Transcript
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
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