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2013+内分泌学会临床指南：多囊卵巢综合征的诊断和治疗

Objective:The aim was to formulate practice guidelines for the diagnosis and treatment of poly-cystic ovary syndrome (PCOS).

Participants:An Endocrine Society-appointed Task Force of experts,a methodologist,and a med-ical writer developed the guideline.

Evidence:This evidence-based guideline was developed using the Grading of Recommendations,Assessment,Development,and Evaluation (GRADE)system to describe both the strength of rec-ommendations and the quality of evidence.

Consensus Process:One group meeting,several conference calls,and e-mail communications enabled https://www.doczj.com/doc/8112014258.html,mittees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines.Two sys-tematic reviews were conducted to summarize supporting evidence.

Conclusions:We suggest using the Rotterdam criteria for diagnosing PCOS (presence of two of the following criteria:androgen excess,ovulatory dysfunction,or polycystic ovaries).Establishing a diagnosis of PCOS is problematic in adolescents and menopausal women.Hyperandrogenism is central to the presentation in adolescents,whereas there is no consistent phenotype in postmeno-pausal women.Evaluation of women with PCOS should exclude alternate androgen-excess disor-ders and risk factors for endometrial cancer,mood disorders,obstructive sleep apnea,diabetes,and cardiovascular disease.Hormonal contraceptives are the first-line management for menstrual ab-normalities and hirsutism/acne in PCOS.Clomiphene is currently the first-line therapy for infertility;metformin is beneficial for metabolic/glycemic abnormalities and for improving menstrual irreg-ularities,but it has limited or no benefit in treating hirsutism,acne,or infertility.Hormonal con-traceptives and metformin are the treatment options in adolescents with PCOS.The role of weight loss in improving PCOS status per se is uncertain,but lifestyle intervention is beneficial in over-weight/obese patients for other health benefits.Thiazolidinediones have an unfavorable risk-benefit ratio overall,and statins require further study.

ISSN Print 0021-972X ISSN Online 1945-7197Printed in U.S.A.

Received May 24,2013.Accepted September 26,2013.

Abbreviations:BMI,body mass index;CI,confidence interval;DM,diabetes mellitus;HC,hormonal contraceptive;HDL,high-density lipoprotein;HgbA1c,hemoglobin A1c;IGT,impaired glucose tolerance;IR,insulin resistance;IVF,in vitro fertilization;LDL,low-density lipoprotein;NAFLD,nonalcoholic fatty liver disease;NASH,nonalcoholic steatohepatitis;OGTT,oral glucose tolerance test;17-OHP,17-hydroxyprogesterone;OHSS,ovarian hy-perstimulation syndrome;OR,odds ratio;OSA,obstructive sleep apnea;PCO,polycystic ovary (or ovaries);PCOS,PCO syndrome;RR,relative risk;T2DM,type 2DM.

doi:10.1210/jc.2013-2350J Clin Endocrinol Metab https://www.doczj.com/doc/8112014258.html, 1

J Clin Endocrin Metab. First published ahead of print October 22, 2013 as doi:10.1210/jc.2013-2350

Summary of Recommendations

1.0Diagnosis of PCOS

Diagnosis in adults

1.1We suggest that the diagnosis of polycystic ovary syn-drome(PCOS)be made if two of the three following cri-teria are met:androgen excess,ovulatory dysfunction,or polycystic ovaries(PCO)(Tables1and2),whereas dis-orders that mimic the clinical features of PCOS are ex-cluded.These include,in all women:thyroid disease,hy-perprolactinemia,and nonclassic congenital adrenal hyperplasia(primarily21-hydroxylase deficiency by se-rum17-hydroxyprogesterone[17-OHP])(Table3).In se-lect women with amenorrhea and more severe pheno-types,we suggest more extensive evaluation excluding other causes(Table4)(2|QQQE).Diagnosis in adolescents

1.2We suggest that the diagnosis of PCOS in an ado-lescent girl be made based on the presence of clinical and/or biochemical evidence of hyperandrogenism(after exclusion of other pathologies)in the presence of persis-tent oligomenorrhea.Anovulatory symptoms and PCO morphology are not sufficient to make a diagnosis in ad-olescents,as they may be evident in normal stages in re-productive maturation(2|QQEE).

Diagnosis in perimenopause and menopause

1.3Although there are currently no diagnostic criteria for PCOS in perimenopausal and menopausal women,we suggest that a presumptive diagnosis of PCOS can be based upon a well-documented long-term history of oligomen-orrhea and hyperandrogenism during the reproductive years.The presence of PCO morphology on ultrasound

Table1.Summary of Proposed Diagnostic Criteria for PCOS in Adults

Category

Specific

Abnormality Recommended Test NIH

Rotterdam

(2of3Met)

Androgen

Excess PCOS

Society

(Hyper-

Androgenism

with1of2

Remaining

Criteria)

Androgen

status Clinical

hyperandrogenism a

Clinical hyperandrogenism may

include hirsutism(defined as excessive

terminal hair that appears in a male

pattern)(1,295),acne,

or androgenic alopecia.

X X XX

Biochemical

hyperandrogenism a

Biochemical hyperandrogenism refers

to an elevated serum androgen level

and typically includes an elevated

total,bioavailable,or free serum T

level.Given variability in T levels and

the poor standardization of assays

(31),it is difficult to

define an absolute level that is

diagnostic of PCOS or other causes of

hyperandrogenism,and the Task Force

recommends familiarity with local

assays.

X X XX

Menstrual

history Oligo-or

anovulation

Anovulation may manifest as frequent

bleeding

at intervals?21d or

infrequent bleeding

at intervals?35

d.Occasionally,

bleeding may be

anovulatory despite falling at a normal

interval(25–35d).

A midluteal

progesterone documenting

anovulation may

help with the

diagnosis if bleeding intervals

appear to suggest

regular ovulation.

X X X

Ovarian

appearance Ovarian

size/morphology on

ultrasound

The PCO morphology has been

defined by

the presence of12or more

follicles2–9mm in diameter

and/or an

increased ovarian volume

?10mL

(without a cyst or dominant follicle)

either ovary(78)

X X

The Task Force suggests using the Rotterdam criteria for the diagnosis of PCOS,acknowledging the limitations of each of the three criteria(Table

2).All criteria require exclusion of other diagnoses(listed in Table3)that cause the same symptoms and/or signs(6–9).

a Clinical or biochemical hyperandrogenism is included as one criterion in all classification systems.If clinical hyperandrogenism is present with the absence of virilization,then serum androgens are not necessary for the diagnosis.Similarly,when a patient has signs of hyperandrogenism and ovulatory dysfunction,an ovarian ultrasound is not necessary.

2Legro et al Guidelines on PCOS J Clin Endocrinol Metab

would provide additional supportive evidence,although this is less likely in a menopausal woman(2|QQEE).

2.0Associated morbidity and evaluation

Cutaneous manifestations

2.1We recommend that a physical examination should document cutaneous manifestations of PCOS:terminal hair growth(see hirsutism guidelines,Ref.1),acne,alo-pecia,acanthosis nigricans,and skin tags(1|QQQE). Infertility

2.2Women with PCOS are at increased risk of anovu-lation and infertility;in the absence of anovulation,the risk of infertility is uncertain.We recommend screening

Table2.Diagnostic Strengths and Weaknesses of the Main Features of PCOS as Adapted from the NIH Evidence-Based Methodology Workshop on PCOS

Diagnostic Criteria Strength Limitation

Hyperandrogenism Included as a component

in all major

classifications

Measurement is performed only in blood

A major clinical concern for patients Concentrations differ during time of day

Animal models employing

androgen excess

resembling but not

fully mimicking human

disease

Concentrations differ with age

Normative data are not clearly defined

Assays are not standardized across

laboratories

Clinical hyperandrogenism is

difficult to quantify and may vary by

ethnic group,

eg,low rates of hirsutism in

women with PCOS from east Asia

Tissue sensitivity is not assessed

Ovulatory

dysfunction Included as a component

in all major

classifications

Normal ovulation is poorly defined

A major clinical concern

for patients

Normal ovulation varies over a woman’s

lifetime

Infertility a common clinical complaint Ovulatory dysfunction is difficult to

measure objectively

Anovulatory cycles may have bleeding

patterns that are interpreted as normal

PCO morphology Historically associated with syndrome Technique dependent

May be associated with hypersensitivity to

ovarian stimulation Difficult to obtain standardized

measurement

Lack of normative standards across the menstrual cycle and lifespan(notably in adolescence)

May be present in other disorders that mimic PCOS

Technology required to accurately image not universally available Transvaginal imaging possibly

inappropriate in

certain circumstances

(eg,adolescence)or certain cultures

Table3.Other Diagnoses to Exclude in All Women Before Making a Diagnosis of PCOS

Disorder Test Abnormal Values

Reference for Further Evaluation and Treatment of Abnormal

Findings;

First Author,Year(Ref.)

Thyroid disease Serum TSH TSH?the upper limit of normal

suggests hypothyroidism;

TSH?the lower limit,

usually?0.1mIU/L,suggests

hyperthyroidism Ladenson,2000 (10)

Prolactin excess Serum prolactin?Upper limit of normal for the assay Melmed,2011

(11)

Nonclassical

congenital adrenal

hyperplasia Early morning

(before8AM)

serum17-OHP

200–400ng/dL depending on the assay

(applicable to the early follicular phase of

a normal menstrual

cycle as levels rise with ovulation),

but a

cosyntropin stimulation test

(250?g)is needed if levels fall near the

lower limit and should

stimulate17-OHP?1000ng/dL.

Speiser,2010

(12)

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ovulatory status using menstrual history in all women with PCOS seeking fertility(1|QQEE).

2.3We recommend excluding other causes of infertil-ity,beyond anovulation,in couples where a woman has PCOS(1|QQEE).

Pregnancy complications

2.4Because women with PCOS are at increased risk of pregnancy complications(gestational diabetes,preterm delivery,and pre-eclampsia)exacerbated by obesity,we recommend preconceptual assessment of body mass index (BMI),blood pressure,and oral glucose tolerance (1|QQQE).

Fetal origins

2.5The evidence for intrauterine effects on develop-ment of PCOS is inconclusive.We suggest no specific in-terventions for prevention of PCOS in offspring of women with PCOS(2|QEEE).

Endometrial cancer

2.6Women with PCOS share many of the risk factors associated with the development of endometrial cancer including obesity,hyperinsulinism,diabetes,and abnor-mal uterine bleeding.However,we suggest against routine ultrasound screening for endometrial thickness in women with PCOS(2|QQQE).

Obesity

Table4.Diagnoses to Consider Excluding in Select Women,Depending on Presentation

Other Diagnoses a Suggestive Features

in the Presentation

Tests to Assist

in the Diagnosis

Reference for

Further Evaluation

and

Treatment of

Abnormal Findings;

First Author,Year

(Ref.)

Pregnancy Amenorrhea(as opposed to

oligomenorrhea),

other signs and symptoms

of pregnancy including breast fullness,

uterine cramping,etc Serum or urine hCG

(positive)

Morse,2011

(17)

HA including

functional HA Amenorrhea,clinical history of low body

weight/BMI,

excessive exercise,and a physical exam in

which signs of

androgen excess are lacking;

multifollicular

ovaries are sometimes present

Serum LH and FSH

(both low to low normal),

serum estradiol(low)

Wang,2008

(18)

Primary ovarian insufficiency Amenorrhea combined with symptoms of

estrogen deficiency

including hot flashes and urogenital

symptoms

Serum FSH

(elevated),

serum estradiol(low)

Nelson,2009

(296)

Androgen-secreting tumor Virilization including

change in voice,male

pattern androgenic alopecia,and

clitoromegaly rapid onset of

symptoms

Serum T and DHEAS

levels(markedly elevated),

ultrasound

imaging of ovaries,MRI of

adrenal glands(mass or

tumor present)

Carmina,2006

(16)

Cushing’s

syndrome Many of the signs and symptoms of

PCOS can overlap with

Cushing’s(ie,striae,obesity,

dorsocervical fat(ie,buffalo hump,

glucose intolerance);

however,Cushing’s is more likely to be

present when a large number of signs and

symptoms,especially those with high

discriminatory

index(eg,myopathy,plethora,violaceous

striae,easy bruising)are present,and this

presentation

should lead to screening.

24-h urinary collection for

urinary free cortisol

(elevated),

late night salivary

cortisol(elevated),

overnight dexamethasone

suppression test

(failure to suppress

morning serum cortisol

level)

Nieman,2008

(19)

Acromegaly Oligomenorrhea and skin changes

(thickening,tags,hirsutism,

hyperhidrosis)

may overlap with PCOS.However,

headaches,

peripheral vision loss,enlarged jaw

(macrognathia),frontal bossing,

macroglossia,

increased shoe and glove size,etc,are

indications for screening Serum free IGF-1level

(elevated),

MRI of pituitary(mass or

tumor present)

Melmed,2009

(20)

Abbreviations:DHEAS,dehydroepiandrosterone sulfate;HA,hypothalamic amenorrhea;hCG,human chorionic gonadotropin;MRI,magnetic resonance imaging.

a Additionally there are very rare causes of hyperandrogenic chronic anovulation that are not included in this table because they are so rare,but they must be considered in patients with an appropriate history.These include other forms of congenital adrenal hyperplasia(eg,11?-hydroxylase deficiency,3?-hydroxysteroid dehydrogenase),related congenital disorders of adrenal steroid metabolism or action(eg,apparent/cortisone reductase deficiency,apparent DHEA sulfotransferase deficiency,glucocorticoid resistance),virilizing congenital adrenal hyperplasia(adrenal rests, poor control,fetal programming),syndromes of extreme IR,drugs,portohepatic shunting,and disorders of sex development.

4Legro et al Guidelines on PCOS J Clin Endocrinol Metab

adolescents and women with PCOS for increased adipos-ity,by BMI calculation and measurement of waist circum-ference(1|QQQE).

Depression

2.8We suggest screening women and adolescents with PCOS for depression and anxiety by history and,if iden-tified,providing appropriate referral and/or treatment (2|QQEE).

Sleep-disordered breathing/obstructive sleep apnea (OSA)

2.9We suggest screening overweight/obese adolescents and women with PCOS for symptoms suggestive of OSA and,when identified,obtaining a definitive diagnosis us-ing polysomnography.If OSA is diagnosed,patients should be referred for institution of appropriate treatment (2|QQEE).

Nonalcoholic fatty liver disease(NAFLD)and nonal-

coholic steatohepatitis(NASH)

2.10We suggest awareness of the possibility of NAFLD and NASH but recommend against routine screening (2|QQEE).

Type2diabetes mellitus(T2DM)

2.11We recommend the use of an oral glucose toler-ance test(OGTT)(consisting of a fasting and2-hour glu-cose level using a75-g oral glucose load)to screen for impaired glucose tolerance(IGT)and T2DM in adoles-cents and adult women with PCOS because they are at high risk for such abnormalities(1|QQQE).A hemoglobin A1c(HgbA1c)test may be considered if a patient is unable or unwilling to complete an OGTT(2|QQEE).Rescreen-ing is suggested every3–5years,or more frequently if clinical factors such as central adiposity,substantial weight gain,and/or symptoms of diabetes develop (2|QQEE).

Cardiovascular risk

2.12We recommend that adolescents and women with PCOS be screened for the following cardiovascular disease risk factors(Table5):family history of early cardiovas-cular disease,cigarette smoking,IGT/T2DM,hyperten-sion,dyslipidemia,OSA,and obesity(especially increased abdominal adiposity)(1|QQEE).

3.0Treatment

Hormonal contraceptives(HCs):indications and screening

3.1We recommend HCs(ie,oral contraceptives,patch, or vaginal ring)as first-line management for the menstrual abnormalities and hirsutism/acne of PCOS(refer to hir-sutism guidelines in Ref.1,recommendation2.1.1,which treat these two problems concurrently)(1|QQEE).

