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REGULASI
NEURO-ENDOKRIN
Hypothalamus
Hipofisis
Kelenjar Target
Hipothalamus-Hipofisis (Pituitary)-
Genitalia Interna
Regio Hipothalamus
Hipofisis
Tuba Fallopii
Hipofisis Anterior/
Adenohipofisis
Uterus
Ovarium
HIPOFISIS
POSTERIOR
ADH/Vasopresin
OXYTOCIN
Genitalia Interna
1. Tuba Fallopii
2. Ovarium
3. Uterus
4. Vagina
5. Rectum
6. Kandung Kencing
7. Formix Posterior
Ovarium dengan tahap perkembangan
pematangan folikel ovarium
Lapisan Fungsional
Endometrium
Regulasi Hipotalamus-Hipofisis
HIPOTALAMUS
Inhibiting Hormon Releasing Hormon
( GnIH) ( GnRH)
ADENO-HIPOFISIS
Inhibin
FSH
OVARIUM
Sekresi Hormon
HORMON ESTROGEN
Negative Feedback Lebih Kurang Positive Feedback
Siklus Menstruasi
Siklus Menstruasi
LH
FSH
Progesteron
Oestradiol
Folikel
Ovarium
Endometrium
Siklus Menstruasi
LH
FSH
Progesteron
Oestradiol
Folikel
Ovarium
Endometrium
Siklus Menstruasi
Siklus Menstruasi
Ovulasi
The steroidogenic pathways used in the biosynthesis of the corticosteroids are shown, along with the structures of the intermediates and products. The pathways
that are unique to the zona glomerulosa are shown in blue, whereas those that occur in the inner zona fasciculata and zona reticularis are shown in gray. The
zona reticularis does not express 3-HSD, and thus preferentially synthesizes DHEA. CYP11A1, cholesterol side-chain cleavage enzyme; 3-HSD, 3-
hydroxysteroid dehydrogenase; CYP17, steroid 17-hydroxylase; CYP21, steroid 21-hydroxylase; CYP11B2, aldosterone synthase; CYP11B1, steroid 11-
hydroxylase.
Polycystic Ovarial Syndrome
Patofisiologi
Beberapa teori patogenesis PCOS:
Gangguan unik dari sekresi dan aksi insulin yg
menyebabkan kondisi hiperinsulinemia dan
resistensi insulin.
Gangguan neuro-endokrin primer yg sebabkan
peningkatan denyutan LH baik frekuensi dan
amplitudo-nya.
Gangguan sintesis androgen yg mempengaruhi
produksi androgen ovarium.
Peningkatan metabolisme cortisol yang mempe-
ngaruhi produksi androgen di kortex adenal.
Hyperinsulinemia and Insulin Resistance
Insulin resistance, defined as reduced glucose response to a given
amount of insulin, is a characteristic metabolic disturbance associated
with PCOS. Both obese and nonobese women with PCOS have a higher
incidence of insulin resistance and hyperinsulinemia than age-matched
controls; however, obese women with PCOS have significantly
decreased insulin sensitivity compared with nonobese women who have
PCOS.
Insulin resistance is known to precede the development of type 2
diabetes mellitus. Studies have shown that 30% to 40% of women with
PCOS have impaired glucose tolerance, and as many as 10% develop
type 2 diabetes mellitus by the age of 40.[3,8]
Several studies have also shown a strong correlation between insulin
resistance and hyperandrogenism. This association dates back to 1921,
when Achard and Thiers reported on a bearded woman who was also a
diabetic.[5] Insulin acts synergistically with LH to enhance androgen
production in the ovarian theca cells. Insulin also decreases hepatic
synthesis and secretion of sex hormone-binding globulin, the hormone
that binds testosterone in the circulation, thus increasing the amount of
free testosterone that is biologically available.[8,9] Women with PCOS
and hyperinsulinemia typically have elevated free testosterone, but the
total testosterone concentration may be at the upper range of normal or
only modestly elevated.[8]
LH Secretion
LH hypersecretion is a characteristic hallmark of
PCOS. LH is secreted in a pulsatile manner.
