Each hair follicle develops at about 8-10wks of gestation as a derivative of epidermis. Number of hair follicles is set from birth Main difference between sexes is the degree of differentiation of the hair Hair grows in a mosaic pattern(in a given area ,hair are in different stages of development) 2
Adults have two types of hair: Vellus and Terminal. Vellus hair : Soft, fine, colorless, and usually short. Grow on the face, chest, and back and give the impression of "hairless" skin. Terminal hair : longer, coarser, darker hair that grows on the scalp, pubic, and armpit areas in both adult men and women.
Anagen : Growth phase,85- 90 % of the life cycle Catagen : The transitional period from growing to resting lasting 2 to 4 weeks Telogen : Quiescent phase ,lasting 2-4 monthsThe growth phase or the anagen phase is primarily influenced by disorders that stimulate hair growth as well as therapeutic modalities.
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 dependent : Forearms ,hands , lower legs
The production rate of testosteronein the normal female is 0.2 to 0.3 mg/dayNormal total testosterone concentrationin serum is below 0.8ng/ml
1% Free 2% Free 19% Albumin 19% Albumin 80% SHBG 79% SHBGNormal women Hirsute women
IT MAY BE EITHER HYPERTRICHOSIS HIRSUTISM VIRILIZATION 11
HYPERTRICHOSIS : REFERS TO HAIR DENSITY OR LENGTH BEYOND THE ACCEPTED LIMITS OF THE NORMAL FOR THE PARTICUALR AGE,RACE OR SEX.• May be generalised or localised and may consist of lanugo, vellus or terminal hair.• Frequently associated with the use of medication such as antiepileptics 12
HIRSUTISM : APPEARANCE OF EXCESSIVE COARSE (TERMINAL)HAIR IN A PATTERN NOT NORMAL IN THE FEMALE The abnormal distribution of excess hair growth ,such as face ,chest or upper abdominal hair Affects 5-10% of women May also signal the presence of a hormone imbalance or a hormone-producing tumor. dpankar 13
VIRILIZATION : REFERS TO CONCURRENT PRESENTATION OF HIRSUTISM WITH A BROAD RANGE OF SIGNS SUGGESTIVE OF ANDROGEN EXCESS,SUCH AS Acne, Frontotemporal balding, Deepening of the voice , Decrease in breast size Clitoral hypertrophy Increased muscle mass Amenorrea / oligomenorrhea 14
Increased serum androgens Decreased levels of SHBG-> increased free testosterone Increased responsiveness of target organ to normal circulating androgens Increased activity of 5 alpha reductase 1% Free 2% Free 19% Albumin 19% Albumin 80% SHBG 79% SHBG Normal women Hirsute women
Main stimulus- Testosterone Testosterone – binds – androgen receptors Activation of 5 alpha reductase Androstenediol DHT Terminal hair
Tumors of the ovaries and the adrenal glands secrete excess hormones including androgen.Ovarian tumors Adrenal tumors Granulosa -theca cell tumors Adrenal adenoma Arrhenoblastoma Adrenal carcinoma Gonadoblastomas Lipoid cell tumors ACTH secreting tumors Dysgerminoma Brenners tumor
Functional adrenal hyperandrogenism Hypereactio luteinalis of pregnancy - transient increase in androgen levels during pregnancy Thecoma of pregnancy - Transient androgen secreting tumor during pregnancy True hermaphroditism - condition where both male and female internal sex organs are present
Genetics There are very obvious family and racial differences in hirsutism patients. In some women, the skin is very sensitive to even low levels of androgens and their follicles produce primarily terminal (coarse and dark) hair.
In 70-80 % cases of hirsutism5-10% of women in reproductive ageFulfills the Rotterdam criteria Hyperandrogenism Amenorrhoea /oligomenorrhoea USG features of PCODAnovulationInfertilityObesity
It is a familial disorder of adrenal steroid biosynthesis Autosomal recessive mode of inheritance. The defect is expressed as adrenal enzyme deficiency. 5 major Enzymes deficiencies are clinically important 21-Hydroxylase 11-b-Hydroxylase 17-a-Hydroxylase 3-b-Hsteroid hydrogenase 20,22 Desmolase deficiency
The enzyme deficiency causes reduction in end- products, accumulation of hormone precursors & increased ACTH production.The clinical picture reflects the effects of inadequate production of cortisol & aldosterone and the increased production of androgens & steroid metabolites.
