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Translation and implementation of the Australian-led PCOS guideline: clinical summary and translation resources from the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome

Authors:

Abstract

INTRODUCTION: We have developed the first international evidence-based guideline for the diagnosis and management of polycystic ovary syndrome (PCOS), with an integrated translation program incorporating resources for health professionals and consumers. The development process involved an extensive Australian-led international and multidisciplinary collaboration of health professionals and consumers over 2 years. The guideline is approved by the National Health and Medical Research Council and aims to support both health professionals and women with PCOS in improving care, health outcomes and quality of life. A robust evaluation process will enable practice benchmarking and feedback to further inform evidence-based practice. We propose that this methodology could be used in developing and implementing guidelines for other women's health conditions and beyond. Main recommendations: The recommendations cover the following broad areas: diagnosis, screening and risk assessment depending on life stage; emotional wellbeing; healthy lifestyle; pharmacological treatment for non-fertility indications; and assessment and treatment of infertility. Changes in management as a result of this guideline: •Diagnosis:▪when the combination of hyperandrogenism and ovulatory dysfunction is present, ultrasound examination of the ovaries is not necessary for diagnosis of PCOS in adult women;▪requires the combination of hyperandrogenism and ovulatory dysfunction in young women within 8 years of menarche, with ultrasound examination of the ovaries not recommended, owing to the overlap with normal ovarian physiology; and▪adolescents with some clinical features of PCOS, but without a clear diagnosis, should be regarded as "at risk" and receive follow-up assessment.•Screening for metabolic complications has been refined and incorporates both PCOS status and additional metabolic risk factors.•Treatment of infertility: letrozole is now first line treatment for infertility as it improves live birth rates while reducing multiple pregnancies compared with clomiphene citrate.
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MJA 209 (7 Suppl) • 1 October 2018
Translation and implementation of the Australian-led PCOS guideline
Translation and implementation of the
Australian-led PCOS guideline: clinical summary
and translation resources from the International
Evidence-based Guideline for the Assessment
and Management of Polycystic Ovary Syndrome
Helena J Teede1,2, Marie L Misso1,2, Jacqueline A Boyle1,2, Rhonda M Garad1,2, Veryan McAllister1,3, Linda Downes1,2, Melanie Gibson1,2, Roger
J Hart1,4, Luk Rombauts5, Lisa Moran1,2, Anuja Dokras6, Joop Laven7, Terhi Piltonen8, Raymond J Rodgers1,9, Mala Thondan10, Michael F
Costello1,11, Robert J Norman1,9, on behalf of the International PCOS Network
1 National Health and Medical Research Council Centre for Research Excellence in PCOS, Monash and Adelaide Universities, Melbourne, VIC. 2 Monash Centre for Health Research and
Implementation, Monash Public Health and Preventive Medicine, Monash University and Monash Health, Melbourne, VIC. 3 Polycystic Ovary Syndrome Association of Australia, Sydney,
NS W. 4 University of Western Australia, Perth, WA. 5 Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC. 6 Obstetrics and Gynecology, University of Pennsylvania,
Philadelphia, PA, USA. 7 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, Netherlands. 8 Obstetrics and
Gynecology, PEDEGO Research Unit, Medical Research Centre, Oulu University Hospital, Oulu, Finland. 9 Robinson Research Institute, University of Adelaide and Fertility SA, Adelaide, SA. 10 Harp
Family Medical Centre, Melbourne, VIC. 11 UNSW Sydney, Sydney, NSW. helena.teedee@monash.edu • doi: 10.5694/mja18.00656
Abstract
Introduction: We have developed the first international
evidence-based guideline for the diagnosis and management
of polycystic ovary syndrome (PCOS), with an integrated
translation program incorporating resources for health
professionals and consumers. The development process
involved an extensive Australian-led international and
multidisciplinary collaboration of health professionals and
consumers over 2 years. The guideline is approved by the
National Health and Medical Research Council and aims to
support both health professionals and women with PCOS in
improving care, health outcomes and quality of life. A robust
evaluation process will enable practice benchmarking and
feedback to further inform evidence-based practice. We
propose that this methodology could be used in developing
and implementing guidelines for other women’s health
conditions and beyond.
Main recommendations: The recommendations cover
the following broad areas: diagnosis, screening and risk
assessment depending on life stage; emotional wellbeing;
healthy lifestyle; pharmacological treatment for non-fertility
indications; and assessment and treatment of infertility.
Changes in management as a result of this guideline:
Diagnosis:
when the combination of hyperandrogenism and
ovulatory dysfunction is present, ultrasound examination
of the ovaries is not necessary for diagnosis of PCOS in
adult women;
requires the combination of hyperandrogenism and
ovulatory dysfunction in young women within 8 years of
menarche, with ultrasound examination of the ovaries
not recommended, owing to the overlap with normal
ovarian physiology; and
adolescents with some clinical features of PCOS, but
without a clear diagnosis, should be regarded as “at risk”
and receive follow-up assessment.
Screening for metabolic complications has been refined and
incorporates both PCOS status and additional metabolic
risk factors.
Treatment of infertility: letrozole is now first line treatment
for infertility as it improves live birth rates while reducing
multiple pregnancies compared with clomiphene citrate.
Polycystic ovary syndrome (PCOS) aects 8–13% of reproductive
age women, with around 21% of Indigenous women aected.1,2
Clinically, reproductive features are prominent and underpin
PCOS diagnosis.3 The Roerdam diagnostic criteria are based on
two of three features: oligo- or anovulation, hyperandrogenism
(clinical or biochemical) and polycystic ovaries on ultrasound,
after exclusion of other causes (Box 1).3 Aetiology includes
genetic causes, in utero hormone exposure and lifestyle factors
(Box 2).4,5 PCOS is an endocrine disorder underpinned by
insulin resistance and hyperandrogenism.5,6 It is associated
with signicant metabolic features including increased rates
of gestational diabetes and type 2 diabetes mellitus as well as
an increase in cardiovascular risk factors (Box 2).7 PCOS has
signicant psychological impact with increased depression and
anxiety and impaired quality of life (Box 2).8,9 There is also an
increased rate of weight gain and prevalence of obesity in PCOS,
increasing severity of the condition, causing considerable concern
for those aected and mandating aention to healthy lifestyle.10
Obtaining a timely PCOS diagnosis is challenging for women,
with many experiencing delays with multiple dierent doctors
involved.11-13 Inadequate information provision and lack of
satisfaction with care has been reported, especially in areas such
as psychological features, lifestyle and prevention. Doctors often
focus on individual features of PCOS such as infertility, rather
than taking a broader approach to care.13 There is also potential
for overdiagnosis, including when isolated polycystic ovarian
morphology on ultrasound is incorrectly equated with PCOS.
Access to timely, accurate diagnosis and information provision
needs signicant improvement.
1 Diagnosis of polycystic ovary syndrome
Adapted from Teede et al.9
Adult
women
Adolescents
Rotterdam diagnostic criteria require two of:
1. Oligo- or anovulation;
2. Clinical and/or biochemical hyperandrogenism;
3. Polycystic ovaries;
after exclusion of other aetiologies
Diagnostic criteria require:
1. Oligo- or anovulation: and,
2. Clinical and/or biochemical hyperandrogenism;
after exclusion of other aetiologies
Ultrasound is not recommended in diagnosis <8 years
post menarche
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Supplement
Clinically, there is considerable variation in care and evidence
of confusion around diagnostic criteria.11,14 Researchers are
frustrated with inadequate priority and funding in PCOS,
especially given the prevalence, disease and economic burden.15
These challenges are exacerbated by inconsistent guideline
quality and recommendations. Past guidelines have not
followed recommended rigorous development processes, have
not involved diverse health professionals including primary
care providers, have not engaged women aected by PCOS, are
country specic or, as in the case of the 2011 Australian PCOS
guidelines,9 are now out of date. In this context, PCOS is a clear
priority area for updated, consistent rigorously co-developed
guidelines, translation resources and health professional and
consumer support.16
The National Health and Medical Research Council (NHMRC)
funded a Centre of Research Excellence to address current gaps.
Through a multidisciplinary national alliance and international
network, including primary care providers and women with
PCOS, we have developed the International evidence-based
guideline for the assessment and management of polycystic ovary
syndrome 2018 and co-designed an extensive range of translation
resources (Box 3).16
The guideline addresses:
screening, diagnostic assessment, risk assessment and life
stage (Algorithm 1);
prevalence, screening, diagnostic assessment and treatment
of emotional wellbeing (Algorithm 2);
lifestyle (Algorithm 3);
pharmacological treatment for non-fertility indications
(Algorithm 4); and
assessment and treatment of infertility (Algorithm 5).
