HIRSUITISM 4.pdf for postgraduate students

HIRSUITISM
Dr Nima Thendup Bhutia
1 HIRSUITISM 2 - 2 February 2025

INTRODUCTION
• Excessive terminal hair growth in androgen dependent areas of the body
in women.
• Seen in 5-10% of women ,and signals precocious puberty when seen in
children.
• It causes significant emotional distress.
• Depending on effect of androgen on hair growth –
▪ Nonsexual skin – non responsive eg- eyebrows , eyelashes , lateral and
occipital areas of scalp.
▪ Ambosexual skin – responsive to low levels – eg – axilla and pubic hair.
▪ Sexual skin – responsive to high levels eg – chin , face ,chest ,lower
abdomen, upper arms , upper thighs.

Hirsuitism v/s Hypertrichosis
• Female
• Puberty or later
• Androgen dependent sites
• Terminal hairs
• Good response to treatment of
the underyling cause
• Both male and female
• Independent of age
• Excessive hair growth in any
part of the body
• Lanugo/villous/terminal
• Congenital forms shows poor
response to medical
management

PATHOGENESIS
• Pro- androgens include – Dehydroepiandrsterone (DHEA) , DHEA-S
(sulfate) , androstenedione
• Pro androgens convert to testosterone and DHT (most potent) to exert
their effects.
• They transformed the vellus hair to terminal hairs , increase the
growth rate and increase the anagen phase.

• Sebaceous glands have enzymes – 3-β hydroxysteroid dehydrogenase
and 17-β hydroxysteroid dehydrogenase.
• Hair follicles have 5-α reductase. This enzyme has two isoenzymes.
• Type1 (chromosome 5) – sweat glands, sebocytes, kerationcytes, root
sheath and dermal papilla cells.
• Type 2 (chromosome 2) – hair follicles.

ANDROGEN BIOSYNTHESIS

CAUSES
• Hyperandrogenic hirsutism
▪ PCOS (72-82%)
▪ Androgen secreting tumors (0.2%)
▪ Nonclassical congenital adrenal hyperplasia (2-4%)
▪ Idiopathic hyperandrogenemia (6-15%)
• Non-hyperandrogenic hirsuitism
▪ Drugs
▪ Endocrinopathies
▪ Pregnancy
▪ Postmenopausal
• Idiopathic Hirutism (4-7%)

Hyperandrogenic hirsutism
• POLYCYSTIC OVARIAN SYNDROME
▪ Most common cause of hirsutism.
▪ Hyperandrogenism and hyperinsulinemia
▪ 2003 European society for human reproduction and American society
of reproduction medicine (ESRHE/ASRM) Rotterdam’s cONSESUS –
❑ Hyperandrogenism (Clinical or biochemical)
❑ Ovulatory dysfunction (lack of menses or irregular menses)
❑ PCOM ( usg – checking no of antral follicles and ovarian volume)
{two out of three for diagnosis}.

▪ NIH has added a PCOS phenotypes .
▪ Phenotype A – Hyperandrogenism + ovulatory dysfunction + PCOM
▪ Phenotype B – Hyperandrogenism + ovulatory dysfunction
▪ Phenotype C – Hyperandrogenism + PCOM
▪ Phenotype D – Ovulatory dysfunction + PCOM

▪ PCOS characterized by increased LH hormone levels
▪ LH : FSH ratio >2
▪ The circulating high LH levels of causes stimulation of the ovarian theca
cells to produce androgens.

▪ The hyperinsulinemia and insulin resistance increases conversion of
progesterone to androstenedione in ovaries , which ultimately gets
converted to testosterone
▪ It stimulates the release of IGF-1  stimulates 5-α reductase
(increases hirsutism) .
▪ IGF-2 promotes LH stimulated androgen production by ovaries.
▪ The IR inhibits the SHBG production and hence testosterone level
rises.

