EXCESSIVE HAIR GROWTH IN ADOLESCENT

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EXCESSIVE HAIR GROWTH IN ADOLESCENT

• Dr. DPankar Banerji
• Consulting Gynecologist
• Infertility Specialist
• Ideal Fertility IVF and Genetic Center
• Jabalpur, India

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EXCESSIVE HAIR GROWTH

• IT MAY BE EITHER
• HIRSUTISM
• VIRILIZATION

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DEFINITION

• HIRSUTISM APPEARANCE OF EXCESSIVE COARSE
  (TERMINAL)HAIR IN A PATTERN NOT NORMAL IN THE
  FEMALE
• Definition highlights the abnormal distribution
  of excess hair growth ,such as facial ,chest,or
  upper abdominal hair

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DEFINITION

• HYPERTRICHOSIS GROWTH OF HAIR IN EXCESS OF THE
  NORMAL WHILE LIMITED TO A NORMAL PATTERN OF
  DISTRIBUTION
• It is frequently associated with the use of
  medication such as antiepileptics

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DEFINITION

• VIRILIZATION REFERS TO CONCURRENT PRESENTATION
  OF HIRSUTISM WITH A BROAD RANGE OF SIGNS
  SUGGESTIVE OF ANDROGEN EXCESS,SUCH AS
• ACNE,
• FRONTOTEMPORAL BALDING,
• DEPPENING OF THE VOICE ,
• A DECREASE IN BREAT SIZE
• CLITORAL HYPERTROPHY

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DEFINITION

• INCREASED MUSCLE MASS
• AMENORREA / OLIGOMENORRHEA
• Virilization is seen less frequently than
  hirsutism and may reflect a severe underlying
  pathologic condition ,such as malignancy
• Hirsutism and virilization are closely linked and
  hirsutism may actually be the first manifestation
  of a condition that ultimately will lead to
  virilization in left untreated

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BASIC FACTS ABOUT HAIR

• Hair grows from a individual hair follicle that
  are part of a pilosebaceous gland unit
• Number of hair follicles is set from birth
• Main difference between sexes is the degree of
  differentiation of the hair
• Human hair growth is continuous
• Hair grows in a mosaic pattern(in a given area
  ,hair are in different stages of development)

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BASIC FACTS ABOUT HAIR

• Some condition may cause a high level of
  synchrony between the growth cycles of hair
  ,leading to the appearance of either massive hair
  loss (alopecia)or excess hair for a limited
  period of time

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BASIC FACTS ABOUT HAIR

• Growth cycle of the Hair ACT
• Anagen Growth phase,85- 90 of the life cycle
• Catagen rapid involution Phase
• Telogen Quiescent phase
• The growth phase or the anagen phase is primarily
  influenced by disorders that stimulate hair
  growth as well as therapeutic midalities.

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BASIC FACTS ABOUT HAIR

• Three types of Hair
• Lanugo Body hair seen in the fetus and newborn
• Vellus Fine adult hair covering the body
• Terminal hair Thick pigmented hair of scalp and
  pubic area
• Thickness of the terminal hair varies form one
  individual to other depending upon genetic, and
  possibly nutritional

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BASIC FACTS ABOUT HAIR

• Androgen sensitive hair depend upon androgen
  input for hair growth.
• Face,neck,chest,abdomen,axillary,upper arms
  ,inner thighs and pubic hair, part of the scalp
  hair.
• Less Androgen independent
• Forearms ,hands .lower legs

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BASIC FACTS ABOUT HAIR
PITUITARY
PITUITARY
ACTH
DHEAS
DHEAS
OVARY
DHEA
OVARY
ADRENAL
ADRENAL
AND,STEN,ONE
PERIPHERAL CONVERSION
TESTOSTERONE
HAIR FOLLICLE
DIHYDROTESTERONE
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PRESENTATION

• Most of the cases of virilization seen clinically
  are acute and striking in nature and seldom go
  unrecognized and usually prompt immediate medical
  intervention
• Hirsutism may present in variety of ways

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PRESENTATION OF HIRSUTISM

• HIRSUTISM ALONE
• HIRSUTISM AND ASSOCIATED PILOSEBACEOUS UNIT
  OVERACTIVITY (ACNE)
• HIRSUTISM AND OVULATORY DISORDERS
• HIRSUTISM AND SIGNS OF VIRILIZATION

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PRESENTATION OF HIRSUTISM

• Hirsutism alone is the greatest
  challenge,patients usually go to dermatologist
• Hirsutism wIth acne is frequently in teenage
  girls
• Hirsutism with ovulatory disorders comes mostly
  to gynecologist
• Hirsutism with virilization requires immediate
  work-up

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CAUSES OF HIRSUTISM

• Excess androgen production
• Relative circulating androgen excess and low
  binding globulins
• Excess end organ response
• Patient perception

