ADOLESCENCE
Criteria for the diagnosis of PCOS in adolescents differ from those used for older women of reproductive age (level B).
Groups at risk (e.g., obese, hirsute, irregular menses) should be identified, but physicians should be cautious of overdiagnosing PCOS (level B).
Individual PCOS manifestations in adolescents (e.g., obe- sity, hirsutism, irregular menses) (level B) should be treated.
HIRSUTISM/ACNE/ALOPECIA
Hirsutism, considering ethnic differences, is a good marker for hyperandrogenism (level B).
Isolated acne and alopecia are not necessarily related to and are not good markers for hyperandrogenism (level B).
Hirsutism should be evaluated biochemically (level B).
Prolonged (>6 months) medical therapy for hirsutism is necessary to document effectiveness (level B).
Many drugs used for the treatment of hirsutism are not ap- proved by the U.S. Food and Drug Administration (FDA) for this indication (GPP).
No effective treatment for alopecia is known (level B).
Antiandrogens should not be used without effective contraception (level B).
Flutamideisoflimitedvaluebecauseofitsdose-dependent hepatotoxicity (level B).
Drospirenone in the dosage used in some OCPs is not anti-androgenic (level B).
MENSTRUAL IRREGULARITY
Both amenorrheic and oligomenorrheic women may occasionally ovulate (level B).
Menstrual cycles in women with PCOS may become more regular later in life (level B).
Irregular menses are associated with increased metabolic risk (level B).
The greater the menstrual irregularity, the more severe the PCOS phenotype (level B).
CONTRACEPTION
Overall, the benefits of OCPs outweigh the risks in most patients with PCOS (level B).
Women with PCOS are more likely to have contraindica- tions for OCP use than normal women (level C).
Intheabsenceofotherriskfactors,thereisnoevidenceth at women with PCOS are at increased risk with OCPs com- pared with normal women (level C).
There is no evidence for differences in effectiveness and risk among the various progestogens and when used in combination with a 20 versus a 30 mg daily dose of estrogen (level B).
Subsequent fertility is not negatively affected by OCPs (level C).
There is no definitive evidence that the type of OCP deter- mines efficacy of hirsutism control (level C).
QUALITY OF LIFE
There is evidence of increased prevalence of psychological disorders in women with PCOS (level B).
Psychological issues should be considered in all women with PCOS because of evidence suggesting increased prev- alence and associated comorbidities (level C).
It is unclear if this increased prevalence is due to the disorder itself or its manifestations (e.g., obesity, hirsutism, irregular menses, infertility) (level C).
Based on the consultation and the patient’s perception of her problems, appropriate counseling and intervention should be offered (level C).
PREGNANCY
Women with PCOS who desire a pregnancy may be at in- creased risk for adverse pregnancy outcomes, and this may be exacerbated by obesity and/or insulin resistance (level B).
Health should be optimized before conception, with advice about smoking cessation, lifestyle, diet, and appropriate vi- tamin supplementation (e.g., folic acid) (GPP).
Miscarriage rates are not increased in natural conceptions in women with PCOS, independent of obesity. Miscarriage rates after induction of ovulation mirror those found in other infertile populations (level A).
WomenwithPCOSshouldbeobservedcloselyduringpreg- nancy as they may be at increased risk for the development of GDM, gestational hypertension, and associated complications (level B).
Pregnancy-associated risks are greater in women diag- nosed by more classic (NIH) criteria as opposed to nonhy- perandrogenic women (level B).
Babies born from women with PCOS may have increased morbidity and mortality (level B).
There is no evidence for improved live-birth rates or decreased pregnancy complications with the use of metfor- min either before conception or during pregnancy (level A).
ETHNIC DIFFERENCES IN THE PHENOTYPE
Ethnic origin and culture contribute to the differing mani- festations of PCOS (level B).
Ethnically appropriate thresholds are required for identify- ing anthropometric cutoffs for appropriate metabolic screening in high-risk ethnic groups (level B).
OBESITY
The prevalence of obesity is increasing and has an impor- tant bearing on the phenotype of PCOS (level B).
Some studies suggest that higher BMI is associated with a greater prevalence of menstrual irregularity, hyperandro- genemia, and hirsutism, but more studies are required to confirm this (level B).
Increased BMI and visceral adiposity are associated with greater insulin resistance as in the general population, but its effect on menstrual irregularity and hirsutism re- main unclear (level B).