• ANDROGEN SECRETING TUMORS
▪ Ovarian or adrenal tumors (50% are malignant)
▪ Rare cause of hirsutism
▪ Rapid hirsutism and virilization and palpable mass per abdomen
▪ Very high androgen levels (s.testosterone >200ng/ml)
• NON CLASSICAL CONGENITAL ADRENAL HYPERPLASIA
▪ Due to deficiency of 21-hydroxylase causing increased levls of 17-
hydroxyprogesterone and androstenedione.

• IDIOPATHIC HYPERANDROGENISM
▪ Normal ovarian morphology and regular menstrual cycles with
hyperandrogenism without other explainable causes.
▪ Hormonal profile is similar to PCOS
▪ Main source is ovaries
▪ Accounts to 6-15% of cases

NON-HYPERANDROGENISM
• MEDICATIONS
▪ Anbolic steroids
▪ Danazol
▪ Testosterone
▪ Progestin- only contraceptive pill
▪ Glucocorticoids
▪ Estrogen antagonists
▪ Minoxidil
▪ Cyclosporine
▪ Diazoxide
▪ Phenytoin
▪ Interferon-α
▪ D-penicillamine

• ENDOCRINOPATHIES
▪ Cushing’s syndrome
▪ Hyperthyroidism/ hypothyroidism
▪ Hyperprolactinemia
▪ Acromegaly
• Pregnancy – physiological hyperandrogenism state . Increased SHBG and
high levels of testosterone causes hirsutism
• Postmenopausal women – absence of ovarian estrogen production causes
relative state of hyperandrogenism.

IDIOPATHIC HIRSUTISM
• Hirsutism along with normal ovulatory function and normal androgen levels.
• Not associated with virilization.
• 10-20% of all cases of hirsutism.
• Pathogenesis - due to increased sensitivity of the hair follicles to normal
androgen levels , higher 5-α reductase activity, and alteration in the androgen
receptor function.

• HAIR-AN SYNDROME
• Severe insulin resistance (>80 mcgU/ml basally and/or 500mcgU/ml after oral
glucose challenge).
• Ovaries are enlarged and hyperthecotic due to insulins effect.
• Hyperandrogenismc , Insulin resistance , acanthosis nigricans .
• SAHA SYNDROME
• Seborrhoea
• Acne
• Hirsutism
• Acanthosis nigricans.

EVALUATION
• HISTORY
• PHYSICAL EXAMINATION
• ASSESMENT OF HIRSUTISM (mfg scoring)
• INVESTIAGTIONS

• HISTORY
• PCOS - irregular menses , weight gain , acne , acanthosis nigricans ,
infertility ,hypertension.
• Non classical CAH - irregular menses , primary amenorrhea , prepubertal onset ,
premature pubarche
• Cushing’s syndrome - striae , weight gain, weakness , easy bruising ,fragile skin.
• Hyperprolactinemia - Galactorrhea
• Pituitary tumour - headache , visual disturbances
• Thyroid disease - tremors ,dry skin , hair loss, weight gain/loss , hot or cold intolerance
• Ovarian/adrenal tumour - virilization symptoms.

• ASSESSMENT -
• Rate of growth can be measured by photographs or by calibrated glass capillary tubes
• Vellus index - refers to ratio of vellus hairs in a sample of 100 shaved hairs.
• The disadvantages of the objective methods is that they are costly ,time consuming
and incovinient.
• Most popularly used scoring system is modified Ferriman-Galleway (mFG)
• Each area is given 0-4
• 0- no termainal growth
• 1- minimal amounts of visible terminal hairs
• 2 - hair growth is more than minimal but not yet that of a man
• 3 - equivalent to a not very hairy man
• 4 - equivalent to a hairy man

MODIFIED FERRIMAN-GALLWEY SCORING SYSTEM
<8 – Normal , 8-15 moderately severe ,>16 - severe

• HORMONAL ASSESSMENT -
• To be done in a follicular phase of the menstrual cycle (fasting , early
morning) that is day2 to day 10 of menses.
• OCPs has to be stopped 6 weeks prior to the testing.
• In patients of minimally elevated hormones we can do the hormonal hirsutism
score -
• T/SHBG + A/100
• T/SHBG + A/100 + DHEA -S/100
• OVULATORY ASSESSMENT-
• Basal body temperature and estimated progesterone levels < 3-5ng/ml
(day20-24 - luteal phase of cycles )

