What dose of progestogen is needed to provide endometrial protection and suppress endometriosis in a perimenopausal woman using a transdermal estradiol patch delivering 25–50 µg/day while preserving bone density?

Progesterone Dosing for Endometriosis in Perimenopausal Women on Low-Dose Transdermal Estradiol

For a perimenopausal woman with endometriosis using a 25–50 µg/day transdermal estradiol patch, prescribe 200 mg oral micronized progesterone nightly for 12–14 consecutive days every 28 days (sequential regimen) to provide endometrial protection, suppress endometriosis, and preserve bone density. 1, 2, 3

Rationale for Sequential Dosing

• The 12–14 day duration is critical and non-negotiable—shorter progestogen exposure fails to prevent endometrial proliferation and provides inadequate protection against both endometrial hyperplasia and endometriosis reactivation. 1

• Micronized progesterone 200 mg is the preferred progestogen because it carries lower cardiovascular and thrombotic risk than synthetic progestins while maintaining full endometrial protection. 1, 4

• Sequential regimens (progesterone for 12–14 days, then 14–16 days off) induce predictable withdrawal bleeding but allow the endometrium to stabilize between cycles, which may help suppress ectopic endometrial tissue. 1, 5

Alternative: Continuous Combined Regimen

If the patient cannot tolerate withdrawal bleeding or has breakthrough pain during the progesterone-free interval, switch to continuous daily micronized progesterone 100 mg nightly without interruption. 1, 4

• Continuous progestogen provides the most robust suppression of endometriosis by eliminating cyclical hormonal fluctuation. 1, 6

• The lower daily dose (100 mg continuous vs. 200 mg sequential) is sufficient because uninterrupted exposure maintains stable endometrial suppression. 1, 4

• Continuous regimens eliminate withdrawal bleeding entirely, which many patients with endometriosis prefer. 1

Bone Density Preservation

• The estradiol dose of 25–50 µg/day transdermal is sufficient to prevent bone loss when combined with adequate progestogen. 4, 6

• Studies in women on long-term GnRH agonist therapy (which induces more severe hypoestrogenism than perimenopause) showed stable bone mineral density when 1 mg oral estradiol was combined with cyclic progestogen—your patient's transdermal dose delivers equivalent or higher systemic estradiol. 6

• Ensure calcium 1,000–1,300 mg/day and vitamin D 800–1,000 IU/day supplementation to optimize bone health. 4

Endometriosis-Specific Considerations

• Combined estrogen-progestogen therapy reduces endometriosis reactivation risk compared with unopposed estrogen, which can stimulate ectopic endometrial tissue. 1, 5

• In the only randomized trial of HRT in women with surgically confirmed endometriosis, transdermal estradiol 50 µg/day plus cyclic micronized progesterone 200 mg/day for 14 days resulted in pain recurrence in only 4/115 women (3.5%) over extended follow-up. 5

• If breakthrough pelvic pain occurs despite adequate progestogen, consider switching to continuous norethindrone acetate 5–10 mg daily, which provides more potent endometrial suppression than micronized progesterone. 7

Monitoring Protocol

• Annual clinical review focusing on bleeding patterns, pelvic pain, and menopausal symptoms—no routine hormone level testing is required. 1, 4

• Investigate any abnormal bleeding (heavy, prolonged, or intermenstrual) with endometrial assessment, as this may signal inadequate progestogen opposition. 1, 4

• Reassess bone density at 2 years if the patient has additional osteoporosis risk factors (prior fracture, glucocorticoid use, smoking). 4

Common Pitfalls to Avoid

• Never use progesterone for fewer than 12 days per cycle in sequential regimens—this provides inadequate endometrial protection and may allow endometriosis progression. 1

• Do not prescribe unopposed estrogen (estradiol without progestogen) in a woman with a uterus, even at low doses—this dramatically increases endometrial cancer risk (RR 2.3–9.5) and may reactivate endometriosis. 1, 4

• Avoid synthetic progestins (medroxyprogesterone acetate, norethindrone) as first-line unless micronized progesterone is not tolerated, because they carry higher cardiovascular and breast cancer risk. 1, 4

Alternative Progestogen Options (Second-Line)

If micronized progesterone causes intolerable sedation or gastrointestinal symptoms:

• Dydrogesterone 10 mg daily for 12–14 days per month (sequential) or 5 mg daily continuously. 1, 4

• Medroxyprogesterone acetate 10 mg daily for 12–14 days per month (sequential) or 2.5 mg daily continuously—use only if other options fail, given less favorable metabolic profile. 1, 4

Duration of Therapy

• Continue this regimen until the patient reaches confirmed postmenopause (12 months of amenorrhea off hormonal therapy), then reassess whether to continue, reduce dose, or discontinue based on symptom burden. 1, 4

• For perimenopausal women, HRT can be safely continued through the menopausal transition and beyond if symptoms persist, using the lowest effective dose. 4