Polycystic Ovary Syndrome (PCOS)

Overview

Polycystic Ovary Syndrome (PCOS) is a common, chronic endocrine&ndash;metabolic condition characterized by a combination of ovulatory dysfunction, hyperandrogenism (clinical or biochemical), and polycystic ovarian morphology. It is best understood as a whole-body condition&mdash;affecting reproductive, metabolic, cardiovascular, and psychological health&mdash;rather than only an ovarian disorder. [1&ndash;3]

PCOS prevalence is commonly reported around 10&ndash;13% in reproductive-age women (estimates vary by diagnostic criteria and population). [2] Many individuals experience delayed diagnosis due to symptom variability, normalization of menstrual irregularity, or under-recognition of metabolic and mental health features. [1,2]

Causes

PCOS develops through a complex interaction of genetic susceptibility and environmental factors. No single cause explains all cases. Key mechanisms include:

<ul>
	<li>Insulin resistance and hyperinsulinemia: Insulin can stimulate ovarian androgen production and reduce sex hormone&ndash;binding globulin (SHBG), increasing free androgens. [1,4]</li>
	<li>Androgen excess (ovarian and/or adrenal): Contributes to hirsutism, acne, scalp hair thinning, and follicular arrest (impaired ovulation). [1,3]</li>
	<li>Neuroendocrine dysregulation: Altered gonadotropin secretion patterns (LH/FSH imbalance) can support androgen excess and ovulatory dysfunction in some individuals. [3]</li>
	<li>Adiposity and weight gain (not required for diagnosis): Can worsen insulin resistance and androgen excess, but PCOS also occurs in normal-weight individuals. [1,3]</li>
	<li>Genetic and epigenetic factors: Family clustering is common, and first-degree relatives may have increased metabolic risk. [1]</li>
</ul>

Signs & Symptoms

Symptoms vary widely in type and severity. Common features include:

Menstrual and ovulatory features

<ul>
	<li>
	Irregular cycles (oligomenorrhea/amenorrhea)
	</li>
	<li>
	Anovulation (may present as infertility or difficulty conceiving) [1,3]
	</li>
</ul>

Hyperandrogenism features

<ul>
	<li>
	Hirsutism (terminal hair growth in androgen-sensitive areas)
	</li>
	<li>
	Acne
	</li>
	<li>
	Scalp hair thinning (androgenic alopecia) [1,3]
	</li>
</ul>

Metabolic features

<ul>
	<li>
	Weight gain or central adiposity
	</li>
	<li>
	Insulin resistance, impaired glucose tolerance
	</li>
	<li>
	Dyslipidemia (unfavorable lipid profile) [1,4]
	</li>
</ul>

Psychological and sleep features

<ul>
	<li>
	Higher rates of depression/anxiety symptoms
	</li>
	<li>
	Increased prevalence of obstructive sleep apnea (independent of BMI in some studies) [4&ndash;6]
	</li>
</ul>

Health Risks &amp; Complications

PCOS is associated with several long-term risks, particularly when ovulatory dysfunction and metabolic abnormalities persist:

Metabolic and cardiovascular

<ul>
	<li>
	Increased risk of impaired glucose tolerance and type 2 diabetes; guidelines emphasize regular glycemic assessment and note PCOS as an important diabetes risk state. [4]
	</li>
	<li>
	Higher burden of cardiovascular risk factors and increased risk of clinical cardiovascular disease events in pooled analyses. [7,8]
	</li>
</ul>

Reproductive and pregnancy-related

<ul>
	<li>
	Subfertility/infertility due to anovulation [1,3]
	</li>
	<li>
	Higher risk of adverse pregnancy outcomes and pregnancy complications in meta-analyses (risk influenced by age, BMI, and assisted conception). [9]
	</li>
</ul>

Endometrial

<ul>
	<li>
	Chronic anovulation can lead to unopposed estrogen exposure, increasing risk of endometrial hyperplasia and endometrial cancer; meta-analyses show significantly higher odds of endometrial cancer in PCOS compared with non-PCOS populations. [1,10]
	</li>
</ul>

Psychological health and quality of life

<ul>
	<li>
	PCOS is linked to reduced quality of life and higher prevalence of depressive symptoms in pooled studies. [1,5,6]
	</li>
</ul>

Diagnosis

PCOS is a diagnosis of exclusion and should be assessed in the context of age/life stage.

