813 553
( polycystic ovary syndrome ) ( hirsutism )
( anovulation ) ( amenorrhea )
( androgens ) ( luteining hormone ) 2
( hyper-
insulinemia ) ( hyperandrogenemia )
( hyper- prolactinemia ) ( nonclassic congenital adrenal hyperplasia )
( acromegaly )
( insulin sensitizer )
( Polycystic ovary syndrome ) ( Hirsutism )
( Hyperinsulinemia ) ( Hyperandrogenemia )
1935 Stein
Leventhal
Stein-Leventhal
12
79
2,3
5 ~ 1 0 %
4
2~8
1 0
( theca cells )
23%
5
( hy- perandrogenemia ) ( anovulation )
6
( ) ( tran-
scription )
( impaired glucose toler- ance ) 2
hyperinsulinemic-euglycemic clamp technique
H O M A
QUICKI ( I
0)
( G/I ratio ) I
0G/I
ratio
74.5
( sex hormone-binding globulin, SHBG )
8
-1 ( insulin-like growth factor-bind- ing protein-1, IGFBP-1 )
-1 ( insulin-like growth factor-1, IGF-1 ) IGF-1
IGF-1
androstene-
dione
3,8,910
3 , 11
12
( transmembrane ) ( tyrosine kinase ) ( extracellular domain )
( phosphorylation )
( insulin receptor substrate, IRS )
IRS ( serine phosphorylation )
14
P450c17 ( cytochrome P450c17 )
15
6,9
30~75%
9
( gonadotropin releasing hor- mone, GnRH )
( pituitary )
( follicle stimulating hormone, FSH )
16,17
( granulosa cell )
( aromatase )
( )
9
DHEAS: dehydroepiandrosterone sulfate, IGFBP-1: insulin-like growth
factor-binding protein-1, IGF-1: insulin-like growth factor-1, LH: luteining hormone, SHBG: sex hormone-bind-
ing globulin
81
18
1 9 , 2 0
6,9
P450c17
17-hydroxylation 17,20- lyase
17 -hydroxysteroid dehydrogenase ( 17 HSD ) androstenedione
P450c17 3 -hydroxysteroid de- hydrogenase ( 3 HSD )
5 ~ 1 0
20
( cortisol ) 5 - ( 5 -reductase ) 5 - 5 -dihydro- cortisol
11 hydroxysteroid dehydrogenase type 2 ( 11
HSD2 ) ( cor-
tisone ) ( ) 5 -
11 HSD1
P450scc: mitochondrial cholesterol side-chain cleavage enzyme;
3 HSD: 3 -hydroxysteroid dehydrogenase; 11 HSD1: 11 hydroxysteroid dehydrogenase type 1
17 HSD: 17 -hydroxysteroid dehydrogenase; DHEA: dehydroepiandrosterone
5 -
5 -
5 - d i h y - d r o t e s t o s t e r o n e
Rodin
2211 HSD1
( )
ACTH
5 - 11 HSD1
23
2003
24(1) (
) (2) (3)
9
83
( 1 )
5 -
25
6~8
( norgestimate, desogestrel, gestodene )
( norgestrel, levonorgestrel )
( vascular reactivity )
9
( 2 ) cyproterone acetate
5 -dihydrotestosterone
25
Spironolac-
tone 100~200
mg
9flutamide
26
( 3 )
13
( 4 ) ( long-acting GnRH
agonists ) Lupron Depot 3.75 mg
- -
2~3
25
( 1 ) clomiphene citrate
/ 1.
2.
1.
2.
3. SHBG
4.
1. clomiphene citrate
2. rFSH
3. metformin
1. metformin
2. thiazolidinediones
3~7 5 clomiphene citrate 50mg
100~200 mg
( 2 ) clomiphene citrate ( recombinant
FSH, rFSH ) 3
150 IU rFSH 75 IU rFSH
3~7 ( estradiol )
human chorionic gonadotrophin 10,000 IU 3
27
28
25
medroxy-progesterone
2004
2006 1 5
3 3 ( 1 )
9 0 8 0
( 2 ) 130 mmHg
85 mmHg ( 3 )
100 mg/dL ( 4 ) TG
150 mg/dL ( 5 )
HDL 40 mg/dL 50 mg/dL
29
( 1 )
( 2 )
-1 ( plasminogen activator inhibitor-1, PAI-1 ) ( fibronogen )
( fibrinolysis ) ( 3 )
( 4 ) C- ( C-reactive protein, CRP ) ( resistin ) - ( tumor necro-
sis factor- , TNF- ) -6 ( inter-
leukin-6, IL-6 ) ( angiotensinogen ) ( leptin )
2
( o b s t r u c t i v e sleep apnea )
30,31,32
Metformin biguanide Metformin
( he- patic gluconeogenesis )
( hepatic glucose production )
metformin
3 0
m e t -
85
f o r m i n 21%
50%
metformin clomiphene clomiphene Thiazolidinediones ( TZD )
rosiglitazone ( avandia ) pioglitazone ( actos )
- ( peroxisome proliferator-activated receptor, PPAR- )
TZD
PAI-1
31,32
metformin TZD
( somatostatin analogs )
14
3 2
Octreotide
80-110 3
337 octreotide
IGF-1
Octreotide-LAR
32
octreotide-LAR IGFBP-1
IGF-1
2
3 4
20~30 2
2
5 ~ 1 0 %
32
( wedge resection )
( laparoscopic ovar- ian diathermy )
35
35
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87
New Conception of Polycystic Ovary Syndrome
Chien-Liang Chen
1,2, Chih-Tsueng He
2, Guang-Chueng Chin
2, and Tai-sheng Kuo
1The clinical features of polycystic ovary syndrome (PCOS) include hirsutism, acne, amenorrhea, anovula- tory infertility and recurrent miscarriages. The endocrine features include elevated androgens and luteinizing hor- mone levels. The metabolic aspects of this syndrome include hyperinsulinemia, obesity, lipid abnormalities and an increased risk for type 2 diabetes mellitus. In PCOS, hyperinsulinemic insulin resistance plays a pathogenic role, that augments androgen production. Diagnostic criteria for PCOS are hyperandrogenism and ovulatory dys- function with the exclusion of specific disorders, such as hyperprolactinemia, nonclassic congenital adrenal hy- perplasia, Cushing's syndrome, androgen-secreting neoplasm and acromegaly. Therapeutic considerations fo- cus on the management of menstrual irregularities and hyperandrogenemia. Insulin sensitizer treatment has been associated with a reduction in serum androgen and insulin concentration, and with an improvement of ovulation and fertility. Lifestyle modification with weight reduction has proven beneficial and pharmacological therapy with insulin-sensitizing agents has potential benefit in the treatment of the comorbidities in women with PCOS. ( J Intern Med Taiwan 2007; 18: 78-87 )
1
Department of Internal Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan
2
