1.
PCOS
Def: polycystic ovary syndrome is a hormonal condition
yang dapat mempengaruhi kemampuan perempuan
hamil, bikin irregular menstruasi, acne and unwanted
hair, meningkatkan risk DM n hipertensi
 nama polycyst ga berarti pasti pny cyst, bisa ga bisa
iya
cause: unknown, tapi genetic katanya berpengaruh
terutama ibu, sistes, or twins. Trs ada bbrp penelitian yg
blg autosomal dominant inheritence with expression.
pathophysiology: terjadi gangguan hormone:
 Gonadotropins: GnRH yang disekresi secara
pulsatile -> produksi LH increase dibandingkan dg
FSH.
 Insulin resistance: tubuh ga bisa manage blood
sugar yg ada. Dikarenakan tjd abnormality di
insulin receptor-mediated signal transduction.
insulin juga berperan thd irregular mens and
hirsutism. Selain itu, Insulin resistence jg bikin
high risk in DM2, hypertension, dyslipidemia, and
cardiovascular dz.
 Androgen: insulin dan LH yg tinggi simulate
production Androgen (by theca cell) -> ovary
secrete testosterone n androstenedione.
Tingginya androstenedione -> aromatase -> tinggi
estrogen
Tinginya free testosterone ->
dehydroepiandrosterone sulfate (DHEAS – male
sex hormone yg play role in secondary sexual at
puberty)
Symptoms: hair loss, unwanted hair, susah hamil
 Sex hormone-binding Globulin: di perempuan
PCOS, SHBG rendah. Karena sintesis SHBG
disuppressed sama insulin, androgen, corticoid,
progestins, and growth hormone. SHBG ini
gunanya buat bind sex steroid.
SHBG rendah -> androgen n testosterone gak bisa
bind sm receptor endorgan
Makanya walaupun total testosterone masih
normal, tp secara klinis udh hyperandrogenic krn
free testosterone yg tinggi.
Low SHBG jg linked to risk of DM2
 Progesterone: hormone progesterone terganggu yg
bikin irregular mens
 Anovulation: krn produksi GnRH secara pulsatility
and impaired gonadotropin secretion berpengaruh
thd irregular mens. Anovulation jg mempengaruhi
thd insulin resistence
Sign n symp:
Short term: obese, infertility, depression, sleep apnea,
irregular menses, abnormal lipid level, hirsutism, acne,
alopecia, insulin resistence
Long term: DM, endometrial ca, cardiovascular dz
 Menstrual dysfunction:
o Every woman beda2 bisa amenorrhea (absence 3
month) to oligomenorrhea (fever than 8 mens in 1
month).
o Without ovulation and progesterone prod from
corpus luteum -> menstrual period is not
triggered.
o Amenorrhea can be caused by increased androgen
level (androgen can counteract estrogen to
produce an atrophic endometrium -> thin
endometrial stripe -> amenorrhea)
o biasa yg ada PCOS dari masa menarche (baru
mulai mens) juga sudah experience irregular
menstruation
o BUT 50% postmenarchal girls normally have
irregular periods 2-4 years due to HPA axis
immaturity —> makanya some diagnosis bilang
to confirm PCOS harus >18 y.o
 Hyperandrogenism
symptoms: hirsutism, acne, androgenic alopecia
a. Hirsutism
 coarse, dark, terminal hairs like those in males
 within a hair follicle, testosterone is converted by
the enzyme 5alpha-reductase to DHT
(dihydrotestosterone)
 testosterone and DHT convert short, solf vellus hair
to coarse terminal hair (DHT lebih effective than
testosterone) conversion is IRREVERSIBLE
 most affected area: upper lip, chin, sideburn, chest,
linea alba of lower abd. (escutcheon)
Ferriman-Gallwey Scoring system - degree of
hirsutismg - hirsutism if score >8
b. Acne
o blockage of follicular opening by hyperkaratosis
o sebum production
o proliferation of commensal propionibacterium
acnes
o inflammation
 in hair follicle, testosterone is converted within
sebaceous gland to DHT by 5-alpha reductase
 androgen excess —> overstimulation of androgen
receptor in pilosebaceous unit —> increased sebum
production —> inflammation and comedone
formation
 inflammation —> long term side effect e.g.
