Review

Polycystic ovary syndrome: An update on diagnosis and management

Nayoung Sung, MD, MSCP, Jawaria Amir, MD, Ula Abed Alwahab, MD and Tommaso Falcone, MD
Cleveland Clinic Journal of Medicine March 2026, 93 (3) 176-183; DOI: https://doi.org/10.3949/ccjm.93a.25090

ABSTRACT

Polycystic ovary syndrome (PCOS) is a common but complex heterogeneous endocrine disorder characterized by androgen excess, insulin resistance, and ovulatory dysfunction, presenting challenges in diagnosis and management. This review provides an overview of PCOS, incorporating key updates from the 2023 international evidence-based guideline. We aim to enhance understanding of PCOS and improve individualized and evidence-based patient care.

KEY POINTS

  • PCOS is a heterogeneous disorder with reproductive, metabolic, and psychological consequences across the lifespan.

  • The 2023 international guideline emphasizes a sequential approach to diagnosing PCOS, beginning with clinical and biochemical assessment, followed by selective use of ultrasonography or antimüllerian hormone measurement in adults.

  • PCOS management should be individualized, beginning with lifestyle modification, and includes pharmacologic interventions targeting menstrual irregularities, hyperandrogenism, obesity (with glucagon-like peptide 1 receptor agonists), and fertility management.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with a prevalence of approximately 10% to 13%.1 Prevalence and presentation differ among racial and ethnic groups, possibly reflecting the effects of ethnic origin, race, and environmental factors.2

Patients typically present with irregular menstrual cycles, hyperandrogenism, obesity, or fertility concerns. However, the impact of PCOS extends beyond the reproductive years, affecting health throughout the lifespan. Therefore, long-term management is essential, not only to control symptoms but also to prevent associated metabolic conditions. Although the underlying cause of PCOS remains uncertain, progress in understanding its pathophysiology has guided targeted therapeutic approaches.

WHAT CAUSES PCOS?

Genetic factors play a significant role in the development of PCOS, but environmental factors have an even greater impact. In individuals with genetic predisposition, environmental exposures may trigger epigenetic modifications that contribute to the pathogenesis of PCOS.

Genetic factors

PCOS has a strong genetic component. A family history of PCOS is a well-established risk factor; in a study of first-degree female relatives of 93 patients with PCOS, 24% of the mothers and 32% of the sisters also had PCOS.3 A twin study further supports a strong genetic contribution, showing higher concordance in monozygotic than in dizygotic twins.4 Moreover, genome-wide association studies have identified multiple risk gene loci associated with PCOS, revealing associations with genes involved in gonadotropin action, insulin signaling, and androgen biosynthesis.5,6

Recent studies suggest that PCOS can also affect men, as male relatives of affected women exhibit early-onset androgenic alopecia and metabolic abnormalities, including insulin resistance, type 2 diabetes mellitus, and obesity.7,8

Although genetic predisposition contributes to the development of PCOS, its pathogenesis is believed to be driven by the interaction of genetic, environmental, and epigenetic factors.9

Environmental and epigenetic factors

Epigenetic alterations play a crucial role in the development of PCOS. Epigenetics refers to heritable but reversible changes in gene expression that occur without alterations in the DNA sequences and can be modified by environmental factors. Both prenatal and postnatal environmental influences can induce cumulative changes in genetic expression that contribute to PCOS pathogenesis.

Prenatal exposure to elevated levels of androgens such as dihydrotestosterone has been shown in animal models to induce PCOS-like phenotypes in offspring. These exposures lead to epigenetic reprogramming, particularly DNA methylation, affecting genes involved in reproductive and metabolic pathways.10

Postnatal environmental factors, including poor diet, exposure to endocrine-disrupting chemicals such as bisphenol A and advanced glycation end products, emerging pollutants (eg, pharmaceuticals, personal care products, microplastics, and nanoparticles), and sedentary lifestyle may further modify these epigenetic changes.8,11–13 However, current evidence remains limited, and further research is needed to clarify these associations. These postnatal influences can disrupt the ovarian follicular microenvironment, leading to inflammation, oxidative stress, and hyperinsulinemia-induced androgen excess, which impair folliculogenesis and contribute to chronic anovulation and follicular arrest.14,15

Metabolic and inflammatory factors

The main components of PCOS pathophysiology include hyperandrogenism, ovarian dysfunction, and insulin resistance.

