Polycystic Ovary Syndrome (PCOS)
(Hyperandrogenic Chronic Anovulation; Stein-Leventhal Syndrome)
By JoAnn V. Pinkerton, MD, University of Virginia Health System
Reviewed By Oluwatosin Goje, MD, MSCR, Cleveland Clinic, Lerner College of Medicine of Case Western
Reserve University
Reviewed/Revised Aug 2025
Polycystic ovary syndrome is a clinical syndrome defined by the presence 2
of 3 findings: hyperandrogenism (eg, hirsutism, acne), ovulatory dysfunction,
and polycystic ovarian morphology. Insulin resistance and obesity are often
present. Diagnosis is by clinical criteria, hormone tests, and imaging to
visualize polycystic ovaries and exclude a virilizing tumor. Treatment is based
on symptoms, insulin resistance, and fertility goals.
Polycystic ovary syndrome (PCOS) occurs in 5 to 10% of women (1). In the United States, it is the most
common cause of infertility.
PCOS is a clinical syndrome that involves ovulatory dysfunction (anovulation or oligo-ovulation), androgen
excess, and polycystic ovaries. The presence of ovarian cysts alone is not sufficient to make the
diagnosis, and some patients do not have polycystic ovaries.
General reference
1. Dumesic DA, Oberfield SE, Stener-Victorin E, et al: Scientific statement on the diagnostic
criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome.
Endocr Rev 36 (5):487–525, 2015. doi: 10.1210/er.2015-1018
Pathophysiology of PCOS
The etiology of PCOS is unclear. However, some evidence suggests that patients have a functional
abnormality of cytochrome P450c17 affecting 17-hydroxylase (the rate-limiting enzyme in androgen
production); as a result, androgen production increases. Pathogenesis appears to involve genes involved
in the regulation of androgen biosynthesis as well as environmental factors, such as diet, nutrition,
environmental toxins, and low socioeconomic status. Racial and ethnic differences are noted, particularly
for metabolic issues and psychosocial issues (1).
Both metabolic hormones (insulin, growth hormones ghrelin, LEAP-2) and reproductive hormones
(gonadotropin-releasing hormone [GnRH], luteinizing hormone/follicle-stimulating hormone [LH/FSH] ratio,
androgens, and estrogens) are abnormal. These hormone abnormalities result in increased rates of
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metabolic disorders, such as diabetes and insulin resistance, having overweight and obesity, infertility, and
menstrual cycle dysfunction (2, 3).
Polycystic ovaries typically contain many 2- to 6-mm follicular cysts and sometimes larger cysts containing
atretic cells. Ovaries may be enlarged with smooth, thickened capsules or may be normal in size.
Pathophysiology references
1. VanHise K, Wang ET, Norris K, Azziz R, Pisarska MD, Chan JL. Racial and ethnic disparities in
polycystic ovary syndrome. Fertil Steril. 2023;119(3):348-354. doi:10.1016/[Link].2023.01.031
2. Joshi A. PCOS stratification for precision diagnostics and treatment. Front Cell Dev Biol.
2024;12:1358755. Published 2024 Feb 8. doi:10.3389/fcell.2024.1358755
3. Yang J, Chen C. Hormonal changes in PCOS. J Endocrinol. 2024;261(1):e230342. Published
2024 Feb 15. doi:10.1530/JOE-23-0342
Complications of PCOS
Polycystic ovary syndrome has several significant potential complications.
Infertility is related to ovulatory dysfunction.
Estrogen levels are elevated and are not consistently opposed by progesterone due to chronic or
intermittent anovulation, increasing risk of endometrial hyperplasia and endometrial cancer.
Androgen levels are often elevated causing hirsutism. Hyperinsulinemia due to insulin resistance may be
present and may contribute to increased ovarian production of androgens. Over the long term, androgen
excess increases the risk of obesity, cardiovascular disorders, including hypertension, hyperlipidemia, and
metabolic syndrome. Risk of androgen excess and its complications may be just as high in women who
are not overweight as in those who are not.