scarring
c. Alopecia
 hari loss progress slowly
 caused by: excess 5alpha reductase activity in hair
follicle lead to increase in DHT and increased
androgen receptor
 Insulin Resistance
a. Acanthosis Nigricans
- thickened, gray brown plaques seen on back of
nexk, axilla, waist, groin
- insulin resistance —> hyperinsulinemia —>
stimulate keratinocyte and dermal fibroblast
growth —> produce skin changes
 b. increased risk of impaired glucose tolerance
(IMG) and DM Type 2
 Endometrial neoplasia
- PCOS —> increase risk endometrial cancer
(3x)
 Infertility
- due to anovulatory cycle
 Pregnancy loss
- PCOS —> increase rate early miscarriage (30-
50%)
- can be due to LH hypersecretion, women with
PCOS taking metformin (lower insulin level)
DIAGNOSIS
1. Thyroid-stimulating Hormone and Prolactin
-thyroid disease can lead to menstrual dysfunction
-hyperprolactinemia —> inhibit GnRH secretion —>
irregular menstruation, amenorrhea, galactorrhea
2.Testosterone
-ovary or adrenal tumor —> produce testosterone —>
virilization
-sx: clitoromegaly — clitoral index (>35mm2 abnormal)
-total testosterone more sensitive than free testosterone level
-total testosterone >200 ng/dL —> ovarian lesion
3. Dehydroepiandrosterone Sulfate (DHEAS)
-hormone produced by the adrenal gland
-DHEAS >700 μg/dL —> adrenal neoplasm
4. Gonadotropins
-measure FSH, LH and estradiol level —> to exclude
premature ovarian failure and hypogonadotropic
hypogonadism
-LH to FSH ratio >2:1
5. 17-alpha Hydroxyprogesterone
-congenital adrenal hyperplasia (CAH) —> autosomal
recessive disorder —> result from complete/partial def.
of enzyme 21-hydroxylase or 11-hydroxylase —>
androgen production
-sx: ambiguous genitalia, life-threatening hypotension
 late onset CAH: enzyme def. leads to cortisol def. —> in
response ACTH level is increased to normalize cortisol
production (can cause adrenal gland hyperplasia)
 normally affect 21-hydroxylase, kalo def. —>
accumulation of 17-hydroxyprogesterone
 17-hydroxyprogesterone >200 ng/dL —> ACTH
stimulation test
ACTH Stimulation test
-synthetic ACTH 250 μg injected —> 1 hour later —> level
17-hydroxyprogesterone is measured
-ACTH given stimulate uptake of cholesterol and synthesis
of pregnenolon
-kalo 21-hydroxylase rusak —> progesterone, 17-
hydroxyprogesterone, 17-hydroxypregneolone
accumulate in the adrenal cortex and circulate in blood
6. Cortisol
-Cushing syndrome: exposure to endo/ exogenous
glucocorticoid
-Cushing disease: increase ACTH secretion by pituitary
tumor
-Sx: menstrual dysfunction, androgen excess, truncal obesity,
dyslipidemia, glucose intolerance
8. Sonography
-histology: PCOS —> increase no. of ripening and atretic
follicle, cortical stromal thickness, no. of hilar cell nests
-PCOS: >12 small cysts (2-9mm in diameter) or
-increase in volume (>10 mL) or both
TREATMENT
1. Oligo/Anovulation (<8 menses per year)
o Hormonal agent- oral contraceptive pills (COCs)
which induces:
 regular mesntrual cycle
 lower androgen level
 thin the endometrium
 suppress gonadotropin release —> decrease
ovarian androgen production
 estrogen level in COCs increase SHBG —> bind to
free androgen
o Insulin sensitizing agent- Metformin —> decrease
androgen level —>
 increase rate of ovulation
2. Hirsutism
a. Lowered effective androgen level
- COCs
- GnRH agonist
- 5alpha-reductase inhibitor —> block conversion of
testosterone to DHT
b. Androgen-receptor antagonist — competitive inhibitor of
androgen binding to the androgen receptor; side effect:
metrorrhagia (bleeding from uterus)
3. Surgical therapy
 Laparoscopic ovarian drilling — restore ovulation in
women thats resistant to Clomiphene citrate
 Oophorectomy — for women not seeking fertility