3.2We recommend screening for contraindications to HC use via established criteria(see Table6and Ref.3) (1|QQQE).For women with PCOS,we do not suggest one HC formulation over another(2|QQEE).

Role of exercise in lifestyle therapy

3.3We suggest the use of exercise therapy in the man-agement of overweight and obesity in PCOS(2|QQEE). Although there are no large randomized trials of exercise in PCOS,exercise therapy,alone or in combination with dietary intervention,improves weight loss and reduces cardiovascular risk factors and diabetes risk in the general population.

Role of weight loss in lifestyle therapy

3.4We suggest that weight loss strategies begin with calorie-restricted diets(with no evidence that one type of diet is superior)for adolescents and women with PCOS who are overweight or obese(2|QQEE).Weight loss is likely beneficial for both reproductive and metabolic dys-function in this setting.Weight loss is likely insufficient as a treatment for PCOS in normal-weight women.

Use of metformin

3.5We suggest against the use of metformin as a first-line treatment of cutaneous manifestations,for prevention of pregnancy complications,or for the treatment of obe-sity(2|QQEE).

3.6We recommend metformin in women with PCOS who have T2DM or IGT who fail lifestyle modification Table5.Cardiovascular Risk Stratification in Women with PCOS

At risk---PCOS women with any of the following risk factors: Obesity(especially increased abdominal adiposity)

Cigarette smoking

Hypertension

Dyslipidemia(increased LDL-cholesterol and/or non-HDL-

cholesterol)

Subclinical vascular disease

Impaired glucose tolerance

Family history of premature cardiovascular disease(?55y of age in male relative;?65y

of age in female relative)

At high risk---PCOS women with:

Metabolic syndrome

T2DM

Overt vascular or renal disease,cardiovascular diseases

OSA

The Androgen Excess and Polycystic Ovary Syndrome Society relied upon evidence-based studies and concluded that women with PCOS be stratified as being either at risk or at high risk for cardiovascular disease using the criteria shown(167).

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(1|QQQE).For women with PCOS with menstrual irreg-ularity who cannot take or do not tolerate HCs,we suggest metformin as second-line therapy(2|QQQE). Treatment of infertility

3.7We recommend clomiphene citrate(or comparable estrogen modulators such as letrozole)as the first-line treatment of anovulatory infertility in women with PCOS (1|QQQE).

3.8We suggest the use of metformin as an adjuvant therapy for infertility to prevent ovarian hyperstimulation syndrome(OHSS)in women with PCOS undergoing in vitro fertilization(IVF)(2|QQEE).

Table6.Considerations for Use of Combined HCs,Including Pill,Patch,and Ring,in Women with PCOS Based on Relevant Conditions

Criteria Further Classification

Conditions

1234

A condition for

which

there is no

restriction

for the use

of the

contraceptive

method

A condition

for which

the

advantages of

using

the method

generally

outweigh the

theoretical

or proven

risks

A condition

for which

the

theoretical

or proven

risks usually

outweigh the

advantages

of using the

method

A condition

that

represents an

unacceptable

health risk if

the contra-

ceptive method

is used

Age Menarche to?40y;

?40y;

Smoking Age?35y;

Age?

35y and smokes?

15cigarettes/d

;

Age?

35y and smokes

15cigarettes/d

;

Obesity BMI?30kg/m2;

BMI?

30kg/m2

;

Hypertension History of

gestational

hypertension

;

Adequately

controlled

hypertension

;

Elevated blood

pressure levels

(properly taken

measurements):

systolic,

140–159mm Hg;or

diastolic,

90–99mm Hg

;

Elevated blood

pressure levels

(properly taken

measurements):

systolic,

?160mm Hg;

or diastolic,?

100mm Hg

;

Dyslipidemia Known

hyperlipidemias

;;

Depression Depressive disorders;

Unexplained

vaginal

bleeding

(suspicious for

serious

condition)

Before evaluation;

Diabetes History of gestational

diabetes

;

Nonvascular

diabetes,

insulin or

non-insulin

dependent

;

Vascular disease

including

neuropathy,

retinopathy,

nephropathy

;;

Diabetes duration

?20y

;;

The boxes indicate the recommendation for the condition.The four possible recommendations are a spectrum ranging from condition1,which favors the use of the pill,to condition4,which discourages the use of the pill.[Adapted from:US Medical Eligibility Criteria for Contraceptive Use. MMWR Recomm Rep.2010;59:1–86(3),with permission.?Centers for Disease Control and Prevention.]

6Legro et al Guidelines on PCOS J Clin Endocrinol Metab

Use of other drugs

3.9We recommend against the use of insulin sensitiz-ers,such as inositols(due to lack of benefit)or thiazoli-dinediones(given safety concerns),for the treatment of PCOS(1|QQQE).

3.10We suggest against the use of statins for treatment of hyperandrogenism and anovulation in PCOS until ad-ditional studies demonstrate a favorable risk-benefit ratio (2|QQEE).However,we suggest statins in women with PCOS who meet current indications for statin therapy (2|QQEE).

Treatment of adolescents

3.11We suggest HCs as the first-line treatment in ad-olescents with suspected PCOS(if the therapeutic goal is to treat acne,hirsutism,or anovulatory symptoms,or to prevent pregnancy)(2|QQEE).We suggest that lifestyle therapy(calorie-restricted diet and exercise)with the ob-jective of weight loss should also be first-line treatment in the presence of overweight/obesity(2|QQEE).We suggest metformin as a possible treatment if the goal is to treat IGT/metabolic syndrome(2|QQEE).The optimal dura-tion of HC or metformin use has not yet been determined.

3.12For premenarchal girls with clinical and biochem-ical evidence of hyperandrogenism in the presence of ad-vanced pubertal development(ie,?Tanner stage IV breast development),we suggest starting HCs(2|QQEE). Method of Development of Evidence-Based Clinical Practice Guidelines

The Clinical Guidelines Subcommittee of The Endocrine Society deemed the diagnosis and treatment of PCOS a priority area in need of practice guidelines and appointed a Task Force to formulate evidence-based recommenda-tions.The Task Force followed the approach recom-mended by the Grading of Recommendations,Assess-ment,Development,and Evaluation(GRADE)group,an international group with expertise in development and implementation of evidence-based guidelines(4).A de-tailed description of the grading scheme has been pub-lished elsewhere(5).The Task Force used the best avail-able research evidence to develop the recommendations. The Task Force also used consistent language and graph-ical descriptions of both the strength of a recommendation and the quality of evidence.In terms of the strength of the recommendation,strong recommendations use the phrase “we recommend”and the number1,and weak recom-mendations use the phrase“we suggest”and the number 2.Cross-filled circles indicate the quality of the evidence, such that QEEE denotes very low quality evidence;QQEE,low quality;QQQE,moderate quality;and QQQQ,high quality.The Task Force has confidence that persons who receive care according to the strong recom-mendations will derive,on average,more good than harm. Weak recommendations require more careful consider-ation of the person’s circumstances,values,and prefer-ences to determine the best course of action.Linked to each recommendation is a description of the evidence and the values that panelists considered in making the recom-mendation;in some instances,there are remarks,a section in which panelists offer technical suggestions for testing conditions,dosing,and monitoring.These technical com-ments reflect the best available evidence applied to a typ-ical person being treated.Often this evidence comes from the unsystematic observations of the panelists and their values and preferences;therefore,these remarks are considered.

The Endocrine Society maintains a rigorous conflict of interest review process for the development of clinical practice guidelines.All Task Force members must declare any potential conflicts of interest,which are reviewed be-fore they are approved to serve on the Task Force and periodically during the development of the guideline.The conflict of interest forms are vetted by the Clinical Guide-lines Subcommittee(CGS)before the members are ap-proved by the Society’s Council to participate on the guideline Task Force.Participants in the guideline devel-opment must include a majority of individuals without conflict of interest in the matter under study.Participants with conflicts of interest may participate in the develop-ment of the guideline,but they must have disclosed all conflicts.The CGS and the Task Force have reviewed all disclosures for this guideline and resolved or managed all identified conflicts of interest.

Conflicts of interest are defined by remuneration in any amount from the commercial interest(s)in the form of grants;research support;consulting fees;salary;owner-ship interest(eg,stocks,stock options,or ownership in-terest excluding diversified mutual funds);honoraria or other payments for participation in speakers’bureaus,ad-visory boards,or boards of directors;or other financial https://www.doczj.com/doc/8112014258.html,pleted forms are available through The En-docrine Society office.

Funding for this guideline was derived solely from The Endocrine Society,and thus the Task Force received no funding or remuneration from commercial or other entities.

1.0Diagnosis of PCOS

Diagnosis in adults

1.1We suggest that the diagnosis of PCOS be made if two of the three following criteria are met:androgen ex-

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cess,ovulatory dysfunction,or PCO(Tables1and2), whereas disorders that mimic the clinical features of PCOS are excluded.These include,in all women:thyroid disease, hyperprolactinemia,and nonclassic congenital adrenal hyperplasia(primarily21-hydroxylase deficiency by se-rum17-OHP)(Table3).In select women with amenor-rhea and more severe phenotypes,we suggest more exten-sive evaluation excluding other causes(Table4) (2|QQQE).

1.1Evidence

PCOS is a common disorder with systemic metabolic manifestations.Its etiology is complex,heterogeneous, and poorly understood.There are three definitions for PCOS currently in use that variably rely on androgen ex-cess,chronic anovulation,and PCO to make the diagnosis (Table1).However,all criteria are consistent in that PCOS is considered a diagnosis of exclusion.All three sets of diagnostic criteria include hyperandrogenism,either clin-ical or biochemical,and anovulation(6–9).The Rotter-dam criteria were the first to incorporate ovarian mor-phology on ultrasound as part of the diagnostic criteria(8, 9).

The panel from a recent National Institutes of Health (NIH)-sponsored Evidence-Based Methodology work-shop on PCOS endorsed the Rotterdam criteria,although they identified the strengths and weaknesses of each of the three cardinal features(Table2).These criteria allow the diagnosis to be made clinically(based upon a history of hyperandrogenic chronic anovulation)as well as bio-chemically with androgen assays or with ultrasound ex-amination of the ovaries.We do not endorse the need for universal screening with androgen assays or ultrasound if patients already meet two of the three criteria clinically.It is recommended that the features leading to the diagnosis are documented.We recommend using the current defi-nition of the Rotterdam criteria to document PCO mor-phology(at least one ovary with12follicles of2–9mm or a volume?10mL in the absence of a dominant follicle?10mm),in the absence of age-based criteria.

Disorders that mimic PCOS are comparatively easy to exclude;therefore,all women should be screened with a TSH,prolactin,and17-OHP level(Table3)(10–12).Hy-perprolactinemia can present with amenorrhea or hirsut-ism(13,14).Thyroid disease may present with irregular menstrual cycles.In women with hyperandrogenism,non-classic congenital adrenal hyperplasia should be excluded because it can be found in1.5–6.8%of patients presenting with androgen excess(15,16).In select women who pres-ent with amenorrhea,virilization,or physical findings not associated with PCOS,such as proximal muscle weakness (Cushing’s syndrome)or frontal bossing(acromegaly),other diagnoses should be considered and excluded(Table 4)(16–20Morse278,Wange279,Carmina13,Nieman 281,Melamed282).

1.1Values and preferences

In the absence of evidence-based diagnostic criteria,we have relied on the recommendations of the NIH Panel as noted above.The presence of specific phenotypic features may result in different risk and comorbidity profiles.For example,hyperandrogenism may be more highly associ-ated with metabolic abnormalities,whereas irregular menses and PCO morphology may be more highly asso-ciated with infertility.When interpreting published re-search,clinicians should note that criteria different from their own may be used when performing research.The committee notes that the diagnosis of PCOS is problematic in women who are perimenarchal or perimenopausal be-cause amenorrhea and oligomenorrhea are natural stages in reproductive maturation and senescence,as are changes in circulating androgens and ovarian morphology.There-fore,we discuss the diagnosis of PCOS separately in these groups.Finally,because there is evidence of a genetic com-ponent to PCOS and familial clustering of reproductive and metabolic abnormalities in male and female relatives, a careful family history should be taken,and further screening of first-degree relatives is a consideration. Diagnosis in adolescents

1.2We suggest that the diagnosis of PCOS in an ado-lescent girl be made based on the presence of clinical and/or biochemical evidence of hyperandrogenism(after exclusion of other pathologies)in the presence of persis-tent oligomenorrhea.Anovulatory symptoms and PCO morphology are not sufficient to make a diagnosis in ad-olescents because they may be evident in normal stages in reproductive maturation(2|QQEE).

1.2Evidence

All PCOS diagnostic criteria were derived for adults (Table1),not adolescents.Furthermore,normal adoles-cent physiology may mimic symptoms of PCOS.Oligom-enorrhea is common after menarche during normal pu-berty and is therefore not specific to adolescents with PCOS.Anovulatory cycles comprise85%of menstrual cycles in the first year after menarche,59%in the third year,and25%by the sixth year.Anovulatory cycles are associated with higher serum androgen and LH levels(21). Approximately two-thirds of adolescents with PCOS will have menstrual symptoms,and for one-third it will be the presenting symptom,with the spectrum from primary amenorrhea to frequent dysfunctional bleeding(22). Therefore,it is appropriate to evaluate persistent oligom-

8Legro et al Guidelines on PCOS J Clin Endocrinol Metab

enorrhea or amenorrhea as an early clinical sign of PCOS, especially when it persists2years beyond menarche(23).

Acne is common although transitory during adoles-cence(24);thus,it should not be used in isolation to define hyperandrogenism in adolescents(25).Hirsutism may de-velop slowly and thus be less severe in adolescents than in adults due to the shorter exposure to hyperandrogenism (26).However,hirsutism was a major symptom in about 60%of adolescents in one study(27)and may be sugges-tive of PCOS in adolescents(28).The Ferriman-Gallwey hirsutism score was standardized only in adult Caucasians and may have a lower cut-point in adolescents(29).An-drogenic alopecia has not been studied in adolescents and should be viewed cautiously in diagnosing PCOS(25).

There is a lack of well-defined cutoff points for andro-gen levels during normal pubertal maturation(30),as well as the lack of T assay standardization(31).Furthermore, hyperandrogenemia appears to be exacerbated by obesity because a significant proportion of obese girls have ele-vated androgen levels across puberty compared with nor-mal-weight girls(32).Hyperandrogenemia during pu-berty may be associated with infertility in later life(33), and adult cutoffs should be used until appropriate puber-tal levels are defined.

Lastly,the Rotterdam ultrasound PCO criteria were not validated for adolescents.Recommending a transvag-inal ovarian ultrasound in this group raises practical and ethical concerns.Transabdominal ultrasound,already limited in evaluating the ovaries,is rendered even less tech-nically adequate with obesity,common in adolescent PCOS(34).In addition,multifollicular ovaries are a fea-ture of normal puberty that subsides with onset of regular menstrual cycling(35)and may be difficult to distinguish from PCO morphology(20).It is possible that elevated anti-Mullerian hormone levels may serve as a noninvasive screening or diagnostic test for PCO in this population, although there are no well-defined cutoffs(36,37).

In summary,the diagnosis of PCOS in adolescents should be based on a complete picture that includes clin-ical signs and symptoms of androgen excess,increased androgen levels,and exclusion of other causes of hyperan-drogenemia in the setting of oligomenorrhea.

1.2Values and preferences

In making this recommendation,the committee ac-knowledges that the diagnosis of PCOS in adolescents is less straightforward than in adults.A high index of aware-ness is needed to initiate a thorough medical and labora-tory evaluation of adolescent girls with signs and symp-toms of PCOS,including a family history of PCOS.Until higher quality evidence becomes available,this recom-mendation places a higher value in making an early diag-nosis of PCOS in adolescents for timely initiation of ther-apy,which outweighs harms and burdens of misdiagnosis.