Diverse PCOS features are considered, including reproductive
(hyperandrogenism, anovulation, infertility), metabolic
(insulin resistance, impaired glucose tolerance, gestational
and type 2 diabetes, adverse cardiovascular risk proles) and
psychological features (increased anxiety and depression and
worsened quality of life).17 The guideline recognises variable
presentation across the lifespan; ethnicity, which has an impact
on dermatological and metabolic
features; and cultural factors aecting
experiences of women with PCOS.
The guideline abstract is provided
in Box 4 and the full guideline is
available at hps://www.monash.
edu/medicine/sphpm/mchri/pcos.
Guideline development
process and methods
The guideline and translation
program were developed through the
integration of clinical perspectives,
the preferences of women and
the best available evidence.
International society-nominated
panels included consumers and
experts in the elds of paediatrics,
endocrinology, gynaecology, primary
care, reproductive endocrinology,
psychiatry, psychology, dietetics,
exercise physiology, public health,
project management and evidence
synthesis translation. Governance
included an international advisory
and a project board, ve guideline
development groups, and consumer and translation commiees.
The NHMRC Australian Centre for Research Excellence in PCOS
co-funded the guideline in partnership with the European
Society of Human Reproduction and Embryology and the
American Society for Reproductive Medicine. Thirty-seven
organisations across 71 countries collaborated to address 60
prioritised clinical questions based on 40 systematic and 20
narrative reviews, generating 166 recommendations. Methods
met NHMRC standards and procedures for externally developed
guidelines18 and are outlined in the full guideline and Box 5.19
These involved rigorous systematic review, training, online
communication and face-to-face meetings to discuss the evidence
and apply the Grading of Recommendations, Assessment,
Development, and Evaluation (GRADE) framework. Evidence
quality, feasibility, acceptability, cost, implementation and
ultimately recommendation strength were agreed across the
panel. Convened commiees from partner and collaborating
organisations provided peer review and the guideline was
approved by the NHMRC.20-22
Women with PCOS and health professionals as the end users
played a fundamental role in developing the guideline and
resources. Stakeholder engagement and processes for guideline
and translation resource development are outlined in Box 5.19 A
summary of the recommendations is published elsewhere.20-22
The MJA has also published an editorial accompanying this
supplement.23
In this supplement, we aim to optimise translation and
implementation of the guideline (Box 4) by providing a brief clinical
summary in the Australian context, noting key changes in practice,
and by supporting health care providers, especially those in primary
care, with co-designed, practical information, tools and consumer
resources to improve outcomes and quality of life for women with
PCOS (Box 3). We also highlight implications for Aboriginal and
Torres Strait Islander women who are at high risk of PCOS.
The guideline is underpinned by a robust evaluation process
which will enable practice benchmarking and feedback data to
be collected to guide further alignment with evidence-based care.
Downloads of the guideline and its resources will be monitored;
focus groups and surveys will measure awareness in consumers
and knowledge and practice change by health professionals. This
2 Aetiology and clinical manifestations of polycystic ovary syndrome
Adapted from Teede et al.9
Genetics
Androgens
Hirsutism
Acne
Diabetes
Metabolic syndrome
Cardiovascular risk
Insulin
Ovarian follicles
Anovulation
Oestrogen
Menstrual disturbances
Sub fertility
Psycho-social issues: body image, self esteem, depression, anxiety
Lifestyle
In utero hormonal exposures
Obesity exacerbates hormonal changes
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Translation and implementation of the Australian-led PCOS guideline
information will then be compared with data that were collected
before the guideline release, to measure change.
This strategic international approach involved strong partnership
between consumers, multidisciplinary health professionals,
academics and professional societies and we propose that this
is transferable to other women’s health conditions and beyond.
Such an approach can reduce duplication of eort and promote
consistency of care and focus on provision of useful, accessible
and meaningful resources to support both health professionals
and people aected by a variety of conditions.24
Screening, diagnostic assessment, risk
assessment and life stage (Algorithm 1)
We aim to improve accuracy and to simplify
and facilitate timely diagnosis, while avoiding
overdiagnosis, especially in adolescents. The guideline
endorses the consensus-based Roerdam diagnostic
criteria3,20 for adult women and supports them with
best available evidence. Algorithm 1 (hps://www.
monash.edu/__data/assets/pdf_file/0018/1411641/
Algorithm-1-20180618.pdf) highlights the rened
diagnostic criteria in adolescents, which require
both hyperandrogenism and irregular cycles, with
ultrasound now not recommended for diagnosis within
8 years of menarche, owing to overlap with normal
reproductive physiology. Adolescents with clinical
features but not a clear diagnosis are deemed “at risk”,
with follow-up assessment recommended. Diagnostic
features are rened, including irregular cycles, clinical
and biochemical hyperandrogenism, and polycystic
ovarian morphology. Exclusion of thyroid disease
(thyroid-stimulating hormone), hyperprolactinemia
(prolactin) and non-classic congenital adrenal
hyperplasia (17-hydroxyprogesterone) is
recommended, with further evaluation in patients with
amenorrhea and more severe clinical features including
consideration of hypogonadotropic hypogonadism,
Cushing disease or androgen-producing tumours. The
guideline recognises that PCOS is an insulin-resistant
and metabolic disorder; tests for insulin resistance,
however, lack accuracy and should not be incorporated
into the diagnostic criteria for PCOS at this time. Anti-
Müllerian hormone is likewise not recommended for
diagnosis at this time.
Complication screening is recommended in PCOS.
Cardiovascular risk factor screening is updated
and simplied, including monitoring weight and
weight change, assessing body mass index, family
history, ethnicity, smoking status, blood pressure
and glycaemic status in all patients with PCOS, and
waist circumference and lipid proles in those with
additional risk factors. Frequency and type of testing
are guided by presence of both PCOS and other risk
factors. Obstructive sleep apnoea and endometrial
cancer risk are also addressed.
Prevalence, screening, diagnostic
assessment and treatment of emotional
wellbeing (Algorithm 2)
Algorithm 2 (hps://www.monash.edu/__data/assets/
pdf_le/0004/1411645/Algorithm-2.pdf) highlights
the increased prevalence of psychological features in
PCOS, including anxiety and depressive symptoms,
psycho-sexual dysfunction, eating disorders and
disordered eating, and adverse impact on body
image. The importance of these issues for women
is recognised, along with the resulting signicant
impairment of quality of life. It is vital to ascertain and focus on
the individual areas of most importance to women with PCOS.
Appropriate screening is recommended based on risk, along
with consideration of PCOS features that may have an impact
on treatment.
In models of care, identication of priority areas for the
individual with PCOS is paramount to enable targeted treatment
that improves quality of life. Primary care providers are well
positioned to assess, provide care and coordination and, if
needed, refer to ensure that care is targeted to need and priority.
3 Resources for women and health professionals to support
evidence-based care in polycystic ovary syndrome (PCOS)
Resources for health professionals
Algorithm 1 Screening, diagnostic assessment, risk assessment and
life stage
https://www.monash.edu/__data/assets/pdf_
file/0018/1411641/Algorithm-1-20180615.pdf
Algorithm 2 Prevalence, screening, diagnostic assessment and
treatment of emotional wellbeing
https://www.monash.edu/__data/assets/pdf_
file/0004/1411645/Algorithm-2.pdf
Algorithm 3 Lifestyle
https://www.monash.edu/__data/assets/pdf_
file/0008/1411649/Algorithm-3.pdf
Algorithm 4 Pharmacological treatment for non-fertility indications
https://www.monash.edu/__data/assets/pdf_
file/0019/1411651/Algorithm-4-20180801.pdf
Algorithm 5 Fertility treatment
https://www.monash.edu/__data/assets/pdf_
file/0003/1411653/Algorithm-5-20180619.pdf
Online programs Webinars, interviews with experts and women with PCOS
Certificate programs Online (fee-paying education programs)
GP Tool and care plan Outline of PCOS for GPs to be used during the
consultation
https://www.monash.edu/__data/assets/pdf_
file/0003/1411662/PCOS-GP-Tool-20180622.pdf;
https://www.monash.edu/medicine/sphpm/mchri/pcos/
resources/practice-tools-for-health-practitioners
Resources for women
Infographic 1 What is PCOS and do I have it?
https://www.monash.edu/__data/assets/pdf_
file/0009/1410858/PCOS-Quiz.pdf
Infographic 2 Lifestyle and PCOS
https://www.monash.edu/__data/assets/pdf_
file/0006/1410855/PCOS-and-Lifestyle-Management.pdf
Infographic 3 Emotional wellbeing and PCOS
https://www.monash.edu/__data/assets/pdf_
file/0004/1410853/PCOS-and-Emotional-Well-being.pdf
Infographic 4 PCOS medical treatment
https://www.monash.edu/__data/assets/pdf_
file/0020/1410860/PCOS-Treatment.pdf
Infographic 5 Fertility and PCOS
https://www.monash.edu/__data/assets/pdf_
file/0005/1410854/PCOS-and-Fertility.pdf
Video series A series of videos delivered by experts on all aspects of PCOS
Mobile app Available on Apple iTunes and Google platforms —
multilingual options in development
Written resources Fact sheets, e-resources, booklets and tools available online
Online programs Webinars and online resources and presentations
Question prompt list Question list embedded in the app or available stand-
alone to improve interaction between women with PCOS
and their health professionals
All resources are available at https://www.monash.edu/medicine/sphpm/mchri/pcos
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4 Abstract from the International evidence-based guideline
for the assessment and management of polycystic ovary
syndrome 2018
Objective: To develop and translate rigorous, comprehensive evidence-
based diagnosis, assessment and treatment guidelines, to improve the
lives of women with polycystic ovary syndrome (PCOS) worldwide.
