Polycystic ovary syndrome (PCOS) occurs in 5 to 10% of women (1 General reference Polycystic ovary syndrome is a clinical syndrome typically characterized by anovulation or oligo-ovulation, signs of androgen excess (eg, hirsutism, acne), and multiple ovarian cysts in the... read more ). In the US, it is the most common cause of infertility.
PCOS is usually defined as a clinical syndrome, not by the presence of ovarian cysts. But typically, ovaries 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.
This syndrome involves anovulation or ovulatory dysfunction and androgen excess of unclear etiology. 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 environmental and hereditary factors.
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
Polycystic ovary syndrome has several significant potential complications.
Infertility is related to ovulatory dysfunction Ovulatory Dysfunction Ovulatory dysfunction is abnormal, irregular (with ≤ 9 menses/year), or absent ovulation. Menses are often irregular or absent. Diagnosis is often possible by menstrual history or can be confirmed... read more .
Estrogen levels are elevated, increasing risk of endometrial hyperplasia and, potentially, endometrial cancer Endometrial Cancer Endometrial cancer is usually endometrioid adenocarcinoma. Typically, it manifests as postmenopausal uterine bleeding. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy... read more .
Androgen levels are often elevated, increasing the risk of metabolic syndrome Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), hypertension, abnormal fasting plasma glucose or insulin resistance, and dyslipidemia. Causes... read more and obesity Obesity Obesity is excess body weight, defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders (particularly in people with excess abdominal fat)... read more and causing hirsutism Hirsutism and Hypertrichosis Hirsutism is the excessive growth of thick or dark hair in women in locations that are more typical of male hair growth patterns (eg, mustache, beard, central chest, shoulders, lower abdomen... read more . 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 cardiovascular disorders, including hypertension and hyperlipidemia. Risk of androgen excess and its complications may be just as high in women who are not overweight as in those who are.
Calcification of coronary arteries and thickening of the carotid intima media is more common among women with PCOS, suggesting possible subclinical atherosclerosis Atherosclerosis Atherosclerosis is characterized by patchy intimal plaques (atheromas) that encroach on the lumen of medium-sized and large arteries. The plaques contain lipids, inflammatory cells, smooth muscle... read more .
Type 2 diabetes mellitus Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) consists of multiple episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of... read more and impaired glucose tolerance are more common, and risk of obstructive sleep apnea Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) consists of multiple episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of... read more 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 Nonalcoholic Fatty Liver Disease (NAFLD) Fatty liver is excessive accumulation of lipid in hepatocytes. Nonalcoholic fatty liver disease (NAFLD) includes simple fatty infiltration (a benign condition called fatty liver), whereas nonalcoholic... read more (1 Complications reference Polycystic ovary syndrome is a clinical syndrome typically characterized by anovulation or oligo-ovulation, signs of androgen excess (eg, hirsutism, acne), and multiple ovarian cysts in the... read more ).
1. 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.
Symptoms and Signs of PCOS
Symptoms of polycystic ovary syndrome typically begin during puberty and worsen with time. Ovulatory dysfunction is usually present at puberty, resulting in primary amenorrhea; thus, polycystic ovary syndrome is unlikely if regular menses occurred for a time after menarche. 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, usually oligomenorrhea, amenorrhea Amenorrhea Amenorrhea (the absence of menstruation) can be primary or secondary. Primary amenorrhea is failure of menses to occur by age 15 years in patients with normal growth and secondary sexual characteristics... read more , 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 have acne, and some have signs of virilization, such as temporal hair thinning.
Other symptoms may include weight gain (sometimes seemingly hard to control), fatigue, low energy, sleep-related problems (including sleep apnea), mood swings, depression, anxiety, and headaches. In some women, fertility is impaired. Symptoms vary from woman to woman.
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.
If women with PCOS become pregnant and if obesity is present, risk of pregnancy complications is increased. These complications include gestational diabetes Diabetes Mellitus in Pregnancy , preterm delivery Preterm Labor Labor (contractions resulting in cervical change) that begins before 37 weeks gestation is considered preterm. Risk factors include prelabor rupture of membranes, uterine abnormalities, infection... read more , and preeclampsia Preeclampsia and Eclampsia Preeclampsia is new-onset or worsening of existing hypertension with proteinuria after 20 weeks gestation. Eclampsia is unexplained generalized seizures in patients with preeclampsia. Diagnosis... read more .
Diagnosis of PCOS
Tests to exclude other endocrinologic disorders, such as measurement of serum testosterone, follicle-stimulating hormone (FSH), prolactin, and thyroid-stimulating hormone (TSH) levels
PCOS is suspected if women have at least two typical symptoms (eg, irregular menses, hirsutism).
The diagnosis requires at least 2 of the following 3 criteria:
Ovulatory dysfunction causing menstrual irregularity
Clinical or biochemical evidence of hyperandrogenism
> 10 follicles per ovary (detected by pelvic ultrasonography), usually occurring in the periphery and resembling a string of pearls
Testing includes pregnancy testing and measurement of FSH, prolactin, and TSH to exclude other possible causes of symptoms.
