Complications
It has been suggested that women with polycystic ovary syndrome (PCOS) have a high incidence of spontaneous pregnancy loss. However, whether early pregnancy loss is increased is controversial because studies have been inadequate. Overweight or obese BMI and fertility treatment use have been associated with pregnancy loss, but the association between pregnancy loss and PCOS status on its own remains unclear.[12]
Once pregnancy is established, morbidity increases, particularly if the woman is obese.
Hyperglycemia may cause congenital anomalies.
Meta-analyses have found increased rates of gestational diabetes, pregnancy-induced hypertension, preeclampsia, cesarean delivery, miscarriage, hypoglycemia, preterm delivery, newborn admission to the neonatal intensive care unit, neonatal asphyxia, and perinatal mortality in PCOS.[194][195][196][197] The increased risks of miscarriage, gestational diabetes, pregnancy-induced hypertension, and cesarean section in PCOS seem to be independent of obesity.[197]
Guidelines recommend offering an oral glucose tolerance test to all women with PCOS when planning pregnancy or fertility treatment. If not performed preconception, offer testing at the first prenatal visit and again at 24-28 weeks gestation.[53]
Women with polycystic ovary syndrome (PCOS) have 3 times the normal risk for type 2 diabetes. About 20% to 40% of obese women with PCOS have glucose intolerance or type 2 diabetes by the end of their fourth decade.[203] In one meta-analysis, the odds ratio of prevalent impaired glucose tolerance was 3.3 and that of prevalent diabetes was 2.9 in PCOS.[65]
One meta-analysis examining nonobese women with PCOS found their odds of type 2 diabetes was 1.5 compared with nonobese controls.[204] A subsequent meta-analysis found that women with PCOS and obesity had a risk ratio for developing type 2 diabetes of 3.24 compared with women without PCOS; nonobese women with PCOS had a risk ratio of 1.62, but the increased risk was not statistically significant compared with women without PCOS.[205] Conversely, 20% to 50% of reproductive-age women with type 2 diabetes have PCOS, and up to 1 in 5 girls with type 2 diabetes may have PCOS.[206][207][208]
Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease in later life.[188] The cardiometabolic profile is adversely altered in PCOS and numerous CVD risk factors (e.g., body mass index [BMI], dyslipidemia, hypertension, insulin resistance, metabolic syndrome, deficiencies in insulin secretion) are increased.[209] Markers of early or subclinical atherosclerosis are also often increased in PCOS, as well as inflammatory and thrombotic markers.[57][222][223]
For example, women with PCOS have higher coronary artery calcium scores on electron-beam computed tomography scan and greater carotid intima-media thickness, even after adjusting or matching for BMI.[224][225][226] Black women may have an increased cardiometabolic risk compared with white women.[227] However, there is no definitive evidence that PCOS is associated with an increase in CVD events (e.g., myocardial infarction [MI]).
A study of postmenopausal women (mean age 71 years), which retrospectively assigned PCOS diagnosis, found an increased CVD rate in the nondiabetic, non-oophorectomized subgroup.[228] In contrast, one retrospective cohort study (mean duration of follow-up 24 years, mean age at last follow-up 47 years) found no increase in dyslipidemia, hypertension, or cardiovascular events in women with PCOS.[229] Similarly, there was no increase in either CHD or MI in 346 PCOS women and 8950 controls of mean age 39 years.[230] These results suggest that while PCOS might increase the risk of CVD in older women, it does not increase premature CVD. Consistent with this, a 20-year retrospective study (>12,000 patient-years follow-up) found that CVD risk in PCOS increased with age: >25% of those ages 65 years and older had angina or MI.[231]
Meta-analyses suggest that women with PCOS have a 1.3-fold greater risk of developing composite CVD, ischemic heart disease, and stroke compared with women without PCOS.[232][233][234] A large meta-analysis of 9 cohort studies found PCOS was associated with an increased risk of stroke but not all-cause mortality; among 5 studies wherein risk estimates were adjusted for body mass index, the risk of stroke was slightly attenuated but lost statistical significance.[234] One meta-analysis of 16 studies examined a broad composite outcome consisting of coronary artery disease, CVD, MI, angina, heart failure, and ischemic heart disease; PCOS was associated with this composite outcome in premenopausal but not postmenopausal women in the 12 population-based studies included. Numbers of cases in each component of the composite outcome were too low for reliable conclusions.[235]
Guidelines recommend assessing all women with PCOS for individual cardiovascular risk factors and global CVD risk.[53][64] Specific CVD risk factors include family history of early CVD (<55 years in a male relative and <65 years in a female relative); cigarette smoking; impaired glucose tolerance or type 2 diabetes; hypertension; dyslipidemia; obstructive sleep apnea; and obesity (especially central obesity).
