Hyperandrogenism

DR. SHASHWATI SEN
MBBS (LHMC, New Delhi)
DGO (MAMC, New Delhi)
DNB (NBE, New Delhi)
Jr. Consultant, Kamala Nehru Memorial Hospital
Consultant, Mohak Hospital
Dr. Shashwati Sen, KNMH, Allahabad.

HYPERANDROGENISM
 A common endocrine disorder of women.
 Prevalence of 5-10%.
 Androgens stimulate growth and increase the diameter
and pigmentation of hair.

PUBERTY

ANDROGENS IN WOMEN
 Sources of androgens
- Ovaries – Testosterone
Androstenedione
Dehydroepiandrosterone (DHEA)
- Adrenal gland – also DHEAS
 Testosterone is the major circulating androgen.
 Approx. 1% is free testosterone.

NORMAL VALUES
 Testosterone 20-80 ng/dl
(Equilibrium Dialysis is a laborious, time
consuming and costly method)
 Androstenedione 20-250 ng/dl
 DHEA 130-980 ng/ml
 DHEAS < 350 mcg/dl

CLINICAL MANIFESTATIONS
 Hirsutism
 Acne
 Androgenic alopecia
 Virilization

HIRSUTISM
 Excessive growth of terminal hair in women in a male-
like pattern.
 Sensitive marker for increased androgen production.
 Assessed using a standardized system eg. The
modified Ferriman Gallwey System.

CAUSES OF HIRSUTISM
 PCOS
 Androgen producing ovarian and adrenal tumor
 CAH
 Cushing’s Syndrome
 Drugs
 Obesity
 Idiopathic

POLYCYSTIC OVARIAN SYNDROME
 The average daily production of androgens is increased in
women with PCOS.
 Chronic anovulation
 Menstrual disturbances
 Hirsutism (but virilization does not occur)
 Infertility
 Acanthosis nigricans
 Mechanism – Increased LH stimulation
Insulin resistance
 TVS – Increased ovarian volume >10ml
Presence of 12+ follicles/ovary, 2-9mm diam.

POLYCYSTIC OVARY

PUBERTY AND PCOS
HYPOTHALAMUS
GnRH
PITUITARY
LH FSH
OVARY
THECA GRANULOSA
aromatase
Androgen Estrogen

PCOS DEFINITION
CRITERIA CLINICAL OR
BIOCHEMICAL
HYPER
ANDROGENISM
OLIGO
MENORRHOEA
OR OLIGO
OVULATION
POLYCYSTIC
OVARIES ON
USG
NICHD (1990) Yes Yes No
ROTTERDAM
(2003)
Yes Yes
2 of 3 criteria
Yes
AE-PCOS (2009) Yes Yes
1 of 2 criteria
Yes

BIOCHEMICAL CHANGES IN PCOS
 Testosterone 80-150 ng/dl (never >200 ng/dl)
 Androstenedione 20-500 ng/dl
 DHEAS <500 mcg/dl (never >700 mcg/dl)
 17-OH Progesterone <300ng/dl
 SHBG decreased
 Fasting glucose : fasting insulin <4.5
 LH:FSH increased
 Prolactin normal
 TSH normal

ANDROGEN PRODUCING TUMOR
 Ovary - Sertoli-Leydig tumors
Lipid cell tumors
Hilar cell tumors
Theca cell tumors
Brenner tumors
 Adrenal - Adenomas
Carcinomas
 Investigation – S. Testosterone
Pelvic USG, CT, MRI

CUSHING’S SYNDROME
 Causes: Medication
Cushing’s Disease
Adrenal tumors
Bronchial carcinoids
 Excess cortisol
 Classical features – Central obesity, striae, atrophy of skin, easy
bruisability, hyperpigmentation, hypertension, hyperglycemia,
menstrual disturbances.
 Laboratory diagnosis
1) 24-hour urinary free cortisol excretion >110mcg.
2) Overnight Dexamethasone suppression test.
1mg dexamethasone given at 11pm. Serum cortisol
measured at 8am next morning. Values >5 mcg/dl is diagnostic.