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DISORDERS OF EXCESS ANDROGEN PRODUCTION

• Source of androgen
• Exogenous
• Endogenous (most common)
• Two primary endogenous sources
• Adrenal glands
• Ovaries

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DISORDERS OF EXCESS ANDROGEN PRODUCTION

• ADRENAL ANDROGEN EXCESS
• May be linked to genetically determined steroid
  synthesis enzyme deficiency
• Malignant adrenal neoplastic process
• Other conditions like Cushings syndrome

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DISORDERS OF EXCESS ANDROGEN PRODUCTION

• ADRENAL ANDROGEN EXCESS
• Three recognised adrenal enzyme deficiencies
• 21 alpha Hydroxylase defieiency
• 11-beta-Hydroxylase deficiency
• 3-beta-ol-dehydrogenase deficiency
• Classical forms are usually presented in prenatal
  or neonatal period as ambiguous genitalia in
  female
• Nonclassic forms are linked with hirsutism

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DISORDERS OF EXCESS ANDROGEN PRODUCTION

• 21-alpha-Hydroxylase deficiency
• Most common ,lt1 to gt10
• Prevalence depends on ethnic origin(common in
  slavs,1/50 Hispanics 1/40, ashkenazi jews 1/27
• Cushings syndrome Hirsutism with weight gain
  and growth retardation as the primary
  manifestation,with acne and other cutaneous
  problems

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DISORDERS OF EXCESS ANDROGEN PRODUCTION

• OVARIAN ORIGIN
• Most common cause is
• POLYCYSTIC OVARIAN SYMDROME
• Other
• Neoplastic ovarian disease

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Lab.Evaluation of Hirsutism

• Three basic hormonal evaluation
• 1. Total testosterone
• 2. DHEAS
• 3. AM 17-hydroxyprogesterone

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Total TestosteroneNormal Value (0.2 0.9 ng/ml)
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DHEAS (600 2800 ng/ml)
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AM 17 hydroxyprogesterone(0.1 0.8 ng/ml )
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RELATIVE ANDROGEN EXCESS AND SHBG

• lt3 TESTOSTERONE IS FREE
• Mostly bound to Sex hormone binding
  globuline(SHBG)
• Dcrease in SHBG leads to Excess free Testosterone
• Causes of Reduced SHBG PCOS(Chronic
  anovulation) and Obesity

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EXCESS REPONSIVITY TO ANDROGEN

• TESTOSTERONE TARGET CELLS
• 5-ALPHA -REDUCTASE
  
• DIHIDROTESTOSTERONE RECEPTOR

• Excessive response of the receptor to DHT(may be
  due to mutation of the highly polymorphic region
  in gene of the receptor located on X Chromosome
• Over activity of the 5-alpha-reductase (Type 1
  and Type 2,type 1 is involved in hirsutism )

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BASIC APPROACH TO THE DIAGNOSIS OF HIRSUTISM AND
VIRILIZATION

• SYMPTOMS AND HISTORY
• SIGNS
• PHYSICAL EXAMINATION
• INVESTIGATION

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APPROACH TO DIAGNOSIS

• It should be methodical.
• First step True nature of presentation
• Patient may present with ovulatory problems and
  hirsutism may not be reported
• There may be normal hair pattern but patient
  complains about hirsutism
• Evident virilization should investigated at once

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APPROACH TO DIAGNOSIS

• Careful history regarding the timing of onset and
  chronological progression
• Precocious puberty with androgen excess suggests
  adrenal enzyme defect
• Family history androgen excess disorders

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APPROACH TO DIAGNOSIS

• Physical examination
• Establish presence of hirsutism and quantifying
  it
• Presence of acne and virilization and rule out
  hypertrichosis
• Skin hyperpigmentation,acanthosis nigricans
  suggests insulin resistance.Often associated with
  PCO

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APPROACH TO DIAGNOSIS

• Measurement of weight and height and blood
  pressure defects relates to adrenal enzyme
  defects
• Galactorrhoea
• Tanner staging Hirsutism before Tanner stage 3
  to 4 is alarming and suggests a serious pathology
• Visual genital examination for virilization

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APPROACH TO DIAGNOSIS

• Semiobjective scoring system Ferriman and
  Gallwey system ,between 6-12 is the lower limit.