Participants: Extensive health professional and patient engagement
informed guideline priority areas. International Society-nominated
panels included consumers, paediatrics, endocrinology, gynaecology,
primary care, reproductive endocrinology, psychiatry, psychology,
dietetics, exercise physiology, public health, project management,
evidence synthesis and translation experts.
Evidence: Best practice evidence-based guideline development
involved extensive evidence synthesis and the Grading of
Recommendations, Assessment, Development, and Evaluation
(GRADE) framework covered evidence quality, feasibility, acceptability,
cost, implementation and ultimately recommendation strength.
Process: Governance included an international advisory board from
six continents, a project board, five guideline development groups with
63 members, consumer and translation committees. The Australian
Centre for Research Excellence in PCOS, funded by the National Health
and Medical Research Council (NHMRC), partnered with European
Society of Human Reproduction and Embryology and the American
Society for Reproductive Medicine. Thirty seven organisations across 71
countries collaborated with 23 face to face international meetings over
15 months. Sixty prioritised clinical questions involved 40 systematic
and 20 narrative reviews, generating 166 recommendations and
practice points. Convened Committees from partner and collaborating
organisations provided peer review and the guideline was approved by
the NHMRC.
Conclusions: We endorse the Rotterdam PCOS diagnostic criteria in
adults (two of clinical or biochemical hyperandrogenism, ovulatory
dysfunction, or polycystic ovaries on ultrasound) and where irregular
menstrual cycles and hyperandrogenism are present, highlight
that ultrasound is not necessary in diagnosis. Within eight years of
menarche, both hyperandrogenism and ovulatory dysfunction are
required, with ultrasound not recommended. Ultrasound criteria are
tightened with advancing technology. Anti-Müllerian hormone levels
are not yet adequate for diagnosis. Once diagnosed, assessment and
management includes reproductive, metabolic and psychological
features. Education, self-empowerment, multidisciplinary care
and lifestyle intervention for prevention or management of excess
weight are important. Depressive and anxiety symptoms should be
screened, assessed and managed with the need for awareness of
other impacts on emotional wellbeing. Combined oral contraceptive
pills are firstline pharmacological management for menstrual
irregularity and hyperandrogenism, with no specific recommended
preparations and general preference for lower dose preparations.
Metformin is recommended in addition or alone, primarily for metabolic
features. Letrozole is first-line pharmacological infertility therapy; with
clomiphene and metformin having a role alone and in combination.
In women with PCOS and anovulatory infertility, gonadotrophins are
second line. In the absence of an absolute indication for IVF, women
with PCOS and anovulatory infertility, could be offered IVF third line
where other ovulation induction therapies have failed. Overall evidence
is low to moderate quality, requiring significant research expansion in
this neglected, yet common condition. Guideline translation will be
extensive including a multilingual patient mobile application and health
professional training.
Reproduced with permission from the author Helena Teede on behalf of
Monash University, which holds the copyright: https://www.monash.edu/__
data/assets/pdf_file/0004/1412644/PCOS-Evidence-Based-Guideline.pdf
Ethnic and cultural dierence and life stage need consideration.
Care should address short and long term psychological features
and be mindful of how reproductive and metabolic features may
aect psychological wellbeing.
Lifestyle (Algorithm 3)
Algorithm 3 (hps://www.monash.edu/__data/assets/pdf_
le/0008/1411649/Algorithm-3.pdf) highlights that healthy
lifestyle and prevention of excess weight gain are critical for all
women with PCOS from adolescence. Lifestyle interventions are
similarly eective in women with and without PCOS, and are
rst line treatment in the majority of women with PCOS who
are overweight. Modest weight loss of 5–10% of body weight
is recommended to improve PCOS features, primarily through
caloric restriction. No specic diet oers greater benet in PCOS.
Exercise recommendations are made for weight maintenance,
health and weight loss. Incorporating behavioural strategies
such as goal seing, self-monitoring, stimulus control, problem
solving, assertiveness training, slower eating, reinforcing
changes and relapse prevention are recommended to improve
adherence and ecacy.
Pharmacological treatment for non-fertility
indications (Algorithm 4)
Algorithm 4 (hps://www.monash.edu/__data/assets/
pdf_le/0019/1411651/Algorithm-4-20180801.pdf) outlines
recommendations regarding pharmacological treatment for non-
fertility indications. Combined oral contraceptive pills (COCPs)
continue to be recommended as rst line medical treatment for
hyperandrogenism and regulation of menstrual cycles in PCOS.
COCP ecacy is largely related to hepatic-mediated oestrogenic
eects on sex hormone-binding globulin, which in turn decrease
free testosterone levels. Other forms of hormonal contraception
are less eective in this regard. COCP use for 6–12 months
reduces androgens and hirsutism. Mood impacts have not been
shown in PCOS; however, general population studies have noted
COCP impact on libido and mood. No one preparation has been
shown to be superior in PCOS, with all COCP agents increasing
sex hormone-binding globulin and improving clinical outcomes.
Based on general population data, COCPs are recommended at
the lowest eective oestrogen dose balancing ecacy, metabolic
risk prole, side eects, costs and availability, and 35 mg
ethinyl estradiol preparations are not recommended rst line
treatment. Where COCPs and lifestyle changes fail in meeting
treatment goals, metformin, as an insulin sensitiser, may assist in
prevention of weight gain and improvement in metabolic features.
Metformin improves body mass index, cyclicity, androgen
levels and metabolic features, has demonstrated ecacy in
combination with lifestyle modication, and is recommended in
addition to lifestyle intervention, not as a substitute. Low dose
therapy is recommended initially, with subsequent titration to
reduce the mild and self-limiting gastrointestinal side eects.
Anti-androgens in PCOS have limited evidence and are only
recommended for hirsutism when at least 6 months of COCPs
with cosmetic therapy have failed. Bariatric surgery can improve
clinical features; however, registry studies demonstrate concerns
around pregnancy outcomes and should only be considered in
PCOS after lifestyle therapy fails.
Assessment and treatment of infertility (Algorithm 5)
Algorithm 5 (hps://www.monash.edu/__data/assets/
pdf_le/0003/1411653/Algorithm-5-20180619.pdf) outlines
recommendations on pre-conception care and infertility
management. While infertility assessment and management
require specialist care, optimisation of psychological health,
lifestyle intervention and provision of evidence-based resources
to inform women on infertility treatment recommendations are
well placed in primary care. The key change recommended in
the guideline is the use of letrozole as rst line pharmacological
treatment in PCOS-associated and anovulatory infertility.
Compared with clomiphene citrate, letrozole improves live
birth rate, with a reduced rate of multiple pregnancy. However,
in Australia, this involves o-label prescription and requires
explanation and consent from the patient. Clomiphene citrate is
recommended alone or combined with metformin. Metformin can
be used alone, recognising lower success rates than other agents.
When rst line therapy has failed, exogenous gonadotrophins
in women with clomiphene citrate-resistant PCOS are generally
recommended second line, as is laparoscopic ovarian drilling.
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Translation and implementation of the Australian-led PCOS guideline
Importantly, in vitro fertilisation is indicated for women with
PCOS and anovulation, after failure to respond to first and
second line ovulation induction, or if there are other factors
contributing to infertility. Algorithm 5 provides a detailed
explanation regarding drug choice, based on clinical and
other factors.
General practice tool, care plan and consumer
resources to support care
Tools and resources have been developed with and for general
practitioners, including a GP tool and care plan template to
support decision making and evidence-based care in clinical
practice (hps://www.monash.edu/medicine/sphpm/mchri/
pcos/resources/practice-tools-for-health-practitioners). A
key component of the range of consumer tools, developed in
partnership with consumers, is the PCOS app (AskPCOS). This
is the rst evidence-based PCOS app that has a range of unique
features (eg, a comprehensive repository of information,
question prompt list) to increase PCOS-related health
literacy. GPs and other health professionals are the preferred
source of consumer information, yet there is a clear need for
complementary, additional, high quality, evidence-based
resources for aected women. Such resources are accessible by
searching “Monash PCOS” in your Web browser, or see Box
3 for direct links to the guideline resources for women and
health professionals. These resources address demonstrated
gaps, including inadequate and generally poor quality existing
information, to support clinical care and improve knowledge,
consumer engagement and health outcomes.
