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Rate of polycystic ovary syndrome in mental health disorders: a systematic

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Article in Archives of Women's Mental Health · February 2022

DOI: 10.1007/s00737-021-01179-4

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Archives of Women's Mental Health
https://doi.org/10.1007/s00737-021-01179-4

REVIEW ARTICLE

Rate of polycystic ovary syndrome in mental health disorders:

a systematic review
Katie M. Douglas1 · Anna J. Fenton2 · Kate Eggleston1,3 · Richard J. Porter1,3

Received: 1 February 2021 / Accepted: 31 August 2021

© The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2021

Abstract
Background Polycystic ovary syndrome (PCOS) is associated with increased risk of many mental health conditions, includ-
ing mood and anxiety disorders. Whether PCOS is more common in mental health conditions than in the general population
is less clear. A systematic review investigating this question may provide clarity regarding whether increased prevalence of
PCOS is seen in particular mental health disorders, and thus, whether screening female mental health patients for PCOS is
warranted.
Aims To systematically synthesise and review research examining rates of PCOS in mental health disorders.
Methods Peer-reviewed articles assessing the prevalence of PCOS within a sample of reproductive-aged females with a
diagnosis of Axis I or II mental health disorder were included. Key studies were identified through a comprehensive search
of PubMed and Web of Science.
Results Eleven studies met inclusion criteria, assessing rate of diagnosed PCOS in samples with bipolar disorder (n = 7),
autism spectrum disorders (ASD; n = 2), bulimia nervosa (n = 1), and post-traumatic stress disorder (PTSD; n = 1). Overall,
there was limited evidence of elevated rates of PCOS in bipolar disorder, compared with population estimates or healthy
control group rates. In ASD, bulimia nervosa, and PTSD samples, significantly increased rates of PCOS were reported
compared with healthy control samples, although studies were relatively small.
Conclusions This review highlights complexities and methodological considerations in this area of research. There are a
limited number of studies assessing PCOS in mental health samples, and thus, important areas of future research have been
identified.
Trial registration This systematic review was registered on PROSPERO (ID: CRD42020151420; https://​www.​crd.​york.​ac.​
uk/​prosp​ero/) on 28 April 2020.

Keywords PCOS · Polycystic ovary syndrome · Androgens · Bipolar disorder · Psychiatric disorders

Introduction different diagnostic criteria, see Ndefo et al. (2013)). Meta-

analysis of PCOS prevalence across continents (Europe,
Polycystic ovary syndrome (PCOS) is a heterogeneous syn- Asia, America, Australasia), using the National Institute of
drome, with no single diagnostic criterion sufficient for diag- Health (NIH) and Rotterdam criteria, has reported rates of
nosis (Teede et al. 2018, 2010). Prevalence of PCOS varies 6% (18 studies) and 10% (15 studies), respectively (Bozdag
depending on diagnostic criteria used (for an overview of et al. 2016).
Alongside comorbidity with physical health conditions,
PCOS is associated with significant psychiatric comorbidity.
* Katie M. Douglas In their meta-analysis of 30 cross-sectional studies spanning
katie.douglas@otago.ac.nz 10 countries, Cooney et al. (2017) reported increased odds
1 of moderate and severe depression and anxiety symptoms
Department of Psychological Medicine, University of Otago,
PO Box 4345, Christchurch, New Zealand 8140 in PCOS versus non-PCOS samples, which were significant
2 when body mass index (BMI) was taken into account. Con-
Oxford Women’s Health, Christchurch, New Zealand
sistently, Brutocao et al. (2018) reported increased risk of
3
Canterbury District Health Board, Christchurch, depression, anxiety disorders (across diagnoses), bipolar
New Zealand