Ovarian hyperandrogenism is observed in approximately 90% of patients with PCOS.9,16

Ovarian dysfunction. The hyperandrogenic intraovarian environment enhances granulosa cell proliferation, resulting in elevated antimüllerian hormone levels that impair follicular maturation, leading to follicular arrest and anovulation and the polycystic ovarian morphology on ultrasonography.17,18 Dysregulation of the hypothalamic-pituitary-ovarian axis by hyperandrogenism increases gonadotropin-releasing hormone pulse frequency and is associated with the increased ratio of luteinizing hormone to follicle-stimulating hormone observed in PCOS.

In addition to intrinsic ovarian dysfunction, extrinsic factors such as hyperinsulinemia and proinflammatory cytokines further stimulate androgen production by theca cells in the ovary, exacerbating the hyperandrogenic state.16

Insulin resistance and compensatory hyperinsulinemia in PCOS stimulate ovarian androgen production and suppress hepatic synthesis of sex hormone–binding globulin, leading to increased circulating free androgens.19 Elevated insulin levels have been observed in the follicular fluid of women with PCOS.20

Inflammation. Adipose tissue contributes to a chronic low-grade inflammation in PCOS through elevated inflammatory cytokines, including tumor necrosis factor alpha, transforming growth factor beta, interleukin 6, and interleukin 1 beta.21 Alterations in the intestinal microbiome may contribute to systemic inflammation by increasing intestinal permeability and activating immune pathways.22 This inflammatory state is thought to exacerbate insulin resistance, enhance ovarian androgen production, and impair folliculogenesis.

A STEPWISE APPROACH TO DIAGNOSING PCOS

The diagnosis of PCOS has evolved. The 2023 international evidence-based guideline23 for assessing and managing PCOS emphasizes a sequential diagnostic approach beginning with clinical assessment followed by biochemical testing and, in adults, selective use of ultrasonography or antimüllerian hormone measurement. PCOS is diagnosed when a patient has irregular cycles and clinical hyperandrogenism, or irregular cycles and biochemical hyperandrogenism, or either irregular cycles or hyperandrogenism alone plus, in adults, polycystic morphology on ultrasonography or elevated antimüllerian hormone levels (Figure 1).23

Figure 1
Figure 1

Diagnostic algorithm for polycystic ovary syndrome (PCOS).

Based on information from reference 23.

Irregular menstrual cycles

Menstrual irregularities are a main manifestation of PCOS, resulting from anovulation. They are defined as cycle intervals shorter than 21 days or longer than 35 days or fewer than 8 cycles per year in women who are between 3 years after menarche and perimenopause.23,24 Chronic anovulation not only contributes to infertility but also increases the long-term risk of endometrial hyperplasia and endometrial cancer due to persistent unopposed estrogen exposure.

Clinical and biochemical hyperandrogenism

Hyperandrogenism is another hallmark feature of PCOS and manifests clinically as acne, hirsutism, and androgenic alopecia (female-pattern hair loss). Acne is commonly observed on the face, chest, and back, while hirsutism is characterized by excessive terminal hair growth in a male-pattern distribution such as the upper lip, chin, chest, and abdomen. Additionally, androgenic alopecia, or hair thinning over the crown and frontal scalp, may further contribute to cosmetic concerns and distress among patients.

Biochemical hyperandrogenism is confirmed by elevated total or free testosterone levels or both, measured using liquid chromatography mass spectrometry and tandem mass spectrometry assays (which are preferred over direct immunoassays), or elevated androstenedione or dehydroepiandrosterone sulfate.

Polycystic ovaries on ultrasonography and antimüllerian hormone elevation

Transvaginal ultrasonography is used to assess polycystic ovarian morphology, defined as 20 or more follicles in at least 1 ovary in adults. Being invasive, it is not recommended for adolescents, who have naturally high follicle counts anyway. Transabdominal ultrasonography is not a good alternative, owing to difficulty in obtaining accurate transabdominal images.

