Approach to Hirsutism1

P. Krishna BharadwajModeratorsDr. T. Muneeswar reddy MDAssociate professor

Dr. N. Padmaja MDAssistant professor

DefinitionsHirsutismDefined as androgen dependent excessive male pattern hair growthVirilisationCondition in which androgen levels are sufficiently high to cause• Deepening of voice• Breast atrophy• Increased muscle bulk• Clitoromegaly• Increased libido

DefinitionsHypertrichosisrefers to hair density or length beyond the accepted limits of the normal for the particular age, race or sex. Androgen independent excess hair growth

Hair follicle growth and differentiation

• Vellus : fine, soft, not pigmented• Terminal : long, coarse, pigmented

Differentiation of Pilosebaceous unit

PSU

Sebaceous gland with vellus hair

Cycle of hair growth

Hormone regulation in hair growth cycle

• Androgen insensitive:

• Less sensitive: axillary and pubic hair

• Highly sensitive: chest, upper abdomen and back

Androgens on scalp hair???

Hair loss occurs in scalp as androgens cause scalp hair spend less time in the anagen phase.

Correlation between androgens and hair growth

• Only modest correlation• Reason: hair growth on follicles depend on

local growth factors and end organ variability in sensitivity to androgens

Genetic and ethnic factors• Dark haired individuals tend to be more

hirsute than fair skinned.• Asians and native Americans have less hair in

androgen sensitive regions.• Mediterranean people have more in the same.

Causes of Hirsutism

Clinical assessmentHistory: • Age at onset• Rate of progression• Associated signs and symptoms like acne and

galactorrhea• Age of onset of menstrual cycles• Pattern of cycle• Features of Cushing's syndrome• Use of any medications• Family history

Physical examination• BMI• Blood pressure measurement• Cutaneous signs like acanthosis nigricans and

skin tags• Body fat distribution

Objective assessment• Modified scale of FERRIMAN and GALLWEY• 9 androgen sensitive sites graded from 0 to 4• Usually 95% of women have score less than 8• Scores > 8 suggests excessive androgen

mediated hair growth• Limitations are ethnic considerations where

other features like acne and thinning of scalp hair should be sought

Hirsutism scoring scale of FERRIMAN AND GALLWEY1

Hirsutism scoring scale of FERRIMAN AND GALLWEY1

Hirsutism scoring scale of FERRIMAN AND GALLWEY1

Hormonal evaluation

OVARIES

ANDROGENS

LH

ACTH

Principal hormones• Testosterone• Androstenedione• Dihydroandrostenedione DHEA• Sulfated DHEA [DHEA-S]

Mechanism

Testosterone Dihydrotestosterone

Isoenzymes of 5 α reductase:Type 1 sebaceous glandsType 2 hair follicles and prostate gland

5 α reductase

PSU

Lab evaluation• Testosterone• DHEAS• Free testosteronePlasma testosterone level>12nmol/l = virilizing tumour>7nmol/l = suggestiveDHEAS level >18.5µmol/l = adrenal tumour

Other investigations• CT or MRI for localising adrenal mass• Trans vaginal USG for determing increased

stroma and enlarged ovaries in PCOS• Measurement of AMH levels• Dexamethasone suppression test• Overnight dexamethasone suppresion test• Measurement of 17(OH) progesterone levels

Clinical evaluation of hirsutism

Treatment• Pharmacological• Non pharmacological

Non pharmacological means must be considered in all patients either as only treatment or as an adjunct to drug therapy

Non pharmacological treatment

• Bleaching• Depilatory• Epilatory

“Shaving does not increase the rate or density of hair growth”

Pharmacological therapyInterrupting steps in androgen synthesis and action:• Suppression of adrenal and/or ovarian androgen

production• Enhancement of androgen binding to plasma

proteins esp. SHBG• Impairment of peripheral conversion to active

androgen• Inhibition of androgen action at target tissue level

Pharmacological therapyCombined OCPs are first lie endocrine treatment

for hirsutism and acne, after cosmetic and dermatologic treatment

• Estrogen component is ethinyl estradiol or mestranol

• Progestin component predicts the choice of OCP

Effect of OCPs• May not be evident for 6months• Maximum effect may require 9-12 month

depending on length of the hair growth cycle

Suppression of adrenal androgens

• Adrenal androgens are more sensitive than cortisol to suppressive effect of glucocorticoids.

• Dexamethasone or prednisone should be taken at night time to prevent the nocturnal surge of ACTH.

Anti androgens• Competitive inhibition of binding of

testosterone and DHT to the androgen receptor.

• Cyproterone acetate is a prototype• Given on day 1 to day 15 and ethinyl estradiol

on day 5 to day 26 of menstrual cycle.• Spironolactone is a weak antiandrogen• As effective as cypro when used at high doses

Anti androgens• Flutamide is a potent non steriodal anti

androgen• Its hepatocellular toxicity limits use.

Enzyme inhibitors• Finasteride is a 5 α reductase type 2 inhibitor• Predominance of 5 α reductase type 1 in PSU

limits its efficacy

Others• Eflornithine cream has been approved as

novel treatment for removal of unwanted facial hair in women

• Overall, choice of any specific agent must be tailored to the unique needs of the patient being treated.

References1. Kasper DL et al, Harrison’s principles of

internal medicine. 19th edition. New York: McGraw-Hill; 2015. p. 331-5.

2. Ehrmann DA et al: Hyperandrogenism, hirsutism, and polycystic ovary syndrome, in LJ DeGroot and JL Jameson [eds], Endocrinology, 5th ed. Philadelphia, Saunders, 2006