Diagnosis in perimenopause and menopause

1.3Evidence

The natural history of PCOS through perimenopause into menopause is poorly studied,but many aspects of the syndrome appear to improve.Ovarian size,follicle count, and anti-Mullerian hormone levels(a marker of antral follicle count)decrease with normal aging in women with and without PCOS(38–40).However,the decline in ovar-ian volume and follicle count may be less in women with PCOS than in normal women(39,41,42).Similarly,an-drogen levels decline with age in women with and without PCOS(serum T declines?50%between the ages of20and 40y)(43–45),with reports of improved menstrual fre-quency in PCOS(46,47),although there is little evidence to support a decline in serum T associated with the meno-pause transition per se(43).

The diagnosis of PCOS in postmenopausal women is more problematic than in adolescents.There are no age-related T cutoffs for the diagnosis.Furthermore,T assays used to diagnose hyperandrogenemia in women are im-precise(31),even for assays utilizing tandem mass spec-trometry technology(48).Nevertheless,supporting stud-ies have shown that peri-and postmenopausal mothers of women with PCOS with a history of irregular menses tended to have features of PCOS as well as metabolic ab-normalities,implying that aspects of the PCOS phenotype may persist with age(49).Very high T levels and/or vir-ilization may suggest an androgen-producing tumor in postmenopausal women.

1.3Values and preferences

We recognize that the diagnosis of PCOS in postmeno-pausal women is problematic but feel that it is unlikely that a woman can develop PCOS in the perimenopause or menopause if she has not had symptoms earlier.We rec-ognize that there are few prospective studies to document the natural history of ovarian function with age in women with PCOS.

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2.0Associated morbidity and evaluation Cutaneous manifestations

The major clinical manifestations of hyperandro-genism include hirsutism,acne,and androgenic alopecia. The history of skin problems should assess the age at onset, the rate of progression,previous long-term treatments(in-cluding anabolic agents),any change with treatment or with fluctuations in body weight,and the nature of the skin complaint relative to those of other family members. In rare instances,male pattern balding,increased muscle mass,deepening of the voice,or clitoromegaly may occur, suggesting virilizing androgen levels and a possible under-lying ovarian or adrenal neoplasm or severe insulin-resis-tant states(9,50).Notably,in obese,insulin-resistant women with PCOS,acanthosis nigricans is often present, as are skin tags(51).

Hirsutism

The prevalence of hirsutism in the general population ranges from5–15%,with relevant differences according to ethnicity and geographic location(9).In a large study of patients with clinical hyperandrogenism,72.1%of950 patients were diagnosed with PCOS(16).Therefore, PCOS represents the major cause of hirsutism,but the presence of hirsutism does not fully predict ovulatory dys-function.Overall,hirsutism is present in approximately 65–75%of patients with PCOS(although lower in Asian populations)(15,52).Hirsutism may predict the meta-bolic sequelae of PCOS(53)or failure to conceive with infertility treatment(54).Hirsutism often tends to be more severe in abdominally obese patients(9).The most com-mon method of visually assessing hirsutism is still the mod-ified Ferriman-Gallwey score(1,55).

Acne and alopecia

Acne is common in women with PCOS,particularly in the teenage years,and the prevalence varies(14–25%), with some difference in relation to ethnicity and patient age(56).The combined prevalence of acne with hirsutism in PCOS is still poorly defined,although there is clinical evidence that the prevalence of each of these features is higher than the combination of the two(57).Androgenic alopecia may be graded by well-known subjective meth-ods,such as the Ludwig score(58).Androgenic alopecia is less frequent and presents later,but it remains a distressing complaint with significant psychopathological comor-bidities(9).It may be associated with hirsutism and acne, although there is a poor correlation with biochemical hy-perandrogenism.Some studies have demonstrated an as-sociation between androgenic alopecia with metabolic syndrome(59)and insulin resistance(IR)(60,61).Some studies found that acne and androgenic alopecia are not good markers for hyperandrogenism in PCOS,compared with hirsutism(53,62).

2.1Values and preferences

Evaluating hirsutism,acne,and alopecia in women with PCOS depends on careful grading,but is subjective. We place value on recognizing these particularly stressful symptoms,even if they do not correlate with objective findings.Alopecia and acne may be related to hyperan-drogenism and are distressing;therefore,our preference is to document and consider consultation with a dermatol-ogist and to determine whether they are related to other etiologies in the case of alopecia or in the case of acne if unresponsive to HCs.More research is needed to quantify the relationship between cutaneous signs of hyperandro-genism and cardiovascular disease.

Infertility

2.2Women with PCOS are at increased risk of anovu-lation and infertility;in the absence of anovulation,the risk of infertility is uncertain.We recommend screening ovulatory status using menstrual history in all women with PCOS seeking fertility.Some women with PCOS and a eumenorrheic menstrual history may still experience an-ovulation and a midluteal serum progesterone may be helpful as an additional screening test(1|QQEE).

2.3We recommend excluding other causes of infertil-ity,beyond anovulation,in couples where a woman has PCOS(1|QQEE).

2.2–2.3Evidence

Infertility was one of the original symptoms of PCOS described by Stein and Leventhal(63)and is a common presenting complaint(64).Among a large series of women presenting with PCOS,close to50%reported primary infertility,and25%reported secondary infertility(65). Population-based studies of infertility have suggested that anovulatory infertility(encompassing PCOS)is common, accounting for25–40%of cases(65,66).Furthermore, PCOS is estimated to be the most common cause of ovu-latory dysfunction,accounting for70–90%of ovulatory disorders(67).Prolonged periods of anovulation are likely associated with increased infertility(68).Women with PCOS had a monthly spontaneous ovulation rate of32% on placebo in a multicenter trial that randomly assigned subjects to placebo or troglitazone(69).Nevertheless,life-

10Legro et al Guidelines on PCOS J Clin Endocrinol Metab

time fecundity in Swedish women with PCOS was similar to controls,and almost three-fourths of women with PCOS conceived spontaneously(70),

Some women with PCOS and a eumenorrheic men-strual history may still experience anovulation,and a mid-luteal serum progesterone may be helpful as an additional screening test.Although the primary mechanism of infer-tility is presumed to be oligo-or anovulation,there are other potential factors including diminished oocyte com-petence(71,72)and endometrial changes discouraging implantation(73,74).Other factors associated with PCOS,such as obesity,have also been associated with subfertility and delayed conception(75).Male factor in-fertility or tubal occlusion must also be considered(one study in PCOS found a nearly10%rate of severe oligo-spermia and a5%rate of bilateral tubal occlusion)(76).

2.2–2.3Values and preferences

In making this recommendation,we emphasize the overall increased infertility burden among women with PCOS and ovulatory dysfunction,although there are spontaneous conceptions,which may increase with im-proved menstrual frequency and aging.The natural his-tory of fertility in women with PCOS and the influence of milder phenotypes lacking ovulatory dysfunction are not well understood or described.

Pregnancy complications

2.4Because women with PCOS are at increased risk of pregnancy complications(gestational diabetes,preterm delivery,and pre-eclampsia)exacerbated by obesity,we recommend preconceptual assessment of BMI,blood pressure,and oral glucose tolerance(1|QQQE).

2.4Evidence

There is a growing body of evidence that PCOS has implications for adverse pregnancy outcomes.Confound-ers include iatrogenic multiple pregnancy due to ovulation induction,higher complications in pregnancies resulting from infertility treatment per se,and higher rates of obe-sity in women with PCOS.Some studies have suggested increased early pregnancy loss in women with PCOS(77, 78).A meta-analysis of studies comparing IVF outcomes in women with and without PCOS demonstrated no sig-nificant difference in miscarriage rates between the two groups(odds ratio[OR],1.0;95%confidence interval [CI],0.5–1.8)(79).

The link between PCOS and gestational diabetes was initially suggested by retrospective data(80).A study of99 women with PCOS and737controls noted a higher rate of gestational diabetes,but it was largely explained by a higher prevalence of obesity in the PCOS group(81,82).In contrast,a meta-analysis in which confounding factors such as BMI were taken into account demonstrated that PCOS was independently associated with an increased risk for gestational diabetes and hypertension(83).This meta-analysis demonstrated a small but significant asso-ciation between premature singleton births(?37wk ges-tation)and PCOS(OR,1.75;95%CI,1.16–2.62),and between PCOS and pre-eclampsia(OR,3.47;95%CI, 1.95–6.17).Most studies reporting an association be-tween hypertension or pre-eclampsia and pregnancy in PCOS are small and poorly controlled and show mixed results(82).In one of the largest studies,PCOS(n?99) was not a significant predictor of pre-eclampsia compared with control pregnancies(n?737),when controlled for nulliparity(more common in PCOS)(81).Although only a small absolute difference in gestational age was noted between cases and controls,increased neonatal morbidity was present(83).

2.4Values and preferences

In making this recommendation,we believe that a pri-ority should be placed on reducing the overall increased morbidity from pregnancy complications such as gesta-tional diabetes,pre-eclampsia,and preterm delivery in women with PCOS.Whether these increased risks are due to PCOS itself or the features associated with PCOS such as IR or obesity requires further study.

Fetal origins

2.5The evidence for intrauterine effects on develop-ment of PCOS is inconclusive.We suggest no specific in-terventions for prevention of PCOS in offspring of women with PCOS(2|QEEE).

2.5Evidence

Nonhuman primate models and sheep models suggest that androgen exposure in utero may program the fetus to express features characteristic of PCOS in adult life(84–86).Human data are limited,but there is evidence of fetal programming by androgens in girls with classic adrenal hyperplasia or with a mother with a virilizing tumor(87, 88).Androgen levels may be increased in pregnant women with PCOS(89).Nevertheless,an Australian study of 2900pregnant women demonstrated no relationship be-tween T levels at18and34weeks gestation and the pres-ence of PCOS in244female offspring aged14–17years (90).The relationship between T levels during pregnancy in women with PCOS to outcomes remains to be deter-mined using accurate assay methodology.

There is evidence that cardiovascular disease in humans is related to intrauterine events.Intrauterine growth re-striction has been associated with increased rates of cor-

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onary heart disease,hypertension,and T2DM,providing evidence for fetal programming of adult diseases(91). There are limited data to suggest that intrauterine growth restriction may be associated with subsequent develop-ment of PCOS in some populations(92).In addition,a subset of girls born small for gestational age are at risk for developing premature adrenarche,IR,or PCOS(93,94), although this has not been confirmed in longitudinal,pop-ulation-based studies in northern Europe(95).Available data support the concept that rapid postnatal weight gain and subsequent adiposity can exacerbate metabolic ab-normalities and PCOS symptoms(94,96–98). Endometrial cancer

2.6Evidence

An association between PCOS and endometrial cancer was first described in1949(99).There have been few studies with cohorts large enough to adequately assess the risk of endometrial cancer in women with PCOS.In a long-term follow-up of women with PCOS in the United Kingdom,morbidity data over31years were available on 319compared with1060control women.Women with PCOS did not have a higher all-cause mortality but did show a3.5increased relative risk(RR)of development of endometrial cancer(100).A more recent meta-analysis assessing the association between PCOS and endometrial cancer suggested that women with PCOS had an increased risk of developing endometrial cancer(RR?2.7;95%CI, 1.0–7.29)(101),confirmed by a subsequent systematic review with a3-fold increased risk(102).

Several factors in the epidemiology of endometrial can-cer suggest a link to PCOS.Young women with endome-trial cancer are more likely to be nulliparous and infertile, have higher rates of hirsutism,and have a slightly higher chance for oligomenorrhea(103).Obesity and T2DM, common in women with PCOS,are also endometrial can-cer risk factors(104–107).In a woman with these risk factors,low physical activity scores further elevated the cancer risk(108).

There currently are no data supporting routine endo-metrial biopsy of asymptomatic women(109)or ultra-sound screening of the endometrium(110).Ultrasound screening in women without abnormal bleeding shows poor diagnostic accuracy for diagnosing intrauterine pa-thology(110,111).The American Cancer Society recom-mends against routine cancer screening for endometrial cancer in women at average or increased risk(with the exception of Lynch syndrome),but women should be counseled to report unexpected bleeding and spotting (112).

2.6Values and preferences

In making this recommendation for increased aware-ness of endometrial cancer risk in women with PCOS, particularly those with abnormal uterine bleeding,pro-longed amenorrhea,diabetes,and/or obesity,we believe that a priority should be placed on the consequences of development of endometrial cancer,and this priority off-sets the limited data available for independent association with PCOS.

Obesity

2.7Increased adiposity,particularly abdominal,is as-sociated with hyperandrogenemia and increased meta-bolic risk(see cardiovascular disease prevention guide-lines,Ref.2).Therefore,we recommend screening adolescents and women with PCOS for increased adipos-ity by BMI calculation and measurement of waist circum-ference(1|QQQE).

2.7Evidence

Prevalence of obesity in PCOS

The prevalence of obesity varies greatly across the world;however,studies in different countries with signif-icantly different background rates of obesity(30–70%) have yielded similar rates for the prevalence of PCOS(52, 113).Whether the incidence of PCOS may parallel the growing epidemic of obesity is unknown,although a mod-est but nonsignificant trend in the prevalence of PCOS with increasing BMI has been reported(114).Obesity may also cluster in PCOS families(97,115),and referral bias to specialty clinics may also elevate the association of PCOS with obesity(116).

Impact of obesity on the phenotype of PCOS Obesity in general and abdominal obesity in particular cause relative hyperandrogenemia,characterized by re-duced levels of SHBG and increased bioavailable andro-gens delivered to target tissues(117,118).Abdominal obesity is also associated with an increased T production rate and a non-SHBG-bound androgen production rate of dehydroepiandrosterone and androstenedione(119).Es-trogen levels,particularly estrone,may also be higher in PCOS(120).

Menstrual disorders are frequent when the onset of ex-cess weight occurs during puberty rather than during in-fancy(121).In adult overweight and obese women with

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PCOS,menstrual abnormalities and chronic oligoanovu-lation are more frequent than in normal-weight women (118).Obese women with PCOS exhibit a blunted respon-siveness and lower pregnancy rates to pharmacological treatments for ovulation induction,such as clomiphene citrate,gonadotropins,or pulsatile GnRH(54,68,122).

Obesity increases the risk of the metabolic syndrome, IGT/diabetes mellitus(DM),dyslipidemia,and IR(118, 119,123–128).Longitudinal studies have shown that IR may worsen over time(125).Consequently,obesity has a negative impact that may exceed that of the PCOS status per se.

2.7Values and preferences

In making this recommendation,the committee be-lieves that excess weight and obesity may have an impor-tant impact on the early development of PCOS and on the clinical presentation(93,129,130).Obesity may change in degree and possibly in distribution from adolescence to postmenopausal age,and these changes should be monitored.

Depression

2.8We suggest screening women and adolescents with PCOS for depression and anxiety by history and,if iden-tified,providing appropriate referral and/or treatment (2|QQEE).

2.8Evidence

Small observational community-and patient-based case control studies consistently demonstrate an increased prevalence of depression in women with PCOS.In women with PCOS compared with non-BMI-matched controls, self-rated questionnaires demonstrate an increased rate of depressive symptoms(131–133).Similarly,in studies with direct psychiatric interviews,there was a higher lifetime incidence of a major depression episode and recurrent de-pression(OR,3.8;95%CI,1.5–8.7;P?.001)and a history of suicide attempts that was seven times higher in PCOS cases vs controls(134).In a longitudinal study ex-amining changes in depression scores,the incidence of depression was19%in1–2years of follow-up(135).The increased prevalence of depression and depressive symp-toms in women with PCOS appears to be independent of obesity,androgen levels,hirsutism,acne,and infertility (131–133,135–137).Thus,studies of depression using different patient groups and methods of identification demonstrate an increased prevalence of depression in women with PCOS(138).