Antimüllerian hormone measurement is now incorporated into the diagnostic criteria for adults as a useful biomarker reflecting increased follicle number, and it can be used in place of ultrasonography.23 However, antimüllerian hormone elevation alone is insufficient for diagnosis and should be interpreted in conjunction with clinical and other biochemical findings. Measuring antimüllerian hormone is not recommended for diagnosis in adolescents. Levels can be affected by age (they are highest between ages 20 and 25), body mass index (they are lower in women with higher body mass index), use of oral birth control pills, and history of ovarian surgery.17

Exclude other conditions

Clinicians must rule out other endocrine issues such as thyroid dysfunction, hyperprolactinemia, premature ovarian failure, androgen-secreting tumors, non-classic congenital adrenal hyperplasia, and Cushing syndrome to ensure an accurate diagnosis.

Blood work typically includes total and free testosterone, dehydroepiandrosterone sulfate, luteinizing hormone, follicle-stimulating hormone, estradiol, thyroid-stimulating hormone, and prolactin.

SCREEN FOR COMORBIDITIES

Metabolic disturbances

Given the high prevalence of metabolic disturbances in PCOS, screening for glucose and lipid abnormalities should be performed regardless of body mass index. Recommended tests include a 75-g oral glucose tolerance test, hemoglobin A1c, fasting glucose level, and fasting lipid profile. Although obesity, particularly central adiposity, often coexists with PCOS and is associated with a higher risk of insulin resistance, metabolic syndrome, and type 2 diabetes, lean individuals with PCOS and a normal body mass index also have an increased risk of insulin resistance and cardiometabolic disease.25

Routine measurement of fasting insulin or insulin resistance indexes is not recommended, as insulin assays have limited clinical utility due to poor standardization and variability.26

Obstructive sleep apnea

Obstructive sleep apnea is also more common in those with PCOS, even after controlling for age and body mass index, and is associated with an increased risk of metabolic syndrome.27,28 Therefore, screening for sleep apnea using validated tools like the Berlin questionnaire is recommended, particularly in those with obesity.

Psychological conditions

Mood disorders, including depression and anxiety, are highly prevalent in women with PCOS.29 These mental health issues are often compounded by body image concerns related to weight gain, hirsutism, and acne. The psychological impact can substantially impair quality of life and may lead to reduced self-esteem, social withdrawal, and decreased overall well-being. Screening for anxiety, depression, body image disorders, and eating disorders is crucial and warrants further referrals and treatment.

MANAGING PCOS

Lifestyle management

Healthy lifestyle behaviors encompassing healthy eating and physical activity should be recommended in all women with PCOS to optimize general health, quality of life, body composition, and weight (maintaining weight, preventing weight gain, or modest weight loss).

There is no evidence to support any one type of diet composition over another for anthropometric, metabolic, hormonal, reproductive, or psychological outcomes. It is important to tailor dietary changes to food preferences, allowing for a flexible, individualized, and collaboratively decided approach to achieving nutritional goals, and avoiding unduly restrictive and nutritionally unbalanced diets.

To prevent weight gain and maintain health, patients with PCOS should aim for a minimum of 150 to 300 minutes of moderate-intensity activities or 75 to 150 minutes of vigorous-intensity aerobic activity per week or an equivalent combination of both spread throughout the week, plus muscle-strengthening activities (eg, resistance, flexibility) on 2 nonconsecutive days per week.

Drug treatment of overweight and obesity in PCOS

Growing evidence supports the use of obesity medications, especially off-label use of glucagon-like peptide (GLP) 1 receptor agonists such as liraglutide, semaglutide, and exenatide, as they can improve the metabolic profile, reduce insulin stimulation on the ovary, and improve ovarian function and ovulation.30

In a large meta-analysis, GLP-1 receptor agonists significantly reduced fasting insulin levels, the glucose level at 2 hours in the oral glucose tolerance test, and measures of insulin resistance. However, other variables measured were unchanged, including dehydroepiandrosterone sulfate, total and free testosterone, sex hormone–binding globulin, and free androgen index.30 This only proves that PCOS is an intrinsic ovarian hyperandrogenism syndrome that is exacerbated by insulin resistance and metabolic syndrome, so weight loss alone may not restore and undo the whole pathology in PCOS.

Healthcare professionals should ensure concurrent effective contraception when pregnancy is possible for women who take GLP-1 receptor agonists, as pregnancy safety data are lacking.