Considerations for Aboriginal and Torres Strait
Islander women
Given the higher prevalence and more severe clinical features of
PCOS in Aboriginal and Torres Strait Islander women,2,25 early
diagnosis and management are vital to prevent and manage
the reproductive, metabolic and psychological features of
PCOS. This must be undertaken in a culturally appropriate and
respectful manner.
In diagnosis, high quality ultrasound access may be challenging,
as Aboriginal and Torres Strait Islander women are more likely
to live in remote locations.26 The reduced guideline focus on
ultrasound in PCOS diagnosis may assist here. Regarding
screening for features of PCOS, Aboriginal and Torres Strait
Islander women have increased risks of obesity, type 2 diabetes,
5 Guideline development process
GDG = guideline development group. *Time points and tasks where prioritisation of engagement from GDG
is required.
Reproduced with permission from Misso and Teede.19
Disseminate,
implement,
update
(steps 16 - 18
up to 6 months)
Formulate
guidance
(3 months)
Systematic
review of
evidence
(6 months - 1 year)
Establish
GDG and
scope
(up to 6 months)
22. Revise and update
21. Evaluate
20. Implement
19. Disseminate*
18. Obtain endorsements
17. Public consulation
16. Finalise guideline
content
15. Write narrative
clinical context*
14. Reach consensus
among GDG*
13. GRADE
recommendation(s)*
12. Draft
recommendation(s)*
11. Synthesise evidence
1. Create multidiciplinary guideline
development group including consumers
2. Scope and define topics*
3. Identify and prioritise clinical questions*
4. Define PICO*
5. Identify existing guidelines to adapt
If <5 years and high quality, skip to
step 13 to adapt for local use
If >5 years and high quality,
update
6. Systematically search for evidence
7. Identify and select evidence*
8. Appraise methodological quality of
included studies
9. Extract data
10. Synthesise data
dyslipidaemia and mental health disorders,
independent of PCOS.27 They are more
likely to be overweight or obese at all ages,
with obesity contributing around 16% of the
disparity in health burden.28 Diabetes is a key
cause of mortality and disability-adjusted life-
years in Aboriginal and Torres Strait Islander
women,28 and PCOS amplies these risks,
making screening more critical.
Lifestyle management is the rst line treatment
for PCOS and associated complications.
However, access to culturally appropriate
care, services and lifestyle programs is
suboptimal, because socio-economic factors,
as well as lack of access to healthy food
for those living in remote locations, create
barriers to modifying lifestyle. Improving
this situation is likely to require broader
community and government action. There
is lile information about exercise among
Aboriginal and Torres Strait Islander women.
However, low participation rates in sports, less in women than
men, have been noted.28 Facilitators of engagement include
having a group, family, community or team focus, choice of
activities and realistic goal aainment.29,30 Overall, we anticipate
that the lifestyle recommendations in the guideline will be broadly
applicable to Aboriginal and Torres Strait Islander women, but
we acknowledge the socio-economic and geographical barriers
and the need for adaptation to engage this population, especially
in rural and remote locations.
Although the data are unclear, it is likely that infertility rates
among Aboriginal and Torres Strait Islander women are at
least similar to the national prevalence (the limited reports
suggest they are actually higher) despite the younger age of
rst birth and increased total fertility rate.31,32 This emphasises
the need for early diagnosis and for prevention. Socio-economic
and geographic barriers may also aect uptake of medication
recommendations (eg, letrozole) or procedures (eg, laparoscopic
surgery). See also hp://www.naccho.org.au/wp-content/
uploads/1.National-guide-to-a-preventive-health-assessment-
for-Aboriginal-and-Torres-Strait-Islander-people-2.pdf.
Resources are currently in the co-development phase with
Aboriginal and Torres Strait Islander women.
Conclusion
The International evidence-based guideline on the assessment and
management of polycystic ovary syndrome 2018 has been rigorously
developed and informed by consumers, multidisciplinary health
professionals and leading PCOS experts from six continents. The
guideline is designed to address the needs of health professionals
in providing beer, timely care and improved outcomes for
women with PCOS, as well as enabling women to be more
informed and involved in their treatment.
The PCOS guideline and translation resources aim to accelerate
the delivery of consistent, evidence-based care across
Australia. GPs are well supported in the implementation of the
recommendations from the PCOS guideline by the provision
of the range of freely available practice tools, tailored to the
Australian context. GPs can also augment the PCOS-related
health literacy of consumers by directing them to the range of
consumer resources.
Collaborating authors: Estifanos Baye, Monash Centre for Health Research and
Implementation, Melbourne; Leah Brennan, Australian Catholic University, Melbourne;
Cheryce Harrison, Monash Centre for Health Research and Implementation, Melbourne;
Samantha Hutchison, Monash Health Centre for Research Implementation, Melbourne;
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MJA 209 (7 Suppl) • 1 October 2018
Supplement
Anju Joham, Monash Centre for Health Research and Implementation, Melbourne; Louise
Johnson, Victorian Assisted Reproductive Treatment Authority, Melbourne; Cailin Jordan,
Genea Hollywood Fertility, Perth; Jayashri Kulkarni, Monash Alfred Psychiatry Research Centre,
Melbourne; Darren Mansfield, Monash Health, Melbourne; Kate Marsh, Northside Nutrition
and Dietetics, Sydney; Ben W Mol, Monash University, Melbourne; Alexia Peña, Robinson
Research Institute, University of Adelaide, Adelaide; Raymond Rodgers, Robinson Research
Institute, University of Adelaide, Adelaide; Jane Speight, Deakin University, Geelong; Nigel
Stepto, Victoria University, Melbourne; Eliza C Tassone, Monash Centre for Health Research
and Implementation, Melbourne; Angela Wan, Monash University, Melbourne; Jane Woolcock,
Women’s and Children’s Hospital, Adelaide.
Acknowledgements: We gratefully acknowledge the contribution of the many women
with PCOS and health professionals who guided and contributed to this work. We thank our
funding, partner, engaged and collaborating organisations for their roles in prioritising topics
and identifying gaps, and contributing members for guideline development, providing peer
review and assisting with dissemination. We acknowledge those who independently assessed
the guideline against AGREEII criteria and completed methodological review, and those within
the NHMRC who managed the approval process. This guideline was approved by all members of
the guideline development groups and has been approved by the NHMRC.
Specifically, our funding, partner, collaborator and engaged organisations include:
The NHMRC through the funded Centre for Research Excellence in Polycystic
Ovary Syndrome and the members of this Centre who coordinated this international
guideline effort.
Our partner organisations which co-funded the guideline: the American Society
for Reproductive Medicine and the European Society of Human Reproduction and
Embryology.
Our collaborating and engaged societies and consumer groups: Androgen Excess
and Polycystic Ovary Syndrome Society; American Pediatric Endocrine Society; Asia Pacific
Paediatric Endocrine Society; Asia Pacific Initiative on Reproduction; Australasian Paediatric
Endocrine Group; Australian Diabetes Society; British Fertility Society; Canadian Society of
Endocrinology and Metabolism; Dietitians Association Australia; Endocrine Society (US);
Endocrine Society Australia; European Society of Endocrinology; European Society for
Paediatric Endocrinology; Exercise and Sports Science Australia; Fertility Society Australia;
International Society of Endocrinology; International Federation of Fertility Societies;
International Federation of Gynaecology and Obstetrics; Italian Society of Gynaecology
and Obstetrics; Japanese Society for Paediatric Endocrinology; Latin American Society for
Paediatric Endocrinology; Nordic Federation of Societies of Obstetrics and Gynaecology;
PCOS Challenge; PCOS Society of India; Paediatric Endocrine Society; Polycystic Ovary
Association Australia; Royal Australasian College of Physicians; Royal Australian College
of General Practitioners; Royal Australian and New Zealand College of Obstetricians and
Gynaecologists; Royal College of Obstetricians and Gynaecologists (UK); South African
Society of Gynaecology and Obstetrics; Verity UK; Victorian Assisted Reproductive
Technology Association (VARTA).
Our Australian translation partners: Jean Hailes for Women’s Health
and VARTA.
Funding: The guideline and translation program was primarily funded by the NHMRC
Centre for Research Excellence in PCOS grant (APP1078444) and partnership grant
(APP1133084). This funding was supported by a partnership with the European Society of
Human Reproduction and Embryology and the American Society for Reproductive Medicine.
Translation costs were supported by the NHMRC Centre for Research Excellence and
partnership grant. Jean Hailes for Women’s Health funded the cost of this MJA supplement.
Competing interests: Disclosures of conflicts of interest were declared at the outset
and updated throughout the guideline process, aligned with NHMRC guideline processes.
Full details of conflicts declared across the guideline development groups are available
at https://www-monash-edu.ezproxy.lib.monash.edu.au/medicine/sphpm/mchri/pcos/
guideline in the register of disclosures of interest.