Transvaginal ultrasonography is done to detect polycystic ovaries and exclude other possible causes of symptoms. However, transvaginal ultrasonography is not done in adolescent girls (see below).
The diagnosis is not based on measurement of serum androgens. For patients who meet diagnostic criteria, other causes of hirsutism or virilization (eg, androgen-secreting tumors) should be excluded by measuring serum androgens including
Early-morning serum 17-hydroxyprogesterone is measured to exclude adrenal virilism Adrenal Virilism Adrenal virilism is a syndrome in which excessive adrenal androgens cause virilization. Diagnosis is clinical and confirmed by elevated androgen levels; determining the cause may involve adrenal... read more
Serum free testosterone is more sensitive than total testosterone but is technically more difficult to measure (see algorithm Diagnosis of primary and secondary hypogonadism Diagnosis of primary and secondary hypogonadism Hypogonadism is defined as testosterone deficiency with associated symptoms or signs, deficiency of spermatozoa production, or both. It may result from a disorder of the testes (primary hypogonadism)... read more ). Normal to mildly increased testosterone and normal to mildly decreased FSH levels suggest PCOS.
Also, serum cortisol is measured to exclude Cushing syndrome Cushing Syndrome Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more .
Pearls & Pitfalls
Diagnosing PCOS in adolescent girls
Diagnosing PCOS in adolescents is complicated because physiologic changes during puberty (eg, hyperandrogenism, menstrual irregularity) are similar to features of PCOS. Thus, separate criteria for diagnosis of PCOS in adolescents (1 Diagnosis reference Polycystic ovary syndrome is a clinical syndrome typically characterized by anovulation or oligo-ovulation, signs of androgen excess (eg, hirsutism, acne), and multiple ovarian cysts in the... read more ) 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 or symptoms that persist for 1 to 2 years)
Evidence of hyperandrogenism (based on persistently elevated testosterone levels above adult norms [the best evidence], moderate-to-severe hirsutism, or moderate-to-severe inflammatory acne vulgaris as an indication to test for hyperandrogenemia)
Often, a 17-hydroxyprogesterone test is also done to screen adolescents for nonclassic congenital adrenal hyperplasia Overview of Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia is a group of genetic disorders, each characterized by inadequate synthesis of cortisol, aldosterone, or both. In the most common forms, accumulated hormone precursors... read more .
Pelvic ultrasonography is usually indicated only if serum androgen levels or degree of virilization suggests an ovarian tumor. Transvaginal ultrasonography 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.
1. 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 polycystic ovary syndrome aims to
Manage hormonal and metabolic abnormalities and thus reduce risks of estrogen excess (eg, endometrial hyperplasia) and androgen excess (eg, diabetes, cardiovascular disorders)
Hormonal medications are used to cause regular shedding of the endometrium and reduce the risk of endometrial hyperplasia and cancer. Women are usually given an intermittent progestin (eg, medroxyprogesterone 5 to 10 mg orally once a day for 10 to 14 days every 1 to 2 months) or combination oral contraceptives to. These treatments also reduce circulating androgens and usually help make menstrual cycles more regular. Hormonal contraceptives are first-line therapy for menstrual abnormalities, hirsutism, and acne in women who have PCOS and who do not desire pregnancy.
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, make menstrual cycles more regular, 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 Treatment references Polycystic ovary syndrome is a clinical syndrome typically characterized by anovulation or oligo-ovulation, signs of androgen excess (eg, hirsutism, acne), and multiple ovarian cysts in the... read more ). However, weight loss is unlikely to benefit normal-weight women with PCOS.
Metformin 500 to 1000 mg twice a day is used to help increase insulin sensitivity in women with PCOS, irregular menses, and diabetes or insulin resistance if lifestyle modifications are ineffective or if they cannot take or cannot tolerate hormonal contraceptives. 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. Because metformin may induce ovulation, contraception is needed if pregnancy is not desired. 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.
Insulin sensitizers (eg, glucagon-like peptide-1 receptor agonists or thiazolidinediones) combined with metformin are being studied (2 Treatment references Polycystic ovary syndrome is a clinical syndrome typically characterized by anovulation or oligo-ovulation, signs of androgen excess (eg, hirsutism, acne), and multiple ovarian cysts in the... read more ). Other studies are evaluating the role of microbiota treatments for PCOS (3 Treatment references Polycystic ovary syndrome is a clinical syndrome typically characterized by anovulation or oligo-ovulation, signs of androgen excess (eg, hirsutism, acne), and multiple ovarian cysts in the... read more ).