Inositol could be considered in women with PCOS, based on individual preferences and values, noting that although it poses limited risk of harm and could possibly improve metabolic measures, its clinical benefits in terms of ovulation, hirsutism, or weight are limited.31 Inositol’s mechanism in PCOS is thought to involve its function as an intracellular second messenger that regulates insulin and follicle-stimulating hormone signaling and enhances glucose transport and utilization.32

Metformin has been used off-label for PCOS for a long time. However, enthusiasm for it has been declining, as outcomes in earlier reports have not been replicated in newer ones.33,34 Although metformin can improve insulin resistance, weight, lipid profiles, and menstrual regularity, current evidence does not support its use as a first-line treatment for weight loss, ovulation induction, or clinical hyperandrogenism.26,33,34 Perhaps the reason for this discrepancy is that current patients with PCOS tend to have higher body mass indexes, more insulin resistance, and poorer lifestyle than patients in the past.

However, metformin may help restore menstrual regularity in younger patients (teens to early twenties) with normal weight or overweight (body mass index < 30 kg/m2).35 It surely should be considered in patients with prediabetes or overt diabetes. Additionally, using metformin before or during an in vitro fertilization cycle may reduce the number of retrieved oocytes and the risk of ovarian hyperstimulation syndrome.36,37

Metformin should be started at a low dose and titrated up slowly to minimize side effects. Extended-release forms are favored for that reason as well. The maximum dose should not exceed 2,000 mg daily.

For women with obesity who do not achieve adequate metabolic or reproductive improvement with lifestyle interventions or pharmacologic therapy, bariatric surgery may be considered. Studies show substantial improvements in weight, insulin resistance, hyperandrogenism, and ovarian function after surgery.38

Managing menstrual irregularities

Chronic anovulation and menstrual irregularities are experienced by 75% to 85% of women with PCOS.39 Oligomenorrhea, the most common presentation of chronic anovulation, is associated with an increased risk for developing endometrial neoplasia. Continuous unopposed estrogen stimulation of the endometrium leads to abnormal patterns of growth and can lead to endometrial hyperplasia and neoplasia.40 A meta-analysis demonstrated that premenopausal women with PCOS may have a 4-fold increased risk of endometrial cancer.41

Oral contraceptives. While lifestyle changes such as weight loss and exercise can help regulate the menstrual cycle, hormonal contraceptives are the first-line pharmacologic therapy for menstrual abnormalities associated with chronic anovulation. The combined hormonal contraceptives provide endometrial protection through their progestin component, which attenuates the endometrial growth and thereby decreases the risk for developing endometrial hyperplasia.40,42

Preferred formulations include combined oral contraceptives containing ethinyl estradiol in a low dose (20–30 μg) or estradiol valerate, in combination with a minimal or antiandrogenic progestin.42,43 Ultra–low-dose formulations (containing < 20 μg ethinyl estradiol) are generally avoided in adolescents and young adults, as they may adversely affect bone mineral accrual.44

When combined oral contraceptives are not tolerated or are contraindicated, progestin-only continuous or cyclic regimens can also provide effective endometrial protection and cycle regulation.45 Compared with progestin-only regimens, combined oral contraceptives are more effective in treating both menstrual irregularities and symptoms associated with hyperandrogenism, and therefore may be preferred in patients with hyperandrogenism.43

Management of hyperandrogenism

Hyperandrogenism in PCOS manifests as hirsutism, acne, and androgenic alopecia.

Combined oral contraceptives are considered first-line pharmacologic therapy for managing these symptoms, and formulations containing progestins with antiandrogenic effects such as drospirenone or dienogest may provide additional benefit.46,47

Spironolactone. If symptom control is insufficient with combined oral contraceptives alone, an antiandrogen such as spironolactone can be added at dosages of 50 to 200 mg per day. Because spironolactone carries a risk of fetal toxicity, effective contraception is essential, and spironolactone should be discontinued at least 1 month before attempting conception.

Lifestyle changes, particularly weight loss and regular exercise, can also reduce androgen levels and improve symptoms.