13
Vol.:(0123456789)

disorder, and obsessive compulsive disorder in their meta-
analysis of 57 PCOS samples.
However, while increased risk of mental health disorders
in PCOS has been widely researched and recognised, the rate
of PCOS in mental health samples has received relatively
less attention. This may mean that vigilance for symptoms
of PCOS in those treating mental health conditions is low.
Rates of PCOS in different mental health conditions, and the
likely diagnostic yield which might be expected if routine
screening was carried out, remains unknown. One exception
is in the field of bipolar disorder research. Several bipo-
lar disorder studies have investigated the effect of sodium
valproate or similar compounds on aspects of PCOS symp-
tomatology. Insulin resistance and the stimulating effects
of sodium valproate on androgen biosynthesis have been
suggested as possible mechanisms by which sodium val-
proate may induce PCOS features (Joffe and Hayes, 2008).
However, whether PCOS is more prevalent in females with
bipolar disorder, not being treated with sodium valproate,
has not been as well studied.
To our knowledge, a systematic review of studies exam-
ining rates of PCOS in mental health samples has not been
conducted. Doing so may provide clarity regarding whether
increased prevalence of PCOS is seen in particular mental
health disorders, and if so, whether screening female men-
tal health patients for PCOS is warranted. Identification of
PCOS early on in a mental health assessment may allow
clinicians to identify the treatment option that most directly
treats the underlying cause of mental health symptoms. The
current review aims to synthesise and critically review stud-
ies that examine prevalence rates of PCOS in samples of
females with mental health conditions.
Methods
Protocol and registration
Details of the protocol for this systematic review were reg-
istered on PROSPERO (CRD42020151420) and can be
accessed at https://​www.​crd.​york.​ac.​uk/​prosp​ero/​displ​ay_​
record.​php?​Recor​dID=​151420. Study design and reporting
was guided by PRISMA guidelines.
Search strategy
Up to 1 August 2020, a systematic review of electronic data-
bases was carried out for relevant papers using PubMed and
Web of Science. In the initial search, the following search
items were used: “PCOS” or “Polycystic Ovary Syndrome”
or “androgen” and “psychiatric disorder” or “mental disor-
der” or “depression” or “bipolar disorder” or “psychosis”
or “eating disorder” or “anxiety disorder” or “autism” or
13
K. M. Douglas et al.
“personality disorder”. To ensure inclusion of all available
articles, reference lists of all relevant papers were checked.
Further, Web of Science was used to review articles that had
cited the relevant articles found using the aforementioned
search strategies. Covidence (www.​covid​ence.​org), the
programme recommended by the Cochrane Foundation to
streamline systematic reviews, was used to assist and man-
age the screening process.
Inclusion criteria
Any peer-reviewed article assessing the prevalence of diag-
nosed PCOS within a sample of non-pregnant, reproduc-
tive-aged females with a Diagnostic and Statistical Manual
of Mental Disorders (DSM) mental health disorder was
included (including Axis I and Axis II disorders in relation
to DSM-IV and earlier editions). In addition, peer-reviewed
articles that examined objectively at least two diagnostic
symptoms of PCOS (PCO morphology, hyperandrogen-
ism, menstrual abnormality) in females with a DSM mental
health disorder were included (for example, PCO morphol-
ogy via ultrasound, and hyperandrogenism using serum
analysis). This decision was based on the fact that having
these two criteria would fulfil diagnosis for PCOS, even if
studies did not explicitly report PCOS rates. All studies were
limited to full-text, English language publications.
Exclusion criteria
During the full-text screening process, reasons for exclu-
sion were (i) examination of PCOS symptoms only, but
not reporting the percentage of patients above a diagnostic
cut-off (n = 8; this included 3 studies that examined at least
two objective symptoms of PCOS, as per Inclusion Crite-
ria above), (ii) assessment of rate of psychiatric disorder
in PCOS sample (not vice versa; n = 5); and (iii) sample
size with n < 10 (n = 2). In relation to the first reason for
exclusion, corresponding authors from four studies were
contacted via email to request additional unpublished data
(percentage of PCOS diagnosis in mental health samples).
One author from one study responded and was unable to pro-
vide the requested data in their binge eating disorder sample.
Full study review
Articles were screened by two reviewers (KD, RP), who
independently reviewed titles and abstracts of studies to
accept or reject for full-text review. The same two reviewers
then independently examined full texts of the studies that
had passed initial screening. If consensus was not reached
regarding inclusion of a paper at this stage, reviewers dis-
cussed in order to achieve consensus.
Rate of polycystic ovary syndrome in mental health disorders: a systematic review

For each study, the following data was extracted: (1)
recruitment method, (2) characteristics of the sample,
including psychiatric diagnosis, sample size, mean age,
and major exclusion criteria, (3) criteria used to diagnose
PCOS, (4) presence of control group (either non-med-
icated psychiatric disorder group in the case of bipolar
disorder studies, or healthy control groups), (5) study out-
comes (percentage of total sample or odds ratio where
reported). See Fig. 1 for PRISMA flow diagram of review
process.
Assessment of risk of bias
The Joanna Briggs Critical Appraisal Checklist for Stud-
ies Reporting Prevalence Data (Munn et al. 2015) was
used as a formal risk of bias tool for each study (https://​
jbi.​global/​criti​cal-​appra​isal-​tools) (see Online Resource
1 for risk of bias ratings for each study). Differences in
design and assessment between studies were discussed
between two co-authors (KD, RP). Studies were weighted
by quality when synthesising the evidence.
Results
Study characteristics
Eleven studies meeting criteria were identified (see Table 1).
A further three studies reported at least two objective, diag-
nostic symptoms of PCOS; however, rates of PCOS could
not be calculated from these papers due to androgen data
being presented as group means rather than the percentage
of individuals above a certain diagnostic threshold (Eriksson
et al. 2012; Roepke et al. 2010; Raphael et al. 1995). Of the
11 PCOS prevalence studies, mental health conditions sam-
pled included bipolar disorder (n = 7), autism spectrum dis-
orders (ASD; n = 2), post-traumatic stress disorder (PTSD;
n = 1), and bulimia nervosa (n = 1). In 8 studies, PCOS was
diagnosed at the time of study participation according to
standardised criteria (Rotterdam; n = 3, NIH; n = 5) (mean
age in these studies ranged from 25 to 37 years). One study
used both Rotterdam and NIH criteria to diagnose PCOS
in ASD, but did so retrospectively by obtaining data from
medical files (either evidence of a PCOS diagnosis, or evi-
dence of core symptoms that would result in a PCOS diag-
nosis) (Cherskov et al. 2018). In the two remaining studies,