Calcification of coronary arteries and thickening of the carotid intima media is more common among
women with PCOS, suggesting possible subclinical atherosclerosis (1). This may be due to insulin
resistance, obesity, or elevated androgen levels and correlates with visceral fat.
Type 2 diabetes mellitus and impaired glucose tolerance are more common, and risk of obstructive sleep
apnea is increased.
Studies indicate that PCOS is associated with low-grade chronic inflammation and that women with PCOS
are at increased risk of nonalcoholic fatty liver disease (2).
PCOS is associated with an increased risk of depression, anxiety, eating disorders, low self-esteem, and
negative body image (3).
Complications references
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1. Gomez JMD, VanHise K, Stachenfeld N, Chan JL, Merz NB, Shufelt C. Subclinical
cardiovascular disease and polycystic ovary syndrome. Fertil Steril. 2022;117(5):912-923.
doi:10.1016/[Link].2022.02.028
2. Rocha AL, Oliveira FR, Azevedo RC, et al: Recent advances in the understanding and
management of polycystic ovary syndrome. F1000Res 26;8, 2019. pii: F1000 Faculty Rev-565. doi:
10.12688/f1000research.15318.1 eCollection 2019.
3. Kurki MI, Karjalainen J, Palta P, et al. FinnGen provides genetic insights from a well-phenotyped
isolated population [published correction appears in Nature. 2023 Mar;615(7952):E19. doi:
10.1038/s41586-023-05837-8.]. Nature. 2023;613(7944):508-518. doi:10.1038/s41586-022-05473-8
Symptoms and Signs of PCOS
Symptoms of PCOS typically begin during puberty and worsen with time. Ovulatory dysfunction is usually
present at puberty, sometimes resulting in primary amenorrhea. Premature adrenarche is common,
caused by excess dehydroepiandrosterone sulfate (DHEAS) and often characterized by early growth of
axillary hair, body odor, and microcomedonal acne.
Typical symptoms include irregular menses (oligomenorrhea or amenorrhea); fertility is impaired in many
patients. Other common symptoms are mild obesity and mild hirsutism. However, in up to half of women
with PCOS, weight is normal, and some women are underweight.
Body hair may grow in a male pattern (eg, on the upper lip, chin, back, thumbs, and toes; around the
nipples; and along the linea alba of the lower abdomen). Some women develop acne. Virilization
(clitoromegaly, deepening of the voice, increased muscle mass, male pattern baldness, breast atrophy)
suggests more severe hyperandrogenism (adrenal hyperandrogenism, androgen-secreting tumor).
Areas of thickened, darkened skin (acanthosis nigricans) may appear in the axillae, on the nape of the
neck, in skinfolds, and on knuckles and/or elbows; the cause is high insulin levels due to insulin
resistance.
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Acanthosis Nigricans in Polycystic Ovary Syndrome
IMAGE
IMAGES PROVIDED BY THOMAS HABIF, MD.
Other symptoms vary across patients, and may include weight gain (sometimes seemingly out of
proportion to diet and exercise), fatigue, low energy, sleep-related problems (including sleep apnea), mood
swings, depression, anxiety, and headaches. Symptoms vary across patients.
Diagnosis of PCOS
Clinical criteria
Hormone blood tests for androgens and to exclude other endocrinologic disorders, such as
measurement of serum testosterone, follicle-stimulating hormone (FSH), prolactin, and
thyroid-stimulating hormone (TSH) levels
Pelvic ultrasound
Diagnosis of PCOS is usually made based on the Rotterdam criteria, which requires at least 2 of the
following 3 findings (1):
Oligo-ovulation and/or anovulation
Clinical and/or biochemical evidence of hyperandrogenism
Polycystic ovaries (transvaginal ultrasound with 12 or more follicles in each ovary measuring
2 to 9 mm in diameter, and/or increased ovarian volume [>10 ml])
Blood tests include measurement of testosterone, which may be mildly elevated in PCOS; levels > 150
ng/dL suggest an ovarian or adrenal androgen-secreting tumor. Serum free testosterone is more sensitive
than total testosterone but is technically more difficult to measure.
