Review
Polycystic ovary syndrome
Lancet Diabetes Endocrinol
2022; 10: 668–80
Published Online
August 4, 2022
https://doi.org/10.1016/
S2213-8587(22)00163-2
Monash Centre for Health
Research and Implementation,
School of Public Health and
Preventive Medicine, Monash
University, Melbourne, VIC,
Australia (A E Joham PhD,
L J Moran PhD, J Boyle PhD,
Prof H J Teede PhD);
Department of Endocrinology
and Diabetes, Monash Health,
Melbourne, VIC, Australia
(A E Joham, H J Teede); Robinson
Research Institute, University
of Adelaide, Adelaide, SA,
Australia (R J Norman MD);
Department of Physiology and
Pharmacology, Karolinska
Institutet, Stockholm, Sweden
(E Stener-Victorin PhD);
Department of Obstetrics and
Gynecology, Penn State
University College of Medicine,
Hershey, PA, USA
(R S Legro MD); Institute of
Reproductive and
Developmental Biology,
Imperial College London,
London, UK (S Franks MD)
Correspondence to:
Prof Helena J Teede, Monash
Centre for Health Research and
Implementation, School of
Public Health and Preventive
Medicine, Monash University,
Melbourne, VIC 3168, Australia
helena.teede@monash.edu
668
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Anju E Joham, Robert J Norman, Elisabet Stener-Victorin, Richard S Legro, Stephen Franks, Lisa J Moran, Jacqueline Boyle, Helena J Teede
Polycystic ovary syndrome (PCOS) affects 5–18% of women, and is a reproductive, metabolic, and psychological
condition with impacts across the lifespan. The cause is complex, and includes genetic and epigenetic susceptibility,
hypothalamic and ovarian dysfunction, excess androgen exposure, insulin resistance, and adiposity-related
mechanisms. Diagnosis is recommended based on the 2003 Rotterdam criteria and confirmed with
two of three criteria: hyperandrogenism (clinical or biochemical), irregular cycles, and polycystic ovary morphology.
In adolescents, both the criteria of hyperandrogenism and irregular cycles are needed, and ovarian morphology is
not included due to poor specificity. The diagnostic criteria generates four phenotypes, and clinical features are
heterogeneous, with manifestations typically arising in childhood and then evolving across adolescent and adult
life. Treatment involves a combination of lifestyle alterations and medical management. Lifestyle optimisation
includes a healthy balanced diet and regular exercise to prevent excess weight gain, limit PCOS complications and
target weight reduction when needed. Medical management options include metformin to improve insulin
resistance and metabolic features, combined oral contraceptive pill for menstrual cycle regulation and
hyperandrogenism, and if needed, anti-androgens for refractory hyperandrogenism. In this Review, we provide an
update on the pathophysiology, diagnosis, and clinical features of PCOS, and discuss the needs and priorities of
those with PCOS, including lifestyle, and medical and infertility treatment. Further we discuss the status of
international evidence-based guidelines (EBG) and translation, to support patient self management, healthcare
provision, and to set research priorities.
Introduction defining individual diagnostic features and under­
Polycystic ovary syndrome (PCOS) takes its name from standing phenotypes and variability across the lifespan,
the commonly found multiple growth-arrested follicles in which will inform the true prevalence and lifelong
often enlarged ovaries of women with associated features impacts of PCOS. There is also recognition of the need to
including irregular or absent menstrual periods, correct inappropriate nomenclature given that there are
hyperandrogenism, and related metabolic and no formal cysts, and arrested ovarian follicles are neither
psychological sequelae.1 It remains the most common necessary nor sufficient for diagnosis.
endocrine disease of women of reproductive age,2 the Traditionally, research and knowledge on PCOS have
most common cause of anovulatory infertility,3 and focused mainly on White women who attend hospital-
a substantial contributor to early onset type 2 diabetes4 based clinics, often presenting with severe hirsutism,
and psychological disorders.5 Clinical presentations can weight problems, or menstrual abnormalities. Studies in
be diverse, but little doubt remains about the importance the past 10 years have focused on community-based
of this condition to the individual and to the health cohorts across ethnic groups within the same country or
services supporting their ongoing care. Priority areas to between nations.2,13 PCOS presentation in various
be resolved include increased understanding of European populations differs to that in the USA14 and
pathogenesis and natural history, improved diagnosis, within the USA variability is seen between Hispanic,
development of targeted treatments, and provision of African American, and White populations.15 East Asian
holistic models of care to meet the needs of women.6,7,8,9 populations with PCOS generally have a lower BMI and
For PCOS diagnosis, the 2018 International Evidence- less hirsutism, whereas compared to other populations,
based Guideline (EBG) for Assessment and Manage­ment South Asian populations have greater insulin resistance
of PCOS have ratified that two of three features and metabolic sequelae and greater prevalence of
are required in adults (hyperandrogenism, menstrual overweight and obesity, with other regions understudied.16
disturbance, and multi­ follicular ovarian morphology Escalating rates of overweight and obesity worldwide also
[PCOM]), whereas in adolescents both menstrual dis­ appear to be unmasking latent presentations of PCOS,17
turbance and hyperandrogenism are needed.6 Historically, thus better understanding of the interplay between
the initial National Institute of Health (NIH) consensus PCOS, ethnicity, hyperinsulinaemia, and excess weight
criteria10 were followed by the European Society for is needed.18
Human Reproduction and Embryology/American Society With the heterogeneity of PCOS, many women have
for Reproductive Medicine (ESHRE/ASRM) consensus delayed diagnosis, and report inadequate information
Rotterdam criteria,11 and then the Androgen Excess and provision and dissatisfaction with care.19 Health-care
PCOS Society criteria.12 This history has seen PCOS professionals vary in application of diagnostic criteria,
diagnostic features evolve, and prevalence vary investigation, and treatment.20 Research remains hetero­
from 5–18%.6 The 2018 EBG (approved by 38 professional geneous and under-funded, and has quality limitations.