Fig. 1  PRISMA flow diagram

of studies retrieved for review Records identified through
database searching
(n = 604)

Records screened Records excluded

(n = 348) (n = 329)

Additional studies identified

through reference list checking
(n = 7)

Full-text articles Full-text articles excluded

assessed for eligibility (n = 15)
(n = 26)
- Assessment of PCOS
symptoms, not
diagnosis (n = 8)
- Assessment of rate of
psychiatric disorder in
PCOS sample (n = 5)
- Sample size n < 10 (n =
Studies included in 2)
qualitative synthesis
(n = 11)

13
 Table 1  Reviewed studies examining rate of diagnosed PCOS in mental health samples
Authors Mental health Recruitment site Clinical sample size Age Diagnosis of PCOS Exclusions Comparison groups Relevant findings*
condition

13
Bipolar disorder
Rasgon et al. BD Outpatient clinic n = 22 Recruited NIH criteria (although not OCP, antipsychotics LIT group, n = 10) PCOS rate: No patients met
(2000) According to age = 18–45 years formally stated as such in VAL group, n = 10 PCOS criteria
DSM-IV Mean the paper) LIT + VAL group, n = 2 No evidence of PCO
age = 34–37 years morphology or hyper-
androgenism in total
sample, and no difference
between groups
In total sample, 82%
reported menstrual
disturbance
LIT and LIT + VAL groups:
100% reported menstrual
disturbance in their his-
tories, and abnormalities
preceded BD diagnosis in
all but one case
VAL group: 60% reported
menstrual disturbance in
histories
O’Donovan BD Outpatient clinic n = 32 Recruited NIH criteria. Patients with OCP, hysterectomy VAL group, n = 17 PCOS rate: 41% of VAL
et al. According to age = 15–45 years current menstrual abnor- Non-VAL group, n = 15 group diagnosed with
(2002) DSM-IV Mean age: malities (n = 7) in VAL Non-BD HC group, PCOS, but rate not
BD = 30 years, group only had further n = 22 assessed in non-VAL
HC = 31 years investigation for diagnosed group
PCOS Significantly more current
menstrual disturbance
reported in VAL (47%)
vs. non-VAL (13%) and
HC groups (0%)
In VAL group, 59%
reported onset of men-
strual disturbance after
starting VAL
Rasgon et al. BD Outpatient clinic n = 80 Recruited NIH criteria Steroidal contraceptive use Current VAL group, PCOS rate: 4.2% of overall
(2005) According to age = 18–45 years (past 3 months) n = 58 BD sample had PCOS.
DSM-IV Mean age = 35 years Non-VAL group, n = 22 6% of VAL group and
and 0% of non-VAL had
Receiving long- PCOS (ns)
term treatment No difference in androgen
with ‘anti-manic’ levels between groups
agent 65% of total sample
reported menstrual dis-
turbance. 50% reported
menstrual disturbance
occurred prior to starting
BD treatment
In VAL group, 24%
reported menstrual dis-
turbance occurred after
starting VAL. In non-
VAL group, 5% reported
new onset menstrual
disturbance
K. M. Douglas et al.
 Table 1  (continued)
Authors Mental health Recruitment site Clinical sample size Age Diagnosis of PCOS Exclusions Comparison groups Relevant findings*
condition