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For patients with hirsutism or virilization, other etiologies of hyperandrogenism should be excluded by
measuring other serum androgens including
Early-morning serum 17-hydroxyprogesterone to exclude adrenal hyperandrogenism
DHEAS; high levels (> 800 mcg/dL) suggest an adrenal androgen-secreting tumor
Testing includes pregnancy testing and measurement of FSH, prolactin, and TSH to exclude other
possible causes of symptoms. Also, serum cortisol is measured to exclude Cushing syndrome, which may
cause oligomenorrhea, hirsutism, and obesity.
Transvaginal ultrasound is done to detect polycystic ovaries and exclude other possible causes of
symptoms. However, transvaginal ultrasound is not done in adolescent girls.
Pearls & Pitfalls
Polycystic ovary syndrome often causes hirsutism (excess facial and body hair), but
virilization (eg, clitoromegaly, voice deepening, male pattern baldness) suggests adrenal
hyperandrogenism or an androgen-secreting tumor.
Diagnosing PCOS in adolescent girls
Diagnosing PCOS in adolescents is complicated because physiologic changes during female puberty (eg,
hyperandrogenism, menstrual irregularity) are similar to features of PCOS. Thus, separate criteria for
diagnosis of PCOS in adolescents (2) have been suggested: however, no consensus has been reached.
These criteria require that both of the following conditions be present:
Abnormal uterine bleeding pattern (abnormal for age or gynecologic age [age minus age at
menarche] or symptoms that persist for 1 to 2 years)
Evidence of hyperandrogenism (persistently elevated serum testosterone levels above adult
norms, moderate to severe hirsutism, or moderate to severe inflammatory acne vulgaris)
Often, serum 17-hydroxyprogesterone is measured to screen adolescents for nonclassic congenital
adrenal hyperplasia.
Pelvic ultrasound is usually indicated in adolescents only if serum androgen levels or degree of virilization
suggests an ovarian tumor. Transvaginal ultrasound is usually not used to diagnose PCOS in adolescent
girls because it detects polycystic morphology in < 40% of girls and, used alone, does not predict the
presence or development of PCOS.
Diagnosis references
1. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003
consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome
(PCOS). Hum Reprod. 2004;19(1):41-47. doi:10.1093/humrep/deh098
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2. Tehrani FR, Amiri M. Polycystic ovary syndrome in adolescents: Challenges in diagnosis and
treatment. Int J Endocrinol Metab 17 (3): e91554, 2019. doi: 10.5812/ijem.91554
Treatment of PCOS
Usually estrogen/progestin contraceptives or progestins
Sometimes metformin or other insulin sensitizers
Management of hirsutism and, in adult women, long-term risks of hormonal abnormalities
Infertility treatments in women who desire pregnancy
Treatment of PCOS aims to:
Manage hormonal and metabolic abnormalities and thus reduce risks of estrogen excess (eg,
endometrial hyperplasia) and androgen excess (eg, diabetes, cardiovascular disorders)
Relieve symptoms (irregular menses, acne, excess facial and body hair)
Treat infertility
Hormonal medications are used to cause regular shedding of the endometrium and/or to provide
progestins to oppose the proliferative effect of estrogens on the endometrium. This reduces the risk of
endometrial hyperplasia and cancer. Estrogen-progestin contraceptives are often first-line, and result in
regular menses, reduce acne and hirsutism, and provide contraception. These treatments also reduce
circulating androgens, which may decrease acne and hirsutism. Other options include cyclic oral
progestins (eg, medroxyprogesterone 5 to 10 mg orally once a day for 10 to 14 days every 1 to 2 months)
or a levonorgestrel intrauterine device is also an option. Antiandrogenic progestins include drosperinone
and dienogest.