societies and endorsed by the NIH) have now ratified the International efforts are underway to address these
Rotterdam criteria. Emphasis is now on accurately limitations, including patient advocacy, extensive evidence
www.thelancet.com/diabetes-endocrinology Vol 10 September 2022

synthesis that includes indi­vidual patient meta-analysis,
international collaborative guidelines, and translation
activities. A core outcome set (an international initiative to
harmonise outcome reporting in women’s health
research) has been established,21 and efforts to increase
research quality, consistency, and investment are under­
way. This initiative has developed minimum sets
of outcomes that can be measured in a standardised
manner and reported consistently in published PCOS-
related work, and efforts to increase research quality,
consistency, and investment are also on-going. Consumer
groups have prioritised holistic models of care that
focus on the individual rather than isolated symptoms,
and that encompass all features of PCOS with
a strong emphasis on psychological effects. Ultimately,
improved outcomes require a strengthened partnership
between women with lived experience of PCOS and
health professionals alongside recognition and funding
of appropriate models of care, increased high quality
research addressing gaps in literature, regularly
updated guidelines, and effective public health translation
for a more informed and educated public and
health-care workforce.22
Pathophysiology
Pathophysiology of PCOS
Hyperandrogenism is a key feature of PCOS, with causal
links between elevated bioactive testosterone and
PCOM, type 2 diabetes, and endometrial cancer.23 The
main source of hyperandrogenism in PCOS is
ovarian androgen hypersecretion, which is also the most
heritable phenotypic PCOS trait.24 This intrinsic ovarian
hyperandrogenism is driven by gonadotropin releasing
hormone (GnRH) causing luteinizing hormone (LH)
secretion, which further stimulates production of
androgen by ovarian theca cells25 (figure 1). Moreover
this hormonal milieu26 inhibits follicular maturation,
causing excess small antral follicles and ovulatory
disturbance. These small antral follicles then increase
granulosa-cell production of anti-Müllerian hormone
(AMH), with serum concentrations of AMH two to three
times above normal.26
Hyperinsulinaemia due to insulin resistance is also
inherent in PCOS, affecting up to 75–95% of women
based on insulin clamp studies.27 Hyperinsulinaemia and
insulin resistance both decrease hepatic sex hormone
binding globulin (SHBG), and exacerbate the effect of
luteinizing hormone on theca cell androgen production,
increasing circulating concentrations of both total and
free testosterone.28 Similarly, exogenously administered
insulin in type 1 diabetes causes hyperinsulinaemia, with
increased ovarian insulin exposure. This exposure is
associated with greater androgen production, and a high
prevalence of proposed secondary PCOS.18 Moreover,
there is evidence that insulin drives adipose tissue
testosterone production by increasing aldoketo reductase
type 3 (AKR1C3) in women with PCOS and insulin
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Review
Increased GnRH pulsatility
Insulin resistance
Increased AMH
Increase free
fatty acid
Hyperglycemia Hyperinsulinemia
Increased LH
Unaltered or low FSH
Stimulate theca cells
androgen production
Decrease
SHBG
Hyperandrogenemia Follicular arrest
leads to PCOM
Oligo– or anovulation
Figure 1: PCOS pathophysiology
Women with polycystic ovary syndrome (PCOS) have high gonadotropin-releasing hormone (GnRH) pulse
frequency resulting in hypersecretion of luteinizing hormone (LH) leading to stimulation of ovarian theca cell
androgen production. The unaltered (or low) follicle stimulating hormone (FSH) inhibits expansion of follicular
size and maturation, leading to follicular arrest and polcystic ovarian morphology (PCOSM) and oligoovulation
or anovulation. The large number of preantral and small antral follicles increase antimüllerian hormone (AMH)
production. Elevated AMH levels also increase the activity of GnRH neurons and directly stimulate
GnRH-dependent secretion of lutenising hormone, which may further stimulate ovarian hyperandrogenism.
Moreover, insulin resistance results in hyperinsulinemia stimulating GnRH secretion and ovarian theca cell
androgen production, and decreases sex hormone binding globulin (SHBG) production, further contributing
to hyperandrogenism.
resistance29 (figure 1). Further research is needed to
address the relationships and causal pathways between
androgens and insulin in PCOS.
Heritability of PCOS
As with other complex diseases, such as type 2 diabetes,
PCOS is highly heritable, yet is only partially accounted for
by approximately 20 identified susceptibility loci. Variants
with lower allele frequencies can also contribute to PCOS,
with identified rare variants specific to this condition.30 The
Rotterdam diagnostic criteria11 give rise to four different
PCOS phenotypes. Reproductive and metabolic PCOS
phenotypes are associated with specific PCOS susceptibility
loci, supporting genetic pathogenesis.31 Initial genetic
associations between PCOS and mental health disorders
have, however, been refuted.32 Variable inheritance might
relate to interactions between genetic and epigenetic
factors, the latter induced by the aberrant maternal-fetal
environment in PCOS, potentially yielding similar
phenotypic heritability to genetics.33 Epigenetic processes
influence gene activity and expression in target tissues,
and modify cellular and whole-body physiology without
669
 Review
altering DNA. Adipose tissue and skeletal muscle are
pivotal in metabolic dysfunction in PCOS,34,35 and appear to
be regulated by epigenetic mechanisms;35 yet the influence
of these factors remains unclear.
Pregnancy in PCOS and effects on offspring
Women with PCOS have greater weight gain36 and retain
high circulating androgens and insulin and AMH in
pregnancy than in pregnant women without PCOS.37
PCOS is an independent risk factor for cardiometabolic
conditions in pregnancy, including gestational diabetes
and hypertension.38 These conditions can decrease
placental weight, diminish placental aromatase activity,37
and negatively affect fetal development, potentially
predisposing offspring to reproductive, metabolic, and
psychological disorders.39 Daughters of women with
PCOS are reported to have elongated anogenital distance40
in most but not all studies. This finding could be a marker
of in-utero androgen excess, elevated circulating LH,41
increased androgens,42 and AMH concentrations,43 and
PCOM before puberty onset.44 A pilot study investigating
global DNA methylation patterns in neonatal cord blood
suggests a specific PCOS epigenetic signature.45 This
study, together with recent findings that daughters of
women with PCOS are five times more likely to be
diagnosed with PCOS than those from mothers without
PCOS,39 suggests an adverse maternal–fetal environment
that affects fetal epigenetic reprogramming.