MASLD (formerly known as nonalcoholic fatty liver disease [NAFLD]) may be present in 40% to 55% of women with polycystic ovary syndrome (PCOS).[236][237][238] In those with PCOS, higher androgen levels correlate with an increased risk of MASLD.[239][240] The risk of MASLD in PCOS appears to be independent of obesity.[240][241] Ten percent of women with MASLD may develop liver injury and inflammation (metabolic dysfunction-associated steatohepatitis [MASH], formerly known as nonalcoholic steatohepatitis). Of those with MASH, 20% to 30% may progress further to cirrhosis. The increased prevalence of MASLD in PCOS is independent of weight, and women with PCOS may be at higher risk of progressing to MASH and cirrhosis.[242]
Interventions for MASLD include weight loss and insulin-sensitizing agents, antioxidants, and lipid-lowering agents.[243]
Untreated anovulatory women with polycystic ovary syndrome (PCOS) have chronic estrogen exposure with no progesterone exposure, leading to risk of abnormal uterine bleeding, endometrial hyperplasia, and cancer.[244][245] One meta-analysis found a 3-fold increased risk of endometrial cancer in PCOS (9% lifetime risk in PCOS versus 3% in unaffected women).[246]
One meta-analysis of 46 studies found that the prevalence of the metabolic syndrome in polycystic ovary syndrome (PCOS) women is 30%.[198] Other large meta-analyses have suggested an overall two- to three-fold increased odds of prevalent metabolic syndrome in PCOS. Adolescents with PCOS have more than 3 times increased odds of metabolic syndrome compared with controls.[199] One meta-analysis found that when stratified by weight category, the increased odds remained significant only in the overweight or obese women with PCOS.[200] When measured directly, insulin sensitivity has been found to be 30% lower in women with PCOS compared with controls.[201] PCOS is a risk factor for insulin resistance independent of obesity, but insulin resistance is worse in magnitude if obesity is present.[202]
Serum lipids should be checked every 3-5 years after 35 years of age in women with polycystic ovary syndrome (PCOS) for early detection of dyslipidemia. Women with PCOS commonly have increased low-density lipoprotein cholesterol and triglyceride levels and decreased high-density lipoprotein cholesterol levels.[209]
Overall quality of life of women with polycystic ovary syndrome (PCOS), particularly those with hirsutism, has been found to be decreased, with increased rates (15% to 60%) of stress, reactive depression, social isolation, and minor psychological abnormalities.[211][212] PCOS negatively impacts quality of life in adolescent girls, mediated in large part by body weight concerns.[213]
Assessment for mood disorders should be undertaken in all women with PCOS.[57][214] These include depression, anxiety and panic disorders, and eating disorders.[53] A meta-analysis found increased risk of depressive symptoms (3.8-fold) and anxiety symptoms (5.6-fold) in women with PCOS, which remained significant in body mass index-matched analyses.[215] Increased rates of anxiety and depression are also reported among adolescent girls with PCOS.[216] Women with PCOS have more significant body image concerns than women without PCOS, and one meta-analysis found that the odds of carrying a diagnosis of an eating disorder (e.g., binge-eating disorder, bulimia nervosa) were 3.9-fold higher in women with PCOS compared with controls.[217][218]
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