American Diabetes Association 76th Scientific Sessions:

It's Time to Rename Polycystic Ovary Syndrome

Helena J. Teede, MD, Director Monash Centre for Health Research and Implementation, Melbourne, Victoria, Australia, made a case for renaming polycystic ovary syndrome at the 76th Scientific Sessions of the American Diabetes Association, June 10–14, in New Orleans.

polycystic ovary syndromeDr. Teede began her presentation by outlining her talk:

  • Diagnosis and prevalence
  • Insulin resistance
  • Hyperandrogenism
  • Update on clinical features
  • Evidence-based guidelines
  • Revision of the syndrome name

Diagnosis
Dr. Teede detailed the Rotterdam and National Institutes of Health (NIH) diagnostic criteria for polycystic ovary syndrome.

Rotterdam. Two of:

  1. Oligo- or anovulation
  2. Clinical and/or biochemical hyperandrogenism
  3. Polycystic ovaries
  4. And exclusion of other etiologies

 

NIH. All of the following:

  1. Oligo- or anovulation
  2. Clinical and/or biochemical hyperandrogenism
  3. Exclusion of other etiologies

 

Prevalence
The prevalence of the disorder in reproductive-age women has been reported from 6.8% in Greece (NIH criteria) to 21% (Rotterdam criteria) in an indigenous Australian community.

Insulin Resistance
The number of references citing insulin resistance in polycystic ovary syndrome has risen steadily since 1988, when the first of articles on the topic appeared. In 2013, Dr. Teede and colleagues reported on the prevalence of insulin resistance and contributions of intrinsic and extrinsic insulin resistance in women diagnosed with polycystic ovary syndrome according to the Rotterdam criteria.

Using a cross-sectional design, 20 overweight and 20 lean patients, 14 overweight and 19 lean matched controls without the syndrome underwent clinical measures of insulin resistance after a 3-month withdrawal of insulin sensitizers and the oral contraceptive pill.

The investigators found that women with polycystic ovary syndrome (PCOS) were more insulin resistant than controls matched for body mass index (main effect for body mass index and polycystic ovary syndrome P<.001). Insulin resistance was present in 75% of lean patients with polycystic ovary syndrome, 62% of overweight controls, and 95% of overweight patients with the syndrome.

Lean controls (mean glucose infusion rate 339 ± 76 mg/min/m2) were less insulin resistant than lean patients with polycystic ovary syndrome (270 ± 66 mg/min/m2), overweight controls (264 ± 66 mg/min/m2), and overweight patients with the syndrome (175 ± 9 mg/min/m2). The negative relationship between body mass index and insulin resistance reflected by glucose infusion rate was more marked in patients with polycystic ovary syndrome (P<.0001) than controls (P<.01).

The investigators concluded that insulin resistance is exacerbated by increased body mass index, supporting intrinsic insulin resistance in polycystic ovary syndrome. The impact of body mass index on insulin resistance is greater in the syndrome than controls, irrespective of visceral fat.

The findings support the priority of lifestyle intervention and need for effective therapeutic interventions to address intrinsic insulin resistance to prevent diabetes in this high-risk population.

This 2013 study, combined with those of a 2011 clamp study (Hutchison et al)1 led Dr. Teede to the following key findings on the contributions of insulin resistance and obesity to polycystic ovary syndrome:

  • Insulin resistance is inherently increased in the syndrome
  • Insulin resistance is exacerbated by obesity, in fat, obesity impacts insulin resistance in polycystic ovary syndrome profoundly
  • Insulin impacts: Metabolic features; Steroidogenesis; Ovulation, inasmuch as insulin is a reproductive hormone

Hyperandrogenism
Hyperandrogenism is exacerbated by obesity and is a key feature of polycystic ovary syndrome. Hyperandrogenism affects 80% of patients with the syndrome.