Women with PCOS have an increase in both the
LH pulse frequency and amplitude, resulting in
increased 24-hour secretion. This increase in LH
secretion is thought to occur as a result of
increased frequency of hypothalamic
gonadotropin-releasing hormone (GnRH)
pulses. Increased LH, in turn, leads to an
increase in androgen production by the theca
cells within the ovary.[3,8]
Androgen Excess
The increase in LH, together with
hyperinsulinemia, leads to an increase in
androgen production by ovarian theca
cells.[8] The most likely primary factor
driving the increase in testosterone
secretion in PCOS is an increase in
ovarian enzymatic activity involved in the
synthesis of testosterone precursors.[10]
Manifestasi Klinis
Hirsutisme: manifestasi yg paling sering
muncul krn ekses androgen pada PCOS.
Hirsutism dialami oleh 10% wanita usia
reproduksi tanpa PCOS dan 70% wanita
dengan PCOS.
Hirsutism: tumbuhnya rambut yg berlebihan
pd wanita dg pola tumbuh spt pria.
Peningkatan kadar androgen disertai dg
peningkatan produksi sebum & jerawat
(sering muncul pada wanita dg PCOS
Peradangan
Aktivitas
bakteri
Produksi minyak
Sumber
masalah
Alopesia androgenika klinis
Ludwig 1 Ludwig II
Ludwig III
Manifestasi Klinis
Acanthosis nigricans: kondisi penebalan kulit
abnormal, tampak seperti lapisan bludru dan
hiper pigmentasi
Sering muncul pada orang yg mengalami
resistensi insulin, sering muncul di daerah
the nape of the neck, the axilla, and the area
beneath the breasts.
Tidak disertai dg peningkatan melanin &
melanosit
Acanthosis Nigrican
It typically occurs in individuals younger
than age 40, may be genetically inherited,
and is associated with obesity or
endocrinopathies, such as hypothyroidism
or hyperthyroidism, acromegaly, polycystic
ovary disease, insulin-resistant diabetes,
or Cushing's disease
Acanthosis Nigrican
Acanthosis Nigrican
Tingkat Keparahan AN
Acanthosis Nigrican Grade 1
Acanthosis Nigrican Grade 2
Acanthosis Nigrican Grade 3
Acanthosis Nigrican Grade 4
Manifestasi Klinis
Obesitas terjadi pd 30-75% wanita dengan PCOS.
Obesitas pd PCOS ditandai dg waist circumference
(> 80 cm) bukan truncal/overall obesity.
Tipe obesitas tsb biasanya disertai dg insulin
resistance, glucose intolerance, dan dyslipidemia.
Obesitas brhubungan dg penurunan sex hormone-
binding globulin (SHBG) kadar testosteron bebas
meningkat gejala hiperandrogen
Penurunan BB dpt perbaiki sensitivitas insulin dan
perbaiki sindrome metabolik lainya (sindrome X)
Manifestasi Klinis
Di masa lalu, para klinisi mendefinisikan
PCOS berdasarkan gambaran USG ovarium
Bila pada gambaran USG trans-vaginal
tampak multiple subcapsular cysts bentuk
kalung mutiara hitam, maka pasien
didiagnosis PCOS
Meskipun demikian, polycystic ovaries
(banyaknya kista di ovarium) dapat ato tidak
dapat timbul manifestasi PCOS.
Polycystic Ovarian Syndrome
(Stein-Leventhal Ovaries). Both
the right and left ovaries show
numerous
cysts arranged around the
periphery of the ovaries producing
the "string-of-pearls" sign..
Management
Turunkan kadar androgen untuk perbaiki
hirsutisme,
Melindungi endometrium,
Optimalisasi fungsi organ reroduksi sehingga
meningkatkan fertilias, dan
Mengurangi long-term sequelae akibat
resistensi insulin.