What progesterone options are available to induce menses in patients with Polycystic Ovary Syndrome (PCOS)?

Progesterone Options to Induce Menses in PCOS

For women with PCOS who are not attempting to conceive, use medroxyprogesterone acetate (MPA) 10 mg daily for 12-14 days per month to induce withdrawal bleeding and provide endometrial protection. 1

Primary Progesterone Regimens for Inducing Menses

First-Line Option: Medroxyprogesterone Acetate (MPA)

• MPA 10 mg daily for 12-14 days per month is the most established regimen for inducing withdrawal bleeding in PCOS 1
• MPA is the only progestin with robust evidence demonstrating full effectiveness in inducing secretory endometrium when used cyclically 1
• MPA suppresses circulating androgen levels and pituitary gonadotropin levels in women with PCOS 2, 3
• This regimen provides critical endometrial protection against hyperplasia and cancer risk in anovulatory PCOS patients 1, 2

Alternative Option: Oral Micronized Progesterone (OMP)

• OMP 200 mg daily for 12-14 days per month is an effective alternative with a superior safety profile 1
• Can also be dosed as 100 mg in the morning and 200 mg at bedtime for 7 days to induce withdrawal bleeding 4
• OMP has demonstrated advantages over synthetic progestogens including lower cardiovascular risk and better thrombotic safety profile 1
• Does not significantly alter circulating androgen levels when used to induce withdrawal bleeding 4
• May improve fluid retention, breast tenderness, and cervical mucus symptoms when used cyclically 5

Third Option: Dydrogesterone

• Dydrogesterone 10 mg daily for 12-14 days per month is another synthetic progesterone option 1
• Has enhanced oral bioavailability compared to natural progesterone 1
• Can be used at 5 mg daily continuously if avoiding withdrawal bleeding is desired 1

Important Clinical Considerations

Timing and Administration

• Progesterone can be started at any time in amenorrheic PCOS patients if pregnancy is reasonably excluded 2
• Withdrawal bleeding typically occurs 2-7 days after completing the progesterone course 4
• Regular monthly cycling (every 28 days) is recommended to maintain endometrial protection 1

When Combined Oral Contraceptives Are Preferred

• COCs are the first-line medication treatment for long-term PCOS management in women not attempting to conceive 2
• COCs provide superior androgen suppression, increase sex hormone-binding globulin, and reduce endometrial cancer risk 2
• COCs containing norgestimate have favorable side effect profiles for PCOS 2
• However, progesterone-only regimens are appropriate when COCs are contraindicated or not tolerated 5

Critical Pitfall to Avoid

• Do not use progesterone alone without adequate estrogen in women requiring long-term hormone replacement (such as those with premature ovarian insufficiency), as this fails to address bone health and cardiovascular protection 1
• The optimal duration and frequency of progesterone treatment to prevent endometrial cancer in PCOS is not definitively established, but monthly cycling is standard practice 1

Route of Administration Options

• Oral route is most commonly used and convenient for inducing withdrawal bleeding 1, 4
• Vaginal route (200 mg daily for 12-14 days) can be used if oral administration causes side effects or is contraindicated 1
• Vaginal progesterone may have advantages in luteal phase support during ovulation induction but is not typically necessary for simple withdrawal bleeding 6, 7