Concerning the relationship of hyperandrogenism with insulin resistance:

  • The relationship is driven by insulin, directly and via sex hormone binding globulin effects
  • Hyperandrogenism is reversed by insulin sensitizers
  • Androgens drive visceral adiposity
  • The impact of androgens on insulin resistance is at best modest
  • The relevance of hyperandrogenism to metabolic features is unclear

PCOS Is a Changing Paradigm
The key features of polycystic ovary syndrome, as identified in a cohort of 1380 women with the syndrome:

  • Difficulty losing weight 56.2%
  • Irregular menstrual cycles 52.3%
  • Infertility 44.4%
  • Hormone imbalance 41.7%
  • Insulin resistance 35.6%
  • Excess hair growth 35.2%
  • Increased tendency to gain weight 31.3%
  • Anxiety and/or depression 24.4%
  • Increased metabolic risk 13.9%
  • Scalp hair loss 11.4%
  • Pregnancy complications 11%
  • Ovarian cysts 10.7%

Reproductive Complications
In a 2015 study by Hart et al,2 reproductive complications of polycystic ovary syndrome were all statistically significantly greater than in women without the syndrome, at P<.001.
reproductive complications related to PCOSCardiometabolic Complications
Cardiometabolic complications were found to occur at a statistically significantly higher rate in affected vs nonaffected women.

cardiometabolic complications related to PCOS

The Effort to Rename the Condition
In 2012, Dr. Teede and associates conducted a survey among 57 Australian women with polycystic ovary syndrome and 105 general practitioners/primary care physicians. The survey was entitled, Polycystic Ovary Syndrome: Perceptions and Attitudes of Women and Primary Health Care Physicians on Features of PCOS and Renaming of the Syndrome.

Dr. Teede's team, in the effort to optimize the management of PCOS, is updating international evidence-based guideline assessment and management, with the cooperation of the Endocrine Society of Australia, Androgen Excess and PCOS Society, American Society for Reproductive Medicine, and European Society of Human Reproduction and Embryology.

In recent years, the misnomer of polycystic ovary syndrome has been discussed in several journals and at international meetings.

2014 NIH Polycystic Ovary Syndrome Panel
The NIH panel summarized their recommendations:

  • We believe the name, PCOS is a distraction and impediment to progress. It causes confusion and is a barrier to effective education of clinicians and communication with the public and research funders.
  • The name focuses on a criterion—polycystic ovarian morphology—which is neither necessary nor sufficient to diagnose the syndrome.
  • We believe it is time to recognize the advances that have been made since the description of the syndrome by Irvin F. Stein, Sr, and Michael L. Leventhal.
  • It is time to expeditiously assign a name that reflects the complex metabolic, hypothalamic, pituitary, ovarian, and adrenal interactions that characterize the syndrome—and their reproductive complications.
  • The right name will enhance recognition of this major public health issue for women, educational outreach, "branding," and public relations and will assist in expanding research support.

International Consensus Meeting
The International Consensus Meeting was a global collaboration involving patient advocacy groups and professional societies (Endocrine Society of Australia, Androgen Excess and PCOS Society, American Society for Reproductive Medicine, and European Society of Human Reproduction and Embryology, American Congress of Obstetricians and Gynecologists). The vast majority of patient participants (n=1359–1373) agreed that the name polycystic ovary syndrome can be misleading and should not be retained.

The broadest support among the 1359–1373 patients and 1649 health professionals (endocrinologists, obstetrician gynecologists, and others) was for the name of either metabolic reproductive syndrome or reproductive metabolic syndrome.

Next Steps
Dr. Teede said the next steps are to recruit publications to align terminology, and incorporate the revision into the guideline process and across the Core Outcomes in Women's Health (CROWN) initiative, and to involve the International Classification of Diseases process.

Conclusion
Dr. Teede concluded that the name polycystic ovary syndrome was declared confusing among participants in society meetings, a steering committee, an expert panel, and an international consensus meeting. A name change to metabolic reproductive syndrome or reproductive metabolic syndrome is important for a range of stakeholders, especially patients, and is needed to reflect broad clinical features.

Source
Teede HJ. Session: 3-CT-SY17 - Clinical Update and Implications―Renaming PCOS. 76th Scientific Sessions of the American Diabetes Association, June 10-14, New Orleans, LA.

References
1. Hutchinson SK, Stepto NK, Harrison CL, Moran LJ, et al. Effects of exercise on insulin resistance and body composition in overweight and obese women with and without polycystic ovary syndrome. J Clin Endocrinol Metab. 2011;96(1):E48-56.

2. Hart R, Doherty DA. The potential implications of a PCOS diagnosis on a woman's long-term health using data linkage. J Clin Endocrinol Metab. 2015;100(3):911-919.

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Managing Hypertension in Patients with Diabetes
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