Lifestyle changes and pharmacologic approaches are used to manage insulin insensitivity. If obesity is
present, weight loss and regular exercise are encouraged. These measures may help induce ovulation
(which makes menstrual cycles more regular and many improve fertility), increase insulin sensitivity, and
reduce acanthosis nigricans and hirsutism. Weight loss may also help improve fertility. Bariatric surgery
may be an option for some women with PCOS (1). However, weight loss is unlikely to benefit women with
PCOS who do not have obesity.
Metformin 500 to 1000 mg twice a day may be used to help increase insulin sensitivity in women with
PCOS, if lifestyle modifications are ineffective or if they cannot take or cannot tolerate hormonal
medications. Metformin can also reduce free testosterone levels. When metformin is used, serum glucose
should be measured, and kidney and liver function tests should be done periodically. Metformin helps
correct metabolic and glycemic abnormalities and makes menstrual cycles more regular, but it has little or
no beneficial effect on hirsutism, acne, or infertility. Because metformin may induce ovulation,
contraception is needed if pregnancy is not desired.
Insulin sensitizers (eg, glucagon-like peptide-1 receptor agonists or thiazolidinediones) combined with
metformin are being studied (2). A study of PCOS patients with obesity (n = 27) treated with semaglutide
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for 6 months found that almost 80% had at least a 5% decrease in body weight, which was often
associated with normalization of menstrual cycles (3). Other studies are evaluating the role of microbiota
treatments for PCOS (4).
Management of hirsutism
For hirsutism, physical measures (eg, bleaching, electrolysis, plucking, waxing, depilation) can be used
(5). Eflornithine cream 13.9% twice a day may help remove unwanted facial hair.
Weight reduction decreases androgen production in women with obesity and thus may slow hair growth.
Estrogen-progestin contraceptives decrease androgen levels. Spironolactone (50 to 100 mg twice a day)
is also effective, but because this medication may have teratogenic effects, effective contraception is
needed. Cyproterone, an antiandrogen (not available in the United States), reduces the amount of
unwanted body hair in 50 to 75% of affected women.
GnRH agonists and antagonists are being studied as treatment for unwanted body hair due to
hyperandrogenism. Both types of medications inhibit the production of sex hormones by the ovaries. But
both can cause bone loss and lead to osteoporosis.
Acne can be treated with the usual medications (eg, benzoyl peroxide, tretinoin cream, topical and oral
antibiotics). Systemic isotretinoin is used only for severe cases.
Management of infertility
Many patients with PCOS have infertility. Clomiphene is first-line therapy for infertility in patients with
PCOS. The aromatase inhibitor letrozole can also be used to induce ovulation. Other fertility medications
may also be used. They include follicle-stimulating hormone (FSH) to stimulate the ovaries, a
gonadotropin-releasing hormone (GnRH) agonist to stimulate the release of FSH, and human chorionic
gonadotropin (hCG) to trigger ovulation.
If clomiphene and other medications are unsuccessful or if there are other indications for laparoscopy,
laparoscopic ovarian drilling may be considered; however possible long-term complications of drilling (eg,
adhesions, ovarian insufficiency) must be considered. Ovarian drilling involves using electrocautery or a
laser to drill holes in small areas of the ovaries that produce androgens. Ovarian wedge resection is not
recommended.
Weight loss may also be helpful in women with PCOS-associated obesity. Obesity is associated with a
higher risk of pregnancy complications (including gestational diabetes, preterm delivery, and
preeclampsia); preconception or early prenatal assessment of body mass index, blood pressure, and oral
glucose tolerance is recommended.
Management of comorbidities
PCOS is associated with an increased risk of depression and anxiety, and women and adolescents with
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PCOS should be screened for these problems and referred to a mental health care professional and/or
treated as needed.
Patients with PCOS and overweight or obesity should be screened for symptoms of obstructive sleep
apnea using polysomnography and treated as needed.