Transgenerational transmission of PCOS
Although there are strengths and weaknesses of animal
models of PCOS,46 two recent studies report that
PCOS-like reproductive and metabolic traits are passed on
to third-generation female mouse offspring after prenatal
dihydrotestosterone39 or AMH exposure.47 Transcriptional
and mitochondrial perturbations of oocytes39 and ovarian
DNA methylation47 accompany this transgenerational
transmission, raising the possibility that epigenetic
modifications carried by germ cells or somatic cells
transmit PCOS across generations. Whether these results
can be translated to humans remains unknown; however,
epigenetic and transcriptomic signatures have been
detected in daughters of women with PCOS.39,47
Relationships between obesity and development of
PCOS
Obesity per se has a multitude of endocrine effects in
women. These include increased adipose androgen
production,48 suppressed SHBG with increased peripheral
androgen exposure,49 increased insulin resistance, and
hyperinsulinaemia. Obesity is also associated with
prolonged menstrual cycles with associated disordered
gonadotropin production,50 although these findings are
variably reported. PCOS prevalence also increases with
obesity,51 and Mendelian randomisation studies support
a causal role for obesity in PCOS.52 Ethnic and racial
thresholds for obesity prevalence, distribution, and effect
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on PCOS traits are also likely.13 Indirect calorimetry
indicates predictable total daily energy requirements in
PCOS using validated equations, with insulin resistance or
hyperandrogenaemia not adding predictive power
over height, weight, age, and physical activity.53 Studies
also support similar weight loss for degree of caloric
restriction in overweight women with and without PCOS,54
with no specific metabolic PCOS defect yet identified.
Hyperinsulinemia is associated with weight gain,
suppressing lipolysis and promoting lipogenesis in
adipocytes,55 with a likely bidirectional interaction between
hyperinsulinemia and excess weight.15 Appetite-related
mechanisms such as abnormal regulation of some appetite
hormones, including ghrelin and cholecystokinin,56,57
might also contribute to excess weight in PCOS; however,
evidence is inconsistent and further research needed.
Diagnosis of PCOS
PCOS is clinically heterogeneous, with no single diagnostic
test. Diagnostic criteria have evolved from original
1990 NIH criteria,10 including clinical or biochemical
hyperandrogenism and oligomenorrhoea or amenorrhoea,
with the exclusion of other disorders. In 2003, the ESHRE/
ASRM international consensus workshop group met in
Rotterdam and included PCOM as a criteria for adults
and the requirement to exclude thyroid dysfunction,
hyperprolactinaemia, and non-classical congenital
hyperplasia biochemically; and other conditions such as
Cushing’s syndrome if indicated clinically.
The Rotterdam criteria11 were endorsed internationally
by the NIH in 2012, and by the 2018 EBG for adult
women, and were ratified by 38 societies.58 Diagnosis
requires two out of three criteria: hyperandrogenism,
oligomenorrhoea or amenorrhoea, or PCOM. Bio­
chemical hyperandrogenism is only needed if clinical
hyperandrogenism is not evident, and PCOM is only
needed if only one of the oligomenorrhoea or
hyperandrogenism are present (figure 2). Evaluation of
biochemical hyperandrogenism can be done using total
testosterone, calculated free testosterone, free androgen
index, or bioavailable testosterone, and measured
preferably by liquid chromatography–mass spectrometry
(LC-MS) or by high-quality assays.60 Generic cut-off
values are not recommended because they vary by assay,
methods, and laboratories. Signs of clinical hyperan­
drogenism can include acne, androgenic alopecia, and
hirsutism. Hirsutism is defined by excess terminal hair
(terminal hair greater than 5 mm in length) in
androgenic dependent areas,61 which is assessed using
the modified Ferriman-Gallwey score (mFG). This visual
scoring system evaluates terminal hair in nine areas,
with scores of 4–6 indicative of hirsutism depending on
ethnicity.58 PCOM is diagnosed ideally using a high-
quality trans­ducer using transvaginal ultrasound and
based on the presence of 20 or more ovarian follicles on
either ovary, or ovarian volume of 10 mL or greater,
ensuring no dominant follicles are present.6
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In adolescents, PCOM is not recommended in
diagnosis within 8 years of menarche, given the overlap
with normal developmental physiology.7,62 Irregular
menstrual cycle criteria have been more accurately
defined63,64 as: less than 1 year post menarche (part of
normal pubertal transition); more than 1 year post
menarche, with cycles more than 90 days for any
one cycle; 1–3 years post menarche, with cycles less than
21 days or more than 45 days; and more than 3 years post
menarche, with cycles less than 21 days or more than
35 days (or fewer than eight cycles per year).58,65 This
refinement of diagnostic criteria has reduced potential
overdiagnosis due to past PCOM inclusion in adolescents,
with prevalence falling from 30% to 16% at 14–16 years of
age, also identifying a group prone to long-term
PCOS-related complications.63
Phenotypes generated under Rotterdam criteria11 vary in
severity of reproductive and metabolic features (figure 3).
Phenotypes A and B are considered classic PCOS (two-
thirds of cases), with increased BMI common and varying
by ethnicity and across populations. Metabolic features
(metabolic syndrome, impaired glucose tolerance, and
type 2 diabetes) are also prominent in these phenotypes.
The metabolic features occur independent of, but
exacerbated by higher BMI. Phenotype C (ovulatory PCOS)
can represent a milder form of PCOS with less insulin
resistance and fewer metabolic risk factors compared with
phenotypes A and B. For phenotype C, BMI is often
normal or only slightly increased; however, increasing
BMI exacerbates reproductive and metabolic features, and
might alter phenotypic presentation.64 Phenotype D
(normoandrogenic PCOS) includes chronic anovulation
and PCOM, normal serum androgens, and no clinical
hyperandrogenism. High-quality research applying
harmonised approaches and outcomes21,7 is needed to
understand the phenotypes and natural history further,
especially in phenotypes C and D as recent research
suggests that ovarian morphology—and indeed the
presence of ovaries themselves—is not necessary in the
metabolic phenotype of PCOS.66 Similar metabolic
abnormalities have been seen in both men and women
with polygenic risk scores aligned to PCOS-like
phenotypes.66
Ongoing diagnostic challenges
Ongoing challenges in PCOS diagnosis include improving
accuracy of individual diagnostic criteria and consideration
of new diagnostic criteria with these issues being
prioritised in ongoing research and upcoming guideline
updates. Current criteria are all continuous variables and
defining the optimal cut points is based on simplistic
95th centile cut-offs from control populations (variably
defined), with no pathophysiological basis. Research is
underway to define optimal cut-offs by sophisticated
statistical analyses with clustering of diagnostic features
and short-term and long-term clinical outcomes.67
Potential new criteria include AMH levels and measures
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Step 1: irregular menstrual cycles+clinical hyperandrogenism
(exclude other causes)*=PCOS diagnosis
Step 2: if no clinical hyperandrogenism
Test for biochemical hyperandrogenism
(exclude other causes)*=PCOS diagnosis
Step 3: only if irregular menstrual cycles or hyperandrogenism
Adolescents: pelvic ultrasound is not indicated
Consider at risk of PCOS, and reassess in 1–2 years
Adults: request pelvic ultrasound to assess for PCOM
If positive (exclude other causes)*=PCOS diagnosis
Figure 2: PCOS diagnosis
PCOS=polycystic ovary syndrome. PCOM=polycystic ovary morphology.
