Polycystic Ovary Syndrome (PCOS)

A 24 year old obese female presents with irregular menstrual cycles, progressive facial hair growth, acne, and difficulty conceiving for the past 2 years. She reports menstrual periods occurring every 2 to 3 months since adolescence. Physical examination reveals obesity, hirsutism, acne, and acanthosis nigricans. Laboratory investigations show elevated free testosterone with normal prolactin and TSH levels. Pelvic ultrasound demonstrates multiple peripheral ovarian follicles. Diagnosis?

Diagnosis is polycystic ovary syndrome (PCOS).

1. Definition

Polycystic ovary syndrome is a hyperandrogenic chronic anovulatory disorder associated with endocrine and metabolic dysfunction.

2. Epidemiology

1. Most common endocrine disorder in reproductive-age women
2. Most common cause of anovulatory infertility
3. Commonly presents during adolescence or early reproductive years

3. Pathophysiology

1. Increased GnRH pulse frequency favors LH secretion over FSH
2. Increased LH stimulates ovarian theca cells to produce excess androgens
3. Hyperinsulinemia increases ovarian androgen production
4. Insulin decreases hepatic SHBG synthesis leading to increased free testosterone
5. Follicular arrest results in chronic anovulation

4. Clinical Features

4.1 Reproductive Features

1. Oligomenorrhea or amenorrhea
2. Irregular menstrual cycles
3. Infertility due to chronic anovulation
4. Abnormal uterine bleeding

4.2 Hyperandrogenic Features

1. Hirsutism
2. Acne
3. Androgenic alopecia

4.3 Metabolic Features

1. Obesity
2. Insulin resistance
3. Acanthosis nigricans
4. Weight gain

5. Diagnosis

5.1 Rotterdam Criteria

Diagnosis requires at least 2 of the following 3 criteria after excluding other causes:

1. Hyperandrogenism
2. Ovulatory dysfunction
3. Polycystic ovarian morphology on ultrasound

5.2 Important Diagnostic Pearls

1. Polycystic ovaries are not required for diagnosis
2. Elevated LH:FSH ratio may occur but is not diagnostic
3. Adolescents require both hyperandrogenism and ovulatory dysfunction to avoid overdiagnosis

5.3 Laboratory Evaluation

1. Pregnancy test (β-hCG) to exclude pregnancy
2. TSH
3. Prolactin
4. Total and free testosterone
5. 17-hydroxyprogesterone if indicated

5.4 Imaging

Pelvic Ultrasound

1. Multiple peripheral immature follicles
2. “String of pearls” appearance
3. Increased ovarian volume may be present

6. Differential Diagnosis

1. Pregnancy
2. Hypothyroidism
3. Hyperprolactinemia
4. Nonclassic congenital adrenal hyperplasia
5. Cushing syndrome
6. Androgen-secreting tumor

7. Complications

7.1 Reproductive Complications

1. Infertility
2. Endometrial hyperplasia
3. Endometrial carcinoma due to unopposed estrogen

7.2 Metabolic Complications

1. Type 2 diabetes mellitus
2. Dyslipidemia
3. Metabolic syndrome
4. Nonalcoholic fatty liver disease
5. Obstructive sleep apnea
6. Cardiovascular disease

7.3 Psychiatric Associations

1. Depression
2. Anxiety
3. Eating disorders

8. Management

8.1 Lifestyle Modification

1. Weight loss and exercise are first-line therapy for all patients
2. Even 5–10% weight loss improves ovulation and insulin sensitivity
3. Regular physical activity is recommended

8.2 If NOT Seeking Pregnancy

Combined Oral Contraceptive Pills

1. First-line treatment for menstrual irregularity and hirsutism
2. Suppress ovarian androgen production
3. Increase SHBG and reduce free testosterone

Spironolactone

1. Added for persistent hirsutism after approximately 6 months
2. Reliable contraception is required due to teratogenicity

Metformin

1. Improves insulin resistance
2. Helps menstrual regularity
3. Particularly useful in prediabetes or type 2 diabetes

8.3 If Seeking Pregnancy

Letrozole

1. First-line ovulation induction therapy
2. Aromatase inhibitor that increases FSH secretion
3. More effective than clomiphene for live birth rates

Other Fertility Therapies

1. Gonadotropins
2. In vitro fertilization (IVF) in refractory infertility

9. Pregnancy Risks

1. Gestational diabetes
2. Preeclampsia
3. Hypertensive disorders of pregnancy
4. Increased risk of miscarriage

10. Key Clinical Insight

Young woman with irregular menstrual cycles, hirsutism, acne, obesity, and infertility strongly suggests PCOS, especially in the presence of insulin resistance and chronic anovulation

11. Key Exam Points

1. Most common cause of anovulatory infertility
2. Core triad: anovulation, hyperandrogenism, insulin resistance
3. Acanthosis nigricans indicates insulin resistance
4. Diagnosis requires 2 of 3 Rotterdam criteria
5. Polycystic ovaries are not required for diagnosis
6. Most important long-term complication is endometrial carcinoma
7. Combined OCPs are first-line treatment if not seeking pregnancy
8. Letrozole is first-line ovulation induction therapy
9. Weight loss improves fertility and metabolic outcomes
10. Elevated LH:FSH ratio is not diagnostic of PCOS