Joffe et al. BD 16 university-affil- n = 300 Recruited age = 18–45 years NIH criteria Current OCP, preg- Current VAL, n = 108 PCOS rate: 4.7% prevalence
(2006) On same mood stabiliser iated psychiatry Mean age = 33 years nancy, < 6 months Not current VAL, of PCOS in BD reported in
for > 3 months departments postpartum, hysterec- n = 192 patients prior to initiation of
from STEP-BD tomy, bilateral oöpho- For new onset analy- mood stabilisers
rectomy, premature sis: VAL, n = 86. Incidence of new-onset PCOS
ovarian failure, ano- Non-VAL, n = 144 was significantly higher in
rexia nervosa, and use VAL compared with non-VAL
of hormone therapy, groups (10.5% versus 1.4%)
infertility medica-
tions, androgens, or
corticosteroids
Reynolds- BD Outpatient clinic or n = 103 Recruited age = 18–45 years Rotterdam criteria Illicit drug use (previ- HC, n = 36 PCOS rate: 4.8% prevalence of
May et al. According to DSM-IV via advertise- Mean age = 32 years ous 6 months), Smaller sub-analyses PCOS in BD group versus 0%
(2014) ment to general uncontrolled medical investigating type in HC group (ns)
population condition, peri- or of mood stabiliser No difference in androgen levels
post-menopausal, (VAL group, between BD and HC groups
OCP (past 3 months), n = 10) Current self-reported menstrual
pregnancy/breast- disturbance was 38% in BD
feeding, endocrine group versus 15% in HC group
disease, mood (ns). Reported menstrual dis-
disorder secondary to turbance did not correlate with
medical condition ovulation tracking data
Reported menstrual disturbance
and androgen levels did not
differ between VAL and non-
VAL groups
Viswanathan BD Tertiary care centre n = 20 Recruited age = 18–45 years Rotterdam criteria Polytherapy, on hormo- None PCOS rate: 5% of patients had
Rate of polycystic ovary syndrome in mental health disorders: a systematic review

et al. According to DSM-IV and university Mean age = 29 years nal preparations, did (comparison groups PCOS
(2016) and hospital not undergo ultra- were samples with 15% had polycystic ovaries on
Currently on VAL sound, hysterectomy/ epilepsy) ultrasound
oophorectomy 30% reported menstrual distur-
bance
Qadri et al. BD Outpatient clinic n = 200 Recruited age = 18–45 years NIH criteria Pregnancy, < 6 months Past VAL use, n = 114 PCOS rate: 23% of BD patients
(2018) According to DSM-IV Mean age = 25 years post-partum, No history of VAL diagnosed with PCOS
exogenous steroids/ use, n = 86 45% reported menstrual distur-
drugs causing ovarian bance, 27% had polycystic
failure, adrenal or ovaries
pituitary disorders, Rates of PCOS were 19% for past
diabetes VAL group versus 28% for no
history of Val group (ns)
Autism spectrum disorder
Ingudomnukul et al. ASD Volunteers from Autism n = 54 Recruited age = adults. Mean Self-reported life- Epilepsy Mothers of children with PCOS rate: signifi-
(2007) According to DSM-IV Research Centre website age = 38 years time diagnosis ASD, n = 74 cantly increased
of PCOS by a HC mothers of children rate of reported
‘medical doctor’ without ASD, n = 185 PCOS in ASD
group (11.3%),
compared with
mothers of ASD
group (6.7%)
and HC mothers
group (2.7%)

13
 Table 1  (continued)
Authors Mental health Recruitment site Clinical sample size Age Diagnosis of PCOS Exclusions Comparison groups Relevant findings*
condition

13
Cherskov et al. (2018) ASD UK-based primary care n = 971 Recruited age =  > 21 years Rotterdam and Cushing syndrome, adreno- HC group, n = 4855 PCOS rate: signifi-
According to retrospective Clinical Practice Research Mean age = 30 years NIH criteria genital disorders, CAH cantly increased
DSM diagnosis (varied Datalink database (based on data rate of PCOS
editions) from medical within autism
files) sample accord-
ing to Rotterdam
(7.8% versus
3.5% in HC),
and NIH criteria
(7.4% versus
3.1% in HC)
Post-traumatic stress disorder
Dobie et al. (2004) PTSD Mail-out survey (Women’s n = 253 Recruited age = adults Self-reported life- “Too ill to participate”, no Non-PTSD veteran PCOS rate: signifi-
According to DSM-IV (PCL Health Survey) to past Mean age = 42 years time diagnosis postal address group, n = 905 cantly increased
Civilian Version) female veteran outpatients of PCOS by a rate of PCOS in
‘medical doctor’ PTSD compared
with non-PTSD
sample (13.8%
versus 5.9%,
respectively)
Bulimia nervosa
Naessen et al. (2006) BN Advertisement to general n = 77 Recruited age = adults Rotterdam criteria OCP, psychotropic medica- HC group, n = 59 PCOS rate: signifi-
According to DSM-IV population Mean age = 27.5 years tion cantly increased
rate of PCOS in
BN versus HC
groups (16.6%
versus 1.7%)