Michael Costello has declared shares in Virtus Health and past sponsorship from Merck
Serono for conference presentations. Joop Laven has received grants from Ferring
Pharmaceuticals and Euroscreen, and personal fees from Ferring Pharmaceuticals,
Euroscreen, Danone and Titus Health Care. Robert Norman is a minor shareholder
interest in an IVF unit. The remaining authors have no conflicts of interest to declare.
Provenance: Commissioned; externally peer reviewed. n
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2 Boyle JA, Cunningham J, O’Dea K, et al. Prevalence of
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5 Diamanti-Kandarakis E, Dunaif A. Insulin resistance and
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6 Stepto NK, Cassar S, Joham AE, et al. Women with
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resistance on euglycaemic-hyperinsulaemic clamp. Hum
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7 Moran LJ, Norman RJ, Teede HJ. Metabolic risk in PCOS:
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8 Dokras A, Stener-Victorin E, Yildiz BO, et al. Androgen excess-
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9 Teede HJ, Misso ML, Deeks AA, et al. Assessment and
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10 Teede HJ, Joham AE, Paul E, et al. Longitudinal weight
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Obesity 2013; 21: 1526-1532.
11 Gibson-Helm M, Teede H, Dunaif A, Dokras A. Delayed
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J Clin Endocrinol Metab 2017; 102: 604-612.
12 Teede H, Gibson-Helm M, Norman RJ, et al. Polycystic ovary
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health care physicians on features of PCOS and renaming the
syndrome. J Clin Endocrinol Metab 2014; 99: E107-E111.
13 Gibson-Helm ME, Lucas IM, Boyle JA, Teede HJ. Women’s
experiences of polycystic ovary syndrome diagnosis. Fam
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14 Dokras A, Saini S, Gibson-Helm M, et al. Gaps in knowledge
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2017; 107: 1380-1386.e1.
15 Brakta S, Lizneva D, Mykhalchenko K, et al. Perspectives on
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4421-4427.
16 Teede H, Legro R, Norman R. A vision for change in PCOS
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17 Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a
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the lifespan. BMC Med 2010; 8: 41.
18 National Health and Medical Research Council. 2016 NHMRC
Standards for Guidelines. https://www.nhmrc.gov.au/guidelines-
publications/information-guideline-developers/2016-nhmrc-
standards-guidelines (viewed Aug 2018).
19 Misso M, Teede H. Evidence based guideline (EBG)
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20 Teede HJ, Misso ML, Costello MF, at al. Recommendations
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syndrome. Fertil Steril 2018; 110: 364-379.
21 Teede HJ, Misso ML, Costello MF, et al. Recommendations
from the international evidence-based guideline for the
assessment and management of polycystic ovary syndrome.
Clin Endocrinol (Oxf) 2018; doi: 10.1111/cen.13795[Epub ahead
of print].
22 Teede HJ, Misso ML, Costello MF, et al. Recommendations
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syndrome. Hum Reprod 2018; doi: 10.1093/humrep/dey256
[Epub ahead of print].
23 Norman R, Teede H. A new evidence-based guideline
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od.nih.gov/docs/programs/pcos/FinalReport.pdf (viewed
Aug 2018).
25 Davis SR, Knight S, White V, et al. Preliminary indication of a
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PCOS PRIMARY CARE PLAN
Patient and GP
identified problem
list
Patient problems
/ needs / relevant
conditions
Goals - changes to be achieved Required treatments and services including
patient actions
Arrangements for
treatments/services
(when, who, contact
details)
1. Priorities and education Education - PCOS resources: https://www.
monash.edu/medicine/sphpm/mchri/pcos and
AskPCOS app
Patient identified
priorities
Other identified
priorities
Patient's understanding
of their condition
Clear understanding of PCOS and
patient’s role in self- management
Education - PCOS resources
2. Lifestyle Education - PCOS resources
Nutrition Maintain general healthy diet Set joint agreed SMART goals for small achiev-
able changes
Patient to implement
GP to refer to dieti-
cian as required
Weight - prevention of
excess weight gain and
management of weight
loss as needed
Weight
Height
BMI
Target prevention of weight gain or
5-10% weight loss through caloric
restriction
Education - PCOS resources
Review 12 monthly for prevention and 1-2
monthly for weight loss
Patient to monitor
GP to monitor
GP to refer to dieti-
cian if needed
Physical activity Current exercise
Patient prioritised/agreed goals
Education - PCOS resources Patient to imple-
ment/ monitor
GP to monitor
Refer as needed
Smoking Cessation Smoking cessation strategy:
Consider: Quit, Medication
Patient to manage
GP to support
Alcohol intake Current
Target1 standard drink per day
Patient education Patient to implement
GP to monitor/sup-
port
3. Metabolic features Education - PCOS resources
BP Target <130/80 Every 12 months GP to monitor
Lipids ̶ Check in PCOS
with BMI >25kg/m2
Under laboratory recommended
range
Fasting lipids at diagnosis and recheck based
on global CVD risk
GP to monitor
Glucose
routinely and
around pregnancy
Target prevention, regular screen-
ing, early detection and treatment
Assessed in all at baseline, then every 1-3
years, based on additional diabetes risk factors
Fasting plasma glucose or HbA1c ok in PCOS
alone, OGTT with additional risk factors.
OGTT for all with PCOS before and during
pregnancy
GP to monitor
Patient's name:
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4. Reproductive Education - PCOS resources
Menstrual regulation
and endometrial
protection
≥4 cycles per year (if not on
COCP/IUD)
Lifestyle + Medical treatment Patient and GP to
monitor
Hirsutism
Alopecia
Acne
Assess impact on QoL, meet
patients expectations and reduce
adverse patient impact
Cosmetic and/or treatment with COCP alone
for at least 6-12/12 first line
Patient and GP to
monitor
Fertility Target optimal fertility
Reassurance - Vast majority with
PCOS will have a family if desired
and no other infertility factors, but
many may need oral medication
support to do so. Rarely need IVF
Discuss early family initiation where possible
Prevent weight gain/manage excess weight
Preconception care
Further resources at
https://www.varta.org.au/
GP to reassure,
educate, support
lifestyle change
and refer for
management where
needed
5. Psychological Education and PCOS resources
Identify, support and
minimise psychological
impact
Screen clinically or use brief
psychological tool at https://www.
monash.edu/medicine/sphpm/
mchri/pcos
If positive on routine questions further
assess, treat PCOS features and manage
psychological issues
GP to refer
psychologist and or
additional treatment
as needed
6. Other
7. Medication
current
Medication
changes
List: Correct use of medication
Minimise side effects
Education and PCOS resources GP to review
compliance/side
effects
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... Polycystic ovary syndrome (PCOS) is a widespread endocrine and metabolic disorder among reproductive-aged women, affecting 12 to 18% of this population depending on the diagnostic criteria and demographics studied (Kiani et al. 2022;Wolf et al. 2018;Alesi et al. 2022). Abnormal ovulation, hyperandrogenism, polycystic ovarian morphology, and insulin resistance (IR) are the hallmark features of PCOS (Meczekalski et al. 2023;Teede et al. 2018). PCOS represents a substantial health burden for women and poses a considerable economic challenge to communities (Teede et al. 2010). ...
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Background Polycystic ovary syndrome (PCOS) is a common gynecological disease accompanied by multiple clinical features, including anovulation, hyperandrogenism, and polycystic ovarian morphology, leading to infertility. Formononetin (FMN), which is a major bioactive isoflavone compound in Astragalus membranaceus , exerts anti-inflammatory effects. However, whether FMN is effective in the treatment of PCOS remains unknown. This study aims to explore the effects and the possible mechanisms of FMN in PCOS. Methods Dehydroepiandrosterone (DHEA)-induced PCOS rats and dihydrotestosterone (DHT)-induced PCOS cell models were established. Fifty rats were randomly assigned into five groups of 10 rats each: Control, PCOS, PCOS + FMN (15 mg/kg), PCOS + FMN (30 mg/kg), and PCOS + FMN (60 mg/kg). Fasting blood glucose, insulin, luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol were detected in DHEA-induced PCOS rats. Ovarian histological changes and apoptosis were evaluated utilizing H&E and TUNEL staining. Subsequently, the effects of FMN on oxidative stress and inflammatory responses in the DHEA-induced PCOS rat model and DHT-induced PCOS cell model were explored. Besides, the function of FMN on cell viability and apoptosis in DHT-induced PCOS cell model were explored by using CCK-8 assay and flow cytometry. Protein expression was detected via western blot and immunofluorescence staining in the DHEA-induced PCOS rat model and DHT-induced PCOS cell model. Results FMN alleviated PCOS symptoms and reduced inflammation, cell apoptosis, and oxidative stress in DHEA-induced PCOS rats and DHT-induced KGN cells. Additionally, FMN suppressed NLRP3 inflammasome activation in both models. In the DHT-induced PCOS cell model, nigericin (a activator of NLRP3) reversed the functions of FMN on inflammation, apoptosis, and oxidative stress. Conclusion These findings demonstrated that FMN could alleviate PCOS by repressing inflammation, apoptosis, as well as oxidative stress in vivo and in vitro via inhibition of the NLRP3 inflammasome. Highlights FMN improved PCOS symptoms. FMN alleviated cell apoptosis, inflammation and oxidative stress in PCOS. FMN inhibited the activation of NLRP3 inflammasome in PCOS.
