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A 17-year-old woman was evaluated
at the endocrinologic clinic because of oligomenorrhea for one
year. She had been otherwise healthy and attained menarche at
the age of 12 years and had regular monthly periods for 4
years. However, the menstrual periods had gradually decreased
to four to five times a year and became irregular with
prolonged intervals progressively. Increased body hair and
facial acne developed since the same time. She gained weight
by 16 kg over the past three years before seeking medical
attention. She denied any headache, blurred vision or
galactorrhea, or taking medications or herb remedies.
On examination, her weight was 68
kg, with a body mass index (weight in kilograms divided by
square of body height in meters) of 28.4 kg/m2
. The body temperature was
36.8°C, pulse rate 72 beats per minute, respirations
18 breaths per minute, and the blood pressure was
126/80 mmHg. There was no yellowish or coarse
skin, non-pitting edema, moon face, buffalo
hump, supraclavicular fat pad, abdominal striae, galactorrhea while pinching,
or acanthosis nigricans. External genital organs were normal.
Endocrinologic studies showed
serum testosterone 190 ng/dl (normal, <80 ng/dl),
17-hydroxyprogesterone 42 ng/dl (normal, 30-200 ng/dl),
sulphated form of dehydroepiandrosterone (DHEAS) 48 μg/dl
(normal, <430μg/dl), follicular stimulating hormone (FSH)
6.8 mIU/ml (normal [follicular phase], 3.4-10.0 mIU/ml),
luteal hormone (LH) 17.4 mIU/ml (normal [follicular phase]
1.1-11.6 mIU/ml), estradiol (E2) 56 pg/ml ( normal [follicular
phase], 53-258 pg/ml), high sensitivity thyroid-stimulating
hormone (hs-TSH) 1.08 μIU/ml (normal, 0.4-4.0 μIU/ml), free
thyroxine (T4) 12.3 pg/ml (normal, 7-19 pg/ml), cortisol
(after 1 mg dexamethasone overnight test) <0.8 μg/dl, and
prolactin 14 ng/ml (normal <20 ng/ml).
Pelvic ultrasound
disclosed polycysts of the bilateral ovary. Polycystic ovary
syndrome was diagnosed based on the above symptoms,
including oligomenorrha, hirsutism, ovarial polycysts and exclusion
of congenital adrenal hyperplasia, Cushing syndrome and
androgen-secreting tumor by clinical and laboratory
investigations. There was no glucose intolerance by oral
glucose tolerance test. Life style change with diet adjustment
and exercise were encouraged. Glucophage, contraceptives and
spirolactone were prescribed. Menstrual cycle returned to
