Clinical Review & Education
JAMA Insights | WOMEN'S HEALTH
Diagnosis and Treatment of Polycystic Ovary Syndrome
Heather G. Huddleston, MD; Anuja Dokras, MD, PhD
Polycystic ovary syndrome (PCOS) is the most common endocri-
nopathy among reproductive-aged people with ovaries, with an
estimated prevalence between 6% and 10% globally in 2016, de-
pending on diagnostic criteria used.1 The primary clinical features of
PCOS include irregular menstrual cycles and hyperandrogenism.
Metabolic dysregulation, par-
ticularly insulin resistance, is de-
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tectable in most individuals with
PCOS and is independent of, but exacerbated by, obesity. PCOS ap-
pears to affect populations across the world at similar rates, al-
though manifestations vary by lifestyle habits and life stage.
Diagnosis
The 1990 National Institutes of Health criteria represented the first
formal diagnostic approach to PCOS and required both oligomen-
orrhea and hyperandrogenism. The approach was expanded by the
2003 Rotterdam criteria, which added polycystic ovary morphol-
ogy (PCOM) as a third potential feature and required that 2 of 3 cri-
teria (oligomenorrhea, hyperandrogenism, and PCOM) be present
(Figure). A third approach, the Androgen Excess Society criteria of
2006, required hyperandrogenism with either oligomenorrhea or
PCOM or both. All 3 strategies require exclusion of other underly-
ing causes. Although there is currently no universally accepted di-
agnostic strategy, a recent international evidence-based guideline
affirmed the use of the Rotterdam criteria.2,3
For adolescents, 2 international consortia recently recom-
mended that PCOS be diagnosed only when both oligomenorrhea
and hyperandrogenism are present. Assessment of ovarian mor-
phology by ultrasound is not recommended until reproductive
maturity is achieved (8 years postmenarche).2,4 Because normative
data for ultrasound findings in adolescents are lacking, the inciden-
tal finding of PCOM in this group should not be used to diagnose
PCOS, unless both hyperandrogenism and oligomenorrhea are also
present. The timing of diagnosis should be carefully considered.
Cycle irregularity and certain hyperandrogenic signs, particularly
acne, are common for up to 3 years postmenarche and may not
necessarily signal the onset of PCOS. Adolescents with PCOS fea-
tures soon after menarche can be designated “at risk” and reas-
sessed once they are at least 2 years postmenarche.2
Clinical Care
The presentation and management challenges of PCOS are hetero-
geneous and vary among individuals, as well as within individuals
at various life stages. Primary concerns in the reproductive years in-
clude menstrual cycle control, management of hyperandrogenism,
fertility, mental health, and increased cardiometabolic risk.
Menstrual Cycle Control
Anovulatory cycles are common in PCOS and lead to unopposed es-
trogen exposure. In turn, lack of cyclic progesterone exposure causes
unscheduled episodes of menorrhagia and likely underlies the in-
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creased risk of endometrial cancer in PCOS.5 Counseling should in-
clude strategies to counter the effects of unopposed estrogen, in-
cluding the use of combined hormonal contraceptives, cyclic
progestins, or a progestin-containing intrauterine device. Com-
bined hormonal contraceptives can be administered via the oral,
transdermal, or vaginal route and provide additional benefits in treat-
ing clinical hyperandrogenism.
Hyperandrogenism
Clinical signs of hyperandrogenism include hirsutism, acne, and
female pattern hair loss. Standardized assessment of hirsutism
is made with visual scales, such as the Ferriman-Gallwey score,
which assesses 9 body areas on a scale of 0 to 4, with a score of 6
or greater indicative of hirsutism. Combined hormonal contracep-
tives, which lower androgen production and increase sex
hormone–binding globulin, are recommended to treat clinical
hyperandrogenism. There is insufficient evidence to recommend
one specific preparation; however, clinical consensus supports use
of combined hormonal contraceptives with a lower dose of ethinyl
estradiol (30 μg or less) and with less androgenic progestins
(drosperinone, desogestrel). Antiandrogen medications, such as
spironolactone, or mechanical depilation may be added after 6
months if needed.
When patients have contraindications to hormones, other
treatments should be considered, including the use of a progestin
intrauterine device combined with an antiandrogen medication.
Whether female pattern hair loss improves with combined hor-
monal contraceptives, antiandrogens, or both has not been well stud-
ied; however, minoxidil (5%) is approved by the US Food and Drug
Administration for this indication.6 Ovarian wedge resection is not
recommended for the treatment of PCOS due to risks of adhesions
and loss of ovarian reserve.
Fertility and Pregnancy
As a result of decreased ovulation frequency, patients with oligo-
menorrhea often experience subfertility. Oral ovulation induction
therapies, including letrozole and clomiphene citrate, are effective
and considered first-line treatment.3 Although less effective, life-
style strategies and metformin may increase ovulation frequency
and serve as potential adjuncts. Once pregnant, patients with
PCOS have an approximately 2-fold increased risk of gestational
diabetes, preeclampsia, and preterm birth compared with those
without PCOS.2 Individuals planning pregnancy benefit from pre-
conception counseling to optimize metabolic health.
Cardiometabolic Risk
Insulin resistance is detectable in a majority of individuals with
PCOS and contributes to both reproductive and metabolic
dysfunction.7 Because rates of impaired glucose tolerance and
type 2 diabetes are increased, glycemic status should be assessed
with a glucose tolerance test, fasting glucose measurement,
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 JAMA Insights Clinical Review & Education