... Polycystic Ovary Syndrome (PCOS) is a metabolic disorder that affects fertility due to dysfunctional ovulation (9). In some cases, medications are required to induce ovulation in the presence of this metabolic condition (10,11). ...
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Background Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disorder. Current research findings present conflicting views on the effects of different PCOS phenotypes on outcomes in pregnancy and for newborns. Methods This research study followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). A thorough search of literature was carried out using the Cochrane Menstrual Disorders and Subfertility Group trials register, Web of Science, and EMBASE databases from their start to December 2023. The search focused on studies examining the links between hyperandrogenic and non-hyperandrogenic PCOS phenotypes and risks in pregnancy and neonatology. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using either a fixed-effects or random-effects model. Results Our analysis incorporated 10 research studies. Expectant mothers with a hyperandrogenic PCOS subtype had increased ORs for gestational diabetes mellitus (GDM) and preeclampsia (PE) compared to those with a non-hyperandrogenic PCOS subtype, with respective values of 2.14 (95% CI, 1.18–3.88, I² = 0%) and 2.04 (95% CI, 1.02–4.08, I² = 53%). Nevertheless, no notable differences were detected in ORs for outcomes like preterm birth, live birth, miscarriage, cesarean delivery, pregnancy-induced hypertension, small for gestational age babies, large for gestational age newborns, and neonatal intensive care unit admissions between pregnant women with hyperandrogenic PCOS phenotype and those without. Conclusions This meta-analysis highlights that the presence of hyperandrogenism heightens the risks of GDM and PE within the PCOS population. Healthcare providers ought to be aware of this connection for improved patient management.
... PCOS is a multifaceted gynecological disorder characterized by hormonal imbalances and metabolic dysfunction (17)(18)(19). Women with PCOS often experience reproductive disorders, including low pregnancy rates (20,21), low live birth rates (22,23), and high miscarriage rates (24,25). This suggests that many of the symptoms may be related to the endometrial microenvironment and anovulation (26). ...
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Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.
... Clinical HA was defined as the presence of hirsutism [modified FGS > 4] [61], acne, alopecia and/or seborrhea. Biochemical HA was defined by elevated TT (>0.77 ng/mL), fTesto (>3.18 pg/mL), androstenedione (>3.2 ng/mL) and dehydroepiandrosterone sulfate (DHEA-S > 2.75 ng/mL). ...
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MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a post-transcriptional level. Observational studies suggest an association of serum miRNAs and polycystic ovary syndrome (PCOS), a common heterogeneous endocrinopathy characterized by hyperandrogenism (HA), oligo- or amenorrhea (OM) and polycystic ovaries. It is not known whether these miRNA profiles also differ between PCOS phenotypes. In this pilot study, we compared serum expression profiles between the four PCOS phenotypes (A–D) and analyzed them both in PCOS (all phenotypes) and in phenotypes with HA by quantitative-real-time PCR (qRT-PCR). The serum expression of miR-23a-3p was upregulated in phenotype B (n = 10) and discriminated it from phenotypes A (n = 11), C (n = 11) and D (n = 11, AUC = 0.837; 95%CI, 0.706–0.968; p = 0.006). The expression of miR-424-5p was downregulated in phenotype C (n = 11) and discriminated it from phenotypes A, B and D (AUC = 0.801; 95%CI, 0.591–1.000; p = 0.007). MiR-93-5p expression was downregulated in women with PCOS (all phenotypes, n = 42) compared to controls (n = 8; p = 0.042). Phenotypes with HA (A, B, C; n = 32) did not show differences in the analyzed expression pattern. Our data provide new insights into phenotype-specific miRNA alterations in the serum of women with PCOS. Understanding the differential hormonal and miRNA profiles across PCOS phenotypes is important to improve the pathophysiological understanding of PCOS heterogeneity.
... Metformin, from the family of biguanides, is usually prescribed as the frst-line drug for modifying the metabolic features of PCOS, including obesity, IR, impaired glucose metabolism, and T2DM [4,10]. Metformin exerts its therapeutic efects by diminishing glucose production in the liver, inhibiting gluconeogenesis and lipogenesis, and increasing insulin sensitivity across peripheral tissues [11]. ...
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Background. Metformin is commonly prescribed to treat polycystic ovary syndrome (PCOS) patients, but in some cases, it may not be efective even at high doses or may cause intolerable side efects. Terefore, recent studies have examined the impact of combining metformin with other antidiabetic medications. Methods. A systematic search was performed in Scopus, PubMed, Web of Science, and Embase up to 30 June 2023. All interventional studies that assessed the efcacy of diferent antidiabetic agents were included. Results. Among the 3488 records found in the primary search, 16 papers were included. Our study showed that dipeptidyl peptidase-4 inhibitors (DPP4i) had the most signifcant impact on glycemic profle, while thiazolidinediones (TZDs) had the most infuence on lipid levels. However, it was observed that patients taking only metformin experienced a greater increase in high-density lipoprotein cholesterol (HDL-C) levels. Glucagon-like peptide-1 receptor agonists (GLP1RAs) efectively modifed various anthropometric measurements, such as weight, body mass index, waist circumference, and waist-to-hip ratio. Te efects of diferent antidiabetic drugs on hormone levels were inconclusive, although testosterone levels were more afected by GLP1RA, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and TZDs. None of the combined therapies showed a signifcant change in blood pressure. Conclusion. Since PCOS is a metabolic disorder, choosing the best combination of antidiabetic drugs in the clinical course of PCOS patients will be very important. Today, it seems that we need a new metabolic approach for better treatment of the metabolic aspects of these patients.
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Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 10–13% of reproductive‐aged women. Lifestyle management through diet and physical activity changes can improve reproductive, metabolic, and psychological comorbidities. The aim of this systematic review is to understand the barriers and facilitators to lifestyle changes from the perspective of people with PCOS and health care professionals (HCP) using the theoretical domains framework and capability, opportunity, motivation, and behavior model. Six databases were systematically searched for qualitative, quantitative, and mixed‐methods studies to 22nd September 2022. Quantitative outcomes from quantitative and mixed‐methods studies were narratively synthesized and all studies were thematically analyzed. Sixty‐eight papers met the eligibility criteria. HCP education on lifestyle management in PCOS was viewed by all to be inadequate, impacting the quality of care and health outcomes. Lifestyle advice delivered by a multidisciplinary team, including dietitians, was identified as a key component for change. All agreed that there was a need for individualized and PCOS‐specific lifestyle advice. Weight stigma was identified as negatively impacting both those in larger and smaller bodies with PCOS, reducing the quality of care and affecting self‐perception and mental health. People with PCOS perceived that lifestyle management was overly focused on weight loss and fertility, independent of their own personal motivations and goals. Systemic changes, including increasing HCP education on lifestyle management and multidisciplinary collaboration, focusing on lifestyle advice that meets individual needs, and reducing the use of weight‐centric care are necessary for long‐term sustainable changes and improvements in health outcomes in people with PCOS.
Article
Context Women achieving pregnancy with infertility treatment may be at increased risk of stillbirth and neonatal death. Objective To assess associations between clomiphene citrate (CC) use and perinatal death. Design Whole of population data linkage cohort. Setting South Australia. Participants All women giving birth between July 2003 and December 2015 (n=242,077). Methods All births of at least 20 weeks were linked to government records of dispensed medications. A pregnancy was considered exposed to CC if a prescription was dispensed from 90 days before through to the end of a conception window. Descriptive statistics for stillbirths and neonatal deaths were stratified by multiplicity. For singletons, multivariable logistic regression models were used to examine the association of CC exposure with the combined outcome of perinatal death. Main outcome measures Stillbirths and neonatal deaths (with 28 days of birth) combined as perinatal deaths. Results Among singletons, the prevalence of stillbirth was 6.6 per 1,000 births, with neonatal deaths of 2.1 per 1,000 live births. Among singletons conceived with CC, stillbirth and neonatal death had prevalence of 10.2 and 3.1 per 1,000, respectively. For the combined outcome of perinatal death, the odds ratio was 1.54 (95% confidence interval 1.15, 2.07), stable upon adjustment for factors conveying biological (e.g. obesity, pre-gestational diabetes) and social (e.g. disadvantage) risks for perinatal death. Conclusion Risk of perinatal death may be increased in pregnancies that follow use of CC. While established confounding factors related to infertility were taken into account, there may be some residual contribution of underlying infertility.