Because PCOS can increase the risk of cardiovascular disorders, early screening, prevention, and/or
referral to a cardiologist is necessary for women with PCOS and any of the following:
Family history of early-onset cardiovascular disorders
Cigarette smoking
Obesity
Diabetes mellitus
Hypertension
Dyslipidemia
Sleep apnea
Weight reduction with glucagon-like peptide-1 (GLP-1) receptor agonists may improve insulin resistance
and fertility (6).
Women with abnormal uterine bleeding and chronic ovulatory dysfunction should be evaluated for
endometrial hyperplasia or carcinoma.
Treatment references
1. Yue W, Huang X, Zhang W, et al. Metabolic surgery on patients with polycystic ovary syndrome: A
systematic review and meta-analysis. Front Endocrinol (Lausanne) 13:848947, 2022. doi:
10.3389/fendo.2022.848947
2. Xing C, Li C, He B. Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in
Overweight Women With PCOS. J Clin Endocrinol Metab. 2020;105(9):2950-2963.
doi:10.1210/clinem/dgaa337
3. Carmina E, Longo RA. Semaglutide Treatment of Excessive Body Weight in Obese PCOS
Patients Unresponsive to Lifestyle Programs. J Clin Med. 2023;12(18):5921. Published 2023 Sep
12. doi:10.3390/jcm12185921
4. Batra M, Bhatnager R, Kumar A, et al. Interplay between PCOS and microbiome: The road less
travelled. Am J Reprod Immunol. 2022;88(2):e13580. doi:10.1111/aji.13580
5. Martin KA, Chang RJ, Ehrmann,DA, et al. Evaluation and treatment of hirsutism in
premenopausal women: an endocrine society clinical practice guideline [published correction
appears in J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2845. doi: 10.1210/clinem/dgab308.]. J
Clin Endocrinol Metab. 2008;93(4):1105-1120. doi:10.1210/jc.2007-2437
6. Cena H, Chiovato L, Nappi RE. Obesity, Polycystic Ovary Syndrome, and Infertility: A New
Avenue for GLP-1 Receptor Agonists. J Clin Endocrinol Metab. 2020;105(8):e2695-e2709.
doi:10.1210/clinem/dgaa285
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Guidelines for Polycystic Ovary Syndrome
The following is a list of professional medical society or government clinical practice guidelines regarding
this medical issue (this is not a comprehensive list):
American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin. Polycystic
Ovary Syndrome. 2018 (reaffirmed 2022).
Endocrine Society Clinical Practice Guideline. Evaluation and Treatment of Hirsutism in
Premenopausal Women. 2018.
Key Points
Polycystic ovary syndrome (PCOS) is a common cause of ovulatory dysfunction.
Suspect PCOS in women who have irregular menses, mild obesity, and mild hirsutism,
but be aware that weight is normal or low in many women with PCOS.
Test for serious disorders (eg, Cushing syndrome, tumors) that can cause similar
symptoms and for complications (eg, metabolic syndrome)
If pregnancy is not desired, treat women with hormonal contraceptives and
recommend lifestyle modifications; if lifestyle modifications are ineffective, add
metformin or other insulin sensitizers.
If women with PCOS are infertile and desire pregnancy, refer them to reproductive
infertility specialists.
Screen for comorbidities, such as endometrial cancer, mood and anxiety disorders,
obstructive sleep apnea, diabetes, and cardiovascular risk factors (including
hypertension and hyperlipidemia).
More Information
The following English-language resources may be useful. Please note that The Manual is not responsible
for the content of these resources.
Legro RS, Arslanian SA, Ehrmann DA. Diagnosis and treatment of polycystic ovary syndrome: an
Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol
Metab. 2021 May 13;106(6):e2462. doi: 10.1210/clinem/dgab248.]. J Clin Endocrinol Metab.
2013;98(12):4565-4592. doi:10.1210/jc.2013-2350
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Pelvic Venous Disorders Primary Ovarian Insufficiency
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