What is a good levonorgestrel (progestin) and ethinyl estradiol (estrogen) combination for someone with a history of Polycystic Ovary Syndrome (PCOS)?

Levonorgestrel-Ethinyl Estradiol for PCOS

For women with PCOS who are not attempting to conceive, a combined oral contraceptive containing 30-35 μg ethinyl estradiol with levonorgestrel (such as 0.15 mg levonorgestrel/0.03 mg ethinyl estradiol) is an excellent first-line choice, as recommended by the American Academy of Family Physicians. 1

Why This Combination Works for PCOS

Combined oral contraceptives (COCs) are the first-line medication treatment for long-term management of PCOS in women not attempting pregnancy because they address multiple pathophysiologic mechanisms 1:

• Suppress androgen secretion by the ovaries, directly targeting the hyperandrogenism characteristic of PCOS 1
• Increase sex hormone-binding globulin (SHBG), which further reduces free testosterone levels 1
• Reduce endometrial cancer risk, which is elevated in PCOS due to chronic anovulation and unopposed estrogen exposure 1
• Improve hirsutism and acne, common concerns in PCOS patients 2, 1

Specific Formulation Recommendations

Levonorgestrel-containing COCs are particularly appropriate for PCOS because many adolescent medicine providers begin with a COC containing 30-35 μg ethinyl estradiol and a progestin such as levonorgestrel or norgestimate 2. The evidence supports this approach:

• Desogestrel 0.15 mg/ethinyl estradiol 0.03 mg (which metabolizes to etonogestrel, similar to levonorgestrel) demonstrated significant improvements in hirsutism, free and total testosterone levels, and SHBG in PCOS patients after 8 months of treatment 3
• Lower-dose formulations (20 μg ethinyl estradiol) are equally effective at reducing androgens compared to 30 μg formulations in PCOS patients 4
• Levonorgestrel has minimal androgenic activity, making it suitable for hyperandrogenic conditions like PCOS 2

Dosing and Initiation Protocol

Starting the Medication

If started within the first 5 days of menstrual bleeding, no additional contraceptive protection is needed 2, 1. However, many PCOS patients have oligomenorrhea or amenorrhea, so:

• For patients with infrequent menses: Start at any time if reasonably certain the patient is not pregnant 1
• Use backup contraception for the first 7 days when starting outside the first 5 days of bleeding 2, 1

Standard Regimen

• 21-24 hormone pills followed by 4-7 placebo pills in a 28-day pack 2, 1
• Monophasic formulations (same dose in each active pill) are preferred for simplicity 2
• Take one pill daily at the same time each day 5

Extended or Continuous Cycles

Consider extended or continuous cycles for PCOS patients with severe dysmenorrhea, heavy bleeding, or anemia 2:

• Eliminates hormone-free intervals, optimizing ovarian suppression 2
• Reduces menstrual-related symptoms 2
• Most common adverse effect is unscheduled bleeding 2

Managing Missed Pills

If one pill is missed (<24 hours late):

• Take the missed pill as soon as remembered 2
• Continue regular schedule 2

If two consecutive pills are missed in Week 1 or 2:

• Take 2 pills the day remembered and 2 pills the next day 2, 5
• Use backup contraception for 7 days 2, 5

If two consecutive pills are missed in Week 3 or three or more pills missed anytime:

• Continue taking one pill daily until Sunday (for Sunday start) 5
• Discard the rest of the pack on Sunday and start a new pack 5
• Use backup contraception for 7 days 5

Important Clinical Considerations

Cardiovascular Risk

The baseline risk of venous thromboembolism (VTE) in reproductive-age women is approximately 1 per 10,000 woman-years, and COCs increase this risk three to fourfold 1. However:

• COCs remain safe throughout a woman's reproductive years with appropriate screening 2
• Screen for VTE risk factors before prescribing 2
• Completely reversible with no negative effect on long-term fertility 2, 1

Metabolic Monitoring

All women with PCOS should be screened for metabolic complications 1:

• Fasting glucose and 2-hour glucose tolerance test for type 2 diabetes 1
• Fasting lipoprotein profile for dyslipidemia 1

Noncontraceptive Benefits

Beyond treating PCOS, these formulations provide 2, 1:

• Decreased menstrual cramping and blood loss 2, 1
• Improvement in acne 2, 1
• Protection against endometrial and ovarian cancers with >3 years use 2

When COCs Are Not Appropriate

If contraception is contraindicated or not tolerated, use cyclic progestin alone 1:

• Medroxyprogesterone acetate 10 mg daily for 12-14 days per month to induce withdrawal bleeding and provide endometrial protection 1
• Oral micronized progesterone 200 mg daily for 12-14 days per month as an alternative with superior safety profile 1

Common Pitfalls to Avoid

• Don't delay treatment waiting for "perfect" metabolic control—weight loss of even 5% improves PCOS outcomes, but medication can be started concurrently 1
• Don't use progestins with anti-androgenic effects alone in PCOS patients with sexual dysfunction, as they may worsen hypoandrogenism 2
• Don't forget endometrial protection—PCOS patients with chronic anovulation require either COCs or cyclic progestin to prevent endometrial hyperplasia 1
• Counsel about expected bleeding patterns to improve adherence, as irregular bleeding is common initially 2