DIAGNOSTIC ALGORITHM

Part 2

TREATMENT
• LIFE STYLEMODIFICATIONS
• PHARMOCOLOGICAL INTERVENTIONS
▪ SYSTEMIC
▪ TOPICAL
• COSMETIC HAIR REMOVAL

• LIFE STYLE MODIFICATIONS

Systemic therapy
• OCPs
• Estrogen (ethinyl estradiol 0.03 -0.035 mg )
• Progestins are norethindrone acetate , ethynoidiol diacetate ,
desogestrel, gestedene and nirgestimate.
• Usual dose in cyproterone acetate (CA) 50-100mg /day on
menstrual cycle days 5-15 with EE (ethinyl estradiol) 20-35 mcg on
days 5-25
• Mechanism of action - reduces ovarian androgen production by
suppressing LH and FSH , decreases adrenal androgen production ,
• Progestin antagonises 5-α reductase and androgen receptors
• The estrogen increases SHBG , thus decreasing free testosterone
levels.

• In women with PCOS , OCP containing CA is more effective in
treating hirsutism.
• Side effects - include irregular vaginal bleeding , breast tenderness
, mild fluid retention , weight gain , gastrointestinal upset , risk of
thromboembolism , mood changes , abnormal liver function test ,
and loss of libido.
• OCP can be used as mono therapy in women with mild hirsutism.
• Moderate to severe hirsutism - use as an adjuvant to antiandrogens

• ANTI ANDROGENS - SPIRONOLACTONE
• Competitive androgen receptor inhibitor , Inhibits 5-α reductase
• Dose - 50-200mg/day and increased 25mg/day once in 3 months
• Takes 6 months to show effective therapy
• S/e - fatigue ,postural hypotension , headache and syncope.
• Absolute contraindications - pregnancy , hyperkalemia , abnormal uterine
bleeding , chronic renal impairment , anuria and renal insufficiency .
• Avoid using with potassium sparing diuretics
• Measure serum electrolytes and blood pressure every 4 weeks and every 2
weeks after increase each dose increase.
• Category D - Psuedohermaphroditism (take with effective contraception)

• Drosperinone
• Derived from spironolactone (acts by binding to androgen receptors
and inhibiting ovarian androgen synthesis.
• Anti androgenic and anti mineralocorticoid activities.
• Dose - 3mg ( combination with OCP)
• Side effect - migraine , depression , weight changes and nausea.

• Cyproterone acetate
• 17 hydroxyprogesterone acetate derivative with progestogenic effects.
• Competes with testosterone and DHT for androgenic receptors.
• Decreases testosterone by gonadotropin suppression.
• Dose - 50-100mg/day combined with 30-35 mcg of EE
• Side effects - loss of libido and adrenal insufficiency
• Adequate contraception should be used.

• Finasteride
• Inhibits type 2 isoenzymes 5-α reductase and reduces DHT levels.
• Low dose 2.5mg/day is equivalent to 5mg/day therapy with similar
side effects
• S/e - no major side effects
• Should be prescribed with contraception (tetratogenicity)

Topicals
• Eflornithine hydrochloride (13.9%)
• FDA approved
• Irreversibly inhibiting L-ornithine decarboxylase enzyme ,thus impeding
cellular growth and differentiation in hair follicle.
• Twice day application
• Does not remove hair but leads to miniature of the hair (fine and less coarse)
• Adjuvant with other agents and laser .
• Effective in paradoxical laser induced hypertrichosis and in laser resistant
hirsutism.
• Disadvantage - regrowth of hair to pretreatment levels on discontinuing

• Finasteride topical
• 0.25% cream twice daily x 6 months showed significant improvement in 8
patients
• 5% lotion with /without IPL in 75 patients showed minimal clinical benefits.

