Polycystic ovary syndrome (PCOS)
Polycystic Ovary Syndrome (PCOS)
1. Introduction and Overview
Definition:
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age, characterized by a combination of menstrual irregularities, hyperandrogenism (e.g., hirsutism, acne), and polycystic ovaries on ultrasound. It is often associated with insulin resistance and metabolic disturbances.
Epidemiology:
Prevalence: Affects approximately 5-10% of women of reproductive age worldwide.
Age: Typically diagnosed in women aged 18-35 years.
Sex: Exclusively affects females.
Ethnicity: Higher prevalence observed in South Asian, Middle Eastern, and Hispanic populations.
Relevance: PCOS is a leading cause of infertility, and it increases the risk of developing metabolic disorders such as type 2 diabetes, hypertension, and cardiovascular diseases.
2. Etiology
Primary Causes:
Genetic Factors:
Strong hereditary component with a family history of PCOS or related conditions (e.g., type 2 diabetes).
Several candidate genes involved, though no definitive genetic cause has been established.
Hormonal Imbalance:
Elevated levels of luteinizing hormone (LH) and testosterone (hyperandrogenism), combined with low levels of follicle-stimulating hormone (FSH).
Increased ovarian androgen production leading to anovulation and cyst formation.
Dysregulation of the hypothalamic-pituitary-ovarian axis.
Insulin Resistance:
Insulin resistance is common in women with PCOS, leading to compensatory hyperinsulinemia, which stimulates ovarian androgen production and disrupts normal ovulation.
Contributes to metabolic symptoms such as weight gain and type 2 diabetes.
Secondary Causes:
Obesity: Increases insulin resistance, exacerbating PCOS symptoms.
Environmental Factors: Diets rich in refined carbohydrates and high-fat foods may contribute to the development or exacerbation of PCOS.
Endocrine Disruptors: Exposure to environmental chemicals affecting the endocrine system may play a role in the pathogenesis.
Risk Factors:
Family history of PCOS or type 2 diabetes.
Obesity or high BMI.
Early onset of menstruation or obesity in adolescence.
3. Pathophysiology
Normal Physiology:
In a normal menstrual cycle, the hypothalamus secretes gonadotropin-releasing hormone (GnRH), which stimulates the pituitary to release FSH and LH.
FSH promotes follicle growth, while LH triggers ovulation.
The ovaries produce estrogen and progesterone, regulating menstrual cycles and supporting pregnancy.
Mechanisms of Disease:
Increased LH and Hyperandrogenism:
Elevated LH levels (due to GnRH pulsatility disturbances) drive excessive ovarian androgen production.
High androgen levels lead to clinical manifestations such as hirsutism, acne, and alopecia.
Anovulation:
Disruption in follicular development due to an imbalance in FSH/LH secretion prevents ovulation.
Follicles develop into cysts but do not mature or release eggs, leading to menstrual irregularities and infertility.
Insulin Resistance:
Insulin resistance contributes to hyperinsulinemia, which further stimulates ovarian androgen production.
Insulin resistance is also associated with metabolic abnormalities such as obesity and type 2 diabetes.
Key Pathways:
Hyperinsulinemia → Ovarian Androgen Production → Anovulation
Insulin resistance exacerbates both the metabolic and reproductive symptoms of PCOS.
4. Clinical Features
Symptoms:
Menstrual Irregularities:
Oligomenorrhea (infrequent periods) or amenorrhea (absence of periods) due to anovulation.
Hyperandrogenism:
Hirsutism: Excessive hair growth on the face, chest, and abdomen.
Acne: Seborrheic acne due to excess sebum production.
Alopecia: Thinning of hair, particularly along the frontal hairline.
Infertility:
Difficulty conceiving due to anovulation or irregular ovulation.
Obesity:
Central obesity (visceral fat distribution), common in PCOS women.
Signs:
Physical Exam:
Obesity, acanthosis nigricans (skin darkening and thickening), and signs of hirsutism (e.g., facial hair).
Polycystic Ovaries on ultrasound: Multiple small follicles (2-9 mm in diameter) arranged peripherally, giving a "string of pearls" appearance.
Laboratory Findings:
Elevated testosterone and DHEA levels.
LH/FSH ratio typically >2:1, with elevated LH levels.
Possible insulin resistance with elevated fasting insulin and glucose levels.
Stages and Progression:
PCOS can present in adolescence with menstrual irregularities and acne. Over time, metabolic complications such as insulin resistance, type 2 diabetes, and cardiovascular risk factors may develop.
The long-term impact includes infertility and increased risk of endometrial hyperplasia due to unopposed estrogen.
Differentiating Features:
Thyroid disorders: Hypothyroidism may also cause menstrual irregularities and hirsutism.
Congenital Adrenal Hyperplasia (CAH): Can present with virilization but lacks polycystic ovaries on ultrasound.
Cushing’s Syndrome: May present with obesity, hirsutism, and menstrual disturbances but also features characteristic signs such as striae and a buffalo hump.
