Are expanding disease definitions unnecessarily labelling women with polycystic ovary syndrome?BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3694 (Published 16 August 2017) Cite this as: BMJ 2017;358:j3694
All rapid responses
Response to Gibson-Helm and colleagues1
Our paper aimed to investigate areas of potential overdiagnosis of PCOS, and consider the evidence and uncertainty surrounding diagnosis of this condition2. It is widely acknowledged that the Rotterdam criteria resulted in the inclusion of milder phenotypes within the broadened spectrum of PCOS 3,4. At least 8 studies have examined the prevalence of PCOS diagnosis in head to head comparisons from the same study populations and have shown a substantially increased prevalence using the Rotterdam criteria versus other criteria (see Table 4 of our paper)2. The systematic review quoted by Gibson-Helm and colleagues compares the three sets of criteria using studies conducted in different populations5. These summary estimates of prevalence are likely to be confounded by the ethnicity and age of the different populations, and therefore may not be reliable for understanding the impact of changes in the diagnostic criteria on prevalence.
PCOS is a complex and heterogeneous syndrome on a continuum of severity, and in our paper we call for a more tailored, patient-centred approach to diagnosis that weighs up the benefits and harms for each individual woman, wherever her experience sits on this spectrum. We do not recommend delaying treatment for symptoms that are distressing, nor do we suggest delayed diagnosis for women with severe forms of PCOS. We also suggest that while distressing symptoms should be treated without delay, clinicians might consider delaying the use of the PCOS label for women at high risk of overdiagnosis (e.g. adolescents, young women with mild symptoms and women with non-hyperandrogenic phenotypes). If there is any change in symptoms, or additional symptoms are noted at future visits, the diagnosis of PCOS can be confirmed and detailed counselling offered.
We agree that under-recognition of PCOS can cause distress for affected women, and that research is urgently needed to improve the diagnostic criteria and patient experience. However, we are concerned that current diagnostic criteria likely include women with symptoms that are mild. A few studies in different community based populations examining the prevalence of PCOS by age found that prevalence fell considerably after the age of 25, suggesting that the condition can improve with time6-8, whereas studies recruiting clinic based subjects show improvement in symptoms usually by the fourth decade of life9,10. Although high quality longitudinal research in community samples is needed to investigate this further, this suggests that a milder form of the syndrome may exist, however the current diagnostic criteria classify women with both mild and transitory symptoms as having the condition. The benefits and harms of the diagnosis are unclear for this group.
An increasing body of research in various medical conditions, such as hypertension, cancer and common paediatric conditions, such as reflux and conjunctivitis, suggests that there are psychological, social and behavioural harms associated with labelling people unnecessarily11-13. Similarly in women with PCOS with mild symptoms, who are likely at very low risk of future illness3,14 a permanent label may provide more harm than benefit, inducing unnecessary fear and anxiety about future fertility and long-term health. Further research to clarify the benefits and harms of the diagnosis for women particularly at the mild end of the spectrum is urgently needed, and we strongly advocate for this.
We share the same goal with Gibson-Helm and colleagues – we want the best possible outcomes for women who are experiencing distressing symptoms. Unfortunately, some patients have had unfavourable experiences with healthcare providers related to delays in diagnosis and inadequate or inaccurate information about PCOS15. Identification of accurate and reliable diagnostic cut offs for each of the PCOS criteria will maximise the benefits that come with appropriate and timely diagnosis of PCOS for women who are affected by significant symptoms, while minimising the harms that come with unnecessarily labelling of healthy women who are not likely to benefit. Given the spectrum of this syndrome, all women should receive personally relevant information that addresses their individual concerns. We are currently conducting research studies to determine the benefits and harms of diagnosis across the different PCOS phenotypes and spectrum of severity, including women with milder forms of PCOS who have been significantly underrepresented in research to date4,16. Until there is better evidence regarding the relationship between the milder forms and future health risks, women need to be informed of the uncertainties involved with the current diagnostic criteria.
1. Gibson-Helm M, McAllister V, Norman RJ, et al. BMJ rapid response 13th September 2017. http://www.bmj.com/content/358/bmj.j3694/rr
2. Copp T, Jansen J, Doust J, et al. Are expanding disease definitions unnecessarily labelling women with polycystic ovary syndrome? Bmj 2017;358:j3694.
3. Lizneva D, Suturina L, Walker W, et al. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertility and sterility 2016.
4. Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2016;2:16057.
5. Bozdag G, Mumusoglu S, Zengin D, et al. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Human reproduction 2016;31(12):2841-55.
6. Zhuang J, Liu Y, Xu L, et al. Prevalence of the polycystic ovary syndrome in female residents of Chengdu, China. Gynecologic and obstetric investigation 2014;77(4):217-23.