regularity 4 months after treatment. Her hair growth also
decreased at the same time.
<病例解析>
多囊性卵巢症候群(polycystic ovary syndrome ;
PCOS)的發生機率約佔生殖年齡婦女的6-10%。其症狀包括有：月經不規則、稀少甚至無月經及不孕；另外還有多毛、多青春痘等男性荷爾蒙太高的表現及肥胖等。而就字面上來看,
雖然是多囊性卵巢症候群，並不是每個患者都有卵巢的囊狀腫大變化；相對的，有些正常排卵的婦女也表現卵巢囊狀腫大，卻沒有此症候群的表現。診斷上，PCOS有三項基本條件：(1)、月經稀少(一年內的月經來潮小於8次)或無排卵(anovulation)；(2) 、雄性素過多(不論是臨床表現，如多毛、多青春痘或實驗數據顯示)；(3)、排除其它可能的內分泌疾患，包括：非典型的腎上腺增生(non-classical
congenital adrenal
hyperplasia,
CAH)、分泌雄性素的腫瘤、甲狀腺功能異常、庫欣氏症候群(
Cushging
syndrome)與泌乳素過高(hyperprolactinemia)等；排除這些疾病需靠臨床是否有此類疾病的表現及相關實驗數據。另外可以再輔以婦科超音波檢查看看是否有多囊性卵巢(polycystic ovary)。PCOS的實驗室檢查表現有：男性荷爾蒙(包括total testosterone、androstenedione 和
DHEAS)正常或較高；黃體刺激素(LH)可以高或正常；濾泡刺激素(FSH)可以正常或低；LH/FSH常大於2
(但未必)。綜合上面才可更為確立PCOS的診斷。我們的病人臨床上有月經稀少、多毛、多青春痘等雄性素過多的症狀；超音波檢查也有多囊性卵巢；再加上臨床表徵沒有甲狀腺低下、庫欣氏症候群的外觀；而病程演進上，雄性化性徵進展緩慢不似分泌雄性素的腫瘤快速。實驗數據上的total
testosterone、DHEAS及17-hydroxy-progesterone不似 non-classical
congenital
adrenal
hyperplasia (CAH)或分泌雄性素的腫瘤的表現。另外，經由甲狀腺功能和泌乳素濃度的檢測、低劑量類固醇壓抑(low
dose dexamethasone)suppression
test
測試下的皮質醇濃度，也排除掉甲狀腺功能低下、高泌乳素血及庫欣氏症候群的可能，故最後確認診斷為PCOS。
目前PCOS之致病機轉還不是很清楚，一般認為是下視丘的性促素脈衝產生器(
gonadotropin-releasing hormone [GnRH] pulse
generator)異常造成下游腦下垂體賀爾蒙LH分泌的異常，促使卵巢的thecal
cell增生、雄性素合成增多，而相對上FSH的作用便顯不夠，致使卵泡未能排卵而變成很多卵泡囊腫，且無法有月經週期的規則子宮內膜變化；另外，胰島素阻抗(insulin
resistance)而導致血中胰島素過高，也會加成上述的現象及造成其他血糖血脂血壓等異常。基於上述理由，PCOS的病人一旦診斷，就必須特別小心罹患心血管疾病、糖尿病、子宮內膜增厚及癌變的可能性。
針對PCOS的治療，約有一半的病人有肥胖的情況，此時治療首重在減重，不但可減少代謝方面的併發症，也有些可恢復排卵。而若減重無效或病患本身不胖不須減重時，便需以藥物治療。藥物治療主要針對三個方向：一、治療雄性化及少、無月經；二、治療不孕；三、治療胰島素阻抗現象。治療前要先與病人溝通是否有欲生育的意願，若想生育則著重在第二及第三點，可以施予排卵藥(clomiphene)及胰島素增敏劑(metformin或troglitazone)；若無效再考慮施打性腺刺激素(包括GnRHa及hMG等)；再者可進行婦科的手術或試管嬰兒。一旦受孕成功，慎重起見便需停用之前的胰島素增敏劑(雖目前屬於懷孕等級class
B，必要時懷孕中使用也可以)。至於對沒有懷孕打算的病人便主要針對在第一及第三點。一般而言可使用避孕藥(
progesterone +/-
Estrogen)來維持月經的規則性達成子宮內膜的更新，又可治療多毛症；也可使用spirolactone、finasteride等來治療雄性化的症狀。另外，胰島素增敏劑metformin也可改善雄性化的現象。我們的病人因目前尚未結婚，沒有懷孕的計畫，在減重後改善有限的情況下，合併藥物治療後疾病有改善的情況。不過對PCOS的病人得要針對其各階段的需求，如懷孕需求與否,
再作藥物的改變或調整。
<參考文獻>
- Khan KA, Stas S, Kurukulasuriya LR.
Polycystic ovarian syndrome. J Cardiometab Syndr
2006;1:125-30.
- Setji TL, Brown AJ. Polycystic ovary
syndrome: diagnosis and treatment. Am J Med 2007;120:128-32.
- Broekmans FJ, Fauser BC. Diagnostic
criteria for polycystic ovarian syndrome. Endocrine
2006;30:3-11.
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Case Discussion
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