Lifestyle management results in weight loss and improves surrogate markers of metabolic disease/syndrome (level A).
INSULIN RESISTANCE AND THE METABOLIC SYNDROME (METS)
Metabolic disorders associated with PCOS are major predictors of prediabetes, diabetes, and MetS in reproductive-age women (level B).
Patients with MetS are an important clinical subset of women with PCOS (level B).
Not all PCOS phenotypes have similar metabolic risk. The combination of hyperandrogenemia and oligomenorrhea signifies the most at-risk group (level B).
It is critical for public health and for optimum design of long-term studies to stratify women with PCOS according to metabolic risk. This goal would be greatly facilitated by using a specific name for this high metabolic risk PCOS subset (GPP).
TYPE 2 DIABETES (T2D)
PCOS is a major risk factor for developing IGT and T2D (level A).
Obesity (by amplifying insulin resistance) is an exacerbat- ing factor in the development of IGT and T2D in PCOS (level A).
The increasing prevalence of obesity in the population suggests that a further increase in diabetes in PCOS is to be expected (level B).
Screening for IGT and T2D should be performed by OGTT (75 g, 0- and 2-hour values). There is no utility for measur- ing insulin in most cases (level C).
Screening should be performed in the following conditions: hyperandrogenism with anovulation, acanthosis nigricans, obesity (BMI >30 kg/m2, or >25 in Asian populations), in women with a family history of T2D or GDM (level C).
Diet and lifestyle are first choice for improving fertility and prevention of diabetes (level B).
Metformin may be used for IGT and T2D (level A). Avoid use of other insulin sensitizing agents such as thiazolidine- diones (GPP).
CARDIOVASCULAR DISEASE MARKERS
PCOS at any age is characterized by greater odds for ele- vated CVD risk markers. Elevated markers occur without obesity and are magnified with obesity (level B). Dyslipidemia, IGT, and T2D (classic risk indicators of ath- erosclerosis and CVD) are more prevalent in women with PCOS, even when weight matched with normal control women (level B). Altered level softriglycerides,HDL,LDL,andnon-HDL(reflecting altered ApoB/ApoA metabolism) are prevalent in women with PCOS and are more severe in hyperandrogenic women (level B).
Non-HDL cholesterol and waist measurement appear to be the best clinical indicators of elevated CVD risk (level C). All markers reflect a greater magnitude of risk when women are diagnosed using NIH criteria (including hyperandrogenism) compared with the Rotterdam criteria (level B).
Depression and anxiety, major risk factors for CVD, are common in women with PCOS (level B).
The recommended CVD risk assessment at any age is for psychosocial stress, blood pressure, glucose, lipid profile (cholesterol, triglycerides, HDL, LDL, and non-HDL cholesterol), waist circumference, physical activity, nutri-
tion, and smoking (level C).
Because CVD risk increases with age and accompanying
additive environmental insults, periodic reassessment for CVD risk is recommended (GPP).
CARDIOVASCULAR DISEASE OUTCOMES
Life-long metabolic dysfunction in women with PCOS ex- aggerates CVD risk, causing a possible increase in CVD events with age, especially after menopause (level B).
All surrogate markers of cardiovascular risk are higher in PCOS (adjusted for age and BMI), but the association of these markers with cardiovascular events in PCOS remains unclear (level B).
Endothelial dysfunction in PCOS is related to abdominal obesity and insulin resistance (level B).
Coronary artery calcification and carotid intima media wall thickness are also increased in women with PCOS com- pared with matched controls (level B).
Among nondiabetic postmenopausal women with intact ovaries, atherosclerotic CVD is associated with features of PCOS, such as relative androgen excess and a recalled his- tory of irregular menses (level B).
CANCER RISK
There are moderate quality data to support that women with PCOS have a 2.7-fold (95% confidence interval [CI], 1.0–7.3) increased risk for endometrial cancer. Most endo- metrial cancers are well differentiated and have a good prognosis (level B).
Limited data exist that do not support the conclusion that women with PCOS are at increased risk for ovarian cancer (level B).
Limited data exist that do not support the conclusion that women with PCOS are at increased risk for breast cancer (level B).
MENOPAUSE, GENERAL HEALTH
Age may improve many manifestations of PCOS,including normalizing ovarian size and morphology, T levels, and oligo-ovulation before menopause (level B).
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