Adapted with permission from Teede et al, MJA 2018.59 *Exclusion of other
causes requires testing thyroid-stimulating hormone (TSH), prolactin, 17-OH
progesterone, and follicle-stimulating hormone (FSH). If clinical assessment is
suggestive, then other causes need to be excluded (eg, Cushing’s syndrome,
adrenal tumours, etc).
of insulin resistance,58,68 but both present assay and
specificity challenges.68
Clinical features and natural history
Women with PCOS can present with a diverse
range of clinical features that vary between and
within individuals across the lifespan. Reproductive
features including menstrual irregularity, anovulation,
hirsutism, infertility,69 and pregnancy complications70 are
prominent and best recognised in PCOS. Key metabolic
(insulin resistance,27 obesity,17 metabolic syndrome,
type 2 diabetes,4 and dyslipidaemia71) and psychological
features (depression, anxiety, poor self-esteem, body
image concerns, and mental health disorders)72,73 are
inherent in PCOS, and are of great concern to individuals
with this condition.
Metabolic features
The incidence of type 2 diabetes is higher in women with
PCOS, with an earlier age of onset and an incidence of 4⋅19
per 1000 population per year in a cohort of community-
based women with PCOS aged 18–42 years compared to
those without PCOS (1⋅02 per 1000 population [p<0·001]).4
In subgroup analyses of women with PCOS, incidence of
type 2 diabetes was 3⋅21 per 1000 per year in the healthy
weight group, 4⋅67 per 1000 per year in overweight group,
and 8⋅80 per 1000 per year in the obese group.4 This
finding is consistent with other longitudinal cohort studies
showing higher incidence of type 2 diabetes in women
with PCOS.74,75 Dyslipidaemia is also common in women
with PCOS compared with weight-matched controls,71
showing higher concentrations of triglycerides and low
density lipoprotein cholesterol and lower concentrations of
high density with studies showing higher triglyceride
concentrations and low density lipoprotein cholesterol
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 Review
1990 NIH criteria
2003 Rotterdam criteria11 endorsed by NIH10 and international evidence-based PCOS
guidelines
Phenotype A Phenotype A Phenotype A Phenotype A
Hyperandrogenism
Ovulatory dysfunction
PCOM
Figure 3: PCOS diagnostic criteria and phenotypes
PCOM=polycystic ovary morphology. Grey shaded boxes indicate that the selected diagnostic criterion is a feature
of that specific PCOS phenotype. Unshaded boxes indicate that the selected diagnostic criterion is not a feature of
that specific PCOS phenotype. Phenotype A=hyperandrogenism plus ovulatory dysfunction plus PCOM.
Phenotype B=hyperandrogenism plus ovulatory dysfunction. Phenotype C=hyperandrogenism plus PCOM.
Phenotype D=ovulatory dysfunction plus PCOM.
(LDL) concentrations, and lower-high density lipoprotein
(HDL) cholesterol concentra­tions.64,71 The relationship of
PCOS to dyslipidaemia is thought to be mainly mediated
by the deleterious effect of obesity.76 Women with PCOS
are also at increased risk of hypertension.77 Although
clustering of cardiometabolic risk factors is well recognised
in PCOS, the prevalence of cardiovascular disease in
women with PCOS remains unclear. A retrospective
cohort study from primary care data in England studied
time to major adverse cardiovascular event (MACE),
a composite endpoint incorporating myocardial infarction,
stroke, angina, revascularisation, and cardiovascular
mortality. Data were collated from 174 660 women
diagnosed with PCOS over 20 years from 1998 to 2017
(median age 29 years at baseline), and a control population
(matched at a ratio of 1:1 by age, BMI, and primary care
practice) with a median follow-up of 3·83 years for women
with PCOS and 3·00 years for controls.78 This study
suggests that young women with PCOS do have increased
incidence of major cardiovascular events,78 with adjusted
Cox proportional hazard models producing ratios of
1·26 (95% CI 1·13-1·41), 1·38 (95% CI 1·11-1·72), 1·60
(95% CI 1·32-1·94), and 1.50 (95% CI 1·08-2·07) for the
composite outcome, myocardial infarction, angina and
revas­cularisation respectively; although overall, at this
relatively young age, incidence was quite low. Research
looking at polygenic risk scores aligned to PCOS-like
phenotypes in both women and men shows similar
metabolic and hyperandrogenic features in both groups,
suggesting that ovaries may not be the driver for these
abnormalities.66
Reproductive features
PCOS is the primary cause of anovulatory infertility. In
a community cohort study involving 8,612, women with
PCOS had a 15-fold increased risk of infertility and 72% of
women attempting pregnancy reported anovulatory
infertility. These women with PCOS had similar in-vitro
fertilisation (IVF) rates but higher ovulation induction
treatment compared to women without PCOS.68 Although
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infertility in PCOS is increased independently of BMI,
a higher BMI exacerbates anovulation and infertility in
this condition. However, the ultimate effect of PCOS on
aspirational family size by the end of reproductive life
might not be affected when treatment is available, with an
Australian study reporting similar family size79 and
a Danish study reporting greater parity80 for women with
than without PCOS.
