ORIGINAL ARTICLE Oral contraceptive plus antiandrogen therapy and cardiometabolic risk in polycystic ovary syndrome Ayla Harmanci, Nese Cinar, Miyase Bayraktar and Bulent Okan Yildiz Endocrinology and Metabolism Unit, Department of Internal Medicine, Hacettepe University School of Medicine, Hacettepe, Ankara, Turkey Abstract Objective Oral contraceptives alone or in combination with antiandrogens are commonly used in the treatment for polycys- tic ovary syndrome (PCOS). We aimed to determine the effects of ethinyl estradiol/drospirenone (EE-DRSP) plus spironolactone therapy on inflammation and cardiometabolic risk in PCOS. Design Prospective cohort study. Patients Twenty-three lean, normal glucose-tolerant patients with PCOS and 23 age- and body mass index (BMI)-matched healthy control women. Measurements Androgens, high-sensitivity C-reactive protein (hsCRP), homocysteine, lipids, fasting insulin, and glucose levels during a standard 75-g, 2-h oral glucose tolerance test were measured. Patients with PCOS were evaluated before and after receiving EE-DRSP (3 mg/30 lg) plus spironolactone (100 mg/ day) for 6 months. Healthy controls were evaluated at baseline only. Results hsCRP, homocysteine, lipids, insulin and glucose levels were similar between patient and control groups at baseline. EE-DRSP plus spironolactone increased hsCRP and homocyste- ine levels in patients with PCOS (0·50 ± 0·28 vs 1·5 ± 1·3 mg/l, P < 0·05 and 13·1 ± 5·2 vs 17·6 ± 5·3 lM, P < 0·05, respec- tively). BMI, waist-to-hip ratio, LDL, HDL cholesterol and triglycerides, and glucose tolerance did not change. Modified Ferriman–Gallwey hirsutism scores, testosterone levels and free androgen index improved (9·1 ± 4·2 vs 6·2 ± 3·4, P = 0·001; 80·6 ± 31·1 47·8 ± 20·3 ng/dl, P < 0·05; and 10·5 ± 7·4 vs 1·1 ± 0·8, P < 0·001, respectively). Conclusions EE-DRSP plus spironolactone therapy in 6 months improves androgen excess in lean PCOS women with- out any adverse effects on adiposity, glucose tolerance status or lipid profile. However, this combination increases hsCRP and homocysteine levels. (Received 12 March 2012; returned for revision 9 April 2012; finally revised 17 May 2012; accepted 3 June 2012) Introduction Polycystic ovary syndrome (PCOS) is a reproductive-metabolic disorder associated with several cardiovascular risk factors. 1–3 Low-grade inflammation may, in part, influence long-term met- abolic and cardiovascular outcome of PCOS as it is associated with generation and progression of atherosclerosis. 4,5 C-reactive protein (CRP) has been used as a stable surrogate marker of low-grade inflammation in human plasma 5 and is considered as a strong predictor of cardiovascular disease risk. 6 Homocysteine is another surrogate biomarker of endothelial dysfunction and its increased levels indicate an increase in cardiovascular disease risk. 7,8 Conflicting results of CRP and homocysteine levels in patients with PCOS are available in the literature. Some studies have reported increased CRP and homocysteine levels in PCOS, 9,10 while others have not confirmed such a finding. 1 Low-dose combined oral contraceptives (OCs) and antiandro- gens are widely used potent drugs as a first-line treatment in PCOS patients presenting with hyperandrogenism. Low-dose combined OC therapy might be associated with insulin resis- tance and dyslipidaemia, hence increasing cardiovascular risk in PCOS. 11–13 Spironolactone, being a potent androgen and miner- alocorticoid receptor antagonist, has been used in PCOS patients with hirsutism. 14 In addition, recent studies show that spirono- lactone improves endothelial function and has beneficial effects on lipoprotein profile and glucose metabolism. 15 Despite the desirable effects, spironolactone is still considered a drug with teratogenicity and therefore is not preferred as monotherapy. The combined use of OCs and spironolactone results in effective contraception and controls abnormal menstrual bleeding. Addi- tionally, combination of antiandrogens with progesterone-based OCs having antiandrogen effects results in potent synergistic suppression of androgen levels via different mechanisms of action. 14,16,17 As this combination is commonly used in women with PCOS who are not seeking pregnancy, determination of potential long-term cardiometabolic effects associated with this therapy is highly relevant. Correspondence: Bulent Okan Yildiz, Endocrinology and Metabolism Unit Department of Internal Medicine, Hacettepe University School of Medicine, Hacettepe, 06100 Ankara, Turkey. Tel.: +90 312 3051707; Fax: +90 312 3116768; E-mail: yildizbo@yahoo.com 120 © 2012 Blackwell Publishing Ltd Clinical Endocrinology (2013) 78, 120–125 doi: 10.1111/j.1365-2265.2012.04466.x