In less severe forms (late onset CAH) Genitalia is normal at birth. Precocious pubic hair & Clitoromegaly Excess facial or body hair appear later in childhood, often accompanied by tall stature Varying virilizing symptoms ranging from oligomenorrhea to hirsutism and infertility
17-OHP 17-OHP > ng/dl 17-OHP < 200ng/dl ACTH stimulation test Rules outAbnormal adrenal Normal hyperplasia 21-hydroxylase deficiency Adrenal hyperplasia
Testosterone assay Testosterone Testosterone > 200ng/dl <200ng/dl Normal pelvic Palpable scanadnexal mass Anovulatory hirsutism imaginglaparotomy laparotomy
A very rare disease The clinical state of increased free circulating glucocorticoid
HypercotisolismLipid mobilization Hepatic glucose Protein metabolism production ↑Lipid Catabolism Negative nitrogen balanceLipid redistribution Disruption of water and electrocytes metabolism Insulin resistance Proximal muscle Dependent edema Moon-face weakness buffalo hump Hypertension truncal obesity Glucose intolerance Hypokalemic Violaceous striae Hirsutism(65%) Metabolic alkalosis
History- Onset and progression Physical examination Assess the severity of hirsutism (+/- virilisation) Acertain the underlying cause Investigations Treatment
Onset and progression Most of the causes begins in early adolescence Presentation may be late depending upon the cause Rapid progression – androgen secreting tumors
Degree and extent Ferriman gallwey scale Quantifies the extent of hair growth in 9 most androgenic sensitive sites Hair growth is graded 0-4 at each site Score of 8 or more (max 36) indicates hirsutism
Associated signs of virilisation(May occur in CAH, HAIR-AN syndrome, Androgen secreting tumor, Acanthosis nigricans) Clitoral hypertrophy Deepening of voice Acne Male pattern baldness Breast atrophy Android habitus
History of drug intake producing androgenicity Family history- correlated Mild hirsutes- during puberty, pregnancy, postmenopause Hirsutism with rapid onset- Evaluation for adrenal /ovarian tumor High testosterone levels (>200ng/100ml)- Androgen producing tumor Patients with primary amenorrhoea with virilism- karyotyping for y carrying dysgenetic gonads
Late onset CAH- D/t partial deficiency of 21- hydroxylase enzyme 17- OHP is elevated Cushing disease- 24 hr urinary free cortisol excretion- (10-90µg) Late evening plasma cortisol level – (< 15 µg/dl ) Overnight Dexa suppression test
Diagnosis Menstrual Total DHAS LH 17OHP Sourse of Pattern Testoste- Androgens ronePCOS Irregular Elevated mildly Elevated Normal OVARY elevatedCAH Irregular Elevated Often Usually Markedly Adrenals Normal Normal elevatedIdiopatic Regular Normal Normal Normal Normal Skinhirsutism
Principles of management To remove excess hair To suppress or neutralise the action of androgen To remove the source of excess androgen
Best results are achieved by combination treatment including antiandrogens, suppression and topical treatments Goal should be to reduce the time spent mechanically removing unwanted hair. The choice of drug depends mainly on its tolerability by each individual patient.
Weight Reduction Associated with reduction of hyperinsulinemia and androgen excess BMI should not be > 25
Drugs- ( depending upon the site of production of excess androgens) OCPS Progestrogens Antiandrogens Spironolactone Dexamethasone GnRH Analogues Combined approach
CLINICAL BENEFITS Helpful in treatment of Hirsutism Excellent cycle control Decreases acne No weight gain.METABOLIC BENEFITS No effect on carbohydrate metabolism No deterioration in the glycemic and insulinemic response to glucose load. No effect on serum lipid concentration. Safe for long term use
Cyperoterone acetate: A progestin that also has strong antiandrogenic action. Inhibits gonadotrophin secretion and interferes with androgen action on target organs by competing for androgen receptors Dosage- 100mg from D5-D14 with ethinyloestradiol 30µg, from D 5 to D25 Side effects: Nausea, fatique, weight gain, loss of libido, mastalgia
Spironolactone: (Antialdosterone antiandrogenic compound) Inhibits ovarian and adrenal androgen biosynthesis Competes for androgen receptors in hair follicle Inhibits 5 alpha reductase activity Dosage -100-200mg daily, maintenance dose is 25-50 mg daily Side effects- fatigue,menstrual irregularities, hyperkalaemia
Finasteride: 5 alpha reductase inhibitor that inhibits conversion of testosterone to more active 5 alpha hydroxy testosterone Dosage- 5 mg daily
Flutamide: Androgen receptor antagonist Dosage – 100-200mg daily Side effects - hepatotoxic , Dry skin Should be combined with a contraceptive Marked beneficial effect in 6 months
Mode of action Suppress pituitary adrenal axis - suppression of endogenous ACTH secretion Use – In adrenal or mixed adrenal and ovarian hyperandrogenism
Metformin: Antihyperglycemic drug ,in treatment of hirsutism associated with insulin resistance (e.g. PCOD) Eflornithine: (13.9% cream) US FDA approved It irreversibly inhibits ornithine decarboxylase (ODC), an enzyme that catalyzes the rate-limiting step for follicular polyamine synthesis, which is necessary for hair growth. Improvement occurs gradually over a period of 4-8 weeks or longer. Most reported adverse reactions consisted of minor skin irritation.
How long should treatment be continued? After 1 – 2years, medication can be stopped to observe the return of ovulatory cycles. Even in anovulatory pts, testosterone suppression continues for 6months to 2 years after discontinuing treatment If anovulation persists, return of hirsutism expected.
Bleaching - can cause irritation, purities, skin discoloration Shaving - Shaving does not lead to worsening of hirsutism and is a good short-term solution for facial hair. - Does not affect the rate or duration of anagen phase, or diameter of hair - But yields a blunt tip – illusion of thicker hair Plucking, Waxing - scarring, folliculitis, hyperpigmentation Depilatory creams - Irritant dermatitis Electrolysis - painful, erythema, inflammation, scarring Laser
Removal of the source Adrenal or ovarian tumour – surgically treatedCushing disease – Adrenalectomy Radiation to pituitary Removal of ACTH producing tumorIatrogenic cases – Offending drug to be stopped
Hirsutism is a symptom of underlying cause Commonest cause is PCO Progression may hint to diagnosing tumor Treatment – Medicines/ Cosmetic