Many patients with PCOS have infertility, and those who desire pregnancy should be referred to infertility specialists. Infertility treatments Treatment Ovulatory dysfunction is abnormal, irregular (with ≤ 9 menses/year), or absent ovulation. Menses are often irregular or absent. Diagnosis is often possible by menstrual history or can be confirmed... read more (eg, clomiphene) are used. Clomiphene is currently the first-line therapy for infertility. Weight loss may also be helpful. Hormone therapy that may have contraceptive effects is avoided. The aromatase inhibitor letrozole can also be used to stimulate ovulation. Other fertility medications may also be tried. 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.
Because women with PCOS-associated obesity have a higher risk of pregnancy complications (including gestational diabetes, preterm delivery, and preeclampsia), preconception assessment of body mass index, blood pressure, and oral glucose tolerance is recommended.
For hirsutism Treatment Hirsutism is the excessive growth of thick or dark hair in women in locations that are more typical of male hair growth patterns (eg, mustache, beard, central chest, shoulders, lower abdomen... read more , physical measures (eg, bleaching, electrolysis, plucking, waxing, depilation) can be used (4 Treatment references Polycystic ovary syndrome is a clinical syndrome typically characterized by anovulation or oligo-ovulation, signs of androgen excess (eg, hirsutism, acne), and multiple ovarian cysts in the... read more ). Eflornithine cream 13.9% twice a day may help remove unwanted facial hair.
In adult women who do not desire pregnancy, hormone therapy that decreases androgen levels or spironolactone can be tried. Spironolactone 50 to 100 mg twice a day is effective, but because this medication may have teratogenic effects, effective contraception is needed. Cyproterone, an antiandrogen (not available in the US), reduces the amount of unwanted body hair in 50 to 75% of affected women. Weight reduction decreases androgen production in women with obesity and thus may slow hair growth.
GnRH agonists and antagonists are being studied as treatment for unwanted body hair. Both types of medications inhibit the production of sex hormones by the ovaries. But both can cause bone loss and lead to osteoporosis.
Acne Treatment Acne vulgaris is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying... read more 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 comorbidities
Because risk of depression and anxiety is increased in PCOS, women and adolescents with PCOS should be screened for these problems based on history, and if a problem is identified, they should be referred to a mental health care practitioner and/or treated as needed.
Adolescents and women who have PCOS and overweight or obesity should be screened for symptoms of obstructive sleep apnea Diagnosis Obstructive sleep apnea (OSA) consists of multiple episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of... read more using polysomnography and treated as needed.
Because PCOS can increase the risk of cardiovascular disorders, referral to a cardiovascular specialist for prevention of cardiovascular disorders is necessary if women with PCOS have any of the following:
A family history of early-onset cardiovascular disorders
Clinicians should evaluate cardiovascular risk by determining body mass index (BMI), measuring fasting lipid and lipoprotein levels, and identifying risk factors for metabolic syndrome.
Adult women with PCOS are evaluated for metabolic syndrome Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), hypertension, abnormal fasting plasma glucose or insulin resistance, and dyslipidemia. Causes... read more by measuring blood pressure and usually serum glucose and lipids (lipid profile).
Tests for coronary artery calcification and thickened carotid intima media should be done to check for subclinical atherosclerosis.
Women with abnormal vaginal bleeding should be screened for endometrial hyperplasia or carcinoma using endometrial biopsy and/or transvaginal ultrasonography or office hysteroscopy.
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 10 5(9):2950–2963, 2020.
3. Batra M, Bhatnager R, Kumar A, et al: Interplay between PCOS and microbiome: The road less travelled. Am J Reprod Immunol 88 (2):e13580, 2022. doi: 10.1111/aji.13580 Epub 2022 May 29.
4. Martin KA, Chang RJ, Ehrmann,DA, et al: Evaluation and treatment of hirsutism in premenopausal women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 93 (4):1105–1120, 2008. doi: 10.1210/jc.2007-2437 Epub 2008 Feb 5.
Polycystic ovary syndrome (PCOS) is a common cause of ovulatory dysfunction.
Suspect PCOS in women who have irregular menses, are mildly obese, and are slightly hirsute, 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).
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, et al: Diagnosis and treatment of polycystic ovary syndrome: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 98(12):4565–4592, 2013. doi: 10.1210/jc.2013-2350: This evidence-based guideline uses the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence.
Goodman NF, Cobin RH, Futterweit W, et al: American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society Disease State Clinical Review: Guide to the best practices in the evaluation and treatment of polycystic ovary syndrome–Part 1. Endocr Pract 21(11):1291–300, 2015. doi: 10.4158/EP15748.DSC: This article summarizes the best practices of 2015.
Hoeger KM, Dokras A, Piltonen T: Update on PCOS: Consequences, challenges and guiding treatment. J Clin Endocrinol Metab 106 (3):e1071-e1083, 2021. doi: 10.1210/clinem/dgaa839: This review summarizes key points for diagnosis and treatment of PCOS from an evidence-based guidelines published in 2018 and updates the information based on recent developments. The diagnostic criteria for PCOS are reviewed, and the remaining controversies and challenges for making a clear diagnosis are discussed.
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