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APPROACH TO DIAGNOSIS

• INVESTIGATION
• FOR VIRILIZATION
• Work-up focuses of the identification on the
  source of androgen excess
• Rule out exogenous androgen
• Evidence of endogenous androgen excess
• Serum total testosterone
• Serum dehydroepiandrosterone sulfate (DHEAS)

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APPROACH TO DIAGNOSIS

• INVESTIGATION
• FOR VIRILIZATION
• Imaging studiesPelvic sonography
• Adrenal imaging(USG,CT)
• Specialized studies
• Selective venous catherization(adrenal or
  ovarian)
• Radioisotope studies

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APPROACH TO DIAGNOSIS

• INVESTIGATION
• HIRSUTISM Goal is to rule out serious potential
  life threatening conditions and gain information
  that helps in treatment
• Evaluation of Androgen excess
• Testosterone ,total preferred
• DHEAS
• In selected cases 17-OHP(fasting morning
  sample)

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APPROACH TO DIAGNOSIS

• Evaluation of accompanying medical disorder
• Ovulation disorder FSH,LH
• Thyroid dysfunctionTSH
• Hyperprolactinemia PRL
• Other investigations ( inselected cases)
• Androgen production Androstenedione,
• 3-alpha Androstenediol glucuronide
• Provocative tests Corticotropin stimulation
  tests,Insulin resistance determination

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THERAPEUTIC OPTIONS

• VIRILIZATION
• GOAL Identify the underlying cause and
  correcting it
• Usually related to malignant process and requires
  surgical approach

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THERAPEUTIC OPTIONS

• HIRSUTISM
• GOAL
• The prevention of further stimulation of hair
  growth
• Cosmetic correction of the problem

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THERAPEUTIC OPTIONS

• BASIC STEPS OF MANAGEMENT OF HIRSUTISM ARE
• DEFINE THE PROBLEM
• QUANTIFY THE DEGREE OF HIRSUTISM
• INDENTIFY THE PATHOPHYSIOLOGY
• CORRECT THE PROBLEM,WHETHER ACUTE OR CHRONIC
• DEFINE SUCESSWITH THE PATIENT
• FOLLOW UP

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THERAPEUTIC OPTIONS

• A key element of any therapeutic plan is to
  define what will ultimately be viewed and
  successful therapy
• Regular follow up is indicated at appropriate
  intervals,usually every 3- 6 months

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THERAPEUTIC OPTIONS

• GENERAL MEASURES
• Eliminating causative factors
• Optimizing weight
• Manage hair
• Bleaching
• Cutting or shaving
• Electrolysis
• Laser epilation

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THERAPEUTIC OPTIONS

• Management of excess ovarian androgen production
  
• Standard therapy is combined EP,most commonly
  OCs
• It reduces ovarian androgen production
• It increases SHBG
• It induces competition at the cellular level for
  binding to the androgen receptor

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THERAPEUTIC OPTIONS

• Choice of OC
• EE Norgestimarte approved in USA
• Cyproterone acetate used as progesterone
  component in Ocs
• OVARIAN SUPPRESSION BY LONG ACTING GnRH ANALOGUE
• Can be used for functional ovarian androgen
  overproduction and even for malignant condition
• But to be used for long with back-up

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THERAPEUTIC OPTIONS

• Long acting GnRH analogues used
• But there is doubt that this therapy will be
  beneficial over Ocs
• INSULIN SENSITIZING AGENTS
• For PCO with acanthosis nigicans
• Commonly used agent is Metformin and
  Troglitazone,Pioglitazone,Rosiglitazone

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THERAPEUTIC OPTIONS

• MANAGEMENT OF EXCESS ADRENAL ANDROGEN PRODUCTION
• Metabolic correction of the disorder,usually with
  exogenous steroids
• Dexamethasone,mostly used,But LIMITED ROLE

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THERAPEUTIC OPTIONS

• Management directed to the target organ and cells
• Competition with Androgen receptorsSpironolactone
  ,Flutamide, Ketoconazole,Cyproterone acetate
• 5-alpha reductase Inhibitors Finasteride

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THERAPEUTIC OPTIONSandrogen receptors competitors

• SIPRONOLACTONE
• Best studied and as Gold standard
• Mechanism Androgen receptors blockade
• Suppression of Androgen biosynthesis
• Increased metabolic clearance of teststerone (
  Testosterone ? Estrogen )
• 50-200 mg/day in two divided doses
• Spironolactone OC is well established regimen

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THERAPEUTIC OPTIONSandrogen receptors competitors

• FLUTAMIDE
• Blocks the androgen receptors
• Decreases androgen production
• May have therapeutic value in cases of PCOS
• Usually used with Ocs
• KETOCONAZOLE
• Equally effective but danger of liver toxicity

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THERAPEUTIC OPTIONS

• SELECTING BEST THERAPY
• Correct underlying medical problem
• Correct thyroid/hyperprolactinemia
• PCO oral contraceptives
• Ocs spironolactone is usually the choice
• 75 80 patients shows response
• Atleast 6 months is needed for evidence of
  response

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THERAPEUTIC OPTIONS

• If response is seen in 6 months then treatment
  should be continued for further 6 months and in
  most cases for number of years