Community-and clinic-based case-control studies and studies using psychiatric interviews demonstrate higher rates of anxiety and panic disorders in women with PCOS (134,137,139).In addition,eating disorders are more common in women with PCOS(OR,6.4;95%CI,1.3–31; P?.01)(132)and include binge-eating disorder(12.6vs 1.9%;P?.01)(133).Although a history of depression or anxiety may be present in many women and adolescents with PCOS,for those without a prior diagnosis,a simple office screen using a two-item questionnaire such as the PHQ-2may be helpful(140).Those identified with de-pression or anxiety should be referred for further therapy.

Sleep-disordered breathing/OSA

2.9We suggest screening overweight/obese adolescents and women with PCOS for symptoms suggestive of OSA, and when identified,obtaining a definitive diagnosis using polysomnography.If OSA is diagnosed,patients should be referred for institution of appropriate treatment (2|QQEE).

2.9Evidence

Women with PCOS develop OSA at rates that equal or exceed those in men.The high prevalence of OSA is thought to be a function of hyperandrogenism(a defining feature of PCOS)as well as obesity(common in PCOS) (141,142),although these factors alone do not fully ac-count for the finding.Even after controlling for BMI, women with PCOS were30times more likely to have sleep-disordered breathing and nine times more likely than controls to have daytime sleepiness(141).It also appeared that women with PCOS taking oral contraceptives were less likely to have sleep-disordered breathing(141),con-sistent with the lower likelihood of sleep-disordered breathing in postmenopausal women treated with hor-mone replacement therapy(143).Finally,women with PCOS had a significantly higher mean apnea-hypopnea index compared with weight-matched controls(22.5?6.0vs6.7?1.7;P?.01),with the difference most pro-nounced in rapid eye movement sleep(41.3?7.5vs 13.5?3.3;P?.01)(143).Thus,the risk imparted by obesity is not sufficient to account for the high prevalence of sleep-disordered breathing in PCOS,suggesting that additional factors must be involved.

Continuous positive airway pressure treatment of OSA in patients with PCOS demonstrated modestly improved IR after controlling for BMI(P?.013)(144).In young obese women with PCOS,successful treatment of OSA improves insulin sensitivity,decreases sympathetic out-put,and reduces diastolic blood pressure.The magnitude of these beneficial effects is modulated by the hours of continuous positive airway pressure use and the degree of obesity.

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2.9Values and preferences

It is difficult to diagnose sleep abnormalities on the basis of a history and physical or by questionnaire.Poly-somnography,when performed,should occur in a certi-fied sleep laboratory with proper accreditation.The in-terpretation and recommendation(s)for treatment of sleep-disordered breathing/OSA should be made by a board-certified expert in sleep medicine.

NAFLD and NASH

2.10We suggest awareness of the possibility of NAFLD and NASH but recommend against routine screening (2|QQEE).

2.10Evidence

NAFLD is characterized by excessive fat accumulation in the liver(steatosis),whereas NASH defines a subgroup of NAFLD in which steatosis coexists with liver cell injury and inflammation(after exclusion of other causes of liver disease(viral,autoimmune,genetic,alcohol consumption, etc).Primary NAFLD/NASH is most commonly associ-ated with IR and its phenotypic manifestations(145).The prevalence of ultrasound-documented NAFLD in the gen-eral population is15–30%(146).Risk factors pertinent to PCOS include increasing age,ethnicity,and metabolic dysfunction(obesity,hypertension,dyslipidemia,diabe-tes).Because many women with PCOS have metabolic dysfunction,the association of PCOS with NAFLD is not surprising,but the available literature,especially in refer-ence to the risk of NASH,is incomplete(147).Clinical studies report a15–60%prevalence of NAFLD in the population,depending on the index used to define liver damage(increased serum alanine aminotransferase or ul-trasound),the presence of obesity,and ethnicity(147–153).Whether androgen excess may be involved in the pathophysiology of NAFLD in women with PCOS is still unclear(153–155).Thus,women with PCOS and meta-bolic risk factors and/or IR may be screened using serum markers of liver dysfunction.If serum markers are ele-vated,noninvasive quantification of fibrosis by ultra-sound and liver biopsy may be considered(156).

2.10Values and preferences

In making this recommendation we believe that a pri-ority should be placed on identifying this potentially major complication in women with PCOS with IR and/or met-abolic syndrome.However,there is currently no simple and reliable screening test for NAFLD because elevated serum transaminases have low sensitivity and specificity. We also believe that investigating the true prevalence of NAFLD in collaboration with gastroenterologists and hepatologists who can identify and apply reliable markers of NASH should be a research priority for future recom-mendations.Finally,there is no approved drug to treat NAFLD,although lifestyle therapy,insulin sensitizers, and antioxidants are thought to be beneficial.

Type2diabetes mellitus

2.11We recommend the use of an OGTT(consisting of

a fasting and a2-hour glucose level using a75-g oral glu-cose load)to screen for IGT and T2DM in adolescents and adult women with PCOS because they are at high risk for such abnormalities(1|QQQE).An HgbA1c may be con-sidered if a patient is unable or unwilling to complete an OGTT(2|QQEE).Rescreening is suggested every3–5 years,or more frequently if clinical factors such as central adiposity,substantial weight gain,and/or symptoms of diabetes develop(2|QQEE).

2.11Evidence

Adolescents and adult women with PCOS are at in-creased risk for IGT and T2DM(125,126,157).A diag-nosis of PCOS confers a5-to10-fold increased risk of developing T2DM(125,126,157).The overall preva-lence of glucose intolerance among US women and ado-lescents with PCOS was30–35%,and3–10%had T2DM.Nonobese women with PCOS had a10–15% prevalence of IGT and a1–2%prevalence of T2DM(125, 126,157).Limited studies have shown poor sensitivity of glycohemoglobin measure for detecting IGT(158,159). Those with T2DM had a significantly higher prevalence of first-degree relatives with T2DM,confirming family his-tory as an important risk factor.Multiple studies have also shown deterioration in glucose tolerance with follow-up (126,158,160).

Because of the high risk of IGT and T2DM in PCOS, periodic screening of patients to detect early abnormalities in glucose tolerance is recommended by several scientific organizations,although an interval for screening has not been specified(161–163).

2.11Values and preferences

In making this recommendation,the committee be-lieves in the strength of the evidence for a tight link be-tween PCOS and diabetes and believes that reducing mor-bidity of IGT/diabetes through early diagnosis and treatment outweighs any unforeseen harm or burdens re-sulting from the screening.We have recommended an OGTT over an HgbA1c because of the potential increased association between IGT and cardiovascular disease in women(164,165)and the potential to identify women at risk for gestational DM before pregnancy.Women with PCOS and IGT early in pregnancy are at greater risk for developing gestational DM(166),but there are currently

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insufficient data to recommend earlier screening for ges-tational DM in women with PCOS.Given the lack of ev-idence of the ideal period for rescreening,we have arbi-trarily recommended a period of3–5years. Cardiovascular risk

2.12Evidence

Members of the Androgen Excess and Polycystic Ovary Syndrome Society conducted a systematic analysis and published a consensus statement regarding assessment of cardiovascular risk and prevention of cardiovascular dis-ease in women with PCOS(167)(Table5).In addition to elevations in triglycerides and decreases in high-density lipoprotein(HDL)-cholesterol,women with PCOS have higher low-density lipoprotein(LDL)-cholesterol and non-HDL-cholesterol,regardless of BMI(117,167). Women with PCOS should have BMI and blood pressure measured at each clinic visit(and consider waist circum-ference if nonobese;?36inches is abnormal),and upon diagnosis of PCOS,additional testing should include a complete fasting lipid profile(total cholesterol,LDL-cho-lesterol,non-HDL-cholesterol,HDL-cholesterol,and triglycerides).

Although hypertension has been an inconsistent find-ing,women with PCOS appear to be at risk,at least later in life(168–170).Although in many studies both systolic and diastolic blood pressures are normal(168–171),in others,mean arterial pressures and ambulatory systolic pressures are elevated in women with PCOS compared with controls(172).In addition,the nocturnal drop in mean arterial blood pressure is lower,a finding that has also been demonstrated in obese adolescents with PCOS (171,173).

Anatomic evidence of early coronary and other vascu-lar disease in PCOS has been documented using varied techniques.Increased carotid artery intima-media thick-ness,an independent predictor of stroke and myocardial infarction,has been noted in PCOS compared with age-matched control women(174).Another marker of ath-erosclerosis,coronary artery calcification,is more com-mon in women with PCOS than in controls,even after adjusting for the effects of age and BMI(175–177).Echo-cardiography revealed both anatomic and functional dif-ferences between women with PCOS and controls includ-ing an increased left atrial size,increased left ventricular mass index,lower left ventricular ejection fraction(178), and diastolic dysfunction(179,180).Of note,the left ven-tricular mass index was linearly related to the degree of IR (178).

Some,but not all,studies(181–183)demonstrate im-paired endothelial function in women with PCOS,as re-flected in reduced brachial artery reactivity to hyperemia (184,185)and reduced vascular compliance,independent of obesity,IR,total T,or total cholesterol(186).Improved endothelial function has been documented when IR is at-tenuated with insulin-lowering medication or through weight loss(187–190).Discrepant findings between stud-ies may be the result of the heterogeneous nature of the populations studied.

Despite the increased prevalence of cardiovascular risk factors in women with PCOS,there are limited longitu-dinal studies,and those are too small to detect differences in event rates(191).Nevertheless,epidemiological data consistently point to increased cardiovascular risk in women with stigmata of PCOS.The Nurses’Health Study noted an adjusted RR of1.53(95%CI,1.24–1.90)for coronary heart disease in women with a history of irreg-ular menstrual cycles(192).In addition,a case-control study based on data in the Women’s Health Study data-base found that women who developed cardiovascular events had lower SHBG and higher calculated free andro-gen index(193).Among postmenopausal women evalu-ated for suspected ischemia,clinical features of PCOS were associated with more angiographic coronary artery disease and worsening cardiovascular event-free survival (194).

2.12Values and preferences

We acknowledge that there is a paucity of studies iden-tifying the rates of cardiovascular events and age of onset in women with PCOS;therefore,we have focused on car-diovascular disease risk factors.However,these may not necessarily equate with events or mortality.

3.0Treatment

HCs:indications and screening

3.2We recommend screening for contraindications to HC use via established criteria(see Table6and Ref.3) (1|QQQE).For women with PCOS,we do not suggest one HC formulation over another(2|QQEE).

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3.1–3.2Evidence

In women with PCOS,the progestin in HCs suppresses LH levels and thus ovarian androgen production,and the estrogen increases SHBG,thus reducing bioavailable an-drogen.In addition,some progestins have antiandrogenic properties,due to their antagonizing effects on the andro-gen receptor and/or to the inhibition of5?-reductase ac-tivity(195),which have led to claims of increased efficacy for specific formulations without supporting level1clin-ical trial evidence.The choice of oral vs parenteral HC(ie, patch or vaginal ring)is uncertain,although risk-benefit ratios may vary among preparations and with different progestins in oral contraception.There is some evidence that extended-cycle HCs(vs cyclic therapy)offer greater hormonal suppression and prevent rebound ovarian func-tion during the pill-free interval(196).

HCs,insulin sensitivity,and glucose tolerance The impact of HCs on carbohydrate metabolism in PCOS women is still in doubt because available studies are small and short-term,and they utilize varying methodol-ogies assessing endpoints.Studies,mostly cross-sectional in healthy women,found decreased insulin sensitivity and increased glucose response to a glucose load during HC use,although these results varied according to the estrogen dose and the type of progestin used(197–202).The resid-ual androgenic activity of the progestin contained in the HC formulation may influence glucose metabolism more than the dose of ethinyl estradiol(203–207).Some of these studies found that HCs had deleterious effects on glucose tolerance in obese,but not in lean,women with PCOS (208–210),but our systematic review did not confirm this (211).

No data are available assessing the long-term effect of HCs on glucose tolerance in nondiabetic and diabetic women with PCOS.A Cochrane meta-analysis concluded that HCs do not have a significant effect on glucose tol-erance,although this conclusion was based on limited and low-quality evidence(203).On the other hand,long-term studies performed in healthy women are promising be-cause HC use did not result in an increased incidence of T2DM either in the general population(202)or in women with a history of gestational DM(205,206)and was not associated with an increased risk of complications in women with type1diabetes(205).Therefore,the Amer-ican Diabetes Association along with the Centers for Dis-ease Control and Prevention(CDC)concluded that HCs are not contraindicated in women with diabetes without vascular complications(3,212).

HCs and lipids

As with glucose metabolism,the effect of HCs on lipid balance appears to be related to the formulation used.When estrogenic activity prevails,there is an increase in HDL-cholesterol and a decrease in LDL-cholesterol levels, whereas the opposite occurs when androgenic activity is higher(198,202,205,213–215).However,lipids seem to be less sensitive to the residual androgenic properties of the progestins(198,213,216–218).The ability of HCs to increase HDL-cholesterol levels is the most favorable and promising metabolic effect in PCOS and may overcome the negative impact on triglycerides and LDL-cholesterol because low HDL-cholesterol may be the critical link be-tween PCOS and the metabolic syndrome(208, 219–223).

HCs and body weight

The impact of HCs on body weight and fat distribution is similar between healthy women and women with PCOS. In particular,BMI and the waist-to-hip ratio were un-changed(209,211,220,224–226)or occasionally im-proved,independent of coexistent obesity(227).

3.1–3.2Values and preferences

In evaluating the benefits and risks of HC treatment in women with PCOS,we believed concerns related to un-treated menstrual dysfunction and quality of life related to anovulatory bleeding and hirsutism to be the primary con-siderations.Screening recommendations follow the cur-rent World Health Organization and CDC medical eligi-bility guidelines(Table6)(3,228).In making these recommendations,the committee strongly believes that larger controlled studies should be performed to evaluate the risk of long-term HC use in women with PCOS,par-ticularly in the presence of obesity,IR,and lipid disorders. There are insufficient data about whether women with PCOS face increased risk of thromboembolism on partic-ular HC preparations,although preparations may vary with respect to thromboembolic risk in the general pop-ulation.There are insufficient data to define the optimal duration of treatment with HCs.Women with severe hir-sutism or contraindications to hormonal contraception may require other therapies such as antiandrogens(spi-ronolactone,flutamide,finasteride,etc)or mechanical hair removal(laser,electrolysis,etc)(see hirsutism guide-lines in Ref.1).

Role of exercise in lifestyle therapy

16Legro et al Guidelines on PCOS J Clin Endocrinol Metab

3.3Evidence

It is well recognized in the general population that car-diovascular fitness,as measured by maximal oxygen con-sumption during exercise,is an independent predictor of cardiovascular mortality(229).This remains significant after adjustment for age,smoking,cholesterol measures, diabetes,hypertension,and family history of cardiovas-cular disease.Overall,there is good evidence in the general population that metabolic status is improved with exercise alone,and this reduces the risk of diabetes(230).Thirty minutes per day of moderate to vigorous physical activity is effective in reducing the development of metabolic syn-drome and diabetes(231,232).There are few trials of exercise therapy targeting women with PCOS,and no large randomized trials are available(233),but there is a suggestion of weight loss,improved ovulation,and de-creased IR(234–239).(Orio283,Thomson284,Steves vic285,Moro286,Thomson219,Palmba252)

3.3Values and preferences

Despite the limited evidence in PCOS,we suggest that the benefits of exercise in improving metabolic disease are strong enough to favor its recommendation,despite a pau-city of controlled trials available for review.

Role of weight loss in lifestyle therapy

a treatment for PCOS in normal-weight women.

