Substituting serum anti-Müllerian hormone for polycystic ovary morphology increases the number of women diagnosed with polycystic ovary syndrome: a community-based cross-sectional study.

STUDY QUESTION: Can serum anti-Müllerian hormone (AMH) replace polycystic ovary morphology (PCOM) determined by ultrasound as a diagnostic component of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Despite good correlations between serum AMH and PCOM, the use of a high serum AMH as a proxy for PCOM resulted in the reclassification of PCOS in 5% of study participants, with the main effect being more women identified, although some women previously classified as having PCOS were no longer classified as such. WHAT IS KNOWN ALREADY: AMH has been proposed as an alternative to PCOM as a diagnostic component of PCOS. Previous studies are limited by poorly defining PCOS, use of infertile women as comparators, measurement of hormones by immunoassay that lack precision in the female range, low-resolution ovarian ultrasound and inconsistent handling and storage of serum samples. STUDY DESIGN, SIZE, DURATION: This is an Australian cross-sectional study of 163 non-healthcare-seeking women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum AMH was measured by both the Ansh picoAMH assay and the Beckman Coulter Access 2 (BA2) assay, in parallel with androgens measured by liquid chromatography-tandem mass spectrometry, in blood samples of women, not pregnant, breast feeding or using systemic steroids, who also underwent high-resolution ovarian ultrasound. PCOS was determined by the Rotterdam criteria with PCOM defined by the Androgen Excess-PCOS Taskforce recommendation of ≥25 follicles in at least one ovary. Cut-off serum concentrations that best identified women as having PCOM were identified by receiver operator characteristic (ROC) curves. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 163 women, mean (SD) age 32.5 (5.5) years, who provided a blood sample and had both ovaries visualized on ultrasound were included in the analysis. Women with isolated PCOM had higher median (range) Ansh AMH and BA2 AMH concentrations than those with no PCOS characteristics [56.9 pmol/l (34.6, 104.2) versus 18.7 (3.2, 50.9), P = 0.002 and 38.5 pmol/l (22.2, 100.2) versus 16.7 (3.5, 38.9), P = 0.002, respectively]. An AMH ≥ 44.0 pmol/l, suggested by the ROC curve, identified 80.6% of women with PCOM, falsely identified 15.2% of women without PCOM as having PCOS and had a positive predictive value of 55.6%. The negative predictive value was 94.9%. An AMH BA2 assay cut-off of ≥33.2 pmol/l provided a sensitivity of 80.6%, a specificity of 79.5% and a positive predictive value for PCOM of 48.1%. The negative predictive value was 94.6% for PCOM. When serum AMH was used in the place of PCOM as a diagnostic criterion for PCOS, the Ansh assay resulted in an additional seven women classified as having PCOS and no longer classified one woman as having PCOS. For the BA2 assay, eight additional and two fewer women were classified as having PCOS. Overall, both assays resulted in six more women being classified as having PCOS. LIMITATIONS, REASONS FOR CAUTION: Women with functional hypogonadotrophic hypogonadism were not excluded and may have been misclassified as having an oligo-amenorrhoea-PCOM phenotype. As study participants were predominantly Caucasian/White, our findings cannot be generalized to women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Although serum AMH reflects the number of developing ovarian follicles, the absolute values vary between assays and specific reference ranges for individual assays are required. Irrespective of the assay used, replacing PCOM with serum AMH to diagnose PCOS in a community-based sample altered the number of women classified as having or not having PCOS. Consequently, although overall the risk of women being identified as having PCOS would be increased, some women would no longer be classified as having this condition. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Norman Beischer Research Foundation and the Grollo-Ruzzene Foundation. S.R.D. is an NHMRC Senior Principal Research Fellow (Grant No. 1135843). S.R.D. reports unrelated support that includes grants from the NHMRC Australia, personal fees for educational activities from Besins Healthcare, Abbott Chile, BioFemme and Pfizer Australia, personal Advisory Board/consultancy fees from Theramex, Abbott Laboratories, Astellas, Mayne Pharmaceuticals, Roche Diagnostics, Lawley Pharmaceuticals and Que Oncology and has received institutional grant funding from Que Oncology and Ovoca research. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Use of community-based reference ranges to estimate the prevalence of polycystic ovary syndrome by the recognised diagnostic criteria, a cross-sectional study.

