
Unknown
Association or risk
factor for other
diseases
Cardiovascular diseases
Benign prostatic hyperplasia
Prosate cancer
Age-related disorders?
Gene expression
profiles
Decreased expression of genes
required for anagen onset and
maintenance / increased
expression of catagen and
telogen inducers
Increased expression of markers for
mitochondrial dysfunction and
oxidative stress
Treatment
Minoxidil
Finasteride
Estrogens (anecdotal)
Minoxidil
Nutritional supplements
hGH (anecdotal)
Mirmirani P,Karnik P. Compberative gene expression profiling of senescent and androgenetic alopecia using
microarray analysis. In: Trüeb RM, Tobin DJ. Aging Hair. Springer, Berlin 2010: pp. 49 ff
Efficacy of Topical Minoxidil in Senescent Alopecia
Before treatment
Personal observation
After 6 months of treatment
Biology of Hair Aging
Intrinsic (Chronologic) Aging:
 Genetic: AGA, familial premature graysing (AD),
progerias (rare)
 Hormones und hormone metabolism: AGA
 Replicative senescence: Graying, senescent alopecia?
 Oxidative metabolism (melanogenesis): Graying
Extrinsic (Accelerated) Aging:
 Oxidative stress from UV-R
 Oxidative stress from tobacco smoking
 Others?
Trüeb RM. Is androgenetic aopecia a photaggravated dermatosis? Dermatology
2003;207:343-348
Trüeb RM. Association between smoking and hair loss: another opportunity for
health education against smoking? Dermatology 2003;206:189-191
Oxidative Stress from Smoking
D'Agostini et al. Induction of alopecia in mice exposed to cigarette smoke.
Toxicol Lett 2000; 3;114:117-23
D'Agostini et al. Chemoprevention of smoke-induced alopecia in mice by
oral administration of L-cystine and vitamin B6.
J Dermatol Sci 2007;46:189-98
Premature senescence of balding DPC in vitro in association with expression of
p16(INK4a)/pRB suggests that balding DPC are sensitive to environmental stress
and identifies alternative pathways that could lead to novel therapeutic strategies
for treatment of AGA.
Bahta AW, Farjo N, Farjo B, Philpott MP. Premature senescence of balding dermal papilla cells in vitro
isassociated with p16(INK4a) expression. J Invest Dermatol 2008;128:1088–94
Value of Nutritional Intervention in Aging Hair
Nutritional Intervention?
Structural Ageing of Skin:
 Atrophy
 Degeneration
 Functional impairment
Immune Ageing of Skin:
 Decrease in
immunocompetence
Photoageing of Skin:
 Cumulation of genotoxic and
oxidative damage to
 Exhaustion of antioxidative
defense network
Skin:
 Vulnerability
 Impaired wound healing
 Decreased hydration
 Pruritus
 Eczema
 Infections
 Carcinogenesis
Hair:
 Hair loss
 Hair greying
 Hair weathering
Double-Blinded, Placebo-Controlled Study in Healthy Women with Hair Loss
Using Oral Combination of Cystine and B-Vitamins
Global photographic
assessment
85
Anagen rate (%)
Normal range
Trichoscan
80
Verum
Placebo
75
70
From:
Lengg et al. Therapy 2007;4:59
65
0
Verum (N=15) 72.5
Placebo (N=15) 75.3
3
6
78.5
78.2
80.5
75.6
months
p = 0.003
p = 0.85
Active compound led to statistically significant improvement and normalization of mean anagen hair rates within 6
monts of treatment, independent of age (smoking status not examined)
Hair count and cumulative hair shaft diameter did not show any change in both groups
(as opposed to studies with topical minoxidil)
Summary and Conclusions
The complaint of hair loss is frequent in women and causes considerable distress
In a minority of patients hair loss is imaginary
The number of hair lost per day depends on the amount of hair on the scalp and seasonal
effects
There are effective therapies of hair loss, though with limitations with respect to
indications and efficacy
Ther role of nutrition is overemphasized by the lay and underestimated by physicians
Iron deficiency is overestimated as a single cause of hair loss in women, as well as the
role of antiandrogens in the treatment of femal pattern hair loss
Androgenetic alopecia and ageing of hair are two distinct entities, though with some
common denominators
Treatment should target multiple factors responsible for hair loss
Treatment success depends on comprehension of the underlying pathology and
unpatronizing sympathy on the part of the physician
Thank you
for your
attention!
References:
Trüeb RM. Diffuse Hair Loss: pp. 259-272 In: Blume-Peytavi U,
Tosti A, Whiting DA, Trüeb RM (eds.) Hair Growth and
Disorders, Springer Berlin Heidelberg 2008
www.derma-haarcenter.ch
Trüeb RM. Systematic approach to hair loss in women. J Dtsch
Dermatol Ges 2010;8:284-7