CLINICAL STUDY Increased micronucleus frequencies in peripheral blood lymphocytes in women with polycystic ovary syndrome Elif Yesilada 1 , Ibrahim Sahin 2 , Hamdi Ozcan 3 , Ibrahim Halil Yıldırım 1 , Saim Yologlu 4 and Cagatay Taskapan 5 Departments of 1 Medical Biology and Genetics, 2 Endocrinology and Metabolism, 3 Dermatology, 4 Biostatistics and 5 Biochemistry, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey (Correspondence should be addressed to E Yesilada; Email: eyesilada@inonu.edu.tr) Abstract Objective: We aimed to assess possible genomic instability in women with polycystic ovary syndrome (PCOS). Design: The frequency of micronuclei in cultured peripheral lymphocytes was used as a biomarker of genomic instability in somatic cells. Methods: Nineteen women, diagnosed with PCOS and 19 healthy female volunteers of corresponding ages and body-mass index (BMI) were included in the study. Micronuclei frequencies were assessed in cytokinesis-blocked lymphocytes. Results: The frequency of micronucleated cells (per thousand) was 9.00 (5.00) (interquartile range in parentheses) for patient group and 3.0 (3.0) for the control group (P , 0.0001, Mann-Whitney U-test). The serum levels of follicle-stimulating hormone (FSH), estradiol, prolactin, glucose and dehy- droepiandrosterone sulfate (DHEAS) and the homeostasis model of assessment of insulin resistance (HOMA-IR) were not different between the two groups (P . 0.05). Serum total testosterone, luteiniz- ing hormone (LH) and insulin levels and hirsutism score in the PCOS group were significantly (P ¼ 0.007, P , 0.0001, P ¼ 0.009 and P , 0.0001 respectively) higher than those of the control group (2.3 (2.1) nmol/l vs 1.7 (0.4) nmol/l; 8.5 (5.88) mU/ml vs 4.8 (4.4) mU/ml; 6.8 (5.1) mU/ml vs 9.7 (4.2) mU/ml; 19.5 (6.5) vs 4.0 (2.5) respectively). However, the mean level of sexhormone-bind- ing globulin (SHBG) in PCOS group was significantly (P ¼ 0.004) lower than in control group (36.4(22.6) nmol/l vs 48.6(25.2) nmol/l respectively). Conclusion: These findings suggest that women with PCOS have a high incidence of genomic instabil- ity, and this condition is positively correlated with the hirsutism score, BMI, LH and serum total tes- tosterone and insulin levels, and is negatively correlated with SHBG. European Journal of Endocrinology 154 563–568 Introduction Polycystic ovary syndrome (PCOS), characterized by hyperandrogenism and chronic anovulation, is a common endocrine disorder in women. PCOS, which is associated with polycystic ovaries, hirsutism, obesity and insulin resistance, is a leading cause of female infertility (1). Recently, it has been suggested that women with PCOS show higher levels of leukocyte count, a marker of low-grade inflammation and cardi- ovascular risk, than controls (2). Epidemiologic studies have demonstrated that the prevalence of PCOS in women is 3.5–10%, depending on the diagnosis cri- terion (3, 4). The genetic mechanisms underlying PCOS remain largely unknown (5). Although an autosomal dominant model was proposed (6), later studies did not confirm this. Chromosomal studies in patients with PCOS have produced contradictory findings. There have been reports that X-chromosome aneuploidies and polyploi- dies (7), as well as other cytogenetic abnormalities (8), are associated with PCOS in a limited number of sub- jects. One well-characterized case had both endocrine and ultrasound stigmata of PCOS (as well as multiple other anomalies, including heart and facial dysmor- phies) and a large deletion on the long arm of the chromosome 11 (9). However, other cytogenetic ana- lyses have failed to identify common karyotypic abnorm- alities (10). A number of studies reported that PCOS is an oligo- genic disorder, and more studies are necessary to define its genetic basis (5, 11). Different combinations of multiple gene polymorphisms and environmental factors explain the heterogeneity of PCOS (5). European Journal of Endocrinology (2006) 154 563–568 ISSN 0804-4643 q 2006 Society of the European Journal of Endocrinology DOI: 10.1530/eje.1.02117 Online version via www.eje-online.org