Long-term cardiometabolic disease risk in women with PCOS: a systematic review and meta-analysis

Abstract

Background: Polycystic ovary syndrome (PCOS) is associated with cardiometabolic disease, but recent systematic reviews and meta-analyses of longitudinal studies that quantify these associations are lacking.

Objective and rationale: Is PCOS a risk factor for cardiometabolic disease?

Search methods: We searched from inception to September 2019 in MEDLINE and EMBASE using controlled terms (e.g. MESH) and text words for PCOS and cardiometabolic outcomes, including cardiovascular disease (CVD), stroke, myocardial infarction, hypertension (HT), type 2 diabetes (T2D), metabolic syndrome and dyslipidaemia. Cohort studies and case-control studies comparing the prevalence of T2D, HT, fatal or non-fatal CVD and/or lipid concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) between women with and without PCOS of ≥18 years of age were eligible for this systematic review and meta-analysis. Studies were eligible regardless of the degree to which they adjusted for confounders including obesity. Articles had to be written in English, German or Dutch. Intervention studies, animal studies, conference abstracts, studies with a follow-up duration less than 3 years and studies with less than 10 PCOS cases were excluded. Study selection, quality assessment (Newcastle-Ottawa Scale) and data extraction were performed by two independent researchers.

Outcomes: Of the 5971 identified records, 23 cohort studies were included in the current systematic review. Women with PCOS had increased risks of HT (risk ratio (RR): 1.75, 95% CI 1.42 to 2.15), T2D (RR: 3.00, 95% CI 2.56 to 3.51), a higher serum concentration of TC (mean difference (MD): 7.14 95% CI 1.58 to 12.70 mg/dl), a lower serum concentration of HDL-C (MD: -2.45 95% CI -4.51 to -0.38 mg/dl) and increased risks of non-fatal cerebrovascular disease events (RR: 1.41, 95% CI 1.02 to 1.94) compared to women without PCOS. No differences were found for LDL-C (MD: 3.32 95% CI -4.11 to 10.75 mg/dl), TG (MD 18.53 95% CI -0.58 to 37.64 mg/dl) or coronary disease events (RR: 1.78, 95% CI 0.99 to 3.23). No meta-analyses could be performed for fatal CVD events due to the paucity of mortality data.

Wider implications: Women with PCOS are at increased risk of cardiometabolic disease. This review quantifies this risk, which is important for clinicians to inform patients and to take into account in the cardiovascular risk assessment of women with PCOS. Future clinical trials are needed to assess the ability of cardiometabolic screening and management in women with PCOS to reduce future CVD morbidity.

Keywords: cardiometabolic health; dyslipidaemia; hypertension; long term; meta-analysis; polycystic ovary syndrome; systematic review; type two diabetes mellitus.

Figure 1.

Flow chart of study inclusion for a systematic review and meta-analysis of long-term cardiometabolic disease risk in women with polycystic ovary syndrome.

Figure 2.

Forest plots and funnel plot for meta-analysis of hypertension and type 2 diabetes among women with PCOS compared to women without PCOS. (a) Forest plot for hypertension (HT); (b) Funnel plot for meta-analysis of HT; (c) Forest plot for and type 2 diabetes (T2D); (d) Funnel plot for meta-analysis of T2D. The dashed lines in the funnel plots indicate the aggregated point estimate for the corresponding meta-analysis.

Figure 3.

Forest plot for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides (mg/dl) concentration among women with PCOS compared to women without PCOS. Forest plots for (a) total cholesterol (TC); (b) low-density lipoprotein cholesterol (LDL-C); (c) high-density lipoprotein cholesterol (HDL-C); (d) triglycerides (TG).

Figure 4.

Forest plot for non-fatal coronary events, non-fatal cerebrovascular events, composite outcome for non-fatal cardiovascular disease events and composite outcomes for fatal and non-fatal cardiovascular disease events among women with PCOS compared to women without PCOS. Forest plots for (a) non-fatal coronary events; (b) non-fatal cerebrovascular events; (c) composite outcome for non-fatal cardiovascular disease events; (d) composite outcome for fatal cardiovascular disease events.