What is the first-line medication treatment for polycystic ovarian syndrome (PCOS)?

First-Line Medication Treatment for Polycystic Ovarian Syndrome (PCOS)

Combined oral contraceptives (COCs) are the first-line medication treatment for long-term management of PCOS in women who are not attempting to conceive. 1

Treatment Approach Based on Reproductive Goals

For Women Not Attempting to Conceive:

1. Lifestyle Modifications

   • Weight loss (even 5% of initial weight) improves metabolic and reproductive abnormalities 1
   • Regular exercise program is beneficial even without weight loss 1

2. First-Line Pharmacological Treatment: Combined Oral Contraceptives

   • Benefits:

     • Suppresses androgen secretion by the ovaries 1
     • Increases circulating sex hormone binding globulin 1
     • Restores regular menstrual cycles 2
     • Reduces risk of endometrial cancer 1
     • Improves hyperandrogenism (acne, hirsutism) 2

   • Considerations before prescribing:

     • Assess cardiometabolic risk factors: age, smoking, obesity, glucose tolerance, hypertension, dyslipidemia, thrombophilia, and family history of venous thromboembolism 3
     • COCs increase risk of venous thromboembolism, related to estrogen dose and progestin type 2
     • May decrease insulin sensitivity in some patients, particularly those with obesity 4

3. Alternative/Additional Treatments:

   • Medroxyprogesterone acetate (depot or intermittent oral therapy)

     • Suppresses circulating androgen levels and pituitary gonadotropin levels 1

   • For hirsutism management:

     • Combined approach with antiandrogens (spironolactone, flutamide, finasteride) and COCs 1
     • Topical eflornithine hydrochloride cream (FDA-approved for hirsutism) 1

For Women Attempting to Conceive:

1. Lifestyle Modifications

   • Weight control and regular exercise program as first step 1

2. First-Line Ovulation Induction: Clomiphene Citrate

   • Recommended by ACOG based on good and consistent scientific evidence 1
   • Approximately 80% of PCOS patients ovulate with clomiphene, and half of these conceive 1

3. Second-Line Treatment (if clomiphene fails): Gonadotropins

   • Low-dose gonadotropin therapy is preferred over high-dose
   • Induces higher rate of monofollicular development with lower risk of ovarian hyperstimulation 1

4. Role of Insulin-Sensitizing Agents:

   • Metformin and thiazolidinediones improve frequency of ovulation 1
   • Not FDA-approved specifically for PCOS treatment 1
   • Metformin appears safe during early pregnancy, but effects not fully established 1

Management of Metabolic Aspects of PCOS

• Screening recommendations:

  • All women with PCOS should be screened for type 2 diabetes with fasting glucose and 2-hour glucose tolerance test 1
  • Screen for dyslipidemia with fasting lipoprotein profile 1
  • Calculate BMI and waist-hip ratio 1

• Insulin-sensitizing agents:

  • Metformin and thiazolidinediones may have positive impact on risk factors for diabetes and cardiovascular disease 1
  • Metformin tends to decrease weight while thiazolidinediones tend to increase weight 1
  • Glucose tolerance improves or remains steady over time with metformin use 1

Important Clinical Considerations

• Treatment should be tailored based on the patient's primary concerns (irregular menses, hirsutism, acne, infertility) 5
• The combination of an antiandrogen with COCs is more effective for hirsutism than either treatment alone 1
• Long-term cardiovascular and metabolic effects of treatments need ongoing monitoring 3
• Combination therapy of COCs with weight reduction or insulin sensitizers could further suppress androgen levels and improve metabolic parameters 4