Note: ASD = autism spectrum disorders, BD = bipolar disorder, BN = Bulimia Nervosa, CAH = congenital adrenal hyperplasia, OCP = oral contraceptive pill, HC = healthy control, LIT = lith-
ium, NIH = National Institute of Health, ns = non-significant, PCL = post-traumatic stress disorder checklist, PCOS = polycystic ovary syndrome, PTSD = post-traumatic stress disorder, STEP-
BD = Systematic Treatment Enhancement Program for Bipolar Disorder, VAL = valproate
*
key findings are reported in relation to PCOS rate, and rate of PCOS core diagnostic symptoms, if available (menstrual irregularity, hyperandrogenism, PCO morphology)
K. M. Douglas et al.
Rate of polycystic ovary syndrome in mental health disorders: a systematic review
which assessed PCOS in PTSD (Dobie et al. 2004) and
ASD (Ingudomnukul et al. 2007), self-reported “diagnosed
PCOS” was assessed (mean age in these studies ranged from
38 to 42 years). Of all 11 reviewed studies, 6 included a non-
psychiatric healthy control group as a comparison group.
Bipolar disorder
Seven studies in bipolar disorder were included. Since it has
been suggested that use of sodium valproate is associated
with PCOS, it is important to note the percentage of patients
treated with valproate in these studies.
Relatively low rates of PCOS in bipolar disorder sam-
ples were reported in three USA-based studies (Rasgon et al.
2005, 2000; Reynolds-May et al. 2014). In Reynolds-May
et al. (2014), 4.8% (5 of 103 patients; Rotterdam criteria) of
their bipolar disorder sample were diagnosed with PCOS,
compared with 0% in their smaller healthy control group
(0 of 35 participants, p value not significant). Ten patients
in their bipolar disorder sample were taking valproate and
reported no difference in self-reported or objective (using
ovulation tracking) menstrual abnormality, or androgen lev-
els, compared with females not taking valproate (but tak-
ing other mood stabilisers). Prevalence of PCOS in Rasgon
et al.’s (2005) sample was 4.2% (3 of 72 patients; NIH crite-
ria), with no significant difference in rates between those on
valproate (PCOS rate = 6%; 3 in 50 patients) or not (PCOS
rate = 0%; 0 in 22 patients). Of note, however, Rasgon et al.
(2005) showed that following valproate treatment, 24% self-
reported new onset menstrual abnormality, compared with
5% in the non-valproate group. Those who developed new-
onset menstrual abnormality were, however, prescribed a
significantly higher dose than those who did not develop
menstrual abnormality. In a very small study, Rasgon et al.
(2000) found no cases of PCOS in their bipolar disorder
sample (0 of 22 patients).
A further USA-based study assessed whether PCOS had
its onset after initiation of mood stabiliser medication (Joffe
et al. 2006). The total PCOS rate (NIH criteria) was 8.3% (25
of 300 patients), of whom 4.7% had PCOS prior to initia-
tion of any mood stabiliser, 3% appeared to have developed
PCOS following initiation of valproate, and 0.6% developed
PCOS following initiation of other mood stabiliser medica-
tion. Prior to starting treatment, valproate users who devel-
oped new-onset PCOS had higher BMI, insulin resistance,
and PCO morphology, and were taking more psychotropic
medication than valproate users who did not develop PCOS,
suggesting that it may be factors other than the valproate
itself which contribute to the higher rate after initiation of
valproate.
One study in India reported a much higher rate of PCOS
in inpatients with bipolar disorder (Qadri et al. 2018).
Using NIH criteria, 23% of their large sample (46 of 200
patients) were diagnosed with PCOS, with no difference
in the rate in those on valproate.
Two studies reported rates of PCOS in bipolar groups
treated with sodium valproate only (Viswanathan et al.
2016; O'Donovan et al. 2002). In their sample recruited
from Canada, O’Donovan et al. (2002) reported a high
rate of PCOS in their current valproate group (41%, 7 of
17 patients); however, PCOS was not assessed in their
comparison non-valproate (n = 15) and healthy control
(n = 22) groups. Significantly more current menstrual
abnormalities were self-reported in the valproate (47%)
versus non-valproate (13%) and healthy control (0%)
groups (p < 0.05). Those taking valproate were more likely
to have been hospitalised with bipolar disorder compared
with the non-valproate group (94% versus 40%, p < 0.01),
suggesting a more severe form of the disorder. In addition,
only 60% of women who were invited to participate via
post completed the menstrual history questionnaire mailed
to them at the same time, suggesting selective responding.
Viswanathan et al. (2016) reported a much lower rate of
PCOS in a bipolar sample (India) treated with valproate
(5%; 1 of 20 patients).
Autism spectrum disorders
Two studies examined PCOS rates in ASD (Cherskov et al.
2018; Ingudomnukul et al. 2007). Both recruited UK-
based samples and suggested an increased rate of PCOS
compared with healthy control samples. Cherskov et al.
(2018) used a comprehensive UK-based primary care data-
base to identify 971 females with a diagnosis of autism
(using various editions of the DSM), compared with
4855 age- and region-matched healthy control females.
Within the autism sample, prevalence of PCOS (diagnosis
or evidence of PCOS symptoms that would meet criteria
for diagnosis was obtained from medical files) was 7.8%
according to Rotterdam criteria, and 7.4% according to
NIH criteria (versus 3.5% and 3.1% respectively in healthy
controls). Thus, females with autism had approximately a
two-fold increase in risk for PCOS (Rotterdam, OR = 2.3;
NIH, OR = 2.5, both p < 0.001). This odds ratio held when
adjusting for comorbid psychiatric conditions (depression,
anxiety, psychosis).
Ingudomnukul et al. (2007) assessed retrospectively-
reported ‘testosterone-related medical conditions’ (“Have
you ever been diagnosed by a medical doctor with PCOS?”)
in a sample of females with DSM-IV autism or Asperger’s
Syndrome. Significantly increased prevalence of PCOS was
found in their ASD sample (11.3%, 6 of 54 patients) com-
pared with a healthy control sample made up of mothers
of typically-developing children (2.7%, 5 of 183 mothers,
p < 0.02).
13

