Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. It is characterized by hyperandrogenism (which primarily manifests as hirsutism, acne, and, occasionally, virilization), oligoovulation/anovulation, and/or the presence of polycystic ovaries. The diagnosis involves a complete history and physical examination to evaluate for ovulatory dysfunction and clinical signs of hyperandrogenism. Laboratory tests are performed to confirm biochemical hyperandrogenism and exclude other conditions with a potentially similar clinical picture (e.g., congenital adrenal hyperplasia). Ultrasound may be performed in adults to identify cystic follicles and assess ovarian volume but is not required for diagnosis if ovulatory dysfunction and hyperandrogenism are present. Management consists of lifestyle modifications combined with specific treatment, which is tailored to the patient's reproductive goals. In women who do not wish to conceive, combined oral contraceptive pills are indicated to regulate menses and treat hyperandrogenism. For women who wish to conceive, the goal of treatment is to induce ovulation (e.g., with letrozole). Women with PCOS are twice as likely to develop metabolic syndrome, which is associated with obesity, insulin resistance, hypercholesterolemia, and an increased risk of endometrial cancer. Therefore, all patients should be screened for comorbidities and receive specific treatment for these when necessary.
- Prevalence: 6–12% of women in their reproductive years in the US 
Epidemiological data refers to the US, unless otherwise specified.
- The exact pathophysiology is unknown.
- Strong association with obesity → ↑ in peripheral estrogen synthesis from adipose tissue and ↓ in peripheral sensitivity to insulin 
Reduced insulin sensitivity (peripheral insulin resistance) and the consequent hyperinsulinemia result in:
- Epidermal hyperplasia and hyperpigmentation (acanthosis nigricans) 
- ↑ Androgen production in ovarian theca interna cells → imbalance between androgen precursors and the resulting estrogen produced in granulosa cells
- Inhibition of SHBG in the liver → ↑ free androgens and estrogens ; 
Hyperandrogenism in women is most commonly caused by PCOS.
Onset of symptoms typically occurs during adolescence.
- Menstrual irregularities
- Insulin resistance and associated conditions
- Skin conditions
- Anxiety disorders
Voice change may occur in severe forms of PCOS. However, it typically suggests a different underlying cause of hyperandrogenism.
- Multiple, brown cysts arranged in a circular pattern in the subcapsular region of the ovary
- Cysts are relatively small and of approximately the same size.
- Ovarian hypertrophy with thick capsule
- Stromal hyperplasia and fibrosis
- Multiple enlarged cystic follicles
- Hyperluteinized theca cells
- Decreased granulosa cell layer
- Definition: a state of excess androgen levels that causes symptoms such as growth of facial hair, deepening of the voice, and male-pattern baldness
- For more information about physiological causes of hyperandrogenism, see “Pregnancy.”
|Differential diagnosis of hyperandrogenism in female individuals|
|PCOS|| || |
|Nonclassic CAH|| || || |
|CAH|| || |
|Cushing disease|| || |
|Hypothyroidism|| || |
|Hyperprolactinemia|| || |
|Androgen-secreting tumor (e.g., Sertoli-Leydig cell tumor, adrenal)|| || |
|Acromegaly|| || |
| || |
|Drug-induced (e.g., exogenous steroid and androgen intake)|| || |
Clinical features of hyperandrogenism
- Virilization: the appearance of male secondary sexual characteristics in a female individual
- Rapid onset of virilization is suggestive of exogenous androgen intake or androgen-secreting tumors
- Manifestations of the underlying condition
Diagnostics of hyperandrogenism
- Laboratory tests to identify hyperandrogenemia
- Investigate for the underlying cause.
- Medication to suppress or block androgen and manage symptoms of virilization
- Treat the underlying cause (e.g., surgery for androgen-secreting tumors).
The differential diagnoses listed here are not exhaustive.
Early diagnosis is essential, as PCOS is associated with many conditions, including metabolic dysfunction and impaired fertility. It also has a significant impact on a woman's emotional well-being and quality of life.
- Suspect PCOS in women of reproductive age with features of hyperandrogenism and/or ovulatory dysfunction.
- Use the Rotterdam criteria to establish the clinical diagnosis.
- Obtain an initial diagnostic workup to exclude pregnancy and endocrine disorders (e.g., thyroid dysfunction, hyperprolactinemia, ).
- Perform a detailed assessment to evaluate for comorbidities.
- Screen for metabolic disorders regardless of BMI.
Rotterdam criteria 
- Oligoovulation and/or anovulation
- Hyperandrogenism (based on clinical features or laboratory studies): Examine patients for signs of acne, alopecia, and hirsutism; obtain laboratory studies as needed. 