3.4Evidence

Weight loss is generally recommended as a first-line therapy for obese women with PCOS.Weight loss in PCOS has been accomplished via lifestyle modification, use of medications designed for weight loss,and bariatric surgery(239–242).Studies performed after sustained weight loss(up to61%of initial weight)by bariatric sur-gery(241)or long-term dietary intervention(242)dem-onstrate that normalization of hyperandrogenemia can be achieved in obese women with PCOS.However,few data document subsequent improvements in hirsutism(243, 244).Menstrual function is improved in some women with as little as5–10%reduction in body weight(243); however,there are no long-term data available to assess the sustainability of menstrual cycling and few data on pregnancy outcomes after weight reduction.In the short term,there is some evidence for improved pregnancy rates and a decreased requirement for use of ovulation induc-tion or other fertility treatments in small uncontrolled tri-als of weight reduction(245,246),although there are no randomized controlled trials supporting weight loss in the improvement of pregnancy rates.The response to weight loss is variable;not all individuals have restoration of ovu-lation or menses despite similar weight reduction(241, 242,247,248).Although improvements in reproductive and metabolic status in PCOS have been described with all weight loss methods,there are no long-term studies avail-able in the literature for any of these approaches.Our own meta-analysis showed that weight loss had minimal effects on hirsutism and fertility,although there were significant improvements in some metabolic parameters(mainly gly-cemic effects related to improvements in fasting blood glu-cose and insulin levels)(249,250).

3.4Values and preferences

Taken together,the data in general populations and in our meta-analysis in women with PCOS support the role of lifestyle change for prevention and treatment of meta-bolic dysfunction.We found little evidence to support life-style change as an infertility treatment,although other reports(251)and national guidelines(252)have found a benefit.We attribute the failure to document additional benefits to the lack of well-designed studies in this area. Despite the relative lack of evidence that weight loss im-proves PCOS per se,we recommend lifestyle change in overweight and obese women with PCOS.There may also be some benefit in prevention of weight gain in women with PCOS who exercise regularly and eat sensibly. Use of metformin in adults

3.5We suggest against the use of metformin as a first-line treatment of cutaneous manifestations,for prevention of pregnancy complications,or for the treatment of obe-sity(2|QQEE).

3.6We recommend metformin in women with PCOS who have T2DM or IGT who fail lifestyle modification (1|QQQE).For women with PCOS with menstrual irreg-ularity who cannot take or do not tolerate HCs,we suggest metformin as second-line therapy(2|QQQE).

3.5–3.6Evidence

Metformin use has been suggested for a number of co-morbidities in women with PCOS.Some of these have been discussed in other guidelines including hirsutism(1) and treatment of cardiovascular risk factors in the primary prevention of cardiovascular disease and T2DM in pa-tients at metabolic risk(2).We agree with the suggestion that metformin should not be used for hirsutism.Met-formin studies have not been sufficiently powered to study acne(253,254).We agree with the recommendation that

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lifestyle management be considered first-line therapy for women with PCOS at increased metabolic risk(2).

Metformin has been associated with weight loss in some trials(76,230),but not in our meta-analysis(211).

A systematic review and meta-analysis demonstrated that there was significant weight loss in trials using metformin compared with placebo in women with PCOS(255).The absolute weight lost was estimated to be2.7kg,equaling a2.9%decrease in body weight,comparable to what oc-curs with orlistat treatment(256).However,metformin did not increase weight loss in patients using diet and ex-ercise programs(255,257).Taken together,when weight loss and lifestyle modifications are used to treat obesity, there is no benefit to adding metformin.Therefore,diet and exercise,not metformin,should be the first line of therapy in obese women with PCOS.Metformin may re-main a treatment consideration if the patient fails with diet and exercise.

One of the most important clinical outcomes demon-strated during metformin treatment was the improvement in menstrual cyclicity(258),leading to the possibility that metformin could be used to regulate menses(258).A sys-tematic review and meta-analysis demonstrated an im-provement in ovulation rate in women taking metformin (254).It is unknown whether ovulation occurs at a rate that is adequate to protect against endometrial carcinoma. Trials directly comparing metformin with oral contracep-tives demonstrate that metformin is not as effective as oral contraceptives for menstrual cycle regulation(208,259).

In patients with IGT,lifestyle modification with exer-cise and diet can decrease the progression to T2DM by 58%vs a31%decrease with metformin(230).Further-more,these benefits persist for up to10years after initi-ation,with lifestyle modification reducing diabetes inci-dence by34%and metformin reducing it by18%(230). However,intensive lifestyle modification,not metformin, was the only therapy that restored normal glucose toler-ance in subjects with IGT(230,260).Similar trials in women with PCOS and IGT are too small and limited in duration to determine whether metformin prevented T2DM or caused regression to normal glucose tolerance (259,261).Metformin is recommended for prevention of diabetes in women with PCOS and IGT when lifestyle modification is not successful.

3.5–3.6Values and preferences

The committee believes that a priority should be placed on effective treatment.Although the preferred treatment for prevention of T2DM is diet and lifestyle modification, there are a significant number of women who will fail this option.Although metformin treatment incurs expense and has the potential for side effects,the committee feels that metformin may provide an option for treatment of IGT in those women who fail lifestyle management. Treatment of infertility

3.7We recommend clomiphene citrate(or comparable estrogen modulators such as letrozole)as the first-line treatment of anovulatory infertility in women with PCOS (1|QQQE).

3.8We suggest the use of metformin as an adjuvant therapy for infertility to prevent OHSS in women with PCOS undergoing IVF(2|QQEE).

3.7–3.8Evidence

Clomiphene and metformin have been studied exten-sively for infertility in PCOS with multiple large multi-center trials(76,262–265).In almost all of these,clomi-phene has had improved pregnancy rates vs metformin,as well as providing comparable rates to injectable gonado-tropins(266).A recent meta-analysis of insulin sensitizers for the treatment of infertility in PCOS concluded that “the use of metformin for improving reproductive out-comes in women with PCOS appears to be limited”(254). In this review,there was no evidence that metformin im-proved live birth rates,whether it was used alone(pooled OR,1.00;95%CI,0.16–6.39)or in combination with clomiphene(pooled OR,1.05;95%CI,0.75–1.47)(254). Metformin has been recommended for use in infertility treatment partly because it is thought to be associated with monofollicular ovulation and lower multiple pregnancy rates.None of the trials have been adequately powered to detect differences in multiple pregnancy rates,although multiple pregnancies with metformin have been rare in these trials(?5%)(76,262–266)and more common (around5%)with clomiphene.The benefit of multiple pregnancy reduction must be balanced against the sub-stantially lower pregnancy rates and lower fecundity per ovulation with metformin alone(76).

Aromatase inhibitors have been proposed as oral agents,and although current cumulative evidence suggests an uncertain risk/benefit ratio to treat infertility(267),a recent large NIH-sponsored,multicenter,double-blind, randomized,clinical trial(n?750subjects)has been com-pleted with a marked superiority in live birth rate of letro-zole over clomiphene for the treatment of anovulatory infertility in women with PCOS(with a comparable safety and tolerance profile between drugs)(268).These results may alter recommendations for front-line treatment in subsequent revisions of this guideline.Although concerns about the relative teratogenicity of letrozole compared to clomiphene remain,this trial and other publications are reassuring(269).The relative success of two drugs that modulate estrogen action to achieve pregnancy further

18Legro et al Guidelines on PCOS J Clin Endocrinol Metab

underscores this class of drugs as first-line treatment when compared with insulin sensitizers.

Metformin may have some use as an adjuvant agent for infertility in select women with PCOS,although it is likely to be more effective in obese women than nonobese women(74,267,270).A systematic review of metformin noted that in clomiphene-resistant women,metformin plus clomiphene led to higher live birth rates than clomi-phene alone(RR,6.4;95%CI,1.2–35);metformin also led to higher live birth rates than laparoscopic ovarian drilling)(RR,1.6;95%CI,1.1–2.5)(271).In addition, metformin may prevent the development of OHSS in women with PCOS receiving gonadotropin therapy cycle for IVF(249,272).

The routine use of metformin during pregnancy in women with PCOS is unwarranted,although it may be useful to treat gestational diabetes(273).A meta-analysis of randomized,controlled trials demonstrated no effect of metformin on abortion rate(OR,0.89;95%CI,0.59–1.75;P?.9)(238).A large,randomized,controlled trial demonstrated no difference in the prevalence of pre-ec-lampsia,preterm delivery,or gestational DM in women with PCOS treated with metformin during pregnancy (274).Metformin was associated with a significantly higher incidence of gastrointestinal disturbance,but no serious maternal or fetal adverse effects(76,254,274).

3.7–3.8Values and preferences

The committee recognizes that the use of letrozole for the treatment of infertility in PCOS is promising.How-ever,we believe,as with all recent discoveries,that pub-lication of the finding and digestion,debate,and indepen-dent confirmation in other studies are necessary to establish letrozole as front-line infertility therapy.The committee also acknowledges that metformin may have some benefit as an adjuvant agent in the treatment of in-fertility in obese women,despite conflicting systematic reviews on the topic.Other national guidelines have fa-vored metformin more than in the current guidelines (252).We recommend discontinuing metformin(when used to treat PCOS as opposed to T2DM)with a positive pregnancy test,given the lack of benefit associated with its routine use during pregnancy.In the face of resistance (anovulation)or failure(no conception despite ovulation) with front-line oral agents,referral to a subspecialist in infertility for further care is recommended.

Use of other drugs

3.9We recommend against the use of insulin sensitiz-ers,such as inositols(due to lack of benefit)or thiazolin-ediones(given safety concerns),for the treatment of PCOS (1|QQQE).

3.10We suggest against the use of statins for the treat-ment of hyperandrogenism and anovulation in PCOS until additional studies demonstrate a favorable risk-benefit ra-tio(2|QQEE).However,we suggest statins in women with PCOS who meet current indications for statin therapy (2|QQEE).

3.9–3.10Evidence

Although a large phase II study sponsored by a phar-maceutical company provided evidence of a dose-response improvement in reproductive and metabolic abnormali-ties in PCOS with troglitazone(76),there have been no subsequent large randomized trials of thiazolidinediones in PCOS(254).Both troglitazone(hepatic toxicity)and rosiglitazone(excess cardiovascular events)have been re-moved from the market by the US Food and Drug Admin-istration(FDA),and a recent FDA advisory linked piogli-tazone to bladder cancer.The risk-benefit ratio may also be less favorable for infertility because animal studies sug-gest that thiazolidinediones may be associated with fetal loss(FDA Pregnancy Category C).Although there are no known serious adverse events related to D-chiro-inositol therapy,there are concerns about the formulation of the drug and limited evidence of its efficacy(275).

Dyslipidemia,including elevations in circulating LDL-cholesterol,the precursor to sex steroid biosynthesis,is common in women with PCOS.Statins have multiple ac-tions that include inhibition of the enzyme hydroxymeth-ylglutaryl coenzyme A reductase,which leads to decreased production of cholesterol(thus reducing circulating con-centrations of cholesterol).In addition,there is some ev-idence that ovarian T production may be reduced by ad-ministration of statins(276,277).This effect may be due, at least in part,to inhibition of theca cell growth and by decreasing the concentration of precursor for production of androstenedione(278).Furthermore,statins appear to have antioxidant properties.Clinical trials of statins alone or in combination with other medications among women with PCOS are limited in number,and conclusive evidence that statins ameliorate PCOS symptoms is lacking,al-though improvements in hyperandrogenemia have been noted(276,279–281).Further recent data show that sta-tin use may increase the risk for developing T2DM(282).

3.9–3.10Values and preferences

There are few data to support the use of newer diabetes drugs that improve insulin action,such as the glucagon-like peptide-1analogs or the dipeptidyl peptidase-4inhib-itors in women with PCOS.There are potential serious side effects to statins(myopathy and renal impairment), which may be more common in women then men,and these drugs are theoretically teratogenic(Pregnancy Cat-

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egory X),which merits caution in their use.Until addi-tional studies demonstrate a clear risk-benefit ratio favor-ing statin therapy for other aspects of PCOS,statins should only be used in women with PCOS who meet current in-dications for statin treatment.

Treatment of adolescents

3.11We suggest HCs as the first-line treatment in ad-olescents with suspected PCOS(if the therapeutic goal is to treat acne,hirsutism,or anovulatory symptoms or to prevent pregnancy)(2|QQEE).We suggest that lifestyle therapy(calorie-restricted diet and exercise)with the ob-jective of weight loss should also be first-line treatment in the presence of overweight/obesity(2|QQEE).We suggest metformin as a possible treatment if the goal is to treat IGT/metabolic syndrome(2|QQEE).The optimal dura-tion of HC or metformin use has not yet been determined.

3.11–3.12Evidence

The treatment of PCOS in adolescents is controversial. Many support the symptom-driven approach,whereas others support an approach targeting the underlying re-productive/hormonal and metabolic abnormalities asso-ciated with PCOS(30).There are no adequately powered, randomized,double-blind,placebo-controlled trials in adolescents with PCOS.The dual goal of treating hyperan-drogenism and providing contraception prompts the use of HCs as the mainstay of therapy for adolescents with PCOS(29,283,284).Additionally,benefits such as nor-mal menses and decreased acne and hirsutism are typically of the greatest importance to an adolescent(285).Some of these can also be improved by lifestyle therapy and weight loss.

Nonetheless,the initiation of HCs in early adolescence is controversial,and few data exist to guide recommen-dations.After excluding other causes of primary amenor-rhea,HCs could be considered in a patient with proven hyperandrogenism if the patient has achieved a sexual ma-turity of Tanner stage4–5when menarche should have occurred(286).The best HC for adolescents and the ap-propriate duration of therapy are uncertain(287).A lon-ger duration of treatment with a combined HC may lead to a lower chance of developing signs of hyperandro-genism as an adult(23).Some authors suggest continuing with HC until the patient is gynecologically mature(de-fined by these authors as5years postmenarcheal)or has lost a substantial amount of weight(288).

Small,short-term studies demonstrate that metformin restores menstrual regularity and improves hyperandro-genemia,IR,and glucose intolerance in obese and nono-bese adolescents with PCOS(289–291).Two sequential, randomized,placebo-controlled trials of metformin in ad-olescents with PCOS demonstrated improvements in hy-perandrogenemia,ovulation,and dyslipidemia(223). These promising but limited data lead to the impression that metformin may be more beneficial for adolescents with PCOS than it is for adults with this condition(292, 293).The necessary duration of treatment is yet to be established,and the limited available data are conflicting. In one study,the beneficial effects of metformin on men-strual cycles persisted for6months after discontinuation of metformin(294),but in another study the effects were lost3months after discontinuing the medication(290). There is no literature regarding long-term use in adolescents.

Given the limited data,it is necessary to extrapolate from adult data in making adolescent treatment recom-mendations.Thus,lifestyle therapy should be recom-mended in overweight/obese adolescents.Metformin ther-apy may also be considered for treatment of PCOS based on the limited studies cited above.Because lifestyle change and/or metformin may increase ovulatory frequency and because cutaneous manifestations are common,appropri-ate contraception must be recommended to a sexually ac-tive teenager.

3.11–3.12Values and preferences

In making these suggestions the committee recom-mends individualizing therapy of PCOS and weighing the pros and cons of one therapeutic approach against the other until such time when strong evidence from well-performed,long-term,randomized,controlled trials in ad-olescents becomes available.In recommending metformin in adolescents with PCOS,the committee believes that:1) early treatment with metformin and/or lifestyle changes may yield promising and preventative results;2)priority should be placed on treating PCOS not only as a hormon-al/reproductive disorder,but also as a dysmetabolic syn-drome characterized by IR;and3)the safety of metformin and its reported outcomes outweigh the limited data.Be-cause adolescents have higher user failure rates for hor-monal contraception and because of the known teratoge-nicity of antiandrogens during pregnancy,we have avoided any specific recommendation of antiandrogens in this population;however,these agents may be beneficial in selected individuals.We note that our treatment recom-mendations in adolescents do not extend to girls with pre-cocious pubarche,given the uncertain risk-benefit ratio in this age group.