or hemoglobin A1c assessment. Individuals with PCOS should also

Figure. Diagnosis of Polycystic Ovary Syndrome by Rotterdam Criteria
be screened for cardiovascular disease (CVD) risk factors, including
obesity, dyslipidemia, hypertension, and nonalcoholic fatty liver Polycystic ovaries (PCO) Oligomenorrhea
disease. Lifestyle interventions are recommended to optimize ≥20 follicles per ovary or anovulation (OM)
or an ovarian volume ≥10 mL PCO Cycles <21 d or >35 d,
metabolic health. Metformin can be considered for those who are in at least 1 ovary on or fewer than
D
overweight or obese, particularly when abnormal cardiometabolic transvaginal ultrasound 8 cycles/y
indices are present.2
C A OM
Although there is a clear link between CVD risk factors and PCOS,
longitudinal data are currently insufficient to determine if, and to
Hyperandrogenism (HA) B
what degree, PCOS leads to an increased risk for cardiovascular
Clinical features (hirsutism) PCOS phenotypes
events. Screening for CVD should therefore follow general popula- HA
and/or biochemical evidence
A HA, PCO, and OM
(free or total testosterone
tion recommendations, incorporating family history and presence levels above normal range
B HA and OM
C HA and PCO
of other risk factors, including body mass index, lipid levels, and meta- for women)
D PCO and OM
bolic syndrome factors.3
Exclude other causes of PCOS
Hypo- or hyperthyroidism Functional hypothalamic amenorrhea
Mental Health Hyperprolactinemia Late-onset congenital adrenal hyperplasia
Individuals with PCOS have an increased risk of moderate to severe
Diagnosis during adolescence should not include ultrasound and should be made
anxiety, depression symptoms, and disordered eating.3 These symp- ≥2 y postmenarche.
toms should be assessed routinely, with referrals made to mental Metabolic features, particularly insulin resistance, are common and independent
of but exacerbated by obesity.
health professionals as indicated.
The Rotterdam criteria are described in the PCOS guideline.2
Care at Midlife and Beyond
While many reproductive symptoms (eg, menstrual cycle abnor- Conclusions
malities, hirsutism) abate with the decline of ovarian function, cli- Given the high prevalence of PCOS, clinicians from diverse special-
nicians who provide care for individuals in their postreproductive ties should be familiar with the clinical characteristics of this disor-
years should be aware that individuals with a history of PCOS may der. Optimal quality of life for patients with PCOS requires an indi-
continue to have cardiometabolic and mental health challenges at vidualized approach that considers the array of commonly associated
midlife and beyond. gynecologic, dermatologic, reproductive, and metabolic challenges.

ARTICLE INFORMATION REFERENCES pathophysiology, diagnosis, and treatment of

Author Affiliations: Department of Obstetrics,
Gynecology and Reproductive Sciences, University
of California, San Francisco (Huddleston);
Department of Obstetrics and Gynecology,
University of Pennsylvania, Philadelphia (Dokras).
Corresponding Author: Heather G. Huddleston,
MD, Center for Reproductive Health, 499 Illinois St,
San Francisco, CA 94158 (heather.huddleston@
ucsf.edu).
Conflict of Interest Disclosures: Dr Huddleston
reported receiving stock options in Allara for her
work on the medical leadership team. Dr Dokras
reported receiving consulting fees from AblaCare,
GSK, and Veera Health and grants from the Eunice
Kennedy Shriver National Institute of Child Health
and Human Development.
Submissions: The Women's Health editors
welcome proposals for features in the section.
Please contact ccrandall@mednet.ucla.edu.
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