7. Lauritsen MP, Bentzen JG, Pinborg A, et al. The prevalence of polycystic ovary syndrome in a normal population according to the Rotterdam criteria versus revised criteria including anti-Mullerian hormone. Human reproduction 2014;29(4):791-801.
8. Tehrani FR, Rashidi H, Khomami MB, et al. The prevalence of metabolic disorders in various phenotypes of polycystic ovary syndrome: a community based study in Southwest of Iran. Reproductive biology and endocrinology : RB&E 2014;12:89.
9. Carmina E, Campagna AM, Lobo RA. A 20-year follow-up of young women with polycystic ovary syndrome. Obstetrics and gynecology 2012;119(2 Pt 1):263-9.
10. Pinola P, Piltonen TT, Puurunen J, et al. Androgen Profile Through Life in Women With Polycystic Ovary Syndrome: A Nordic Multicenter Collaboration Study. The Journal of clinical endocrinology and metabolism 2015;100(9):3400-7.
11. Ogedegbe G. Labeling and hypertension: it is time to intervene on its negative consequences. Hypertension 2010;56(3):344-5.
12. Pickering TG. Now we are sick: labeling and hypertension. Journal of clinical hypertension 2006;8(1):57-60.
13. Nickel B, Barratt A, Copp T, et al. Words do matter: a systematic review on how different terminology for the same condition influences management preferences. BMJ open 2017;7(7):e014129.
14. Daan NM, Louwers YV, Koster MP, et al. Cardiovascular and metabolic profiles amongst different polycystic ovary syndrome phenotypes: who is really at risk? Fertility and sterility 2014;102(5):1444-51 e3.
15. Gibson-Helm M, Teede H, Dunaif A, et al. Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome. The Journal of clinical endocrinology and metabolism 2017:jc20162963.
16. Lizneva D, Kirubakaran R, Mykhalchenko K, et al. Phenotypes and body mass in women with polycystic ovary syndrome identified in referral versus unselected populations: systematic review and meta-analysis. Fertility and sterility 2016.
Competing interests: No competing interests
AMH – a valuable tool in diagnosing PCOS
We read Tessa Copp and colleagues article1 on ‘Dangers of over diagnosing polycystic ovary syndrome’ with interest. We agree with them that the condition due to its heterogeneous phenotypic presentations is being over diagnosed. They estimate that the diagnoses in the reproductive aged women increased from 4-6.6% for NIH criteria to 21% for Rotterdam criteria1.
Under ‘how to move forward’ section1 they make various suggestions but do not mention the role of Anti Mullerian Hormone (AMH) in diagnosing PCOS. The Rotterdam consensus defines PCOS and include the antral follicle count (AFC) on ultrasound as the diagnostic criteria. The number of AFC seen has been increasing from 12 to >24 follicles per ovary owing to advancements in imaging technology although this recommendation has not been adopted in the PCOS guidelines2.
Serum AMH is synthesised by small antral follicles, which are precisely the ones seen on ultrasound. Women with PCOS have an AMH concentration higher than in women with normal ovaries. Several clinical studies have confirmed that serum AMH are 2-3 times higher in PCOS compared with levels in women with normal ovaries.
Serum AMH could therefore be used as a surrogate for AFC for the diagnosis of PCOS. A review by Dumont et al3 suggested excessive ovarian production of AMH, secreted by growing follicles, is now considered as an important feature of PCOS. They explained the utility of serum AMH assay in the management of infertility in women with PCOS and its utility as a marker of treatment efficiency on PCOS symptoms. They emphasized the lack of an international standard for the serum AMH assay, mainly because of technical issues, making it difficult to define consensual thresholds, and thus impairing the widespread use of this ovarian marker3.
The authors1 mention diagnosis being challenging in adolescence as features overlap with common features of pubertal development as acne and oligomenorrhoea. AMH is known to be correlated to the severity of PCOS symptoms and is higher when hyperandrogenisim or oligo-anovulation is present. It is difficult to evaluate the ovaries on ultrasound in this population. AMH is a true alternative in adolescents and is recommended by American association of clinical endocrinologists4.
Adolescents with PCOS have a higher serum AMH levels threshold which is set at 30 pmol/L which is in similar range for older women, making it a better marker than abnormal androgen concentration when cut off for adolescents has not been established.
AMH has been demonstrated to be significantly higher in PCOS women who had amenorrhoea compared to oligomenorrhoea and in turn higher in women with normal cycles.
The future will hopefully see international standardisation of serum AMH assays and better cut offs being available to prevent over diagnosis of PCOS.