Core diagnostic approach (adults) 
Current international guidance builds on Rotterdam-style criteria: diagnosis generally requires two of the following three in adults:

<ol>
	<li>
	Clinical and/or biochemical hyperandrogenism
	</li>
	<li>
	Ovulatory dysfunction (irregular cycles/anovulation)
	</li>
	<li>
	Polycystic ovaries on ultrasound or (in adults) elevated anti-m&uuml;llerian hormone (AMH) as an alternative marker in appropriate settings [1]
	</li>
</ol>

Adolescents and early post-menarche

<ul>
	<li>
	Diagnostic caution is essential because normal pubertal physiology can mimic PCOS features. International guidance indicates that AMH and ultrasound are not recommended for diagnosis in adolescents, particularly within years of menarche, due to overlap with normal reproductive development. [1]
	</li>
</ul>

Exclude other causes (typical workup depends on presentation) 
Common exclusions include:

<ul>
	<li>
	Thyroid disease (e.g., TSH abnormalities)
	</li>
	<li>
	Hyperprolactinemia
	</li>
	<li>
	Non-classic congenital adrenal hyperplasia (e.g., 17-hydroxyprogesterone) 
	Additional evaluation may be required if severe virilization or atypical features suggest androgen-secreting tumors, Cushing syndrome, or other endocrine disorders. [1,3]
	</li>
</ul>

Metabolic assessment at diagnosis and follow-up

<ul>
	<li>
	International recommendations emphasize glycemic assessment; the 75-g oral glucose tolerance test (OGTT) is highlighted as the most accurate test for glycemic status in PCOS (HbA1c/fasting glucose are less accurate alternatives if OGTT is not feasible). [4]
	</li>
</ul>

Management

Management is individualized based on symptoms, reproductive goals, and metabolic risk profile, and usually requires long-term follow-up.

1) Lifestyle and weight-related interventions (foundation of care)

<ul>
	<li>
	Nutrition quality, physical activity, sleep, and sustainable behavior strategies improve cardiometabolic risk factors and can improve cycle regularity and symptoms in many patients. [1,3]
	</li>
	<li>
	Weight loss is not the only target; improvements in insulin resistance, fitness, and risk markers are clinically meaningful even without major weight change. [1]
	</li>
</ul>

2) Menstrual irregularity and endometrial protection 
Goals: regulate bleeding patterns and reduce risk of endometrial hyperplasia in chronic anovulation. Options may include:

<ul>
	<li>
	Combined hormonal contraceptives (common first-line for cycle regulation and androgen-related symptoms when contraception is acceptable) [1,3]
	</li>
	<li>
	Cyclic progestin therapy or progestin-containing IUD options in appropriate candidates (clinical decision based on patient factors and clinician assessment) [1,3]
	</li>
</ul>

3) Hyperandrogenism symptoms (hirsutism/acne/hair loss)

<ul>
	<li>
	Combined hormonal contraceptives are frequently used for androgen suppression and symptom control. [1,3]
	</li>
	<li>
	Additional anti-androgen therapy may be considered in selected cases under medical supervision due to safety/teratogenicity concerns and need for reliable contraception. [1,3]
	</li>
	<li>
	Cosmetic/dermatologic measures (e.g., laser hair reduction) can be used as adjunctive care. [1]
	</li>
</ul>

4) Insulin resistance and metabolic risk management

<ul>
	<li>
	Metformin is commonly considered for metabolic features (especially impaired glucose tolerance, type 2 diabetes risk, or when lifestyle measures are insufficient), with individualized decision-making. [1,3]
	</li>
	<li>
	Regular screening for glucose intolerance/diabetes, blood pressure, lipids, and other cardiometabolic risk markers is recommended based on risk profile. [1,4,7]
	</li>
</ul>

5) Fertility and preconception care

<ul>
	<li>
	For anovulatory infertility, international guidance supports letrozole as a first-line ovulation induction option in many contexts, alongside optimization of lifestyle and preconception health. [1,3]
	</li>
	<li>
	Because pregnancy carries higher metabolic risk in PCOS, preconception evaluation and early pregnancy screening for hyperglycemia are emphasized, including OGTT timing guidance in those planning pregnancy or fertility treatment. [4,9]
	</li>
</ul>

6) Psychological health and sleep

<ul>
	<li>
	Screening for depression/anxiety symptoms and addressing sleep quality is part of comprehensive PCOS care. [1,5,6]
	</li>
	<li>
	Clinicians should be aware of increased obstructive sleep apnea prevalence in PCOS and evaluate symptoms (snoring, witnessed apneas, daytime sleepiness) when present. [4]
	</li>
</ul>

Key Points

<ul>
	<li>
	PCOS is a common endocrine&ndash;metabolic condition with reproductive, metabolic, cardiovascular, psychological, and sleep-related features. [1&ndash;4]
	</li>
	<li>
	Adult diagnosis typically requires 2 of 3: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries (with AMH as an adult alternative in some settings). [1]
	</li>
	<li>
	PCOS is associated with increased risk of impaired glucose tolerance/type 2 diabetes, cardiovascular risk, pregnancy complications, and endometrial hyperplasia/cancer&mdash;risk varies by individual profile. [4,7,9,10]
	</li>
	<li>
	Management is long-term and individualized, built on lifestyle strategies, symptom-targeted therapies, metabolic risk monitoring, and reproductive planning when relevant. [1,3,4]
	</li>
</ul>

