Management of Hirsutism

1. Hirsutism
Tevfik Yoldemir MD, BSc, MA, PhD
tevfikyoldemir
profdrdrtevfikyoldemir

2. Definition
Hirsutism;
Excessive growth of androjen
dependent sexual hair.
(face, arms, legs, or chest)
Virilism;
Severe state ( clitoromegaly,
deepening of the voice,
temporal alopesi, changes in body habitus)

3. Physiology of Hair growth
• Lanugo (IU ; 8-22 GW)
• Vellus
• Terminal hair
(androjen effect)
* genetic factors
* ethnic groups

4. Physiology of Hair growth
Hair growth is cyclic;
1. Anagen ( growth)
2. Catagen (rapid involution)
3. Telogen (inactivity)
“ each hair follicle has it
own growth cycle”

5. Hair growth factors
Dermal papilla is the director.
A) Local skin temperature, blood flow, edema
“summer>winter”
B) Drugs: phenitoin, diazoksid, minoksidil,
danazol
C) Hormons : - testosteron
- estrogens
- progestins
- thyroid hormone
- IGF-I (HAIR-AN)

6. Physiology of Androgens
-Limiting step p450c17 gene expression
-depending on LH / ACTH
Production: ovary / adrenal / peripheral
* Ovary: LH theca cell androstenedion
DHEA
testosterone
FSH granulosa cell aromatize
estogens

7. Physiology of Androgens
* Adrenal production:
stimulation with ACTH
main androgen: DHEAS
Sources of circulating androgen in normal women

8. Physiology of Androgens
Circulation:
Testosterone 20-80 ng/dl
%50 peripheral
%25 ovary
%25 adrenals
%80 SHBG. %19 Albumin %1 free ACTİVE
Dihydrotestosterone 2-8ng/dl
most potent
5a reductase peripheral

9. Physiology of Androgens
Circulation
Androstenedione (17 ketosteroid)
not potent
bind mainly to albumin
%10 peripheral
DHEA, DHEA-S (17 ketosteroid)
weak androgens
DHEA %70, DHEA-S % 100 adrenals

10. Etiology
A- OVARIAN DISORDERS
• Nonneoplastic
- PCO syndrome
- Stromal hyperplasia
- Stromal hyperthecosis
- HAIR-AN

11. Etiology
A- OVARIAN DISORDERS
• Neoplastic
- Sertoli Leydig cell tm
- Germ cell tm
- Gynandroblastoma
- Gonadoblastom
( ovarian tumors with functional stroma)

12. Etiology
A- OVARIAN DISORDERS
• Pregnancy related
- Theca lutein cysts
- Luteoma of pregnancy

13. Etiology
B- ADRENAL DİSORDERS
• Enzyme deficiencies
- Congenital adrenal hyperplasia
- Neoplastic
- Cushing syndrome: * adrenal tm
* nonpituitar ACTH
* pituitar ACTH
- Hyperprolactinemia: PRL binds to its
receptors on adrenal gland
result with adrenal stimulation

14. Etiology
C- IATROGENIC MECHANISM
exogenous sources
D- IDIOPATHIC HIRSUTISM
without ovarian or adrenal dysfunction
normal menstrual cycles
! İncrease 5a reductase activity
T 5a reductase DHT
3aandrostanediol glucuronide

15. Diagnosis
Questioning:
Examination: * Ferriman-Gallway system

17. The assessment of hirsutism is notoriously
subjective. One common method of assessing
hirsutism, the modified Ferriman-Gallway score,
also considers nonmidline, nonandrogen-
dependent body hair in the diagnosis

18. Laboratory findings
Screening tests
Testosterone: < 200 ng/dl rule out neoplasms.
DHEA-S: > 700 -800 mg/dl (tm)
17a hydroxyprogesterone: CAH
should measured mornings
>400 ng/dl 21 hydroxylase defic.

19. Laboratory findings
Directed tests:
FSH LH : LH/FSH> 3 PCO (glucose/insulin, SHBG)
Prolactin: mildly elecvated in PCO
TSH:
ACTH stim.test: after 30 minutes IV 250mg ACTH
17aOHP > 400ng/dl = CAH

20. Laboratory findings
Cushing syndrome
1. Overnight dexamethasone suppression test:
baseline morning cortisol level
11.00 PM 1mg dexamethasone tb
08.00 AM cortisol level next morning
2. 24 hour urinary free cortisol
3. Low dose dexamethasone suppression test
0.5mg dexam. Every 6 hours for 2 days
<25mg/24 h cortisol or <3mg/24 h17OHP
rules out cushing syndrome

21. Laboratory findings
Androstanediol glucuronide levels:
marker of peripheral production
eleveted in idiopatic hirsutism
BUT high cost
IMAGING STUDIES
USG: ovarian mass, PCO
CT
MR

23. Treatment
• OC: LH suppression
ovarian T production decreased
increasing SHBG
Desogestrel, gestodene, norgestimate, drospirenone
• GnRH agonists: decrease ovarian steroidogenesis.
! Osteoporosis
• Androgen receptor antagonists:
not approved by FDA
• Dexamethasone 0,5 – 1 mg po (adrenal etiology)

24. Androgen receptor antagonists
• Cyproteone acetate: (not use in the USA)
competitivation with DHT
reduction with 5a reductase activity
50 – 100mg on days CD 1 -10 + OC
effective %50-%75
Side effects: decreased libido, mental depression
hepatotoxicity
Androcur/Diane 35

25. Androgen receptor antagonists
• Spironolactone:
aldosterone antagonist
competing for androgen receptors
inhibiting cytochrome P450
50 – 200mg/d
clinical response in 2 -5 months
side effects: short terms (diuresis, polydipsia)
Aldactone

26. Androgen receptor antagonists
• Flutamide:
potent nonsteroidal antiandrogen
250 mg 1-3 times daily
side effect: amenorrhea, decreased libido,
dry skin, hepatotoxicity, teratogenic
• Finasteride:
selective 5areductase inhibitor
5 mg po 3 months – 1 year