20Legro et al Guidelines on PCOS J Clin Endocrinol Metab

多囊卵巢综合征诊治指南

多囊卵巢综合征诊治指南疾病简介多囊卵巢综合征(polycystic ovary syndrome, PCOS)是生育年龄妇女常见的一种复杂的内分泌及代谢异常所致的疾病，以慢性无排卵(排卵功能紊乱或丧失)和高雄激素血症(妇女体内男性激素产生过剩) 为特征，主要临床表现为月经周期不规律、不孕、多毛和/或痤疮，是最常见的女性内分泌疾病。疾病分类根据PCOS国际诊断标准(详见诊断部分)诊断的PCOS可以进行亚型分型，以便于个体化治疗选择： 1型：经典PCOS，超声卵巢多囊样改变及高雄激素的临床表现和/或高雄激素血症; 2型：超声卵巢多囊样改变及稀发排卵或无排卵; 3型：NIH标准PCOS，高雄激素的临床表现和/或高雄激素血症及稀发排卵或无排卵; 4型：同时具备超声卵巢多囊样改变、高雄激素的临床表现和/或高雄激素血症及稀发排卵或无排卵，此型也被称为经典PCOS。发病原因目前对于PCOS病因学研究有非遗传理论和遗传理论两种。 PCOS非遗传学理论研究认为孕期子宫内激素环境影响成年后个体的内分泌状态，孕期暴露于高浓度雄激素环境下，如母亲PCOS史、母亲为先天性肾上腺皮质增生症高雄激素控制不良等，青春期后易发生排卵功能障碍。 PCOS遗传学理论此理论的主要根据PCOS呈家族群居现象，家族性排卵功能障碍和卵巢多囊样改变提示该病存在遗传基础。高雄激素血症和(或)高胰岛素血症可能是 PCOS 家族成员同样患病的遗传特征，胰岛素促进卵巢雄激素生成作用亦受遗传因素或遗传易感性影响。稀发排卵、高雄激素血症和卵巢多囊样改变的家族成员中女性发生高胰岛素血症和男性过早脱发的患病率增高。细胞遗传学研究结果显示PCOS可能为X连锁隐性遗传、常染色体显性遗传或多基因遗传方式。通过全基因组扫描的发现最大量的与PCOS相关的遗传基因，如甾体激素合成及相关功能

多囊卵巢综合征典型病历.docx

多囊卵巢综合征典型病历基患者姓名林×× 本病历号C556788 情性别女况年龄28 体重68kg 身高163cm 血型 B 型 Rh 因子＋入院日期2000-12-08 出院日期2000-12-16 家庭住址联系电话邮政编码100083 主月经紊乱伴月经量多 5 年余。诉婚后 6 年未孕。现患者既往月经规则。 5 年多前无明显诱因开始出现月经紊乱，周期10 日病至数月不等，经期9 日至 20 多日，经量较前增多 2~3 倍，经期伴头晕、乏力史和下腹轻微坠痛。病发后 1 年在当地医院诊断为功能失调性子宫出血，使用复方炔诺酮（避孕 1 号）治疗 3 个周期，用药期间月经规则，经量中等，经期 5~6 天。停药 2 个月后，再次出现月经紊乱。此后，间断、不规则的应用中西药治疗（具体药物不详），效果不理想，症状反复。 2 年前，自测基础体温（ BBT ）3 个月均提示为单相型，随后给予克罗米酚100mg，每日一次，连用 5 日，促排卵治疗 3 个周期。治疗期间月经周期尚规则，月经量无减少，基础体温呈不典型双相型。 1 年前在当地医院行诊断性刮宫，术中探宫腔深 8.5cm，取子宫内膜病理检查结果为子宫内膜复杂型增生。诊刮术后采用雌孕激素序贯疗法行“人工周期” 3 个月，随后采用克罗米酚100mg，每日一次，

连用 5 日的方案促排卵治疗 3 个周期。近半年来症状又复出现，转诊本院并收入院。发病以来，精神状况尚好，食欲良好，体重增加10kg。既否认肝炎、结核等传染病史或接触史。无高血压、糖尿病、心脏病、肾往病等内科合并症。无重大外伤史或手术史。无输血史。否认药物过敏史。史个出生于北京，大学文化程度，个体经商。否认有毒物、放射线接触史，人无烟酒嗜好。史婚初潮 13 岁，7 天/28～30 天，近 5 年月经不规则详见现病史。末次月经为 11-28，育至今未净。 96 年结婚，爱人体健，婚后性生活正常，无避孕，未孕。史家父亲、母亲体健，否认遗传病家族史。族史体体温： 36.3℃，脉搏： 80 次 /分，呼吸 20 次/分，血压： 100/60mmHg 格发育正常，营养良好，体态偏胖，表情自然，自动体位，查体合作。皮检肤、粘膜无黄染，略苍白，呈慢性贫血外貌。浅表淋巴结未及肿大。头颅无查畸形，双眉无脱落，双眼睑无浮肿及下垂，巩膜无黄染，双瞳等大等圆，对光反射灵敏。鼻腔畅。外耳道通畅、无异常分泌物，乳突区无压痛。口唇无紫绀，口腔粘膜无溃疡，伸舌居中，咽不红，扁桃体不大。颈软，气管居中，甲状腺未及肿大，未见颈静脉怒张，颈部未闻及血管杂音。胸廓无畸形及压痛。双侧乳腺未及结节。双肺叩清，双肺呼吸音清，未闻及干湿罗音。心界无扩大，律齐，各瓣膜区未闻及心杂音及附加音。双侧桡动脉脉搏对称有力，双侧足背动脉搏动对称。周围血管征阴性。腹部平坦，无压痛、反跳痛，肝脾肋下未及，腹部未触及包块。双肾区无叩痛，脊柱、四肢无畸形，双下肢无水肿。生理反射存在，病理反射未引出。专外阴：正常科阴道：通畅，内见少许暗红色血性分泌物

多囊卵巢综合征的诊断和治疗指南

多囊卵巢综合征的诊断和治疗指南多囊卵巢综合征（Polycystic Ovary Syndrome，PCOS）是妇科内分泌临床中十分常见的疾病，在我国有着庞大的患者群。PCOS临床表现异质性，不但严重影响患者的生殖功能，而且雌激素依赖性肿瘤如子宫内膜癌发病率增加，相关的代谢失调包括高雄激素血症、胰岛素抵抗、糖代谢异常、脂代谢异常、心血管疾病危险也增加。PCOS至今病因尚不明确，诊断标准不统一，治疗药物的使用方案混乱，对远期并发症也缺乏合理的防治措施，制定中国的诊治规范迫在眉睫。中华医学会妇产科学分会内分泌学组于2006年11月18日在重庆召开了妇科内分泌学专家扩大会议，会议经过热烈的讨论初步制定了目前中国的PCOS诊断、治疗专家共识，内容如下：流行病学 PCOS占生育年龄妇女的5～10％（中国尚无确切发病率），占无排卵性不孕症患者的30～60％，甚至有报道高达75％。以ESHRE/ASRM建议诊断标准，济南市、烟台市育龄妇女PCOS患病率分别为6.46％和7.2％；济南市汉族PCOS患者主要分布在35岁以下群体。我国尚缺少全国性、大样本、多中心研究。 PCOS的病因多囊卵巢综合征的确切病因尚不清楚，研究表明它可能是由某些遗传基因与环境因素相互作用引起的。一、遗传因素 PCOS有家族聚集现象，被推测为一种多基因病，目前的候选基因研究涉及胰岛素作用相关基因、高雄激素相关基因和慢性炎症因子等（相关候选基因详见附件一）。二、环境因素环境因素包括宫内高雄激素、抗癫癎药物、地域、营养和生活方式等，可能是PCOS的危险因素、易患因素、高危因素，不能算是病因，应进行流调后完善环境与PCOS关系的认识。

多囊卵巢综合征的诊断和治疗专家共识带版(终审稿)

多囊卵巢综合征的诊断和治疗专家共识带版文稿归稿存档编号：[KKUY-KKIO69-OTM243-OLUI129-G00I-FDQS58-

多囊卵巢综合征的诊断和治疗专家共识多囊卵巢综合征（PolycysticOvarySyndrome，PCOS）是妇科内分泌临床中十分常见的疾病，在我国有着庞大的患者群。PCOS临床表现异质性，不但严重影响患者的生殖功能，而且雌激素依赖性肿瘤如子宫内膜癌发病率增加，相关的代谢失调包括高雄激素血症、胰岛素抵抗、糖代谢异常、脂代谢异常、心血管疾病危险也增加。PCOS至今病因尚不明确，诊断标准不统一，治疗药物的使用方案混乱，对远期并发症也缺乏合理的防治措施，制定中国的诊治规范迫在眉睫。中华医学会妇产科学分会内分泌学组于2006年11月18日在重庆召开了妇科内分泌学专家扩大会议，会议经过热烈的讨论初步制定了目前中国的PCOS诊断、治疗专家共识，内容如下：流行病学 PCOS占生育年龄妇女的5～10％（中国尚无确切发病率），占无排卵性不孕症患者的30～60％，甚至有报道高达75％。以ESHRE/ASRM建议诊断标准，济南市、烟台市育龄妇女PCOS患病率分别为6.46％和7.2％；济南市汉族PCOS患者主要分布在35岁以下群体。我国尚缺少全国性、大样本、多中心研究。 PCOS的病因

多囊卵巢综合征的确切病因尚不清楚，研究表明它可能是由某些遗传基因与环境因素相互作用引起的。一、遗传因素 PCOS有家族聚集现象，被推测为一种多基因病，目前的候选基因研究涉及胰岛素作用相关基因、高雄激素相关基因和慢性炎症因子等（相关候选基因详见附件一）。二、环境因素环境因素包括宫内高雄激素、抗癫癎药物、地域、营养和生活方式等，可能是PCOS的危险因素、易患因素、高危因素，不能算是病因，应进行流调后完善环境与PCOS关系的认识。 PCOS诊断标准的演变过程 PCOS的诊断标准一直是本领域专家争论的问题。一、1935年，Stein和Leventhal描述了闭经、多毛和双侧卵巢多囊性增大（polycysticovary，PCO）的无排卵相关综合征（S-L征）。二、1990年NIH制定了PCOS诊断标准：和无排卵；临床或生化显示高雄激素血症；除外其他引起高雄激素血症的疾病，未将卵巢的多囊改变（p olycysticovary，PCO）作为诊断的主要症状。

多囊卵巢综合征的治疗及症状

多囊卵巢综合征的治疗及症状多囊卵巢综合征是育龄女性最常见的内分泌紊乱性疾病，直接导致月经异常、不孕不育等。近两年来，在严密监测下，多采用穴位注射尿促性腺激素治疗多囊卵巢综合征不孕不育患者，具体报告如下：一般资料184例多囊卵巢综合患者均为我院门诊患者。就诊的主要原因是不孕或月经异常。按就诊顺序随机分为2组。穴位注射治疗组(治疗组)100例，传统肌肉注射组(对照组)84例。治疗组年龄21—37岁，平均25．9岁；病程8个月一12年．平均4．5年；月经均异常，其中继发闭经19例，月经稀发29例，多毛2例．肥胖10例；妇科检查：--N或双侧卵巢增大4例。对照组年龄24—36岁，平均26．4岁；病程6个月一10年，平均4．2年；月经均异常，其中月经稀发26例，继发闭经10例，多毛2例，肥胖lo例：妇科检查：一侧或双侧卵巢增大3例。2组年龄、平均病程差异无显著性(P>0．05)。采用传统肌肉注射疗法。疗程均为3个月经周期。观察2组卵地发育及排卵现象。统计受孕率及不是反应情况。结果治疗组曲周期排卵率达86．8％，总妊娠率为68．7％，无明显不良反应发生。而对照组周期排卵率为65．5％。总妊娠率为33 3％，有2例并发卵泡过度刺激综合征，1倒未破裂卵泡黄索化综合征。2组疗效及不良反应比较差异有显著性(P<0．05和P<0．01)。结论穴位注射尿促性腺激素用药量多、卵泡质量好，排卵率、妊娠率高，流产率、多胎率低，不良反应较多，可采用传统的的食疗方阿胶黄精丸调理，虽

然见效慢，但效果和安全上，还是完全可以放心的。 1970年以来，已对PCOS做了大量的研究工作，可是其发病机制迄今仍不清楚。20世纪70年代发现许多PCOS患者的血清LH/FSH比值偏高，因此当时认为促性腺激素分泌紊乱是PCOS发病的主要原因。从20世纪80~90年代迄今对PCOS发病机制的研究主要集中在雄激素分泌过多和胰岛素抵抗方面。目前认为PCOC 的发病机制非常复杂，下丘脑-垂体-卵巢轴紊乱、胰岛素抵抗、肾上腺皮质功能异常，一些生长因子和遗传因素都牵涉其中。此外，多囊卵巢综合征(PCOS)具有典型的家族积聚性，与普通人群相比，多囊卵巢患者的姐妹更容易发生月经紊乱、高雄激素血症和多囊卵巢。因此，目前许多学者认为遗传因素在PCOS的发病机制中起重要作用，但是PCOS的高度异质性却提示其遗传模式可能非常复杂。而精神、饮食、生活、工作等因素又常使一些多囊卵巢综合征的病情继续发展，使其在治疗上更加难以逆转。

多囊卵巢综合征治疗三步走

多囊卵巢综合征治疗三步走多囊卵巢综合征是引起女性月经不调、不孕的常见的妇科内分泌疾病，虽然该病无法彻底治愈，但是经过生活方式的调整和治疗，多数多囊患者都能顺利怀上宝宝。调整生活方式、调节内分泌和药物促排卵是经典的治疗多囊卵巢综合征的方案，其中第一步就是调整生活方式。第一步：调整生活方式虽然多囊的的病因尚不明确，但多数观点认为是遗传和环境因素相互作用的结果，肥胖、高雄激素和胰岛素抵抗就是那三个互为因果、相互促进的因素。要对抗这三个因素就要做到“禁糖、少油、多运动、降体重”，这几点做好，有一部分患者甚至可能自行恢复月经，正常受孕！即使没有恢复正常月经，调整生活方式也会为后面的治疗打下坚实的基础。第二步：调整内分泌调整内分泌的目的不是为了调整月经，而是为了让卵泡发育成熟，能排出优质的卵子，减少流产的概率，还能改善因长期月经不调而造成的子宫内膜问题。好种子（受精卵）、好土壤（子宫内膜）、好环境（女性体内的激素水平），在这样的条件下才能更好的试孕。多囊患者在开始治疗前，都会进行血激素测定，包括雄激素、促黄体生成素、促卵泡生成素、泌乳素等。高雄激素、高泌乳素都会造成不排卵。促黄体生成素和促卵泡生成素的比例异常，可能造成流产。另外，对于多囊患者还会进行胰岛素抵抗的测试，胰岛素抵抗会引发妊娠期的一系列并发症，而且可能影响卵子质量从而引起流产。医生会根据检查结果，帮多囊患者量身定制一套调整内分泌的治疗方案，通常采用中西医结合的方法，如达英-35配合和颜坤泰胶囊连续治疗三个月，可显著改善多囊患者内分泌，促进优势卵泡发育，在医生的指导下停药，同房试孕，妊娠率更高。第三步：药物促排卵 1 / 2