Bulimia nervosa
Naessen et al. (2006), in 77 females with DSM-IV-diagnosed
bulimia nervosa, reported a significantly increased rate of
PCOS (16.6%, Rotterdam criteria) compared with their age-
and BMI-matched healthy control sample (1.7%, 1 in 59
participants, p < 0.05). Significantly increased menstrual
disturbances, hirsutism, and free androgen index was found
in the bulimia group compared with healthy controls.
Post‑traumatic stress disorder
One study assessed the rate of PCOS in PTSD (Dobie et al.
2004). This study did not focus purely on PCOS, but on self-
reported medical problems in a sample of female veterans
who had screened positive (n = 266) or negative (n = 940) for
self-reported PTSD. Cases of PCOS were identified with a
mailed-out, retrospective, self-report questionnaire. Females
with PTSD were more likely to report having been diag-
nosed with PCOS (13.8%) compared with females without
PTSD (5.9%; OR = 2.54, no p value reported).
Discussion
This paper systematically reviewed studies investigating
prevalence rates of PCOS in females with diagnosed mental
health disorders.
Studies were identified in bipolar disorder, ASD, PTSD,
and bulimia nervosa. Overall, across 11 studies, limited
evidence was found of elevated rates of PCOS in bipolar
disorder samples (7 studies), compared with population/
community estimates or healthy control group rates. In ASD
(2 studies), PTSD (1 study) and bulimia (1 study) samples,
significantly increased rates of PCOS were reported, com-
pared with rates in comparison with healthy control samples,
although all are relatively small studies and as we will note,
have methodological issues.
PCOS in bipolar disorder
There is minimal evidence of elevated rates of PCOS in
bipolar disorder samples either when comparing rates with
recruited healthy control samples, or with reproductive-age,
female population estimates (6–10%).
Only one out of the seven bipolar disorder studies
included compared rates with a healthy control popula-
tion from the same region (Reynolds-May et al. 2014). A
further strength of the Reynolds-May et al. study, which
reported a rate of PCOS at 4.8% in their bipolar disorder
sample, was the use of objective and current measurement
of menstrual abnormality, in the form of ovulation tracking
over three consecutive cycles. Rate of anovulation using
13
K. M. Douglas et al.
this method was not significantly raised in the bipolar dis-
order group compared with their healthy control group.
While the number of studies is small, and methodological
inconsistencies were present across studies, there is the
indication therefore that the pathophysiology of bipolar
disorder itself, may not contribute to PCOS status. While
in one study (Qadri et al. 2018), authors suggested a high
rate of PCOS (approximately 25%), they also suggest that
this may be consistent with rates in their particular com-
munity (Kashmir) (Zargar et al. 2005). Unfortunately, a
direct comparison was not carried out.
Several studies in bipolar disorder have related to con-
cerns that use of sodium valproate may induce PCOS-like
symptoms, particularly symptoms of hyperandrogenism
(Joffe and Hayes, 2008; Zhang et al. 2016). This issue
may be less relevant now given warning and recommen-
dations regarding the avoidance of valproate in women of
childbearing age in many countries (Malhi et al., 2021).
However, the evidence is in any case not clear. Cross-
sectional studies comparing PCOS rates in patients on,
or exposed to sodium valproate, compared with other
mood stabilisers, have not found significant differences
(Qadri et al. 2018; Rasgon et al. 2005). Joffe et al. (2006)
examined new-onset PCOS and showed a higher rate of
treatment-emergent PCOS in patients on sodium val-
proate, compared with other mood stabilisers. However,
given important differences between treatment groups in
BMI, insulin resistance and PCO morphology at baseline,
it is possible that sodium valproate exacerbated PCOS
symptoms in an already more ‘at risk’ group. Two stud-
ies (O'Donovan et al. 2002; Rasgon et al. 2005) reported
increased menstrual abnormalities when comparing val-
proate and non-valproate groups. However, both used self-
report to assess menstrual abnormality, which may not
correlate with either objective ovulation tracking (from
progesterone levels) or PCOS diagnosis, as noted in Reyn-
olds-May et al. (2014).
High rates of PCOS symptoms, such as obesity and self-
reported menstrual abnormalities, have been shown in bipo-
lar disorder samples. For example, in Qadri et al. (2018),
54% of their sample had a BMI > 25, and previous stud-
ies in bipolar samples have reported a mean BMI of > 25
(O'Donovan et al. 2002; McIntyre et al. 2003). Such findings
may illustrate a vulnerability to long-term general health
sequelae in bipolar disorder (Young and Grunze 2013), such
as diabetes and cardiovascular disease and in particular the
effects of various medications such as lithium and antipsy-
chotics, as well as valproate. There is, as yet, no clear evi-
dence of increased risk of PCOS per se in bipolar disorder.
However, screening for general metabolic abnormality is
clearly desirable and where there is menstrual abnormal-
ity, hirsutism, acne, or infertility; this should be extended to
include hormonal assessment.
Rate of polycystic ovary syndrome in mental health disorders: a systematic review
PCOS in other mental health disorders