Chapter
The most common endocrinological disorder among the reproductive age group is polycystic ovarian syndrome (PCOS) leading to various systemic dysfunction. Skin is a mirror of PCOS with considerable heterogeneity in the clinical findings and variation in the same patient over time. It alters the aesthetic qualities of a woman by features of hyperandrogenism which are clinically manifested as hirsutism, acne, seborrhoea, female pattern alopecia and acanthosis nigricans. Hirsutism and acanthosis nigricans are the most reliable cutaneous markers of PCOS. Though common, acne and androgenetic alopecia are unreliable markers of hyperandrogenism. This chapter provides an overview of acne management in patients with polycystic ovary syndrome (PCOS).
Article
Androgen excess is a hallmark feature of polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Clinical and preclinical evidence links developmental or chronic exposure to hyperandrogenism with programming and evoking the reproductive and metabolic traits of PCOS. While critical androgen targets remain to be determined, central GABAergic neurons are postulated to be involved. Here, we tested the hypothesis that androgen signalling in GABAergic neurons is critical in PCOS pathogenesis in two well-characterised hyperandrogenic mouse models of PCOS. Using cre-lox transgenics, GABA-specific androgen receptor knockout (GABARKO) mice were generated and exposed to either acute prenatal androgen excess (PNA) or chronic periperpubertal androgen excess (PPA). Females were phenotyped for reproductive and metabolic features associated with each model and brains of PNA mice were assessed for elevated GABAergic input to GnRH neurons. Reproductive and metabolic dysfunction induced by PPA, including acyclicity, absence of corpora lutea, obesity, adipocyte hypertrophy and impaired glucose homeostasis, was not different between GABARKO and WT mice. In PNA mice, acyclicity remained in GABARKO mice while ovarian morphology and luteinising hormone secretion was not significantly impacted by PNA or genotype. However, PNA predictably increased the density of putative GABAergic synapses to GnRH neurons in adult WT mice, and this PNA-induced plasticity was absent in GABARKO mice. Together, these findings suggest that while direct androgen signalling in GABA neurons is largely not required for the development of PCOS-like traits in androgenised models of PCOS, developmental programming of GnRH neuron innervation is dependent upon androgen signalling in GABA neurons.
Article
Polycystic Ovary Syndrome PCOS is an endocrine disorder affecting 8 to 13% of reproductive aged women(1). Dietary and physical activity changes are the first-line therapy to assist with symptom and weight management and to reduce the risk of reproductive, metabolic and psychological comorbidities(2). However, women with PCOS have a higher weight, experience weight gain, and a higher prevalence of living in a larger body. Health care professionals (HCPs) play a crucial role in delivering diet and physical activity advice for people with PCOS. Thus, the aim of this systematic review is to understand the barriers, facilitators, experiences, and perceptions of engagement and compliance with diet and physical activity modifications in people with PCOS and in HCPs providing or referring people with PCOS to diet and physical activity modifications. A mixed-method systematic review was conducted with quantitative studies narratively synthesised and all studies thematically analysed. There were 68 eligible papers, including n = 59 (n = 5198) people with PCOS and n = 17 (n = 2,622) HCPs. Several themes were identified as impacting people with PCOS’ ability to make diet and physical activity changes. HCP education on PCOS management through diet and physical activity was viewed by HCPs and people with PCOS to be inadequate, further impacting the quality of care and health outcomes. Dietary and physical activity advice delivered by a multidisciplinary team, including dietitians, was identified as a key component for change. Both people with PCOS and HCPs agreed that there was a need for individualised and PCOS-specific diet and physical activity advice. However, HCPs viewed that there was limited evidence supporting these recommendations and a lack of time to deliver this care. Weight stigma was identified as impacting both those in larger and smaller bodies with PCOS, reducing the quality of care and affecting self-perception and mental health. People with PCOS perceived that diet and physical activity are overly focused on weight loss and fertility, independent of their own personal motivations and goals. Systemic changes, including receiving diet and physical activity advice that meet the individual’s needs, are necessary for leading to long-term sustainable changes and improvements in health outcomes. A multidisciplinary team approach and an overhaul of HCPs’ perceptions and mentality of weight and weight-centric care for those with PCOS are essential in delivering effective diet and physical activity advice.
Article
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Study question: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise and consumer preference? Summary answer: International evidence-based guidelines, including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. What is known already: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial, and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study design, size, duration: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/materials, setting, methods: Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. In total, 37 societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main results and the role of chance: The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: (i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (ii) reducing unnecessary testing; (iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, reasons for caution: Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider implications of the findings: The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. Study funding/competing interest(s): The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREE-II criteria, and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC.
Article
Full-text available
Study Question What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary Answer International evidence‐based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence‐based care and improve the experience and health outcomes of women with PCOS. What is Known Already Previous guidelines either lacked rigorous evidence‐based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study Design, Size, Duration International evidence‐based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II‐compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/Materials, Setting, Methods Governance included a six continent international advisory and a project board, five guideline development groups (GDGs), and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society‐nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty‐seven societies and organizations covering 71 countries engaged in the process. Twenty face‐to‐face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence‐based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main Results and the Role of Chance The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: (a) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (b) reducing unnecessary testing; (c) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (d) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, Reasons for Caution Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider Implications of the Findings The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program.
Article
Full-text available
Study question: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary answer: International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. What is known already: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study design, size, duration: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/materials, setting, methods: Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main results and the role of chance: The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; ii) reducing unnecessary testing; iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, reasons for caution: Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider implications of the findings: The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. Study funding/competing interest(s): The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREEII criteria and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC.
Article
Full-text available
Polycystic ovary syndrome (PCOS) is the main cause of female infertility worldwide and corresponds with a high degree of comorbidities and economic burden. How PCOS is passed on from one generation to the next is not clear, but it may be a developmental condition. Most women with PCOS exhibit higher levels of circulating luteinizing hormone, suggestive of heightened gonadotropin-releasing hormone (GnRH) release, and anti-Müllerian hormone (AMH) as compared to healthy women. Excess AMH in utero may affect the development of the female fetus. However, as AMH levels drop during pregnancy in women with normal fertility, it was unclear whether their levels were also elevated in pregnant women with PCOS. Here we measured AMH in a cohort of pregnant women with PCOS and control pregnant women and found that AMH is significantly more elevated in the former group versus the latter. To determine whether the elevation of AMH during pregnancy in women with PCOS is a bystander effect or a driver of the condition in the offspring, we modeled our clinical findings by treating pregnant mice with AMH and followed the neuroendocrine phenotype of their female progeny postnatally. This treatment resulted in maternal neuroendocrine-driven testosterone excess and diminished placental metabolism of testosterone to estradiol, resulting in a masculinization of the exposed female fetus and a PCOS-like reproductive and neuroendocrine phenotype in adulthood. We found that the affected females had persistently hyperactivated GnRH neurons and that GnRH antagonist treatment in the adult female offspring restored their neuroendocrine phenotype to a normal state. These findings highlight a critical role for excess prenatal AMH exposure and subsequent aberrant GnRH receptor signaling in the neuroendocrine dysfunctions of PCOS, while offering a new potential therapeutic avenue to treat the condition during adulthood.
Article
Objective: To formulate clinical consensus recommendations for screening depression, anxiety, health-related quality of life (HRQoL), and disordered eating symptoms in women with polycystic ovary syndrome (PCOS) and review prevalence based on phenotypes and ethnicity, changes over time, etiology, and impact of treatment. Design: Systematic reviews and preparation of position statement. Setting: Not applicable. Patient(s): Women with PCOS and controls screened using validated tools. Intervention(s): None. Main outcome measure(s): Depressive symptoms, anxiety symptoms, disordered eating, and HRQoL scores. Result(s): Several studies demonstrate that women with PCOS have an increased prevalence of higher depression and anxiety scores and higher odds of moderate and severe depressive and anxiety symptoms compared with controls. Obesity, hyperandrogenism, and fertility have a weak association with these symptoms. HRQoL scores are consistently reduced in PCOS, with infertility and weight concerns having the most significant impact. Some studies suggest an increased prevalence of disordered eating in women with PCOS compared with controls. The few studies that have evaluated the impact of PCOS-related treatments (lifestyle interventions and pharmacotherapy) show no detrimental effect or some improvement in depressive and anxiety symptoms and HRQoL scores. Conclusion(s): In women with PCOS, screening for depressive and anxiety symptoms should be offered at the time of diagnosis and screening for disordered eating should be considered. Further research is required across PCOS phenotypes, in longitudinal cohorts and on impact of therapy on depressive and anxiety syptoms, HRQOL, and disordered eating.