SUMMARY OF TREATMENTS

Cosmetic hair removal methods

• Electrolysis - thermal or galvanic
• Painful and time consuming process as each follicle has to be
treated individually
• Considered for localised areas.
• Electric current is applied to a fine wire which is targeted to the
hair follicle
• This destroys the hair follicle about 1 min for each hair.
• Many sessions are required for adequate results.
• Thermolysis is similar bit employs high frequency alternating
current
• Faster , less painful and more follicles can be treated in one
session.

Lasers and light based therapy
• US FDA approved.
• Principle - selective photothermolysis wherein the melanin
chromophere in the hair follicle absorbs the selected wavelength of
light and is destroyed
• 3 types of lasers
• Red light system (694nm ruby)
• IPL sources (590-1200nm)
• Infrared light system (1064 nm Nd-yag)
• Side effects - discomfort , PIH , reactivation of herpes ,
folliculitis ,paradoxical hypertrichosis and tattoo changes.

Other modalities
• Ovarian surgery - ovarian androgen secreting tumors - oopherectomy
• Vitamin D - IR and PCOS
• Topilutamide (fluridil) - new topical anti androgen acts by suppressing cutaneous
androgen receptors.
• 2% fluridil gel is safe and effective in IH
• Ketoconazole - reserved in therapy resistant hirsutism
• Plant anti-androgens - Reishi , licorice , white peony ,chaste tree , spearmint
inhibits 5α reductase increases aromatase activity , decreasing prolactin levels
and free testosterone levels.
• Only spearmint has undergone RCT trials.

• Alpha lipoic acid
• Powerful antioxidant and act as a Insulin sensitiser .
• Also helps in weight reduction
• Dose -300 to 1800mg/day
• Inositol
• Myo- inositol is the common isoform of inositol , converted to D-chiro-inositol
(DCI) by enzyme epimerase
• Improves insulin resistance and hyperandrogenism ,hirsutism and lipidprofile
• Combination with OCP shows good results
• Dose 2gm twice daily x 6months - decreased hirsutism score by 2.3

Monitoring and follow up
• Goal of the treatment should be correct the underlying condition , stop the
growth of new hairs and slow down the terminal hairs
• Therapeutic response should be assessed by the patient herself
• mFG score should be recorded at each visit
• If Hirsutism despite therapy , repeated biochemical estimation is needed.
• Effects of treatment is visible only after 6months
• If unsatisfactory consider changing the dose or drug or adding a second drug.
• If desirable of conception all treatment should be stop.

Current evidences support the following treatments
• Topical eflornithine can be used in mild hirsutism as monotherapy .
• Life style modification is must in PCOS with high BMI
• First line therapies include eflornithine, OCPs and physical modalities
• In moderate to severe hirsutism which fail to respond to OCPs or are
contraindicated , anti androgens to be used
• Spironolactone , CA and Finasteride are preferred
• Combination of spironlactone/Finasteride or anti-androgen/OCP enhances efficacy
• No evidence to support insulin sensitiser as monotherapy in absence of endocrine
or metabolic abnormalities
• Statins , vit D and ovarian surgeries lack evidence

Acne and hirsutism
• In many PCOS ,patients present with both acne and hirsutism.
• Lifestyle modification
• OCPs , antiandrogens and metformin can be given (insulin resistance)
• Hair removal should be advised - temporary/ permanent
• For Acne - topical agents ,hormonal therapy is acceptable first line therapy in
adolescents
• Spironolactone
• Oral antibiotics if moderate to severe
• Isoretinoin

Hirsutism and FPHL
• The FPHL is often seen in women with PCOS
• Hormonal changes secondary to reduction of estranged levels
• Triangle sign - alopecia pattern (midline frontal scalp towards vertex)
• Management -
• OCPs
• Cyproterone acetate with EE
• OCPs plus 5-α reductase inhibitors
• OCPs with glutamine
• Minoxidil
•

Thank you

HIRSUITISM 4.pdf for postgraduate students

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