Studies have been conducted in PTSD, bulimia nervosa,
and ASD. Given a relatively consistent finding of depres-
sion and anxiety symptoms in PCOS samples (Cooney
et al. 2017; Brutocao et al. 2018), it was of note that no
studies examining PCOS rates in samples with depres-
sion or anxiety disorders have, to our knowledge, been
conducted. This is an important future area of research. It
would appear important to consider screening for PCOS in
depressed women of childbearing age and studies examin-
ing the likely yield of this are important.
The review process captured some studies that inves-
tigated certain PCOS symptoms, in isolation, in mental
health populations. This includes studies of PCO mor-
phology and androgen levels in borderline personality
disorder (positive study) (Roepke et al. 2010) and premen-
strual dysphoric disorder (negative study) (Eriksson et al.
2012). These studies did not primarily aim to investigate
PCOS diagnosis, and thus, were not included formally
in the review and do not add to the discussion regarding
screening.
Autism spectrum disorders Elevated rates of PCOS were
diagnosed (Cherskov et al. 2018) or self-reported (Ingu-
domnukul et al. 2007) in ASD samples, in comparison with
healthy control samples. Cherskov et al.’s (2018) study was
large (autism n = 971, healthy controls n = 4855) and signifi-
cantly higher rates of PCOS were found in autism. Signifi-
cantly higher rates of anovulation, hyperandrogenaemia and
polycystic ovaries were also reported in the autism sample.
Prenatal hyperandrogenism and steroid dysregulation have
been proposed as key factors leading to the development of
both ASD and PCOS (Cherskov et al. 2018). Findings from
this study suggest that routinely assessing PCOS symptoms
in young women with autism may be helpful in preventing
development of adverse metabolic outcomes and other com-
plications of PCOS. The high incidence of intellectual dis-
ability in ASD may also lead to low reporting of symptoms,
making screening important.
Bulimia Nervosa In Naessen et al. (2006), a substantially
higher rate of PCOS was reported in their bulimia sample
(16.6%) compared with their healthy control sample (1.7%),
as well as increased rates of hirsutism, hyperandrogenism
and self-reported menstrual abnormality. It has been theo-
rised that hyperandrogenism may be the primary condition
that confers risk of bulimic behaviour. This has been sup-
ported by very preliminary research which has shown sig-
nificant symptom reduction in bulimic patients by treatment
with androgen receptor antagonist, Flutamide (Bergman and
Eriksson 1996; Sundblad et al. 2005). Clearly, this is an area
which requires replication, in large samples.
Post‑traumatic stress disorder An elevated rate of self-
reported PCOS was reported in a veterans PTSD sample
(13.8%, n = 266) compared with a veterans non-PTSD sam-
ple (5.9%, n = 940) (Dobie et al. 2004). The study is limited
due to the fact that PTSD was diagnosed using a self-report,
rather than clinician-administered, measure; the PTSD
Checklist-Civilian Version. In addition, enhanced reporting
in distressed compared with well individuals, or higher rates
of diagnosis in individuals having greater medical care, are
both possible explanations for the differences in rates.
Complexity in the overlap between PCOS
symptomatology and mental health conditions
There are a number of complexities in studying the asso-
ciation between PCOS and mental health conditions. First,
PCOS is a heterogeneous condition consisting of a com-
bination of relatively non-specific symptoms. Even the
hallmark of the disorder, polycystic ovaries, is reported
in a high proportion of healthy female samples (Polson
et al. 1988; Clayton et al. 1992). The same heterogeneity
is evident in mental health diagnoses. Second, core fea-
tures of PCOS may, in some instances, be caused by mental
health conditions. For example, amenorrhea occurs within
the syndrome of PCOS, but can also occur as a result of
stress. Reynolds-May et al. (2014) reported that 22% of
their female bipolar disorder sample had experienced
amenorrhea as a result of exercising or stress in the past,
compared with 8% of controls. Obesity is also a complex
factor which can be difficult to address, as it can occur as a
symptom of PCOS, a symptom of a mental health condition
(e.g., binge-eating disorder), a side-effect of psychotropic
medication, and/or a separate risk factor.
Limitations and methodological considerations
This systematic review has a number of limitations. First, the
number of studies reviewed is small. Second, variability in
study designs (e.g., medicated versus unmedicated samples,
small sample sizes, severity of psychiatric symptoms) means
that conclusions about prevalence of PCOS are tentative.
Third, some studies relied on retrospective, self-reported
diagnosis of PCOS by a ‘medical doctor’ (Ingudomnukul
et al. 2007; Dobie et al. 2004), which may be problematic for
a number of reasons; some females never receive a formal
diagnosis of PCOS even though they would meet syndrome
criteria if directly assessed, and those with a mental health
condition may be less likely to be diagnosed because the
primary issue is perceived as being related to mental health.
Fourth, many studies in the review did not include healthy
control groups to compare PCOS rates against. PCOS rates
may differ across ethnicities and regions, although a recent
13