STUDY QUESTION: Does the application of reference ranges for sex steroids and the modified Ferriman-Gallwey (mFG) scale established in the community from which the study sample was drawn, combined with the most conservative polycystic ovary morphology (PCOM) criteria to the recognised diagnostic criteria for polycystic ovary syndrome (PCOS) improve the certainty of diagnosis of PCOS in non-healthcare-seeking women? SUMMARY ANSWER: Despite application of the stringent definitions of the elements used to diagnose PCOS in a non-healthcare seeking community-based sample, the risk of diagnostic uncertainty remains. WHAT IS KNOWN ALREADY: There is heterogeneity in prevalence estimates for PCOS due, in part, to lack of standardisation of the elements comprising the recognised National Institutes of Health (NIH), Rotterdam and Androgen Excess Society (AE-PCOS) diagnostic criteria. The AE-PCOS Society proposed refinements to the definitions of biochemical androgen excess and PCOM that can now be incorporated into these sets of diagnostic criteria to estimate PCOS prevalence. STUDY DESIGN, SIZE, DURATION: An Australian cross-sectional study of 168 non-healthcare-seeking women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 168 included women were aged 18-39 years, euthyroid and normoprolactinemic, not recently pregnant, breast feeding or using systemic hormones. Each provided menstrual history and assessment of the mFG, had measurement of sex steroids by liquid chromatography, tandem mass spectrometry, and a pelvic ultrasound. The presence of PCOS was determined using modified (m) NIH, Rotterdam, and AE-PCOS criteria according to AE-PCOS Society recommendations. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 10.1% of the included participants met the mNIH PCOS criteria, which requires the presence of menstrual dysfunction, while 18.5% met the mRotterdam and 17.5% the AE-PCOS criteria, with the latter requiring hyperandrogenism. Eight of the 27 participants with menstrual dysfunction, 10 of 31 women with PCOM, and 39 of 68 women with hyperandrogenism had no other feature of PCOS. Of the 19 participants with hyperandrogenaemia, 10 met the mNIH criteria (52.5%) and 14 met both the mRotterdam and AE-PCOS criteria (78.9%). Women who had the combination of hyperandrogenism and PCOM explained the greatest discrepancy between the mNIH and the other criteria. LIMITATIONS, REASONS FOR CAUTION: Clinical androgenisation relied on participant self-assessment, which has been shown to be valid when compared with clinician assessment. The sample size was a function of both the strict inclusion criteria and the requirements of non-healthcare-seeking women having a blood draw and pelvic ultrasound which may have introduced a selection bias. WIDER IMPLICATIONS OF THE FINDINGS: Despite applying stringent cut-offs for serum androgens, the mFG scale and the ovarian follicle count, these criteria remain arbitrary. Accordingly, healthy women may be captured by these criteria, and misidentified as having PCOS, while women with the condition may be missed. Consequently, PCOS remains a diagnosis to be made with care. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Grollo-Ruzzene Foundation. Dr S.R.D. is an NHMRC Senior Principal Research Fellow (Grant no. 1135843). S.R.D. has been paid for developing and delivering educational presentations for Besins Healthcare, BioFemme and Pfizer Australia, has been on Advisory Boards for Theramex, Abbott Laboratories, Mayne Pharmaceuticals and Roche and a consultant to Lawley Pharmaceuticals and Que Oncology and has received has received institutional grant funding for Que Oncology research; there are no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: N/A.

Being 'fat' in today's world: a qualitative study of the lived experiences of people with obesity in Australia.

OBJECTIVE: To develop an in-depth picture of both lived experience of obesity and the impact of socio-cultural factors on people living with obesity. DESIGN: Qualitative methodology, utilizing in-depth semi-structured interviews with a community sample of obese adults (body mass index >or=30). Community sampling methods were supplemented with purposive sampling techniques to ensure a diverse range of individuals were included. RESULTS: Seventy-six individuals (aged 16-72) were interviewed. Most had struggled with their weight for most of their lives (n=45). Almost all had experienced stigma and discrimination in childhood (n=36), as adolescents (n=41) or as adults (n=72). About half stated that they had been humiliated by health professionals because of their weight. Participants felt an individual responsibility to lose weight, and many tried extreme forms of dieting to do so. Participants described an increasing culture of 'blame' against people living with obesity perpetuated by media and public health messages. Eighty percent said that they hated or disliked the word obesity and would rather be called fat or overweight. DISCUSSION AND CONCLUSION: There are four key conclusions: (i) the experiences of obesity are diverse, but there are common themes, (ii) people living with obesity have heard the messages but find it difficult to act upon them, (iii) interventions should be tailored to address both individual and community needs and (iv) we need to rethink how to approach obesity interventions to ensure that avoid recapitulating damaging social stereotypes and exacerbating social inequalities.