Article
Context The Polycystic Ovary Syndrome (PCOS) is a common endocrine-metabolic abnormality with a worldwide prevalence of 4%-21%, depending on diagnostic criteria. The National Institutes of Health (NIH) is the largest single funding agency in the world, invests nearly 30.0billionannuallyinbiomedicalresearch.EvidenceAcquisitionUtilizingtheNIHRePortersystemwesearchedforallgrantsawardedbytheNIHforPCOSandthreeotherdisorderswithcomparabledegreesofmorbidity,andsimilarorlowermortalityandprevalences(i.e.RheumatoidArthritis[RA],Tuberculosis[TB],andSystemicLupusErythematosus[SLE]).EvidenceSynthesisWecomparedfundingbytheNIHforPCOS,RA,TB,andSLEresearchfortheyears2006to2015,inclusive.ConclusionPCOS,comparedtoRA,TB,andSLE,wasrelativelylessfunded(totalmean10yearfundingwas30.0 billion annually in biomedical research. Evidence Acquisition Utilizing the NIH RePorter system we searched for all grants awarded by the NIH for PCOS and three other disorders with comparable degrees of morbidity, and similar or lower mortality and prevalences (i.e. Rheumatoid Arthritis [RA], Tuberculosis [TB], and Systemic Lupus Erythematosus [SLE]). Evidence Synthesis We compared funding by the NIH for PCOS, RA, TB, and SLE research for the years 2006 to 2015, inclusive. Conclusion PCOS, compared to RA, TB, and SLE, was relatively less funded (total mean 10-year funding was 215.12M vs. 454.39M, 773.77M, and $609.52M, respectively). Funding for PCOS was largely provided by one NIH institute vs. at least two institutes for SLE and RA; and more individual Research Project Grants were awarded to RA, SLE and TB, than PCOS, while PCOS funding was more likely to be through General Clinical Research Centers Program or Specialized Centers Program awards. Our data suggests that PCOS research may be underfunded considering its prevalence, economic burden, metabolic morbidity and negative impact on quality of life. Greater education of NIH leaders, including those at the NHLBI and NIDDK, other federal and state Agency leads, our elected leaders, and the general public, by professional societies, the scientific community, and patient advocates regarding this disorder is needed.
Article
Objective To identify gaps in polycystic ovary syndrome (PCOS) knowledge and practice patterns among physicians in North America in response to significant dissatisfaction identified among women with PCOS regarding their diagnosis and treatment experience. Design Online survey conducted via American College of Obstetrics and Gynecology of gynecologists (ObGyn) and American Society of Reproductive Medicine of reproductive endocrinologists (REI-ObGyn) in 2015–16. Setting Not applicable. Patient(s) None. Intervention(s) None. Main Outcome Measure(s) Diagnostic criteria used, key features of PCOS, management practices. Result(s) Of the 630 surveys completed, 70.2% were ObGyn and 64.4% were females. Overall 27.7% respondents did not know which PCOS diagnostic criteria they used. In a multivariable analysis including physician type, age, gender, and number of patients with PCOS seen annually, REI-ObGyn were less likely compared with ObGyn to report not knowing which criteria they used (adjusted odds ratio, 0.08; 95% confidence interval, 0.04, 0.16). REI-ObGyn were more likely to use the Rotterdam criteria (odds ratio, 2.26; 95% confidence interval, 1.33, 3.82). The majority of respondents recognized the clinical features associated with PCOS; however, over one-third associated “cysts on ovaries” with PCOS. The majority of responders (>85%) were aware of cardiometabolic comorbidities; however, fewer ObGyn were aware of associated depression, anxiety disorders, and reduced quality of life. More REI-ObGyn recommended lifestyle changes compared with ObGyn (56.4% vs. 41.6%). Conclusion(s) Our large-scale PCOS survey, conducted in response to patient concerns regarding diagnosis and treatment, highlights opportunities for physician education. Focus areas include targeting knowledge of internationally accepted Rotterdam criteria and ensuring consistent care informed by evidence-based guidelines across the reproductive, metabolic, and psychological features of PCOS.
Article
Context: Polycystic ovary syndrome (PCOS) is a complex, chronic and under-recognized disorder. Diagnosis experience may have lasting effects on wellbeing and self-management. Objective: To investigate PCOS diagnosis experiences, information provided and concerns about PCOS. Design: Cross-sectional study using an online questionnaire. Setting: Recruitment via support group websites in 2015-2016. Participants: 1385 women with a reported diagnosis of PCOS, living in North America (53.0%), Europe (42.2%) or other world regions (4.9%), 64.8% of whom were 18-35 years old. Main outcome measures: Satisfaction with PCOS diagnosis experience, satisfaction with PCOS information received at the time of diagnosis, and current concerns about PCOS. Results: One third or more of women reported more than two years (33.6%) and three or more health professionals (47.1%) before a diagnosis was established. The minority were satisfied with their diagnosis experience (35.2%) or with the information they received (15.6%). Satisfaction with PCOS information received was positively associated with diagnosis satisfaction (odds ratio (OR): 7.0 95% confidence interval (CI): 4.9 to 9.9); seeing ≥5 health professionals (OR: 0.5 95%CI: 0.3 to 0.8) and longer time to diagnosis (>2 years OR: 0.4 95%CI: 0.3 to 0.6) were negatively associated with diagnosis satisfaction (independent of time since diagnosis, age and world region). Women's most common concerns were difficulty losing weight (53.6%), irregular menstrual cycles (50.8%) and infertility (44.5%). Conclusions: In the largest study of PCOS diagnosis experiences, many women reported delayed diagnosis and inadequate information. These major gaps in early diagnosis, education and support are clear opportunities for improving patient experience.
Article
STUDY QUESTION What is the reported overall prevalence of polycystic ovary syndrome (PCOS) according to the criteria of the National Institutes of Health (NIH), Rotterdam or the Androgen Excess and PCOS Society (AE-PCOS Society)? SUMMARY ANSWER The reported overall prevalence of PCOS (95% CI) according to diagnostic criteria of the NIH, Rotterdam and the AE-PCOS Society is 6% (5–8%, n = 18 trials), 10% (8–13%, n = 15 trials) and 10% (7–13%, n = 10 trials), respectively. WHAT IS ALREADY KNOWN PCOS is the most common endocrine disorder among women of reproductive age. Although many studies have investigated the prevalence of PCOS, there are discrepancies in their results, in part due to the use of various definitions of the syndrome and its subphenotypes, differences between study cohorts, ethnicities, and types of recruitment and sampling. STUDY DESIGN, SIZE, DURATION A systematic review and meta-analysis were performed on all published studies that have reported the prevalence of PCOS according to at least one subset of diagnostic criteria. PARTICIPANTS/MATERIALS, SETTING, METHODS To identify relevant studies based on the PRISMA statement, PubMed and Ovid databases were searched up to September 2015 by two blind investigators using the terms ‘PCOS’, ‘polycystic ovarian disease’, ‘Stein Leventhal syndrome’, ‘Androgen Excess Society’, ‘National Institute of Health’, ‘Rotterdam’, ‘ESHRE/ASRM’, ‘criteria’ and ‘prevalence’. Articles that represented the prevalence of PCOS according to at least one subset of diagnostic criteria were included. Exclusion criteria were a focus on adolescent subjects, an absence of data on prevalence, inappropriate design or non-English reporting. An appraisal tool to evaluate the methodological quality of the available studies was generated by the authors. MAIN RESULTS AND THE ROLE OF CHANCE A total of 55 reports remained following screening of the abstracts and text for the subject of the study. Of these, 24 articles were eligible and evaluated for qualitative and quantitative synthesis. Since heterogeneity was observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The proportions of PCOS prevalence (95% CI) according to the diagnostic criteria of NIH, Rotterdam and AE-PCOS Society were 6% (5–8%, n = 18 trials), 10% (8–13%, n = 15 trials) and 10% (7–13%, n = 10 trials), respectively. When only unselected population studies were included, the given rates were 6% (5–8%, n = 3 trials), 9% (7–12%, n = 6 trials) and 10% (7–14%, n = 3 trials). The respective proportions for hirsutism, hyperandrogenaemia, polycystic ovaries (PCO) and oligo-anovulation were 13% (8–20%, n = 14 trials), 11% (8–15%, n = 9 trials), 28% (22–35%, n = 12 trials) and 15% (12–18%, n = 19 trials), respectively. LIMITATIONS, REASONS FOR CAUTION The effects of ethnic differences, particularly, on the presence or severity of hirsutism cannot be ruled out in any way. In addition, there was a lack of standardization in defining phenotypes of the syndrome and selection bias was evident in most of the studies regarding recruitment of the cohorts. WIDER IMPLICATIONS OF THE FINDINGS Geographical differences in frequencies of the components of the syndrome, such as oligo-anovulation and clinical/biochemical androgen excess, must be taken into account in the development and implementation of regional diagnostic and precision treatment strategies. Further efforts and resources are required to increase standardization of the methods and comparability of the study results on prevalence and phenotypic characterization of PCOS around the globe. STUDY FUNDING/COMPETING INTEREST(S) No funding to declare. The authors have no conflicts of interest to declare. REGISTRATION NUMBER None.