References

<ol>
	<li>
	Teede, H., Tay, C. T., Laven, J., Dokras, A., Moran, L., Piltonen, T., Costello, M. F., Boivin, J., Redman, L., Boyle, J., Norman, R., Mousa, A., &amp; Joham, A. (2023). International evidence-based guideline for the assessment and management of polycystic ovary syndrome 2023 &ndash; Summary. Monash University.
	</li>
	<li>
	Teede, H. J., Misso, M. L., Costello, M. F., Dokras, A., Laven, J., Moran, L., Piltonen, T., &amp; Norman, R. J. (2023). Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertility and Sterility. (<a href="https://www.asrm.org/practice-guidance/practice-committee-documents/recommendations-from-the-2023-international-evidence-based-guideline-for-the-assessment-and-management-of-polycystic-ovary-syndrome/" style="color:#0563c1; text-decoration:underline">ASRM</a>)
	</li>
	<li>
	Teede, H. J., Misso, M. L., Costello, M. F., Dokras, A., Laven, J., Moran, L., Piltonen, T., &amp; Norman, R. J. (2023). Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human Reproduction, 38(9), 1655&ndash;.<a href="https://doi.org/10.1093/humrep/dead156" style="color:#0563c1; text-decoration:underline"> https://doi.org/10.1093/humrep/dead156</a> (<a href="https://academic.oup.com/humrep/article/38/9/1655/7241786" style="color:#0563c1; text-decoration:underline">OUP Academic</a>)
	</li>
	<li>
	Teede, H. J., Misso, M. L., Costello, M. F., Dokras, A., Laven, J., Moran, L., Piltonen, T., &amp; Norman, R. J. (2023). Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. The Journal of Clinical Endocrinology &amp; Metabolism, 108(10), 2447&ndash;.<a href="https://doi.org/10.1210/clinem/dgad463" style="color:#0563c1; text-decoration:underline"> https://doi.org/10.1210/clinem/dgad463</a> (<a href="https://academic.oup.com/jcem/article/108/10/2447/7242360" style="color:#0563c1; text-decoration:underline">OUP Academic</a>)
	</li>
	<li>
	Keeratibharat, P., et al. (2024). Prevalence of depression and anxiety in women with polycystic ovary syndrome: A systematic review/meta-analysis. BMC Psychiatry. (<a href="https://link.springer.com/article/10.1186/s12888-024-06154-8?utm_source=chatgpt.com" style="color:#0563c1; text-decoration:underline">Springer Link</a>)
	</li>
	<li>
	Eunice Kennedy Shriver National Institute of Child Health and Human Development. (2024, August 21). Polycystic Ovary Syndrome (PCOS). National Institutes of Health. (<a href="https://www.nichd.nih.gov/health/topics/pcos" style="color:#0563c1; text-decoration:underline">NICHD</a>)
	</li>
	<li>
	Tay, C. T., et al. (2024). 2023 international evidence-based PCOS guideline and cardiovascular risk: A systematic review/meta-analysis informing guideline recommendations. Journal of the American Heart Association. (<a href="https://www.ahajournals.org/doi/10.1161/JAHA.123.033572?utm_source=chatgpt.com" style="color:#0563c1; text-decoration:underline">AHA Journals</a>)
	</li>
	<li>
	Pililis, S., et al. (2024). The cardiometabolic risk in women with polycystic ovary syndrome: Contemporary evidence synthesis. Medicina, 60(10). (<a href="https://www.mdpi.com/1648-9144/60/10/1656?utm_source=chatgpt.com" style="color:#0563c1; text-decoration:underline">MDPI</a>)
	</li>
	<li>
	Bahri Khomami, M., et al. (2024). Systematic review and meta-analysis of pregnancy complications in women with polycystic ovary syndrome. Nature Communications. (<a href="https://www.nature.com/articles/s41467-024-49749-1?utm_source=chatgpt.com" style="color:#0563c1; text-decoration:underline">Nature</a>)
	</li>
	<li>
	Johnson, J. E., et al. (2023). Risk of endometrial cancer in patients with polycystic ovary syndrome: A meta-analysis. [Journal]. (<a href="https://pubmed.ncbi.nlm.nih.gov/36960190/?utm_source=chatgpt.com" style="color:#0563c1; text-decoration:underline">PubMed</a>)
	</li>
</ol>

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