Dr Sayantana Das MRCOG
North Middlesex University Hospital NHS Trust
Sterling Way London N18 1QX
Miss Abha Govind MFSRH FRCOG
Consultant Obstetrician Gynaecologist
North Middlesex University Hospital NHS Trust
Sterling Way London N18 1QX
Competing interests: None declared.
1.Copp T, Jansen J, Doust J, Mol BW, Dokras A, McCaffery K. Are expanding disease definitions unnecessarily labelling women with polycystic ovary syndrome? BMJ. 2017 Aug 16;358:j3694. doi: 10.1136/bmj.j3694. PubMed PMID: 28814559.
2.Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):19-25. PubMed PMID: 14711538.
3.Dumont A, Robin G, Catteau-Jonard S, Dewailly D. Role of Anti-Müllerian Hormone in pathophysiology, diagnosis and treatment of Polycystic Ovary Syndrome: a review. Reprod Biol Endocrinol. 2015 Dec 21;13:137. doi: 10.1186/s12958-015-0134-9. Review. PubMed PMID: 26691645; PubMed Central PMCID: PMC4687350.
4.Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society Disease State Clinical Review: guide to the best practices in the evaluation and treatment of polycystic
Competing interests: No competing interests
Copp et al contended that polycystic ovary syndrome (PCOS) is over-diagnosed, recommending a delayed approach to diagnosis and potential treatment of symptoms without a diagnosis (1). This was proposed largely based on uncertainty of diagnosis in adolescents and expanded PCOS diagnostic criteria with multiple phenotypes, some of which may have more limited long-term health effects. Challenges in PCOS diagnosis in adolescents are acknowledged and over-diagnosis is an important consideration in any field, however here a fundamental principle of clinical care was ignored – the experience of the patient. The BMJ commentary failed to engage affected women or to consider the significant evidence regarding diagnosis experience from studies involving women with PCOS.
In a commentary in the Medical Journal of Australia (2) patient advocates, healthcare providers and academics contested the position put forward by Copp et al. Here we summarise this evidence-based counter-case, showing that PCOS is under-recognised and that delays in diagnosis and inadequate information provision are distressing and unacceptable to women with PCOS. We also describe an international initiative aiming to address challenges in PCOS constructively and through partnership with patients, to improve PCOS diagnosis, patient experience, education and health outcomes.
Copp et al suggest that adoption of the internationally endorsed Rotterdam diagnostic criteria has contributed to an increase in PCOS prevalence from 4-6% to 21% (1). We argue that these are selected and extreme estimates drawn from disparate populations; 21% using the Rotterdam criteria comes from a study reporting prevalence of 15% using the original National Institutes of Health (NIH) criteria, in a population with a high risk of metabolic conditions (3). Instead, systematic review evidence shows more a limited impact of diagnostic criteria on prevalence (NIH criteria: 6% and Rotterdam criteria: 10%) (4). It is important to continue to research the ideal cut-offs for each PCOS diagnostic criterion, but we contest that selective reporting of prevalence does not provide evidence of over-diagnosis.
There is also no direct evidence from studies of clinical care that PCOS is over-diagnosed. Rather, evidence from hospital and primary care settings indicate that many cases of PCOS go undetected (5, 6). Community-based studies also suggest PCOS is significantly under-recognised (7).
Copp et al argue that a diagnosis of PCOS may cause women with non-hyperandrogenic phenotypes needless distress, due to potentially incorrect perceptions of metabolic risk (1). While further research is required regarding the long-term health outcomes associated with the different PCOS phenotypes, insulin resistance occurs in 75% and 95% of lean and overweight young women with PCOS (8), with current evidence suggesting limited impact of diagnostic criteria (9). Furthermore, differences in cardiometabolic risk observed across PCOS phenotypes may be largely attributable to differences in adiposity (10). We fully support that more research is needed; however, in the interim, we recommend that informing women about potential variation in metabolic features across the phenotypes is preferable to delaying PCOS diagnosis.
It is internationally accepted that a cautious approach to PCOS diagnosis is recommended for adolescents (11). However, the proposal to delay PCOS diagnosis more broadly (1) neglects the consistently reported experiences of women with PCOS. Mrs Veryan McAllister, President of the Polycystic Ovary Syndrome Association of Australia relates her own experience: “The assertions by Copp et al are extremely upsetting to read from a patient and patient advocacy perspective. As a patient I had to see multiple health care providers, my own diagnosis was delayed six years and caused extreme anxiety, and I am not alone. The labelling of the disease helped me to realise it was real and that there were steps I could take to control it. Whilst this is only my story, it is supported by evidence on women's experiences from around the world“.