Enlarged and/or polycystic ovary on ultrasound
- Ovarian volume ≥ 10 mL
- AND/OR the presence of multiple cystic follicles measuring 2–9 mm (string-of-pearls appearance) in one or both ovaries 
Diagnosing PCOS in adolescents is complex because PCOS symptoms overlap with normal pubertal changes. For this reason, the 2015 Pediatric Endocrine Society consensus does not endorse the use of ultrasound in adolescents to evaluate PCOS. 
Laboratory studies 
Confirm hyperandrogenism: Obtain in all women with clinical features of PCOS, even if features are minimal or unclear. 
- ↑ Testosterone: Use the calculated free testosterone, calculated bioavailable testosterone, or free androgen index. Direct free testosterone has poor sensitivity. 
- ↑ Androstenedione and ↑ dehydroepiandrosterone sulfate: limited role in diagnosis of PCOS, but useful for ruling out other causes of hyperandrogenism 
- Rule out differential diagnoses: e.g., pregnancy, endocrine disorders
- Parameters: An experienced clinician should assess the ovarian volume and, when feasible, the number and volume of follicles. 
- Transvaginal (preferred; use if acceptable to patient): offers the best visualization of ovarian follicles
- Transabdominal: should focus on measuring ovarian volume
Identification of cystic follicles is not mandatory to diagnose PCOS.
Evaluate for comorbidities 
Patients with PCOS are at risk of serious comorbidities, even at a young age. It is important to screen for these at the first visit and at regular intervals.
Metabolic screening and monitoring
- Measure weight, height, and waist circumference; calculate BMI. Measure at baseline and repeat every 6–12 months.
- For patients with elevated BMI: Obtain a fasting lipid profile and screen for symptoms of obstructive sleep apnea.
- Check blood pressure: Obtain at baseline and then at least once a year; measure more frequently based on individual risk.
- Assess glycemic status : Obtain at baseline and repeat every 1–3 years, depending on individual risk.
- Mental health and quality of life: Screen for anxiety, depression, and psychosexual dysfunction.
Women with PCOS are at least twice as likely to have metabolic syndrome as women without PCOS. 
Women with PCOS are also at increased risk for endometrial cancer. Screening is not routinely recommended, but clinicians should maintain a high index of suspicion and conduct a transvaginal ultrasound and/or endometrial biopsy if there are suggestive features (e.g., thickened endometrium, abnormal vaginal bleeding). 
Recommendations for all patients
- Encourage exercise and healthy eating (e.g. caloric restriction), and consider behavioral strategies and modifications (e.g., setting goals, eating more slowly). 
- Target BMI < 25 kg/m2 (can reduce estrone production in the adipose tissue)
- Screen for comorbidities and provide specific treatment.
Tailor additional therapeutic interventions based on:
- Reproductive goals
- Individual risk factors
Features associated with PCOS (e.g., obesity, hyperandrogenism, difficulties conceiving) can have a negative psychosocial impact. If symptoms of anxiety and/or depression are identified, further mental health assessment and a referral to a mental health professional should be offered to the patient.
Patients not planning to conceive 
For patients who do not wish to conceive, the therapeutic goals are to control menstrual irregularities and hyperandrogenism, treat comorbidities, and improve quality of life.
- Combined oral contraceptives (COCs) 
- Metformin: improves menstrual irregularities, metabolic outcomes, and weight (especially when combined with lifestyle modifications)
Antiandrogens: controversial role 
- Examples: spironolactone, finasteride, flutamide
- Indications: can be considered for treatment of hirsutism and androgen-related alopecia in patients unable to take or tolerate COCs
- Additional recommendation: When using antiandrogens as an alternative to COCs, it is advisable to use other forms of contraception.
- Additional interventions: Other measures, like antiobesity medications or bariatric surgery, may be considered on a case-by-case basis.
Patients planning to conceive 
- Letrozole (off-label): first-line therapy for ovulation induction 
Clomiphene: alternative to letrozole
- May be preferred over metformin monotherapy in obese women with anovulatory infertility 
- Mechanism of action: inhibits hypothalamic estrogen receptors → disruption of the negative feedback mechanism governing estrogen production → ↑ pulsatile secretion of GnRH → ↑ FSH and LH → stimulation of ovulation
- Exogenous gonadotropins: The low-dose regimen is the second-line treatment for ovulation induction.
Additional fertility interventions
Laparoscopic ovarian drilling
- A laparoscopic procedure in which ovarian tissue is reduced with a laser beam or surgical needle to decrease its volume and androgen production
- This hormonal shift can induce FSH secretion and improve ovarian function in patients with polycystic ovary syndrome.
- Second-line treatment for ovulation induction; can be performed as a first-line treatment if other indications for laparoscopy exist
- In vitro fertilization: can be offered as third-line therapy
- Bariatric surgery: no evidence of benefit in the treatment of infertility
- Laparoscopic ovarian drilling
- Management of other PCOS manifestations