多囊卵巢综合征诊断标准和诊疗指南介绍_崔琳琳

·标准与指南· 多囊卵巢综合征（polycystic ovarian syndrome，PCOS）是一种常见的妇科内分泌疾病。1935年Stein和Leventhal首次对7位卵巢多囊性增大的病例进行了描述，其症状包括月经稀发或闭经、慢性无排卵性不孕、多毛、肥胖等。在之后的几十年里，对该病的认识逐渐加深，对其临床特征的报道也日趋增加。但其临床异质性使得PCOS的病因难以明确，而临床表现的多样性也给其诊断造成了困难。目前为止，国际上先后提出了3个诊断共识即美国国立卫生研究院（National Institutes of Health，NIH）提出的NIH标准、欧洲生殖和胚胎医学会（European Society of Human Reproduction and Embryology，ESHRE）与美国生殖医学会（American Society for Reproductive M edicine，ASRM）提出的鹿特丹标准和美国雄激素学会（Androgen Excess Society，AES）提出的AES标准。不过，哪一项标准更适于临床应用还存在争议。 NIH标准 1990年4月，在NIH的资助下，专家组第一次对PCOS的诊断做出定义[1]。NIH标准提出PCOS诊断需满足以下条件：①稀发排卵或无排卵。②高雄激素的临床和（或）生化表现。③排除可引起排卵障碍或高雄激素的其他已知疾病如高泌乳素多囊卵巢综合征诊断标准和诊疗指南介绍崔琳琳陈子江△ 【摘要】多囊卵巢综合征（PCOS）是育龄期女性常见的妇科内分泌疾病。由于其临床表现的多样性和高度异质性以及与正常人群表现的重叠，PCOS的诊断一直存在较大争议。自1935年首次发现这一疾病以来，国际上先后出现了3个诊断共识，分别是美国国立卫生研究院（NIH）提出的NIH标准；欧洲生殖和胚胎医学会（ESHRE）与美国生殖医学会（ASRM）提出的Rotterdam标准以及美国雄激素学会（AES）提出的AES标准。2011年，在中国卫生部的支持下，中华医学会妇科内分泌学组根据汉族女性的特点，通过大样本资料的研究，完成了中国PCOS诊断标准的制定。诊断方面的争议也影响了治疗的规范化。目前业内较为公认的是2008年ESHRE和ASRM提出的PCOS不孕症治疗共识。主要对PCOS几个诊断标准进行介绍，同时对PCOS不孕症国际治疗共识进行解读。【关键词】多囊卵巢综合征；不育，女（雌）性；诊断；治疗；标准 Diagnosis Criteria and Guidelines for the Diagnosis and Treatment of PCOS CUI Lin-lin，CHEN Zi-jiang. Center for Reproductive Medicine，Provincial Hospital Affiliated to Shandong University，National Research Center for Assisted Reproductive Technology and Reproductive Genetics，the Key Laboratory for Reproductive Endocrinology of Ministry of Education，Shandong Provincial Key Laboratory of Reproductive Medicine，Jinan250021，China Corresponding author：CHEN Zi-jiang，E-mail：chenzijiang@https://www.doczj.com/doc/8112014258.html, 【Abstract】Polycystic ovary syndrome（PCOS）is one of the most common endocrinal and metabolic diseases in fertile woman.There are many controversies on PCOS diagnosis because of its diversity and heterogeneity in clinical manifestations，and the phenotypes overlapping with normal individuals.Since PCOS was described for the first time in1935，three consensuses have been proposed successively.They are NIH criteria by National Institutes of Health，Rotterdam criteria by both European Society for Human Reproduction and Embryology（ESHRE）and American Society for Reproductive Medicine（ASRM），and AES criteria by Androgen Excess Society.In2011，“Diagnosis criteria for Polycystic Ovary Syndrome”was established by Chinese Medical Association，which was supported by Ministry of Health of China.This Chinese criteria was based on the currently available evidences in Han Chinese.The contradictions of diagnosis have influence on the standardized treatment.So far，the consensus，reached by PCOS Consensus Workshop Group，on the treatment of PCOS infertility，has been well-accepted.This paper described the main criteria of PCOS and the consensus on the treatment of PCOS infertility. 【Key words】Polycystic ovary syndrome；Infertility，female；Diagnosis；Therapy；Criteria （J Int Reprod Health蛐Fam Plan，2011，30：405-408）作者单位：250021济南，山东大学附属省立医院生殖医学中心、国家辅助生殖与优生工程技术研究中心、生殖内分泌教育部重点实验室、山东省生殖医学重点实验室 △通信作者：陈子江，E-mail：chenzijiang@https://www.doczj.com/doc/8112014258.html,

多囊卵巢综合征诊疗常规

多囊卵巢综合征 ·起病多见于青春期，以雄激素过高的临床或生化表现、持续无排卵、卵巢多囊改变为特征。．内分泌特征为血清LH 升高，雄激素升高，E1/E2>1 ·治疗包括降低雄激素水平，调整月经周期，改善胰岛素抵抗，促进排卵。多囊卵巢综合征（polycystic ov syndrome, PCOS ）是一种最常见的妇科内分泌疾病之一。在临床上以雄激素过高的临床或生化表现持续无排卵、卵巢多囊改变为特征，常伴有胰岛素抵抗和肥胖。其病因至今尚未阐明，目前研究认为，其可能是由于某些遗传基因与环境因素相互作用所致。［内分泌特征与病理生理］内分泌特征有：①雄激素过多；②雌酮过多；③黄体生成激素／卵泡剌激素（LH/FSH ）比值增大；④胰岛素过多。产生这些变化的可能机制涉及 1. 下丘脑－垂体卵巢轴调节功能异常由于垂体对促性腺激素释放激素（GnRH ）敏性增加，分泌过量LH ，剌激卵巢间质卵泡膜细胞产生过量雄激素。卵巢内高雄激素抑制卵泡成熟，不能形成优势卵泡，但卵巢中的小卵泡仍能分泌相当于早卵泡期水平的雌二醇（E2 ），加之雄稀二酮在外周组织芳香化酶作用下转化为雌酮（E1 ），形成高雌酮血症。持续分泌的雌酮和一定水平雌二醇作用于于丘脑及垂体，对LH 分泌呈正反馈，使LH 分泌幅度及频率增加，呈持续高水平，无周期性，不形成月经中期LH 峰，故无排卵发生。雌激素又对FSH 分泌呈负反馈，使FSH 水平相对降低，LH/FSH 比例增大。高水平LH 又促进卵巢分泌雄激素；低水平FSH 持续剌激，使卵巢内小卵泡发育停止，无优势卵泡形成，从而形成雄激素过多持续元排卵的恶性循环，导致卵巢多囊样改变。 2. 胰岛素抵抗和高胰岛素血症外周组织对胰岛素的敏感性降低，胰岛素的生物学效能低于正常，称为胰岛素抵抗（insulin resistance 50% 患者存在不同程度的胰岛素抵抗及代偿性高胰岛素血症。过量胰岛素作用于垂体的胰岛素受体（insulin receptor ），可增强LH 释放并促进卵巢和肾上腺分泌雄激素，又通过抑制肝脏性激素结合球蛋白（sex hormone-binding globulin, SHBG ）合成，使游离睾酮增加。 3. 肾上腺内分泌功能异常50% 患者存在脱氢表雄酮（DHEA ）及脱氢表雄酮硫酸盐（DHEAS) 升高，可能与肾上腺皮质网状带P450cl7α 酶活性增加、肾上腺细胞对促肾上腺皮质激素（ACTH ）敏感性增加和功能亢进有关。脱氢表雄酮硫酸盐升高提示过多的雄激素来自肾上腺。｛病理］ 1. 卵巢变化大体检查双侧卵巢均匀性增大，为正常妇女的2 ～5 倍，呈灰白色，包膜增厚、坚韧。切面见卵巢白膜均匀性增厚，较正常厚2 ～4 倍，白膜下可见大小不等、≥12 个囊性卵泡，直径在2--9mm。镜下见白膜增厚、硬化，皮质表层纤维化，细胞少，血管显著存在。白膜下见多个不成熟阶段呈囊性扩张的卵泡及闭锁卵泡，无成熟卵泡生成及排卵迹

(整理)临床指南多囊卵巢综合征的诊断和治疗专家共识

临床指南多囊卵巢综合征的诊断和治疗专家共识中华医学会妇产科学分会内分泌学组多囊卵巢综合征（polycystic ovary syndrome，PCOS）是妇科内分泌临床常见的疾病，在我国有着庞大的患者群。PCOS临床表现异质性，不但严重影响患者的生殖功能，而且雌激素依赖性肿瘤如子宫内膜癌发病率增加，相关的代谢失调包括高雄激素血症、胰岛素抵抗、糖代谢异常、脂代谢异常、心血管疾病危险也增加。PCOS至今病因尚不明确，诊断标准不统一，治疗药物的使用方案混乱，对远期并发症也缺乏合理的防治措施，因此，制定诊治规范迫在眉睫。中华医学会妇产科学分会内分泌学组于2006年11月18日在重庆召开了妇科内分泌学专家扩大会议，会议经过热烈的讨论，初步达成了目前中国的PCOS诊断、治疗专家共识，经过1年多40余场关于PCOS诊断、治疗专家共识的全国巡讲，广泛征求各界意见，2007年11月24日中华医学会妇产科学分会内分泌学组在海南三亚召开了PCOS诊断和治疗专家共识临床问题解答专家会，最终出台了适合目前中国情况的PCOS诊断和治疗专家共识。一、PCOS概述 PCOS占生育年龄妇女的5％～10％（中国尚无确切患病率报道），占无排卵性不孕症患者的30％～60％。目前，我国尚缺少全国性、大样本、多中心的研究结果。PCOS的确切病因尚不清楚，有研究认为，其可能是由于某些遗传基因与环境因素相互作用引起的。 1.遗传因素：PCOS有家族聚集现象，被推测为一种多基因病，目前的候选基因研究涉及胰岛素作用相关基因、高雄激素相关基因和慢性炎症因子等。 2.环境因素：宫内高雄激素、抗癫痫药物、地域、营养和生活方式等，可能是PCOS 的危险因素、易患因素或高危因素，尚需进行流行病学调查后，完善环境与PCOS 关系的认识。二、PCOS的诊断在现阶段推荐2003年欧洲人类生殖和胚胎学会与美国生殖医学学会的专家会议推荐的标准，在中国使用，待中国国内的流行病学调查和相关研究有了初步结果之后，再斟酌是否对此诊断标准进行修正。 1.PCOS诊断标准：（1）稀发排卵或无排卵；（2）高雄激素血症的临床表现和（或）高雄激素血症；（3）卵巢多囊性改变：一侧或双侧卵巢中直径2～9 mm 的卵泡≥12个，和（或）卵巢体积≥10 ml；（4）上述3条中符合2条，并排除其他致雄激素水平升高的病因：先天性肾上腺皮质增生、柯兴综合征、分泌雄激素的肿瘤等，以及其他引起排卵障碍的疾病如：高泌乳素血症，卵巢早衰和垂体或下丘脑性闭经，以及甲状腺功能异常。

多囊卵巢综合征诊断及治疗

多囊卵巢综合征诊断及治疗多囊卵巢综合征（PCOS），是生育年龄妇女常见的一种复杂的内分泌及代谢异常所致的疾病，以慢性无排卵（排卵功能紊乱或丧失）和高雄激素血症（妇女体内男性激素产生过剩）为特征，主要临床表现为月经周期不规律、不孕、多毛和/或痤疮，是最常见的女性内分泌疾病。一、多囊卵巢综合征症状 1、月经异常月经稀少、闭经，少数可表现为功能性子宫出血。多发生在青春期，为初潮后不规则月经的继续，有时伴痛经。 2、多毛较常见发生率可达69%。由于雄激素升高，可见上唇、下颌、胸、背、小腹正中部、大腿上部两侧及肛周的毳毛增粗、增多，但多毛的程度与雄激素水平不成比例(受体数、雌激素、SHBG及毛囊对雄激素的敏感性等多种因素影响)。同时可伴痤疮、面部皮脂分泌过多、声音低粗、阴蒂肥大、出现喉结等男性化征象。 3、不孕由于长期不排卵，患者多合并不孕症，有时可有偶发性排卵或流产，发生率可达74%。 4、肥胖体重超过20%以上，体重指数≥25者占30%～60%。肥胖多集中于上身，腰/臀比例>0.85。多自青春期开始，随年龄增长而逐渐加重。 5、卵巢增大少数病人可通过一般妇科检查触及增大、质地坚韧的卵巢，大多需辅助检查确定。 6、雌激素作用所有病人都表现为雌激素作用良好。检查时，可见宫颈黏液量多。持续、大量雌激素作用可出现内膜增生过快，非典型性增生，甚至癌变。

二、多囊卵巢综合征病因 1、遗传因素（30%）： PCOS是一种常染色体显性遗传，或X一连锁(伴性)遗传，或基因突变所引起的疾病，多数患者染色体核型46，XX，部分患者呈染色体畸变或嵌合型如46，XX/45，XO;46，XX/46，XXq和46，XXq，PCOS起源于青春前肾上腺疾病，即当受到强烈应激刺激时网状带分泌过多雄激素，并在性腺外转化为雌酮，反馈性地引起HP轴GnRH-GnH释放节律紊乱，LH/FSH比值升高，继发引起卵巢雄激素生成增多，即肾上腺和卵巢共同分泌较多雄激素致成高雄激素血症，高雄激素血症在卵巢内引起被膜纤维化增厚，抑制卵泡发育和卵，造成卵巢囊性增大和慢性无排卵。 2、促性腺激素释放异常(30%)： PCOS患者的血LH升高，而FSH正常或降低，LH/FSH≥2～3，静脉注射GnRH 后LH可出现过度反应，认为可能原发于下丘脑-垂体功能失调，在下丘脑中多巴胺能和阿片肽能神经对GnRH神经元的抑制作用失控，可导致LH分泌增加，但更可能是雌激素的反馈抑制异常所致，非周期性的腺外转化而来的雌激素(雌酮E1)将导致对LH分泌的正反馈和对FSH分泌的负反馈抑制，LH刺激卵泡细胞增生，产生大量雄激素，雄激素不能全部转化成雌激素，进一步增加腺外芳香化E1的生成，过多雄激素使卵泡闭锁，卵巢包膜纤维化和包膜增厚，由于缺乏月经周期中期的LH峰值，出现排卵障碍，此外，有人发现PCOS患者的卵巢也可能分泌“抑制素”，抑制FSH的分泌，影响卵泡的发育成熟，出现较多囊状卵泡，近年发现高胰岛素血症和增高的IGF也可使LH分泌增多。 3、雄性激素过多（30%）：在PCOS中，几乎所有的雄激素生成均增多，而性激素结合球蛋白(SHBG)减少，游离雄激素增多，活性增强，至于过多的雄激素来源于卵巢或肾上腺众说不一，大剂量GnRH激动剂可降低促性腺激素，雄烯二酮和睾酮减少，而对来源于肾上腺的DHEAS无影响，据报道大约70%的PCOS患者为卵巢源性雄激素所致：①由于类固醇激素所需酶系功能紊乱，如芳香化酶缺乏，3β-醇甾脱氢酶不足或活性下降，P45OC17A调节异常，雌激素合成障碍，大量雄激素在外周(脂肪，肝，肾内)转换为雌酮，也有人认为卵巢发育不充分使芳香化酶的活性下降，②LH脉冲频率及振幅升高，刺激卵泡膜细胞及间质细胞增生和雄激素的生成，过

