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)

UOG Journal Club: August 2012

Norman RJ M et al., Lancet 2007

HyperandrogenismInfertility

Polycystic ovary syndrome (PCOS)

is the most common cause of:

*At least two of the three criteria are necessary for PCOS diagnosis

• 12 or more follicles 2–9 mm in size in at least one ovary, or ovarian

volume >10 mL at ultrasound examination on cycle day 2–5

• Oligo- and/or anovulation

• Clinical and/or biochemical signs of hyperandrogenism

Revised 2003 consensus.Hum Reprod 2004

Rotterdam criteria for PCOS*

The inclusion of PCO ultrasound criteria into the PCOS definition is controversial because of lack of specificity.

Only ultrasound criteria are met: 12 or more follicles 2–9 mm in size in at least one ovary or ovarian volume >10 mL

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?

Polson DW et al., Lancet 1988Farquhar CM et al., Aust N Z J Obstet Gynaecol 1994

Duijkers IJ et al., Gynecol Endocrinol 2010Johnstone EB et al., J Clin Endocrinol Metab 2010

Polycystic ovaries (PCO)

Polycystic ovaries at ultrasound: normal variant or silent polycystic ovary syndrome?

S. Catteau-Jonard et al., UOG 2012

To determine whether PCO is a normal ovarian state or whether it reflects an abnormality in ovarian folliculogenesis similar to PCOS

Objective

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*

*Ovarian volume was not considered for PCO and PCOS definition

Exclusion criteria: • Women with at least one follicle >9 mm• Serum estradiol level > 300 pmol/L

Comparison of:• Hormonal parameters• Metabolic parameters• Ultrasound parameters

Comparative study (2004–2008)

Clinical examination:•Assessment of hirsutism •Measurement of waist circumference•Body mass index (BMI)•Blood pressure

Serum sampling:•Estradiol,17-OH-progesterone•Testosterone (elevated if ≥ 0.6ng/mL)•Androstenedione (elevated if ≥ 2.2 ng/mL)•DHEAS, LH, FSH, SHBG, insulin•Anti-Mullerian hormone (AMH)•Free-androgen index, HDL cholesterol, triglycerides

Ultrasound examination:•Menstrual cycle day 2–5 •2D transvaginal ultrasound•Follicles 2–9 mm counted

Methodology

DHEAS, dehydroepiandrosterone sulfate; HDL, high-density lipoprotein; LH, luteinizing hormone: FSH, follicle-stimulating hormone; SHBG, sex-hormone-binding globulin

Follicle number = Right ovary + Left ovary

Ovarian area = Right ovary + Left ovary

ANOVA and covariance analysis with Bonferroni correction on log values

Statistical analysis

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

* p<0.05

Number of follicles 2–9 mm and AMH serum level

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.

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)

Comparison of AMH serum levels

Andro-stenedione

Testosterone0.79

(0.17–1.84)

6.09(2.1–17.36)

1.39(0.17–3.57)

< 0.05*

< 0.05*

Controls PCO PCOS P-value

4.37(0.63–7.66)

5.25(1.57–7.70)

0.90(0.14–1.80)

Androgen serum levels except for DHEAS were similar between control and PCO groups and significantly higher in PCOS group than in PCO group.

*Difference between PCO and PCOS groups; results presented as median (range)

LH was significantly higher in PCOS group than PCO group. No difference in FSH and estradiol levels between PCOS and PCO groups was observed.

Hormonal 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

Metabolic parameters

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