Pregnancy features
PCOS is associated with a two to threefold increased risk
for miscarriage, pregnancy-induced hypertension,
preeclampsia, gestational diabetes, and premature birth,
independent of BMI.81 However, in prospective trials in
populations of women with infertility, increased
miscarriage has not been confirmed based on the current
literature.82 Pregnancy loss and stillbirth might be more
common in PCOS than in other populations of women
with infertilty, with epidemiological studies showing
pregnancy loss at 20% in women with PCOS compared
with 15% in those without PCOS. A BMI in the overweight
or obese category was independently associated with
pregnancy loss, although PCOS status on its own was
not.79 Fertility treatment use has also been independently
associated with pregnancy loss, and more research is
needed to tease out the independent relationship of
PCOS status on pregnancy loss.83 Women with PCOS are
also at increased risk for developing gestational diabetes
earlier in pregnancy than women without PCOS,38,81 and
have higher rates of induction of labour and cesarean
section.82 Women with PCOS also experience more
difficulty with lactation than women without PCOS,
driven primarily by obesity.84
Psychological features
There is now greater understanding of the substantial
psychological features associated with PCOS. High levels
of distress and adverse effects on quality of life are
common with studies showing women with PCOS
reporting an increased prevalence of depression, anxiety,
negative body image, low self-esteem, and psychosexual
dysfunction.72,73 Quality of life scores are often reduced in
women with PCOS, with concerns around weight and
infertility having the most detrimental impact.5 Obesity,
hyperandrogenism, and infertility are weakly associated
with symptoms of depression and anxiety scores.5 A 2019
community-based study has shown that women with
PCOS also have an increased prevalence of disordered
eating, with binge-eating disorder being more prevalent
compared to controls.85
Changes in PCOS phenotype with age
The PCOS phenotype is heterogeneous and evolves over
time, with amelioration of reproductive clinical features
as women age. Oligomenorrhoea and hyperandrogenism
are more predominant concerns in younger women with
PCOS. Androgen production decreases with ovarian
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aging and decreased production of adrenal androgens,86
with a lower prevalence of acne and hirsutism with
increasing age. Ovarian volume increases after
menarche87 then falls with age, as does follicle number.88
Obesity, insulin resistance, type 2 diabetes, and metabolic
disturbances occur earlier and at higher prevalence than
in women without PCOS, although differential incidence
of type 2 diabetes might ameliorate with time in PCOS.89
A cross-sectional international study found that irregular
menstrual cycles were a key concern from women aged
25–35 years; excess hair growth, increased weight gain,
and metabolic complications from 36–45 years; and
insulin resistance and metabolic complications over
45 years.19
Medical management
Given the limited understanding of underlying causes of
PCOS, treatments are currently tailored to management
of specific symptoms but future care should be focused
on a holistic approach and patient priorities. Inclusive
models of care addressing these needs have been
prioritised by women with PCOS, moving beyond the
focus of individual symptoms aligned to specific medical
specialities. Care accept­ability and outcomes have also
been shown to improve in the setting of codesigned
models of care.6 A systematic review on models of care
for PCOS shows that definitions differ, but overall they
focus on how and what care is delivered, with core
components being stakeholder engagement, integrated
care, evidence-based approaches, defined outcomes and
evaluation, incorporating behaviour change, and adap­
tability.90 Thus, models of care operationalise how best
practice care can be delivered at a disease, service, or
systems level.
Menstrual cycles
Menstrual cycle abnormalities require management as
oligoovulation, anovulation and reduced progesterone
exposure can all increase the risk of endometrial
hyperplasia and malignancy.91 In those not trying to
conceive, treatment with combined oral contraceptive
pills is recommended to regulate cycles, particularly
if contraception is required or management of
hyperandrogenism is needed. There is no optimal
combined oral contraceptive pills in PCOS,92 and WHO
recommendations apply, including use of preparations
with low dose and natural oestreogens and low
thromboembolic risk.6 The primary anti-androgenic
action of the oral contraceptive pill is the increase in
SHBG and reduced circulating androgens, rather than
the direct anti-androgenic actions of specific progestins
in these preparations.7 If the combined oral contraceptive
pills are not desired or are contraindicated, cyclical pro­
gestogens (such as medroxyprogesterone acetate) can
be prescribed to regulate menses and reduce risk of
endometrial hyperplasia in women with oligorrhoea or
amenorrhoea.93,94 Although metformin improves insulin
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Review
resistance, ovulation, cycle regulation, and metabolic
health, it does not affect hyperandrogenism, and can
enhance fertility rather than providing contraception.92,95
Metformin combined with the combined oral contra­
ceptive pills can be useful for management of metabolic
features.92
Hyperandrogenism
Hirsutism, acne, and alopecia are distressing
symptoms, requiring considerable empathy and
understanding from health professionals, and effective
treatment. Optimal management of hirsutism includes
a combination of hair removal (electrolysis, laser,
shaving) and reduction in androgen levels or exposure.
Use of the combined oral contraceptive pills alone
is first-line medical management needing at least
6–12 months to establish efficacy.58,92 This treatment can
be supplemented with an androgen receptor antagonist
(typically spironolactone or cyproterone acetate) if
necessary, although studies to support this approach
are scarce and short-term.96 With anti-androgens,
concurrent contraception is crucial to limit risk of
adverse pregnancy outcomes (particularly potential
disruption of male sexual differentiation in a developing
fetus because antiandrogens cross the placenta). For
facial hirsutism, topical treatment with eflornithine (an
ornithine decarboxylase inhibitor) reduces hair growth
rates and can be used alone (if hirsutism is not
widespread) or with combined oral contraceptive pills.
Other anti-androgenic treatments have documented
side-effects, and there is insufficient evidence on long
term outcomes to recommend their use, and more
research is needed.58
Mild acne can respond to treatment with benzoyl
peroxidase or topical retinoids, with or without
antibiotics; however, in PCOS, acne is often severe and
persistent, requiring additional treatment with combined
oral contraceptive pills.92,97 Androgenic alopecia is the
most difficult manifestation of hyperandrogenism to
manage, and it is rarely possible to to medically reverse
loss of terminal hair. Treatment aims to limit further hair
loss. As for management of hirsutism and acne, a
combined oral contraceptive pill is recommended to
reduce androgen levels, potentially with additional anti-
androgens.98
Psychological features including anxiety and depression
Screening for psychological features is the first step in
recognition and treatment. Specific screening instruments
are recommended, and are easily applied between,
immediately before, or during clinical visits.58 In most
cases, psychological distress and symptoms of clinical
anxiety and depression are increased, substantially
influenced by the multiple and varied features of PCOS.
Acknowledgement of psychological features and increas­
ing patient empowerment by providing more information
about their condition and management can help to
673
 Review
Step 1: Weight and BMI assessment
Ask for consent and monitor at each visit.
