UOG Journal Club August 2012 Polycystic ovaries at

UOG Journal Club: August 2012 Polycystic ovaries at ultrasound: normal variant or silent polycystic ovary syndrome? S. Catteau-Jonard, J. Bancquart, E. Poncelet, C. Lefebvre-Maunoury, G. Robin, D. Dewailly Volume 40 Issue 2, Date: August 2012, pages 223– 229 Journal Club slides prepared by Ligita Jokubkiene (UOG Editor for Trainees)

Polycystic ovary syndrome (PCOS) is the most common cause of: Anovulation Infertility Hyperandrogenism Affects 5– 10 % of women of reproductive age Norman RJ M et al. , Lancet 2007

Rotterdam criteria for PCOS* • 12 or more follicles 2– 9 mm in size in at least one ovary, or ovarian volume >10 m. L at ultrasound examination on cycle day 2– 5 • Oligo- and/or anovulation • Clinical and/or biochemical signs of hyperandrogenism *At least two of the three criteria are necessary for PCOS diagnosis Revised 2003 consensus. Hum Reprod 2004

Polycystic ovaries (PCO) Only ultrasound criteria are met: 12 or more follicles 2– 9 mm in size in at least one ovary or ovarian volume >10 m. L Observed in 21– 63 % of apparently normal women Is PCO a normal ovarian appearance or does it reflect ovarian follicle abnormality in a similar way to PCOS? The inclusion of PCO ultrasound criteria into the PCOS definition is controversial because of lack of specificity. Polson DW et al. , Lancet 1988 Farquhar CM et al. , Aust N Z J Obstet Gynaecol 1994 Duijkers IJ et al. , Gynecol Endocrinol 2010 Johnstone EB et al. , J Clin Endocrinol Metab 2010

Polycystic ovaries at ultrasound: normal variant or silent polycystic ovary syndrome? S. Catteau-Jonard et al. , UOG 2012 Objective To determine whether PCO is a normal ovarian state or whether it reflects an abnormality in ovarian folliculogenesis similar to PCOS

Comparative study (2004– 2008) Three age-matched groups of 95 women in each group: Control group – no symptoms and normal ovaries at ultrasound PCO group – no symptoms but PCO at ultrasound* PCOS group – PCOS according to Rotterdam criteria* Comparison of: Exclusion criteria: • Hormonal parameters • Metabolic parameters • Ultrasound parameters • Women with at least one follicle >9 mm • Serum estradiol level > 300 pmol/L *Ovarian volume was not considered for PCO and PCOS definition

Methodology Clinical examination: • Assessment of hirsutism • Measurement of waist circumference • Body mass index (BMI) • Blood pressure Serum sampling: • Estradiol, 17 -OHprogesterone • Testosterone (elevated if ≥ 0. 6 ng/m. L) • Androstenedione (elevated if ≥ 2. 2 ng/m. L) • DHEAS, LH, FSH, SHBG, insulin • Anti-Mullerian hormone (AMH) • Free-androgen index, HDL cholesterol, triglycerides Ultrasound examination: • Menstrual cycle day 2– 5 • 2 D transvaginal ultrasound • Follicles 2– 9 mm counted DHEAS, dehydroepiandrosterone sulfate; HDL, high-density lipoprotein; LH, luteinizing hormone: FSH, follicle-stimulating hormone; SHBG, sex-hormone-binding globulin

Statistical analysis Follicle number = Right ovary + Left ovary Ovarian area = Right ovary + Left ovary ANOVA and covariance analysis with Bonferroni correction on log values

Number of follicles 2– 9 mm and AMH serum level * p<0. 05 Number of follicles and AMH level is intermediate in women with PCO: significantly higher than in controls and significantly lower than in PCOS group. Difference in AMH remains significant after adjustment for follicle 2– 9 mm number

Comparison of AMH serum levels Subgroups of PCOS women: • Amenorrhea (Am) – no menstrual periods > 3 months (n = 13) • Oligomenorrhea (Oligo) – < 8 menstrual periods in preceding year (n = 70) • Eumenorrhea (Eum) – regular menstrual cycle 25 – 35 days (n = 12) AMH level was similar between women with PCO and eumenorrheic women with PCOS. Both groups had significantly lower AMH levels than PCOS patients with oligomenorrhea and amenorrhea.

Hormonal parameters Controls PCOS P-value Testosterone 0. 79 (0. 17– 1. 84) 0. 90 (0. 14– 1. 80) 1. 39 (0. 17– 3. 57) < 0. 05* Androstenedione 4. 37 (0. 63– 7. 66) 5. 25 (1. 57– 7. 70) 6. 09 (2. 1– 17. 36) < 0. 05* Androgen serum levels except for DHEAS were similar between control and PCO groups and significantly higher in PCOS group than in PCO group. LH was significantly higher in PCOS group than PCO group. No difference in FSH and estradiol levels between PCOS and PCO groups was observed. *Difference between PCO and PCOS groups; results presented as median (range)

Metabolic parameters No difference in any metabolic markers (BMI, blood pressure, waist circumference, insulin, triglycerides, SHBG, HDL cholesterol) between control and PCO groups BMI, waist circumference and triglycerides significantly higher in women with PCOS than control or PCO group SHBG, HDL cholesterol levels significantly lower in PCOS than control or PCO group

Polycystic ovaries at ultrasound: normal variant or silent polycystic ovary syndrome? S. Catteau-Jonard et al. , UOG 2012 Conclusions • PCO is an abnormal condition that differs from controls by higher AMH serum levels but not by hyperandrogenism. This suggests a granulosa cell abnormality in PCO similar to that observed in PCOS • The absence of hyperandrogenism in PCO does not seem to be linked to the metabolic status