EXCESSIVE HAIR GROWTH IN ADOLESCENT Dr. D’Pankar 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

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

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

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

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

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

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

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

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

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

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

DISORDERS OF EXCESS ANDROGEN PRODUCTION Source of androgen : Exogenous Endogenous (most common) Two primary endogenous sources : Adrenal glands Ovaries dpankar

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 Cushing’s syndrome dpankar

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

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 Cushing’s syndrome :Hirsutism with weight gain and growth retardation as the primary manifestation,with acne and other cutaneous problems dpankar

DISORDERS OF EXCESS ANDROGEN PRODUCTION OVARIAN ORIGIN Most common cause is POLYCYSTIC OVARIAN SYMDROME Other Neoplastic ovarian disease dpankar

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

Total Testosterone Normal Value (0.2 –0.9 ng/ml) dpankar

DHEAS (600 –2800 ng/ml) dpankar

AM 17 –hydroxyprogesterone(0.1 –0.8 ng/ml ) dpankar

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

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 ) dpankar

BASIC APPROACH TO THE DIAGNOSIS OF HIRSUTISM AND VIRILIZATION SYMPTOMS AND HISTORY SIGNS PHYSICAL EXAMINATION INVESTIGATION dpankar

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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