**8.1 Oral contraceptives**

Oral contraceptives (OCPs) are the first-line therapy in women with PCOS to improve their irregular menstrual cycles. OCPs reduce circulating androgens by suppression of Luteinizing Hormone and stimulation of sex hormone-binding globulin (SHBG), leading to a decrease in free testosterone plasma levels. In some women, OCPs can exacerbate hypertension and are associated with a 2-fold increase in the risk of cardiovascular diseases in the general female population [114]. Exogenous estrogens can stimulate the production of AGTN by the liver in female rats [115, 116], which theoretically could lead to higher levels of ANG II. OCPs are contraindicated for smokers due to the higher risk of cardiovascular diseases in this population [117]. OCPs do not seem to affect glucose and insulin homeostasis in healthy individuals [118]. However, the effect of OCPs on women with PCOS remains controversial, mainly due to the heterogeneity of the studies, as shown in a recent meta-analysis [119]. Furthermore, several clinical studies have suggested that the use of oral contraceptives may aggravate insulin resistance and worsen hyperglycemia in obese women with PCOS [120–123]. The long-term impact of OCPs in IR and cardiovascular diseases in women with PCOS remains unknown. Interestingly, previous use of OCPs was associated with an increased risk of development of CVD in PCOS in a Danish study [33]. Prospective randomized long-term clinical trials analyzing the effect of OCPs on cardiovascular morbidity and mortality in women with PCOS, obese and lean, are lacking and desperately needed.