Step 2: Glucose screening (informed by risk)
Low risk Medium risk High risk
PCOS only PCOS + other diabetes risk factors Pre-conception or early pregnancy
HbA1c or fasting glucose, every 3 years OGTT every 1–3 years OGTT and repeat at 24–28 weeks
Step 3: Check blood pressure
At least annually
Step 4: Lipid screening
At diagnosis in overweight or overweight women
Repeat based on risk
Obstructive sleep apnoea (OSA) should be considered
Screen and treat only if symptomatic
No overall metabolic benefit in treating OSA
Figure 4: Metabolic risk assessment in PCOS
PCOS=polycystic ovary syndrome. BMI=Body mass index. HbA1c=glycated haemoglobin. OGTT=oral glucose
tolerance test. OSA=obstructive sleep apnoea. Adapted with permission from Teede et al.59
alleviate psychological symptoms. However, when the
symptoms are severe, psychological or psychiatric
treatment is appropriate. Currently, few studies prioritise
psychological outcomes. As previously mentioned, a new
rigorously developed core outcome set in PCOS
emphasises the need to consider these outcomes in all
future studies.21
Cardiometabolic risks
Recognition and screening for cardiometabolic risk
factors is recommended from a young age, including
empathetic regular weight monitoring as support if
agreed with the individual woman. Blood pressure
should be checked annually. Assessment for dysglycaemia
should occur one to three times per year, with frequency
and specific tests determined by presence of additional
risk factors such as high BMI, and by local resources
(figure 4). Lipid profiles should be checked regularly,75
especially in those above a healthy BMI.7
Fertility management
First-line medical therapy to effectively promote ovulation,
pregnancy, and livebirth includes letrozole and clomifene
citrate.99,100 Overall, there is little evidence for fetal harm
with repeated cycles of these treatments.101 Clomifene
citrate has the highest multiple pregnancy rate, with
letrozole and metformin showing little effect.99 Monitoring
is recommended to avoid multiple follicle development,
and to ensure luteinization of a mature follicle for
clomiphene citrate and letrozole. In women resistant to
674
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these agents, second-line gonadotrophins with follicle
stimulating hormone can be used, with mandatory
hormone and ovarian monitoring to avoid multiple
pregnancy. A low-dose, step-up protocol is generally
favoured aiming for mono-ovulation, with the ovary very
sensitive to exogenous stimulation once a threshold dose
has been reached. Laparoscopic drilling of the ovary is also
an effective second-line therapy, and mainly induces
mono-ovulation;102 however, the mechanisms of action are
undetermined, long-term studies are rare, and peritoneal
adhesions can occur.
IVF for women with PCOS alone is recommended as
third-line infertility therapy, given the associated high
costs, invasive procedures, and increased risk for ovarian
hyperstimulation syndrome.103 Successful strategies to
reduce this risk include a GnRH antagonist protocol,
elective freezing of embryos to allow ovarian recovery,104
and avoidance of high-dose gonadotropin therapy through
in-vitro maturation of oocytes.105 Comparatively, women
with PCOS can experience higher pregnancy rates after
IVF than with other causes of infertility.106
Alongside active fertility treatment, lifestyle manage­
ment needs to be considered as outlined.
Pregnancy issues
As noted, pregnancy in women with PCOS is associated
with higher number of complications. Prevention includes
avoid­ance of multiple pregnancy, optimisation of weight
and metabolic status, and screening for dysglycaemia and
hypertension before, early, and during pregnancy. Preterm
labor is more common than in women without PCOS
therefore active surveillance is needed in later pregnancy.107
Neonates born to women with PCOS have higher
admission rates to high-level neonatal care and there is
greater perinatal mortality independent of multiple births
than in women without PCOS.70
Lifestyle management
Healthy lifestyle and weight management are recom­
mended as initial treatment in PCOS according to the
EBG.6 Lifestyle interventions aim to improve diet or
exercise and can include structured approaches and
behavioural strategies. Weight management is defined
as prevention of weight gain, achieving modest weight
loss (when needed) or maintaining a reduced weight.
In women who are above the healthy weight range,
a 5–10% weight loss is recommended, achievable
through a 30% (500–750 kcal/day) energy deficit, or
1200–1500 kcal/day total intake, depending on indi­
vidual energy requirements. A range of balanced
dietary approaches are recommended as per general
population recommendations, with little evidence that
any specific dietary approach is superior in PCOS.6 For
exercise, in adults a minimum of 150 min per week at
moderate intensity or 75 min per week at vigorous
intensity is recommended for prevention of weight
gain and general health benefits, and a minimum of
www.thelancet.com/diabetes-endocrinology Vol 10 September 2022

250 min per week at moderate intensity or 150 min per
week at vigorous intensity for modest weight loss and
prevention of weight regain. Minimising sedentary
time and including muscle strengthening exercises on
two non-consecutive days per week is also
recommended.6 Goal setting, in particular SMART
(specific, measurable, achievable, realistic, and timely)
goals can help with weight management. In addition,
self-monitoring, stimulus control, problem solving,
slower eating, reinforcing changes, and relapse
prevention can be helpful.6 When available, referral
should be considered to suitably trained allied health
professionals for support.6 Optimising lifestyle and
weight management improves anthropometric,
reproductive, metabolic, and psychological features of
PCOS.108 There are few randomised controlled trials on
lifestyle interventions and birth outcomes, yet other
studies have suggested improved menstrual regularity,
ovulation, pregnancy, and livebirth following weight
losses of more than 5% in women with PCOS.109,110
Research is needed on optimal timing, method, and
degree of weight changes needed to optimise infertility,
pregnancy, and birth outcomes.
Knowledge gaps, needs, and priorities
A broad range of health professionals care for women
with PCOS, including gynaecologists, endocrinologists,
primary care physicians, dietitians, exercise physiologists,
and psychologists. Gaps in knowledge, inconsistency of
approaches, and barriers to providing patient-centred care
have been identified alongside positive factors for optimal
health care.22 Insufficient knowledge of diagnostic criteria
has been reported in primary care providers, obstetricians,
gynaecologists, and reproductive and infertility specialists
in the USA,20 and more broadly.111 Additionally, gaps in
knowledge on psychological features, metabolic compli­
cations, and recommended screening are evident.111,112
In response to the gaps in current health care and
advocacy from women affected by PCOS, an
international collaboration involving 35 professional
and community organisations across 71 countries led to
the development of the 2018 International PCOS EBG.58
The aim was to overcome previous poor quality,
disparate guidelines with little consumer engagement.
Overall, 170 recommendations and practice points were
generated, with international peer-review and formal
NHMRC approval. The Rotterdam diagnostic criteria
were endorsed in adults and were updated in
adolescents. Individual diagnostic features were tigh­
tened, and assessment was agreed across reproductive,
metabolic, and psychological features, and management
recommended including lifestyle, medical, and infer­
tility treatment. Resources were codeveloped with
women and health professionals, ranging from simple
infographics to detailed content. A co-designed PCOS
question prompt list has been developed and integrated
into an evidence-based free AskPCOS app now used in
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Review
over 100 countries, and has been shown to meet
women’s information needs and to enhance self-
management.113 This development is important as many
apps that are used by women with PCOS often are
commercially derived and lack quality, evidence-based
information. For health professionals, systematic
reviews, recommendations, and translation outputs
were published; tools, algorithms, and accessible
screening tools assisted practice; and resources were
translated into multiple languages.