多囊卵巢综合征的治疗

多囊卵巢综合征的治疗发表时间：2013-02-28T14:44:18.797Z 来源：《中外健康文摘》2012年第47期供稿作者：白艳秋[导读] 控制体重的关键是减少饮食和适当增加体育锻炼。如果患者有多毛和痤疮，但无生育要求，可以仅仅治疗多毛和压疮。白艳秋 (漠河县兴安镇中心卫生院 165304) 【中图分类号】R711.75 【文献标识码】A【文章编号】1672-5085（2012）47-0094-03 【摘要】目的讨论多囊卵巢综合征的治疗。方法根据患者临床表现结合检查结果进行诊断并治疗。结论对于肥胖的PCOS患者来说，控制体重是最重要的治疗手段之一。控制体重的关键是减少饮食和适当增加体育锻炼。如果患者有多毛和痤疮，但无生育要求，可以仅仅治疗多毛和压疮。【关键词】多囊卵巢综合征治疗多囊卵巢综合征(polycystic ovarian syndrome，PCOS)是青春期少女和育龄期妇女最常见的妇科内分泌疾病之一，据估计其在育龄期妇女中的发生率为5％～10％。1935年，Stein和Leventhal首次描述了多囊卵巢综合征，因此它又被称为Stein-Leventhal综合征。PCOS在临床上主要表现为功能性高雄激素血症和不排卵，近年发现继发于胰岛素抵抗的高胰岛素血症也是它的特征性表现之一。【诊断】 (一)症状 1．月经失调月经失调是由排卵障碍引起的，多表现为月经稀发或闭经，少部分可表现为月经频发或月经规则。 2．不孕 PCOS是排卵障碍性不孕的主要病因，许多患者正是由于不孕才来就诊的。 (二)体征 1．肥胖一半以上的PCOS有肥胖表现。体重指数(body mass index BMI)=体重(kg)／身高(m2)，是常用的肥胖指标。肥胖的标准为BMI≥25。腰臀围比(waist-to-hip circumference ratio WHR)=腰围／臀围， HER的大小与腹部脂肪的量正相关。根据WHR可以把肥胖分男性肥胖和女性肥胖：WHR≥0．85时称为男性肥胖，WHR＜0．8时称为女性肥胖，PCOS患者多为男性肥胖。 2．多毛和痤疮多毛和痤疮是由高雄激素血症引起的。多毛是指性毛过多，妇女的性毛主要分布于上唇、下唇、腋下、胸正中线、腹正中线和外阴，雄激素水平过高时这些部位的毛发会过多过密。四肢和躯干的毛发生长受雄激素的影响较少，它们主要与体质和遗传有关。压疮主要分布于面部，部分患者的背部和胸部也可有较多的痤疮。 3．黑棘皮症有继发于胰岛素抵抗的高胰岛素血症的患者常有黑棘皮症。 4．妇科检查妇科检查时可发现阴毛呈男性分布，有时阴毛可延伸至肛周和腹股沟内侧；生殖器无异常。 (三)检查 1．内分泌检查测定血清促卵泡素(follicle stimulating hormone， FSH)、黄体生成素(1uteinizing hormone，LH)、泌乳素(prolactin，PRL)、睾酮、硫酸脱氢表雄酮(DHEA-S)、性激素结合球蛋白(SHBG)、雌二醇、雌酮和空腹胰岛素。有月经者在月经的第3～5日抽血化验，闭经者随时抽血化验。 PCOS患者的FSH在正常范围，为3～10U／L。LH水平较正常妇女高，约60％患者的LH／FSH>2.5。多数患者的PRL水平在正常范围，少部分患者的PRL水平可轻度升高(不超过40ng／m1)。妇女体内的睾酮主要来源于卵巢，而DHEA-S主要来源于肾上腺皮质；因此睾酮水平升高说明卵巢分泌的雄激素过多，而DHEA-s水平升高则说明肾上腺皮质分泌的雄激素过多。绝大多数PCOS患者体内的睾酮水平偏高，一半患者体内的DHEA-S水平偏高。妇女体内的大多数睾酮是与SHBG结合的，只有少部分是游离的。当SHBG水平降低时，游离睾酮会增加，此时即使总睾酮在正常范围，患者也可有多毛和压疮等表现。PCOS患者的SHBG水平往往很低。 PCOS患者的雌二醇水平往往低于雌酮水平，这是过多的雄激素在周围组织中转化成雌酮的缘故。有胰岛素抵抗的患者的空腹胰岛素水平升高，>20U／L。 2．特殊检查 (1)超声检查：常发现卵巢体积增大，皮质增厚，皮质内有多个直径在2～10 mm的小卵泡。 (2)基础体温(basal body temperature，BBT)：由于患者存在排卵障碍，因此BBT呈单相。 (3)腹腔镜检查：腹腔镜下见卵巢体积增大，皮质增厚，皮质内有多个小卵泡。 (四)诊断要点 1．病史月经失调为最主要的病史，多表现为月经稀发或闭经。 2．临床表现多数患者肥胖，1／3患者体重正常。许多患者有多毛和痤疮，部分患者有黑棘皮症。 3．辅助检查多数患者的LH／FSH>2．5，患者的睾酮水平高于正常，而SHBG水平则低于正常。约一半患者的DHEA-S水平高于正常，部分患者的空腹胰岛素水平高于正常。超声检查常发现卵巢体积增大，皮质增厚，皮质内有多个直径在2～10 mm的小卵泡。BBT呈单相。 (五)鉴别诊断 1．多囊卵巢虽然患者的卵巢皮质内见多个小卵泡，呈多囊改变。但患者的月经规则，有排卵，内分泌测定无异常发现。 2．库欣综合征由于肾上腺皮质增生，肾上腺皮质分泌大量的皮质醇和雄激素。临床上表现为月经失调、向心性肥胖、紫纹和多毛等症状。内分泌测定：LH在正常范围，皮质醇水平升高，小剂量地塞米松试验无抑制作用。 3．迟发性21-羟化酶缺陷症临床表现与PCOS非常相似，诊断的依据是17-羟孕酮的升高和有昼夜规律的ACTH-皮质醇分泌。 4．卵巢雄激素肿瘤患者体内的雄激素水平更高，睾酮多大于3 ng／ml，男性化体征也更显著。超声检查可协助诊断。 5．高泌乳素血症患者虽有月经稀发或闭经，可是她们常伴有溢乳。内分泌测定除发现泌乳素水平升高外，余无特殊。【治疗】

多囊卵巢综合征的诊断和治疗专家共识

多囊卵巢综合征的诊断和治疗专家共识中华医学会妇产科学分会内分泌学组（中山大学附属第二医院妇产科杨冬梓教授主讲）多囊卵巢综合征（Polycystic Ovary Syndrome，PCOS）是妇科内分泌临床中十分常见的疾病，在我国有着庞大的患者群。PCOS临床表现异质性，不但严重影响患者的生殖功能，而且雌激素依赖性肿瘤如子宫内膜癌发病率增加，相关的代谢失调包括高雄激素血症、胰岛素抵抗、糖代谢异常、脂代谢异常、心血管疾病危险也增加。PCOS至今病因尚不明确，诊断标准不统一，治疗药物的使用方案混乱，对远期并发症也缺乏合理的防治措施，制定中国的诊治规范迫在眉睫。中华医学会妇产科学分会内分泌学组于2006年11月18日在重庆召开了妇科内分泌学专家扩大会议，会议经过热烈的讨论初步制定了目前中国的PCOS诊断、治疗专家共识，内容如下：流行病学 PCOS占生育年龄妇女的5～10％（中国尚无确切发病率），占无排卵性不孕症患者的30～60％，甚至有报道高达75％。以ESHRE/ASRM建议诊断标准，济南市、烟台市育龄妇女PCOS患病率分别为6.46％和7.2％；济南市汉族PCOS患者主要分布在35岁以下群体。我国尚缺少全国性、大样本、多中心研究。 PCOS的病因多囊卵巢综合征的确切病因尚不清楚，研究表明它可能是由某些遗传基因与环境因素相互作用引起的。一、遗传因素 PCOS有家族聚集现象，被推测为一种多基因病，目前的候选基因研究涉及胰岛素作用相关基因、高雄激素相关基因和慢性炎症因子等（相关候选基因详见附件一）。二、环境因素环境因素包括宫内高雄激素、抗癫癎药物、地域、营养和生活方式等，可能是PCOS的危险因素、易患因素、高危因素，不能算是病因，应进行流调后完善环境与PCOS关系的认识。 PCOS诊断标准的演变过程 PCOS的诊断标准一直是本领域专家争论的问题。一、1935年，Stein 和Leventhal描述了闭经、多毛和双侧卵巢多囊性增大（polycystic ovary，PCO）的无排卵相关综合征（S-L征）。二、1990年NIH制定了PCOS诊断标准：月经异常和无排卵；临床或生化显示高雄激素血症；除外其他引起高雄激素血症的疾病，未将卵巢的多囊改变（polycystic ovary，PCO）作为诊断的主要症状。三、2003年欧洲人类生殖和胚胎与美国生殖医学学会的（ESHRE/ASRM）鹿特丹专家会议

多囊卵巢综合征的诊断和治疗专家共识带版

多囊卵巢综合征的诊断和治疗专家共识多囊卵巢综合征（PolycysticOvarySyndrome，PCOS）是妇科内分泌临床中十分常见的疾病，在我国有着庞大的患者群。PCOS临床表现异质性，不但严重影响患者的生殖功能，而且雌激素依赖性肿瘤如子宫内膜癌发病率增加，相关的代谢失调包括高雄激素血症、胰岛素抵抗、糖代谢异常、脂代谢异常、心血管疾病危险也增加。PCOS至今病因尚不明确，诊断标准不统一，治疗药物的使用方案混乱，对远期并发症也缺乏合理的防治措施，制定中国的诊治规范迫在眉睫。中华医学会妇产科学分会内分泌学组于2006年11月18日在重庆召开了妇科内分泌学专家扩大会议，会议经过热烈的讨论初步制定了目前中国的PCOS 诊断、治疗专家共识，内容如下：流行病学 PCOS占生育年龄妇女的5～10％（中国尚无确切发病率），占无排卵性不孕症患者的30～60％，甚至有报道高达75％。以ESHRE/ASRM建议诊断标准，济南市、烟台市育龄妇女PC OS患病率分别为6.46％和7.2％；济南市汉族PCOS患者主要分布在35岁以下群体。我国尚缺少全国性、大样本、多中心研究。 PCOS的病因多囊卵巢综合征的确切病因尚不清楚，研究表明它可能是由某些遗传基因与环境因素相互作用引起的。一、遗传因素 PCOS有家族聚集现象，被推测为一种多基因病，目前的候选基因研究涉及胰岛素作用相关基因、高雄激素相关基因和慢性炎症因子等（相关候选基因详见附件一）。二、环境因素环境因素包括宫内高雄激素、抗癫癎药物、地域、营养和生活方式等，可能是PCOS的危

险因素、易患因素、高危因素，不能算是病因，应进行流调后完善环境与PCOS关系的认识。 PCOS诊断标准的演变过程 PCOS的诊断标准一直是本领域专家争论的问题。一、1935年，Stein和Leventhal描述了闭经、多毛和双侧卵巢多囊性增大（polycystic ovary，PCO）的无排卵相关综合征（S-L征）。二、1990年NIH制定了PCOS诊断标准：月经异常和无排卵；临床或生化显示高雄激素血症；除外其他引起高雄激素血症的疾病，未将卵巢的多囊改变（polycysticovary，PCO）作为诊断的主要症状。三、2003年欧洲人类生殖和胚胎与美国生殖医学学会的（ESHRE/ASRM）鹿特丹专家会议推荐的标准，是目前全球PCOS的诊断标准。 (1)??稀发排卵或无排卵； (2)??高雄激素的临床表现和/或高雄激素血症； (3)??超声表现为多囊卵巢（一侧或双侧卵巢有12个以上直径为2－9mm的卵泡，和/或卵巢体积大于10ml）；上述3条中符合2条，并排除其它高雄疾病如先天性肾上腺皮质增生（CAH）、库兴综合征、分泌雄激素的肿瘤。四、2006年AES（AndrogenExcessSociety）标准 (1)??多毛及/或高雄激素血症（Hirsutismand/orhyperandrogenemia）； (2)??稀发排卵或无排卵及/或多囊卵巢（oligo-ovulationand/orpolycysticovaries）； (3)??排除其它雄激素过多的相关疾病，如CAH、柯兴氏征、高泌乳素血症、严重的胰岛素抵抗综合征、分泌雄激素的肿瘤、甲状腺功能异常等。多囊卵巢综合征（polycysticovariansyndrome,PCOS）诊断

多囊卵巢综合症诊断标准

多囊卵巢综合症就是导致女性不孕得原因之一,通常得症状就是月经失调得症状,如果出现这个症状得女性,需要及时到医院进行诊断。多囊卵巢综合症诊断得方法有多种,但就是所有得多囊卵巢综合症诊断方法都需要依照多囊卵巢综合症诊断得标准来进行诊断。下面将多囊卵巢综合症诊断标准介绍如下: 多囊卵巢综合症就是雄激素过高性得月经失调为主得一种病。多囊卵巢综合症诊断时,可以参照其症状。多囊卵巢综合症得症状常表现为月经不调(月经量少或闭经)、多毛、痤疮(俗称青春痘)、肥胖、卵巢呈多囊性增大,已婚者不孕。多囊卵巢综合症得病理表现太多,每个人都不一样。因此,多囊卵巢综合症诊断标准主要有以下三方面得内容: 1、排卵或者不排卵,表现在月经走势不正常,可以作为多囊卵巢综合症诊断得标准。 2、超声检查有卵巢得多囊性改变,就是最准确得一种多囊卵巢综合症诊断方法。 3、雄激素过高,有多毛得问题、有痤疮得问题,或者说激素水平得测定就是高得。全部符合以下三条者,诊断为PCOS。1)初潮2年后月经稀少或闭经,或BBT单相:2)痤疮,多毛(乳晕、阴部或腿部)或再有肥胖,可有血雄激素升高:血T升高或logT/E2＞0、97,可合并17ɑ－OHP增高;3)B超检查卵巢体积增大(厚×宽×高/２≥6ml),皮质内一个平面上直径2～9mm得卵泡数＞10个。多囊卵巢综合症诊断得症状常表现为月经不调(月经量少或闭经)、多毛、痤疮(俗称青春痘)、肥胖、卵巢呈多囊性增大,已婚者不孕。多囊卵巢综合症就是雄激素过高性得月经失调为主得一种病。多囊卵巢综合症诊断得症状常表现为月经不调(月经量少或闭经)、多毛、痤疮(俗称青春痘)、肥胖、卵巢呈多囊性增大,已婚者不孕。您好:多囊卵巢就是由于丘脑下部-垂体-卵巢轴功能失调,破坏了相互之间得依赖与调节,因而卵巢长期不能排卵、该病典型临床表现为无排卵月经失调,如闭经,功能性子宫出血,月经稀发或不排卵月经,常伴有多毛,肥胖,不孕,双侧卵巢增长或单侧卵巢增大及一些激素水平得改变、多囊卵巢得治疗方法有两种,一种就是药物治疗,另一种就是手术治疗、一般药物治疗并不就是很理想、采用国内先进得显微外科技术不开刀治疗多囊卵巢,这种技术不开刀,恢复快,成功率高、建议详查,明确不孕不育得原因,针对性治疗、S 2、雄激素过多在PCOS中,几乎所有得雄激素生成均增多、而性激素结合球蛋白(SHBG)减少,游离雄激素增多,活性增强、至于过多得雄激素来源于卵巢或肾上腺众说不一、大剂量GnRH激动剂可降低促性腺激素,雄烯二酮与睾酮减少,而对来源于肾上腺得DHEAS无影响、据报道大约70%得PCOS患者为卵巢源性雄激素所致:①由于类固醇激素所需酶系功能紊乱,如芳香化酶缺乏,3β-醇甾脱氢酶不足或活性下降,P45OC17A调节异常,雌激素合成障碍,大量雄激素在外周(脂肪,肝,肾内)转换为雌酮、也有人认为卵巢发育不充分使芳香化酶得活性下降、②LH脉冲频率及振幅升高,刺激卵泡膜细胞及间质细胞增生与雄激素得生成、过多得雄激素促使卵泡闭锁,卵巢粒层细胞早期黄素化,生长停止,不能排卵,形成PCOS、本病多发生在青春期月经初潮后,推测可能起因于性成熟前期,肾上腺功能失调,持续分泌过多雄激素、此外,在应用地塞米松前后测定卵巢与肾上腺静脉血中得各种雄激素水平,其结果支持卵巢与肾上腺就是