review of studies across many world regions concluded that
evidence for geographic variability was limited (Wolf et al.
2018).
Last, although this review has included discussion of
the effect of sodium valproate on PCOS features in bipo-
lar disorder (valproate use was not specifically reported
or analysed in the four studies in non-bipolar samples),
other medications also contribute to PCOS symptomatol-
ogy. Well-established side effects of antipsychotic medica-
tion in women include amenorrhea, metabolic syndrome,
and obesity (Seeman 2009; Knegtering et al. 2003). In the
context of the current review, Reynolds-May et al. (2014)
reported that current atypical antipsychotic use was associ-
ated with elevated rates of self-reported current and past
menstrual abnormality (not objective ovulation tracking)
in their bipolar disorder sample. Studies in the current
review differed in how or if antipsychotic use (and other
psychotropic medication) was accounted for in its associa-
tion with PCOS, with some studies excluding participants
on antipsychotic medication (e.g., Rasgon et al. (2000)),
and others investigating effects in post-hoc analysis (e.g.,
Reynolds-May et al. (2014)). Given this, medications used
to treat psychiatric disorders could contribute to PCOS
symptomatology.
Implications and conclusions
This review has highlighted the need for further, large-scale,
controlled studies investigating the prevalence of PCOS in
female mental health populations. PCOS is a treatable condi-
tion, and thus, being able to determine whether certain men-
tal health conditions are associated with increased risk of
PCOS would be of use in developing screening procedures
for PCOS as part of clinical assessment.
Although evidence of an association between PCOS
and bipolar disorder was limited in the current review,
screening individuals with bipolar disorder who have a
vulnerability for PCOS (e.g., over a certain BMI cut-off)
may be of use in optimising treatment of both conditions.
Screening is likely to be useful in ASD and bulimia ner-
vosa. These findings also suggest that it would be pru-
dent to include assessment of menstrual history in all
women with mental health disorders. There is a scarcity
of research examining PCOS in depression and anxiety
samples, even though the reverse association (e.g., rates
of depression and anxiety in PCOS samples) has received
substantial research attention (Cooney et al. 2017; Bru-
tocao et al. 2018). Surprisingly, there are no studies in
patients with schizophrenia. There is, thus, much scope
for future research in this area.
13
K. M. Douglas et al.
Authors’ contributions KD and RP conceptualised the review and KD
performed the literature search, initial screening of articles for inclu-
sion, and data extraction. RP assisted with discussion and clarification
around articles for inclusion and study quality. All authors contributed
to writing, editing, and final approval of the manuscript.
Funding KD was supported by a Sir Charles Hercus Health Research
Fellowship from the Health Research Council of New Zealand (ref:
19/082) during completion of this paper.
Data availability NA
Code availability NA
Declarations
Ethics approval NA
Consent to participate NA
Consent for publication NA
Conflicts of interest RP and KD have used software provided by Sci-
entific Brain Training Pro (SBT-Pro) for research at no cost. RP has
received support for travel to educational meetings from Servier and
Lundbeck.
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