Education for health-care professionals can improve
confidence, and extensive translation resources have
been codeveloped on the basis of the of the 2018
International PCOS EBG, such as the international PCOS
guidelines, freely available in multiple languages via
partner organisations, with impact evaluation underway.
PCOS status itself is associated with high levels of
distress for affected women. The road to PCOS diagnosis
is often complex and delayed, and diagnosis experience
can be unsatisfactory.19 Diagnosis can evoke mixed
responses, which can vary with symptom severity and
duration.114 Diagnosis can also bring considerable benefits
and relief with an explanation for symptoms, as well as
feelings of being overwhelmed, lacking control, and
feeling anxious about long-term outcomes, particularly
infertility.9,115 Motivational, social, and behavioural effects
of PCOS diagnosis might be positive; however, negative
effects of diagnosis can occur, especially if inadequate
information is provided, highlighting the need for
support and information provision.115
Health professionals must partner effectively with
women to manage PCOS, with a strong focus on what
matters most to those with the condition.7 Research shows
that women generally prioritised understanding and
treating weight concerns, irregular menstrual cycles, and
infertility,19 whereas insulin resistance, diabetes and heart
disease, lifestyle interventions, and infertility were more
of a priority for health-care professionals. Supporting
factors—including clinician empathy, knowl­ edge, and
resources to facilitate trust and addresses the women’s
beliefs and concerns—help incorporate preventive
strategies and facilitate self-efficacy.115 Multidisciplinary For more on the international
models of care can support integrated care with tailored PCOS guidelines see https://
www.monash.edu/medicine/
treatments, education, and lifestyle support, and sphpm/mchri/pcos/resources
incorporate treatments such as laser hair removal
therapy.22,116 A question prompt list, a structured list of
health questions generated and applied by patients, can be
integrated with evidence-based information and answers.
This facilitates patient–provider interactions and can help
to improve patient knowledge and support.
Evidence-based guidelines, translation, and
research priorities
The available evidence for the development of the PCOS
EBG was mostly of low-to-moderate quality, reflecting
isolated, small-scale studies and a lack of PCOS research For the AskPCOS app see
funding,60 which highlights that much research is still https://www.askpcos.org
675
 Review
Search strategy and selection criteria
This Review is informed by a comprehensive and ongoing
process of evidence synthesis that underpins the
International Evidence-Based Guidelines on polycystic ovary
syndrome (PCOS) in 2018, and the upcoming 2023 update.
References for this review were identified through searches of
Cochrane Library, Cochrane Database of Systematic Reviews,
Health Technology Assessment Database, EMBASE, EBM
Reviews (OVID), Medline (OVID), and PsycINFO (OVID).
Databases were searched from inception defined on when
a specific investigation or treatment became available, and
extended up to April, 2022. Terms in the Population,
Intervention, Comparison and Outcome (PICO) framework
were determined by engagement with and prioritisation by
women affected by PCOS internationally, and with a broad
range of health professionals supporting their care. Terms
varied by topic areas and PICO, and included “polycystic ovary
syndrome”, “polycystic ovaries”, “polycystic ovary
morphology”, “ovary”, “diagnosis”, “adipose tissue”, “skeletal
muscle”, “genetic”, “obesity”, “insulin resistance”,
“androgens”, “type 2 diabetes”, “oral contraceptive pill”,
“metformin”, “fertility”, “infertility”, “ovulation”, “pregnancy”,
and “livebirth”, alongside many others. Articles resulting
from these searches, and the relevant references cited in
those articles, were reviewed, which also included
40 systematic reviews and 20 narrative reviews, with recent
search updates. Articles published in English were included.
needed on this common and neglected condition. Research
priorities have been formulated in a multistage process
across community, health professional, and academic
experts, and informed by international surveys with
women and multidisciplinary health-care providers,111
gaps seen from systematic reviews, and recommendations
from the International PCOS Guideline Network.64 Guide­
line processes prioritised adequately funded, multicentre,
and high-quality studies, improved reporting, selection,
allocation, blinding, side-effects, and compliance. Priority
content areas included diagnosis, prevention, and earlier
detection of complications, optimising lifestyle and
medical and surgical management across phenotypes, life
stages, and ethnicities.64 PCOS research across the full
research continuum, from discovery research and
mechanistic studies to clinical, health services, and
epidemiological research, are all crucial to fill these
identified knowledge gaps. A PCOS Core Outcome Set has
also been developed19 alongside guidance to improve
research quality in PCOS.
Conclusion
PCOS is a common condition with substantial health
and economic effects across the lifespan, including
reproductive, metabolic, and psychological features.
Diagnosis and treatment experiences are suboptimal
for women affected by PCOS, and it remains
676
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a much-neglected condition with key research and
clinical care gaps. Partnership between researchers,
health profes­sionals, and women affected by PCOS is
essential to address these gaps, including understanding
the cause, refining the diagnostic features and different
phenotypes, characterising natural history, and devel­
oping specific and effective therapies.
Contributors
All authors were involved in the conception and provision of expertise.
AEJ and HJT were responsible for the planning, author engagement, and
coordination of the review and provided resources. HJT supervised this
Review. All authors were involved in writing and reviewing the original
draft, and editing and approving the final version.
Declaration of interests
AEJ has received grant support from the National Health and Medical
Research Council and a School of Public Health and Preventive Medicine
Bridging Fellowship. She has received honoraria for educational events
from Boehringer Ingelheim Pty. She receives continuing medical
education allowance from Monash Health. She is a board member of the
Androgen Excess and PCOS Society. RJN has received grant support
from the National Health and Research Council. He has received
honoraria for educational events from Merck Pty. He is Chair of the
Vitamin D in PCOS and IVF board, and Chair of the Chinese Herbal
Therapy and Miscarriage board. Up until June, 2020, RJN was a minor
shareholder in Fertility SA. ESV was the President of Androgen Excess
and PCOS Society 2018–20 and is currently board member, and from
2022 she is Chief Scientific Officer of the Society. She received support
for the present manuscript from Novo Nordisk Foundation
(NNF22OC0072904) via payments to Department of Physiology and
Pharmacology, Karolinska Institutet. In the past 36 months she received
grants from Swedish Medical Research Council (project no. 2018-02435)
and Novo Nordisk Foundation (NNF19OC0056647) via payments to
Department of Physiology and Pharmacology, Karolinska Institutet.