Internationally, women with PCOS report commonly seeing numerous healthcare providers about PCOS symptoms, raising their concerns repeatedly, and experiencing difficult delays before receiving a diagnosis (12-17). Longitudinal data suggests that women with PCOS had equally high levels of distress in both the 12 months before and after PCOS diagnosis (18), suggesting distress was related to the features of PCOS rather than receiving a diagnosis. We recognise that a diagnosis can be confusing, worrying or lead to women feeling a lack of control, if support and information are not provided (14-16). Health care providers are the initial and trusted source of information (16, 17), yet evidence shows we are already letting women down in this regard (12, 13). It is difficult to see how delaying diagnosis and treating isolated features of PCOS without a diagnosis or opportunity for education, will address these gaps. Instead, diagnosis creates an important opportunity to provide personally relevant information and enable women to feel more in control of the condition.
The first international evidence-based guideline for PCOS will be launched in 2018 (http://www.pcos-cre.edu.au/evidence-based-guidelines-polycystic-ovary-sy...). This unique initiative is built on input from thousands of affected women and health care providers, aims to address challenges in diagnosis and inconsistency in PCOS care, and will be accompanied by extensive implementation and evaluation programmes. The initiative is led by the NHMRC Australian Centre for Research Excellence in PCOS, in partnership with the European Society of Human Reproduction and Embryology, and the American Society for Reproductive Medicine, with over 30 other societies and patient advocacy groups engaged. We believe this will provide a more constructive, evidence-based and co-developed approach to improving PCOS diagnosis and healthcare and propose that suggestions to delay PCOS diagnosis in adult women are unfounded and likely to only increase confusion and distress.
1. Copp T, Jansen J, Doust J, et al. Are expanding disease definitions unnecessarily labelling women with polycystic ovary syndrome? BMJ 2017;358.
2. Gibson-Helm M, McAllister V, Norman RJ, et al. PCOS overdiagnosis claim "not based on evidence", say experts. MJA Insight 2017;35(11 Sept 2017).
3. Boyle JA, Cunningham J, O'Dea K, et al. Prevalence of polycystic ovary syndrome in a sample of Indigenous women in Darwin, Australia. Med J Aust 2012;196(1):62-66.
4. Bozdag G, Mumusoglu S, Zengin D, et al. The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-Analysis. Human Reproduction 2016;31(12):2841-55.
5. Sivayoganathan D, Maruthini D, Glanville JM, et al. Full investigation of patients with polycystic ovary syndrome (PCOS) presenting to four different clinical specialties reveals significant differences and undiagnosed morbidity. Human Fertility 2011;14(4):261-65.
6. Ding T, Baio G, Hardiman PJ, et al. Diagnosis and management of polycystic ovary syndrome in the UK (2004–2014): a retrospective cohort study. BMJ Open 2016;6(7):e012461.
7. March WA, Moore VM, Willson KJ, et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Human Reproduction 2010;25(2):544-51.
8. Stepto NK, Cassar S, Joham AE, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Human Reproduction 2013;28(3):777-84.
9. Cassar S, Misso ML, Hopkins WG, et al. Insulin resistance in polycystic ovary syndrome: A systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies. Human Reproduction 2016;31(11):2619-31.
10. Moran LJ, Norman RJ, Teede HJ. Metabolic risk in PCOS: phenotype and adiposity impact. Trends in Endocrinology & Metabolism 2015;26(3):136-43.
11. Teede HJ, Misso ML, Deeks AA, et al. Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline. Med J Aust 2011;195(6):S65-112.
12. Gibson-Helm M, Teede H, Dunaif A, et al. Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2017;102(2):604-12.
13. Gibson-Helm ME, Lucas IM, Boyle JA, et al. Women's experiences of polycystic ovary syndrome diagnosis. Family Practice 2014;31(5):545-49.
14. Crete J, Adamshick P. Managing Polycystic Ovary Syndrome: What Our Patients Are Telling Us. J Holistic Nurs 2011;29(4):256-66.
15. Snyder BS. The lived experience of women diagnosed with polycystic ovary syndrome. JOGNN J Obstet Gynecol Neonatal Nurs 2006;35(3):385-92.
16. Jones GL, Hall JM, Lashen HL, et al. Health-Related Quality of Life Among Adolescents with Polycystic Ovary Syndrome. Journal of Obstetric, Gynecologic, and Neonatal Nursing : JOGNN 2011;40(5):577.
17. Avery JC, Braunack-Mayer AJ. The information needs of women diagnosed with Polycystic Ovarian Syndrome--implications for treatment and health outcomes. BMC Womens Health 2007;7:9.
18. Rowlands IJ, Teede H, Lucke J, et al. Young women's psychological distress after a diagnosis of polycystic ovary syndrome or endometriosis. Human Reproduction 2016;31(9):2072-81.
Competing interests: No competing interests