Cosmetic treatments, such as laser hair removal, electrolysis, and topical treatments for acne, can also be beneficial in managing the cosmetic aspects of hyperandrogenism. Topical eflornithine 13.9% cream may be used as an adjunct for facial hirsutism in PCOS, with evidence showing modest hair-growth reduction and enhanced results when combined with laser therapy.48

Fertility management

Many patients with PCOS experience anovulatory infertility.49

Weight loss. For patients with PCOS who are overweight or obese with anovulatory infertility, loss of 5% to 10% of total body weight through lifestyle interventions or bariatric surgery can help regulate the menstrual cycle and increase fecundity.50,51 For patients who cannot achieve spontaneous ovulation with life-style interventions, pharmacotherapeutic options can be considered.

Letrozole, an aromatase inhibitor, and clomiphene, a selective estrogen receptor modulator, are both ovulation-induction agents. A double-blind, randomized trial of 750 women with anovulatory PCOS reported 27.5% cumulative live birth rates for woman on letrozole vs 19.1% for women on clomiphene; therefore, letrozole is considered first-line therapy.52 Although letrozole is not officially approved for ovulation induction, it is commonly used off-label. It is given orally, typically beginning on the third day after the onset of a spontaneous or progestin-induced menses, for a 5-day course. The starting dose for letrozole is 2.5 mg per day, which can be increased by 2.5-mg increments up to a maximum of 7.5 mg per day until ovulation is achieved.

In vitro fertilization. While second-line options include ovulation induction with recombinant gonadotropins or laparoscopic ovarian drilling, in vitro fertilization is typically offered as the next step in patients for whom ovulation induction with letrozole has failed.23 The antimüllerian hormone serum level is positively correlated with oocyte yield in women undergoing ovarian stimulation during in vitro fertilization. It can therefore be used to predict ovarian response to in vitro fertilization and tailor treatment regimens to optimize outcomes and reduce the risk of ovarian hyperstimulation syndrome.53,54

Management of pregnancy-related complications

Pregnant women with PCOS face higher risks of miscarriage, gestational diabetes, higher gestational weight gain, intrauterine growth restriction, preterm delivery, cesarean section, pregnancy-induced hypertension, and preeclampsia.23,55,56

Lifestyle interventions. Weight, blood pressure, smoking, diet, nutritional status, appropriate folate supplementation, exercise, and mental, emotional, and sexual health should be optimized in the preconception period to improve pregnancy outcomes.23 Early lifestyle interventions, such as recommendations for optimizing diet, should be offered to all pregnant women with PCOS to mitigate risk factors.

An oral glucose tolerance test should be offered to patients with PCOS when planning pregnancy. If it is not performed in the preconception phase, it should initially be performed in the first trimester and, if normal, repeated in the second, in gestational weeks 24 to 28.55

Metformin has not been shown to prevent gestational diabetes or pregnancy-induced hypertension in women with PCOS, but it may decrease the risk of preterm delivery and limit excess gestational weight gain.23 Patients, however, should be counseled that the long-term effects of metformin on the baby’s health remain unclear.

SUMMARY

PCOS is a heterogeneous, lifelong endocrine disorder arising from a complex interplay of genetic factors, environmental exposures, metabolic disturbances, and proinflammatory changes leading to ovulatory dysfunction, hyperandrogenism, and cardiometabolic risk. Its diverse reproductive, metabolic, and psychological consequences require early recognition and comprehensive long-term care. The 2023 international guideline23 provides structured, evidence-based recommendations for both diagnosis and management.

PCOS is diagnosed when a patient has irregular cycles and clinical hyperandrogenism, or irregular cycles and biochemical hyperandrogenism, or either irregular cycles or hyperandrogenism alone plus, in adults, polycystic morphology on ultrasonography or elevated antimüllerian hormone levels. Antimüllerian hormone levels are not used for diagnosis in adolescents, and no universally accepted cutoff levels exist. Evaluation should include screening for psychosocial conditions as well as cardiometabolic risk factors.

PCOS management is individualized to address symptoms and prevent long-term complications. Life-style modification remains first-line therapy. Emerging evidence supports the off-label use of GLP-1 receptor agonists for improving metabolic outcomes in PCOS. Low-dose combined oral contraceptives are preferred for cycle regulation and endometrial protection. Importantly, PCOS extends beyond the reproductive years, warranting ongoing, coordinated care across the lifespan.

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

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