PCOS Workup and Management
Diagnostic Workup
The diagnosis of PCOS requires the presence of at least two of three Rotterdam criteria: hyperandrogenism (clinical or biochemical), ovulatory dysfunction, and polycystic ovarian morphology on ultrasound 1, 2.
Essential Diagnostic Components
Hyperandrogenism assessment: Free testosterone levels are more sensitive than total testosterone and should ideally be measured through equilibrium dialysis techniques 1. Clinical hyperandrogenism includes hirsutism (60-80% of patients), acne, or male-pattern hair loss 3.
Ovulatory dysfunction: Cycle length >35 days suggests chronic anovulation; cycles of 32-35 days require further assessment 1. Document menstrual pattern for at least 2-3 years post-menarche in adolescents before diagnosis 1.
Ovarian imaging: Polycystic ovarian morphology is defined as ≥25 follicles (2-9 mm) in the whole ovary or ovarian volume ≥10 mL 1. Ultrasound is not recommended as first-line investigation in women <17 years of age 1.
Exclusion of Mimicking Disorders
Rule out: Thyroid disorders, hyperprolactinemia, congenital adrenal hyperplasia (measure 17-hydroxyprogesterone), Cushing's syndrome, and androgen-secreting tumors 4, 1.
Rapid-onset virilization: Suspect neoplastic causes if hirsutism develops rapidly with clitoromegaly 1.
Metabolic Screening (Mandatory)
Diabetes screening: All women with PCOS require fasting glucose and 2-hour glucose tolerance test 5.
Lipid assessment: Obtain fasting lipoprotein profile 5.
Additional screening: Evaluate for hepatic steatosis, hypertension, obstructive sleep apnea, and mood disorders 4, 6.
Endometrial Protection Assessment
- Endometrial biopsy: Perform in women with prolonged amenorrhea, abnormal vaginal bleeding, or age-related increased risk before initiating treatment 7, 1.
Treatment Algorithm
For Women NOT Attempting Conception
Combined oral contraceptives (COCs) are the first-line pharmacological treatment for long-term management of PCOS in women not attempting pregnancy 5.
Primary Treatment: Combined Oral Contraceptives
Mechanism: COCs suppress ovarian androgen secretion, increase sex hormone-binding globulin, and reduce endometrial cancer risk 5.
Preferred formulations: Norgestimate-containing COCs (e.g., Sprintec) have favorable side effect profiles 5.
Dosing: Standard regimens include 21-24 hormone pills followed by 4-7 placebo pills. Start within first 5 days of menstrual bleeding (no backup contraception needed) or anytime if pregnancy excluded (use backup contraception for 7 days) 5.
Additional benefits: Decreased menstrual cramping, reduced menstrual blood loss, acne improvement 5.
Alternative: Progestin-Only Regimens (When COCs Contraindicated)
Medroxyprogesterone acetate (MPA): 10 mg daily for 12-14 days per month provides endometrial protection and induces withdrawal bleeding 5.
Oral micronized progesterone: 200 mg daily for 12-14 days per month offers superior cardiovascular and thrombotic safety profile 5.
Frequency: Monthly cycling (every 28 days) is mandatory to maintain endometrial protection 5.
Hirsutism Management
Combination therapy: Antiandrogens (spironolactone, flutamide, finasteride) combined with COCs are more effective than either alone 5, 1.
Mechanism: Antiandrogens work through competitive androgen receptor antagonism or 5α-reductase inhibition 1.
Metabolic Management
Metformin: Recommended for women with cardiometabolic features (abdominal obesity, insulin resistance). Improves insulin sensitivity and menstrual irregularities 5, 2.
Dosing: 850 mg daily in lean patients; escalate to 1.5-2.5 g daily in overweight/obese patients 1.
Weight loss: Even 5% weight reduction significantly improves metabolic and reproductive abnormalities 5, 4.
For Women Attempting Conception
Clomiphene citrate is the first-line ovulation induction treatment for women with PCOS, with an 80% ovulation rate and 50% conception rate among ovulators 5, 7.
Clomiphene Citrate Protocol
Starting dose: 50 mg daily for 5 days, beginning on cycle day 5 (after progestin-induced or spontaneous bleeding) 7.
Dose escalation: If no ovulation occurs, increase to 100 mg daily for 5 days in subsequent cycle (may start as early as 30 days after previous course) 7.
Maximum therapy: Do not exceed 100 mg/day for 5 days. If no ovulation after three courses, discontinue clomiphene and reevaluate 7.
Duration limit: Not recommended beyond six total cycles (including three ovulatory cycles) 7.
PCOS-specific caution: Start with lowest dose and shortest duration in polycystic ovary syndrome patients due to increased sensitivity to gonadotropins and risk of ovarian hyperstimulation syndrome 7.
Monitoring and Timing
Ovulation timing: Typically occurs 5-10 days after completing clomiphene course 7.
Coitus timing: Time intercourse to coincide with expected ovulation 7.
Pelvic examination: Required before each treatment cycle to exclude ovarian enlargement or cysts 7.
Second-Line Fertility Options
Low-dose gonadotropins: Preferred over high-dose therapy for clomiphene-resistant patients 5.
Metformin adjunct: Can be combined with clomiphene, though metformin alone has limited benefit for infertility 2.
Lifestyle Interventions (Foundation for All Patients)
Weight loss and exercise are first-line approaches to improve insulin sensitivity, ovulation rates, and metabolic outcomes, with even 5% weight reduction producing significant benefits 8, 5.
Exercise Prescription
Minimum target: 150 minutes per week, with 90 minutes at moderate to high intensity 9.
Moderate intensity: Brisk walking (5-7 km/h), cycling (8-15 km/h), low-impact aerobics, yoga, weight training—activities where uninterrupted conversation is possible 9.
Vigorous intensity: Jogging/running, cycling (>16 km/h), high-impact aerobics, competitive sports—activities where conversation cannot be maintained 9.
Benefits independent of weight loss: Exercise improves insulin resistance, body composition, and reproductive outcomes even without significant weight reduction 9.
Critical Warnings and Pitfalls
Ovarian Hyperstimulation Syndrome (OHSS)
High-risk population: Women with PCOS, especially those with polycystic ovary syndrome, are unusually sensitive to gonadotropins 7.
Early warning signs: Abdominal pain and distention, nausea, vomiting, diarrhea, weight gain 7.
Severe manifestations: Gross ovarian enlargement, ascites, oliguria, pleural effusion, thromboembolism 7.
Management: Use lowest effective clomiphene dose. If ovarian enlargement occurs, withhold further therapy until ovaries return to pretreatment size 7.
Visual Disturbances with Clomiphene
Symptoms: Visual blurring, scotomata, phosphenes can occur during treatment 7.
Action required: Discontinue clomiphene immediately and perform complete ophthalmological evaluation 7.
Endometrial Cancer Risk
Mechanism: Chronic anovulation increases endometrial hyperplasia and cancer risk 1.
Prevention: Ensure regular menstrual cycling (at minimum every 3 months) through COCs, progestins, or weight loss 5.