NONCLASSICAL CAH
 Females are normal at birth
 Present as young adult with signs of
hyperandrogenism
 Autosomal recessive
 Most common defect is 21-OHlase deficiency.
 Serum 17 OH Progesterone level above 800 ng/dl is
diagnostic.
 Levels between 200 – 800 ng/dl require ACTH
stimulation test.

LUTEOMA OF PREGNANCY
 Hirsutism/Virilization during pregnancy.
 Hyperplastic mass of luteinized ovarian cells.
 Regress after delivery.

LABORATORY EVALUATION OF
HIRSUTISM
TESTOSTERONE <200 ng/dl
>200 ng/dl
Postmenopausal
Term pregnancy
PCOS
Adult onset CAH
Idiopathic
Adrenal neoplasm
Ovarian neoplasm
Hyperthecosis ovary
DHEAS <700 mcg/dl
>700 mcg/dl
PCOS
Adult onset CAH
Idiopathic
Adrenal tumors
17-OH Progesterone >800 ng/ml
200-800 ng/dl
Adult onset CAH
ACTH stimulation test

TREATMENT- of hirsutism
General Measures
 Treatment of the cause:
- Stop the offending drugs
- Treat tumors by surgical removal
- Treat medical disorders
 Cosmetic measures
- Removal of hair by shaving, waxing, epilation,
electrolysis, laser.
 Weight reduction
- First line treatment of PCOS in overweight
women.

PHARMACOLOGICAL TREATMENT
 Monotherapy
1) Oral contraceptives (OCP) are the first line
drug to be used in hirsutism.
2) Contain EE (30 or 35 mcg) in combination with
-Progestin
-Cyproterone acetate
- Drospirenone
3) Added benefit of cycle regularity and
contraception.

COMBINED ORAL
CONTRACEPTIVES
 Estrogen component
- stimulate SHBG synthesis.
- suppress Gn production.
 Progestogen component
- inhibits 5 alpha reductase activity.
 The Progestogen component should have NO
androgenic properties.

ANTIANDROGENS
 Have teratogenic potential.
 Do not use antiandrogens as first line monotherapy.
 Adequate contraception required in sexually active
women.
 Examples of antiandrogens:
Cyproterone acetate
Drospirenone
Spironolactone
Flutamide
Finasteride

ANTIANDROGENS
CYPROTERONE ACETATE
 Progestational agent
 Action – Inhibits Gn
Blocks androgen receptor
 Stops further progression of hirsutism.
 Improvement in acne and seborrhea.
 Monitor Liver function if taking long term.
 Used in combination – EE 35mcg + CA 2mg

ANTIANDROGENS
DROSPIRENONE
 Progestin with weak anti androgenic effects.
 A 12 month trial comparing 3 mg Drospirenone with 2
mg Cyproterone showed similar reduction in hirsutism
scores.
 Beneficial against acne.

ANTIANDROGENS
SPIRONOLACTONE
 Aldosterone antagonist
 Action – competes with dihydrotestosterone for
binding to the androgen receptor.
- inhibits ovarian and adrenal steroidogenesis.
 Dose – 200mg daily for 2 weeks f/b maintenance dose
of 25-50mg daily for 6 months.
 Risk of feminization of male fetus.
 A/E – Rarely hyperkalemia, increased diuresis,
postural hypotension.

METFORMIN
 An insulin sensitizing agent.
 Lowers insulin levels, decreases androgen levels and
improves ovulation.
 Dose related GIT side effects.
 Start with a low dose and gradually increase over 3 – 4
weeks.

GLUCOCORTICOIDS
 Suppress adrenal androgen levels in non-classical
CAH.
 Less effective than OCP and Antiandrogens for the
treatment of hirsutism.
 Not much effect in hirsutism of other causes.

GnRH AGONISTS
 Suppression of LH dependent ovarian androgen
production.
 Effective in ovarian hyperthecosis.
 A/E – Severe hypoestrogenism
 Used with E or E+P add-back therapy.
 Add-back therapy does not diminish the efficacy.
 Also, E induces SHBG production.

EFLORNITHINE
 Irreversible inhibitor of Ornithine decarboxylase,
needed to catalyze the rate limiting step for follicular
polyamine synthesis, which is necessary for hair
growth.
 An antiprotozoal drug
 Reduces growth of facial hair.
 Used topically.

THANK YOU

Hyperandrogenism

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Hyperandrogenism