5. Diagnostic Approach
Clinical Diagnosis:
History: Irregular menstrual cycles, signs of hyperandrogenism (hirsutism, acne), and difficulty conceiving.
Physical Examination: Obesity, hirsutism, and acanthosis nigricans.
Laboratory Investigations:
Hormonal Assays:
Elevated testosterone, DHEA-S, and androstenedione.
LH/FSH ratio >2:1, with elevated LH.
Glucose and Insulin:
Fasting glucose, insulin levels, and HOMA-IR (homeostasis model assessment of insulin resistance).
Thyroid Function Tests:
To rule out thyroid dysfunction as a cause of menstrual irregularity or hirsutism.
Imaging Studies:
Transvaginal Ultrasound:
Polycystic ovaries: >12 follicles in one or both ovaries (2-9 mm in diameter), and/or increased ovarian volume.
Diagnostic Criteria (Rotterdam Criteria):
At least two of the following three criteria:
Oligo-/anovulation (irregular or absent menstrual cycles).
Clinical and/or biochemical signs of hyperandrogenism.
Polycystic ovaries on ultrasound.
6. Management
Medical Management:
Menstrual Regulation and Ovulation Induction:
Combined Oral Contraceptives (COCs):
First-line treatment for menstrual irregularities and hyperandrogenism (e.g., ethinylestradiol + desogestrel).
Progestins (medroxyprogesterone acetate) can be used for unopposed estrogen therapy to prevent endometrial hyperplasia.
Clomiphene Citrate: First-line ovulation induction drug for infertility.
Metformin: In cases of insulin resistance, improves ovulation and may aid in weight management.
Letrozole: An alternative to clomiphene for ovulation induction in infertile women.
Hyperandrogenism:
Anti-androgens:
Spironolactone (25–100 mg/day) reduces hirsutism.
Finasteride (5 mg/day) for severe hirsutism (contraindicated in pregnancy).
Insulin Resistance:
Metformin: Improves insulin sensitivity and may help with weight loss.
Lifestyle Modifications: Diet and exercise to manage weight and improve insulin sensitivity.
Surgical Management:
Ovarian Drilling: In cases of treatment-resistant infertility, laparoscopic ovarian drilling may be considered, especially in women with polycystic ovaries.
Emergency Management:
Not typically necessary unless complications like hyperandrogenism or infertility are causing distress or long-term health issues.
7. Prognosis
Natural History:
PCOS is a chronic condition with variable progression. Symptoms may improve with age, particularly hyperandrogenism, but infertility and metabolic complications can persist.
Outcomes with Treatment:
Fertility: Ovulation induction with medications like clomiphene citrate or metformin can result in successful pregnancies.
Metabolic Outcomes: Proper management of insulin resistance and obesity reduces the risk of type 2 diabetes, hypertension, and cardiovascular diseases.
Long-Term Impact:
Increased risk of endometrial cancer due to unopposed estrogen exposure, hence the need for regular endometrial surveillance.
8. Complications
Reproductive:
Infertility: Due to anovulation.
Pregnancy-related Complications: Increased risk of gestational diabetes, pre-eclampsia, and preterm birth.
Metabolic:
Type 2 Diabetes: Due to insulin resistance.
Hypertension: Increased risk, particularly if obesity is present.
Dyslipidemia: Increased risk of elevated LDL and triglycerides.
Psychological:
Anxiety and Depression: Due to cosmetic concerns (hirsutism, acne) and infertility.
9. Prevention
Primary Prevention:
Early recognition of symptoms (e.g., irregular periods, hirsutism) and lifestyle changes (e.g., healthy diet, weight control).
Secondary Prevention:
Screening for metabolic abnormalities, including glucose tolerance tests and lipid profiles.
Tertiary Prevention:
Monitoring and management of endometrial health in women with prolonged anovulation (e.g., progestin therapy).
10. Patient Education
Disease Understanding:
Inform patients that PCOS is a chronic condition but can be managed effectively with medical therapy and lifestyle modifications.
Lifestyle Recommendations:
Emphasize the importance of weight management, healthy eating, and regular physical activity to improve insulin sensitivity and fertility.
Fertility Options:
Discuss ovulation induction therapies and the potential need for assisted reproductive technologies (ART) in cases of infertility.
11. Recent Research and Advances
Metabolic Approaches: The role of liraglutide and sGLT2 inhibitors in improving metabolic outcomes in women with PCOS.
Genetic Insights: Advances in understanding the genetic basis of PCOS may lead to personalized treatments in the future.
12. Case Studies
Example:
A 25-year-old woman with irregular periods and moderate hirsutism is diagnosed with PCOS based on the Rotterdam criteria. She is started on oral contraceptives for menstrual regulation and spironolactone for hirsutism. Metformin is introduced due to signs of insulin resistance.
13. References
Azziz, R., Carmina, E., Dewailly, D., et al. "Polycystic Ovary Syndrome." Lancet, 2016.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. "Revised 2003 Consensus on Diagnostic Criteria and Long-Term Health Risks." Human Reproduction, 2004.
American College of Obstetricians and Gynecologists (ACOG) Guidelines, 2021.