EXCESSIVE HAIR GROWTH IN ADOLESCENT

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

EXCESSIVE HAIR GROWTH

IT MAY BE EITHER
HIRSUTISM VIRILIZATION

dpankar

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

dpankar

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

dpankar

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
dpankar 5

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
dpankar 6

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)
dpankar 7

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

dpankar

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.
dpankar 9

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
dpankar 10

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
dpankar 11

BASIC FACTS ABOUT HAIR

PITUITARY PITUITARY

ACTH
DHEAS

DHEAS
OVARY

DHEA
ADRENAL

ADRENAL

AND,STEN,ONE

OVARY

PERIPHERAL CONVERSION

TESTOSTERONE
HAIR FOLLICLE DIHYDROTESTERONE
dpankar 12

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

dpankar

13

PRESENTATION OF HIRSUTISM
HIRSUTISM ALONE HIRSUTISM AND ASSOCIATED PILOSEBACEOUS UNIT OVERACTIVITY (ACNE) HIRSUTISM AND OVULATORY DISORDERS HIRSUTISM AND SIGNS OF VIRILIZATION
dpankar 14

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
dpankar 15

CAUSES OF HIRSUTISM
Excess androgen production Relative circulating androgen excess and low binding globulins Excess end organ response Patient perception

dpankar

16

DISORDERS OF EXCESS ANDROGEN PRODUCTION

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

dpankar

17

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

dpankar

18

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
dpankar 19

DISORDERS OF EXCESS ANDROGEN PRODUCTION

21-alpha-Hydroxylase deficiency: Most common ,<1% to >10% 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
dpankar 20

DISORDERS OF EXCESS ANDROGEN PRODUCTION

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

dpankar

21

Lab.Evaluation of Hirsutism
Three basic hormonal evaluation 1. Total testosterone 2. DHEAS 3. AM 17-hydroxyprogesterone

dpankar

22

Total Testosterone Normal Value (0.2 0.9 ng/ml)

dpankar

23

DHEAS

(600 2800 ng/ml)

dpankar

24

AM 17 hydroxyprogesterone(0.1 0.8
ng/ml )

dpankar

25

RELATIVE ANDROGEN EXCESS AND SHBG

<3 % 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
dpankar 26

EXCESS REPONSIVITY TO ANDROGEN

TESTOSTERONE
5-ALPHA -REDUCTASE

TARGET CELLS RECEPTOR

DIHIDROTESTOSTERONE

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 )
dpankar 27

BASIC APPROACH TO THE DIAGNOSIS OF HIRSUTISM AND VIRILIZATION

SYMPTOMS AND HISTORY SIGNS PHYSICAL EXAMINATION INVESTIGATION
dpankar 28

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
dpankar 29

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

dpankar

30

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
dpankar 31

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
dpankar 32

APPROACH TO DIAGNOSIS
Semiobjective scoring system : Ferriman and Gallwey system ,between 6-12 is the lower limit.

dpankar

33

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)
dpankar 34

APPROACH TO DIAGNOSIS
INVESTIGATION: FOR VIRILIZATION Imaging studies:Pelvic sonography Adrenal imaging(USG,CT) Specialized studies : Selective venous catherization(adrenal or ovarian) Radioisotope studies
dpankar 35

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)
dpankar 36

APPROACH TO DIAGNOSIS
Evaluation of accompanying medical disorder Ovulation disorder :FSH,LH Thyroid dysfunction:TSH Hyperprolactinemia :PRL Other investigations ( inselected cases) Androgen production :Androstenedione, 3-alpha Androstenediol glucuronide Provocative tests : Corticotropin stimulation tests,Insulin resistance determination
dpankar 37

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

dpankar

38

THERAPEUTIC OPTIONS
HIRSUTISM GOAL: The prevention of further stimulation of hair growth Cosmetic correction of the problem

dpankar

39

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
dpankar 40

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

dpankar

41

THERAPEUTIC OPTIONS
GENERAL MEASURES : Eliminating causative factors Optimizing weight Manage hair Bleaching Cutting or shaving Electrolysis Laser epilation
dpankar 42

THERAPEUTIC OPTIONS
Management of excess ovarian androgen production : Standard therapy is :combined E+P,most commonly OCs It reduces ovarian androgen production It increases SHBG It induces competition at the cellular level for binding to the androgen receptor
dpankar 43

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
dpankar 44

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
dpankar 45

THERAPEUTIC OPTIONS
MANAGEMENT OF EXCESS ADRENAL ANDROGEN PRODUCTION Metabolic correction of the disorder,usually with exogenous steroids Dexamethasone,mostly used,But LIMITED ROLE
dpankar 46

THERAPEUTIC OPTIONS
Management directed to the target organ and cells Competition with Androgen receptors:Spironolactone,Flutamide, Ketoconazole,Cyproterone acetate 5-alpha reductase Inhibitors :Finasteride

dpankar

47

THERAPEUTIC OPTIONS androgen 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
dpankar 48

THERAPEUTIC OPTIONS androgen 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
dpankar 49

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
dpankar 50

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

dpankar

51