RSL has received grant and research support from the National Institutes
of Health, Guerbet USA, Hass Avocado Board, Penn State Clinical and
Translational Science Institute, National Center for Advancing
Translational Sciences, and Patty Brisben Foundation for Women’s
Sexual Health. He has received consulting fees from Insudd Pty, Bayer
Pty, Fractyl Pty, Abbvie Pty, and Ferring Pty. He is an Honorary Professor
at the National Research Center for Assisted Reproductive Technology
and Reproductive Genetics, Shandong University, Jinan, China. He is
a Member of the International Advisory Panel for International evidence-
based guideline for the Assessment and management of Polycystic Ovary
Syndrome (PCOS), funded by The Australian National Health and
Medical Research Council (NHMRC) through the Centre for Research
Excellence in Polycystic Ovary Syndrome (CREPCOS), Monash
University, Melbourne, VIC, Australia. He is a Member of the Steering
Committee for the Eastern Siberia PCOS Epidemiology & Phenotype
study, Scientific Center of Family Health and Human Reproduction,
Irkutsk, Russian Federation. He is a member of the International
Advisory Panel, aiming to develop, disseminate, and implement a core
outcome set for infertility. Funded by the Royal Society of New Zealand
Catalyst Fund and the University of Auckland, New Zealand. He is an
advisor for a metabolomic approach to redefine diagnostic criteria and
classification of polycystic ovary syndrome (Principal Investigator:
Prof Chi Chui Wang, Chinese University of Hong Kong), which is
funded by the Research Fund, Food and Health Bureau, The Government
of the Hong Kong Special Administrative Region. He is an invited
speaker for: 34th Annual Meeting of the European Society of Human
Reproduction and Embryology (ESHRE), Barcelona, Spain; 2018 ASRM
Scientific Congress in Denver, CO; 28th Brazilian Congress of Human
Reproduction, Belo Horizonte, Brazil; 2019 IFFS World Congress,
Shanghai, China; Annual Meeting of ACOG, Nashville, TN; 30 Años
Aniversario IDIMI (Instituto de Investigaciones Materno – Infantil,
Universidad de Chile); 35th Annual Meeting of the European Society
of Human Reproduction and Embryology (ESHRE), Vienna, Austria;
PEACOCKS Biennial Meeting, Mas de Torrent, Costa Brava, Spain;
2019 Canadian Society of Endocrinology and Metabolism/Diabetes
Canada Professional and Annual Meeting, Winnipeg, Manitoba;
www.thelancet.com/diabetes-endocrinology Vol 10 September 2022

University of California at San Diego Ob/Gyn Grand Rounds, San Diego,
CA; Obesity Week, Las Vegas, NV; Seminars in Obstetrics, Gynecology
and Reproductive Biology; and Grand Rounds Obstetrics and Gynecology,
University of Kansas Medical Center, Kansas City, KS; Human
Reproduction Update Chinese Edition Young Editor Meeting; Obesity
and Women’s Health Webinar: NIH Obesity Research Task Force (ORTF)
Seminar Series; Grand Rounds, Department of Ob/Gyn, Yale University
School of Medicine, New Haven, CT; Grand Rounds, Division of Medical
Endocrinology, Yale University School of Medicine, New Haven, CT; Dept
of Ob/Gyn West Penn Hospital, Pittsburgh, PA; The Roland S Kron
Annual Lecture, Department of Ob/Gyn, Medical College of Wisconsin,
Milwaukee, WI; Penn State College of Medicine Emeritus Faculty
Organization Spring Meeting, Penn State College of Medicine, Hershey,
PA; Penn State College of Medicine, Hershey, PA; The PCOS Society
of India; Department of Obstetrics and Gynecology, Penn State College
of Medicine, Hershey, PA; and Penn State College of Medicine, Hershey,
PA. RSL is a member of the medical/scientific Advisory Board for PCOS
Challenge (a patient support group). He is an executive committee
member for the Endocrine Society, for whom he has also been the
Secretary-Treasurer. He is Chair of the Data Monitoring Committee,
The Fertility, IVF and Intrauterine Insemination trial in couples with
uneXplained infertility (the FIIX study). He was Co-Editor in Chief,
Seminars in Reproductive Medicine; Associate Editor, Human
Reproduction Update; Associate Editor, Fertility and Sterility; Editorial
Board, Endocrinology; and is currently the Editorial Editor for Fertility
and Sterility; Associate Editor for Global Reproductive Health; and
Editorial Board, Endocrinology, 2016–19. He owns 1000 shares of Biodesix
(BDSX). He is involved with the NIH: ZHD1 DSR-K (LR) 1 Loan
Repayment Program (annually, 2008 to present); U54 Contraceptive
Center Grant, Special Emphasis Panel ZHD1 DSR – L50 (2017); Special
Emphasis Panel/Scientific Review Group 05 CHHD-W 1 Population
Sciences Subcommittee (2018); and Special Emphasis Panel/Scientific
Review Group 10 ZHD1 DSR-M: National Centers for Translational
Research in Reproduction and Infertility (2020). He is also involved with
the Kuwait Foundation for the Advancement of Science (KFAS) (2017),
Appalachian Translational Research Network (ATRN) (2018), and
Karolinska Institute, Stockholm, Sweden (2020). SF receives grant
support from the Medical Research Council. He is a Medical Advisor
to Verity (UK PCOS patient support group) for more than 10 years.
LJM receives grant support from the National Heart Foundation of
Australia and National Health and Medical Research Council. She is also
the Convenor of Dietitians Australia Discussion Group in PCOS
(continuing professional development group). JB has received grant
support from the National Health and Medical Research Council and
WHiRL. She is the Director on the Royal Australian and New Zealand
College of Obstetricians and Gynaecologists Foundation (unpaid), and
a member of the migrant and refugee health partnership council
(unpaid). HJT receives grant support from the National Health and
Medical Research Council.
Acknowledgments
Funding for this Review was provided by the Novo Nordisk Foundation
(NNF22OC0072904; ESV), via payments to Department of Physiology
and Pharmacology, Karolinska Institutet, and by National Health and
Medical Research Council CRE Women’s Health in Reproductive Life
(WHiRL; JB). This funding had no influence on the content of this
manuscript. We gratefully acknowledge the contribution of
Rachel Hawkes (Verity, London, UK) for her helpful suggestions to the
outline of this manuscript. Throughout this manuscript we refer to
individuals with PCOS as women; however, we acknowledge that not
everyone with PCOS will identify as a woman.
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