What non‑oral combined estrogen and progestogen regimens can suppress menstruation while preserving bone density in a patient on tirzepatide (Mounjaro) who cannot take oral medications?

Non-Oral Combined Hormone Options for Cycle Suppression with Bone Preservation

For a patient on tirzepatide who cannot take oral medications, transdermal combined estrogen-progestin patches are the optimal choice for menstrual suppression while preserving bone density. 1

Primary Recommendation: Transdermal Combined Patches

Use continuous combined transdermal patches containing 17β-estradiol (50 μg daily) plus levonorgestrel (7-10 μg daily) applied without interruption to suppress withdrawal bleeding. 1

Specific Regimen Options:

• First-line approach: Patches releasing 50 μg of 17β-estradiol and 7 μg of levonorgestrel daily, applied continuously without breaks 1
• Alternative continuous regimen: Patches releasing 50 μg of 17β-estradiol and 10 μg of levonorgestrel daily, changed according to manufacturer instructions (typically twice weekly) 1

Why Transdermal Over Oral:

• Transdermal 17β-estradiol avoids first-pass hepatic metabolism, which is particularly important because oral estrogens suppress hepatic IGF-1 production—a critical bone trophic hormone 1
• This first-pass suppression of IGF-1 by oral estrogens can paradoxically worsen bone health in energy-deficient states, despite providing estrogen replacement 1
• Transdermal administration reduces thrombotic risk compared to oral formulations 2
• No interaction with gastrointestinal absorption issues that might be relevant with tirzepatide use 3

Alternative Non-Oral Option: Sequential Combined Patches

If continuous suppression is not desired or tolerated:

• Patches of 17β-estradiol alone (50 μg daily) for 2 weeks, followed by combined 17β-estradiol (50 μg) plus levonorgestrel (10 μg) patches for 2 weeks, then restart the cycle 1
• This induces regular withdrawal bleeding every 4 weeks 1

Critical Bone Health Considerations

Why Combined Hormones Are Necessary:

• Progestin-only methods like depot medroxyprogesterone (DMPA) should be avoided as they adversely affect bone mineral density and can compromise adolescent bone mass accrual 1, 4
• Combined estrogen-progestin formulations provide both endometrial protection and bone preservation 1

Bone-Protective Progestin Selection:

• Levonorgestrel is preferred as it is available in combined transdermal formulations 1
• Micronized progesterone (200 mg) or dydrogesterone (5-10 mg) are acceptable alternatives if using transdermal estradiol with separate progestin, though these would require oral or vaginal administration 1
• Avoid progestins with anti-androgenic effects as they may worsen hypoandrogenism and sexual function 1

Important Caveats About Oral Contraceptives

Standard combined oral contraceptives are NOT recommended even if the patient could take them, because:

• Oral estrogens do not consistently improve bone mineral density in amenorrheic or energy-deficient states 1
• They may mask underlying menstrual dysfunction without addressing root causes 1, 4
• The hepatic first-pass effect suppresses IGF-1 production, potentially compromising bone health 1
• They may compromise attainment of peak bone density, particularly in adolescents 1, 4

Monitoring Requirements

• Ensure adequate calcium (1200 mg/day) and vitamin D (400-600 IU/day) supplementation 1
• Consider checking 25-hydroxyvitamin D levels at baseline and during treatment, particularly if there are risk factors for deficiency 1
• Monitor bone mineral density at baseline and every 2 years if there are concerns about bone health 1
• Adjust 17β-estradiol dose (50-100 μg daily range) according to tolerance and symptom control 1

Contraindications to Screen For

Before initiating transdermal combined hormones, exclude:

• History of estrogen-sensitive cancers 2
• Uncontrolled cardiovascular disease or history of venous thromboembolism 2
• Active liver disease 1
• Diffuse cutaneous disorders that would prevent patch adherence 1

Why This Matters With Tirzepatide

• Tirzepatide causes gastrointestinal side effects (nausea, diarrhea, decreased appetite, vomiting) that could impair oral medication absorption 3
• The transdermal route bypasses these concerns entirely 1
• Weight changes associated with tirzepatide may affect bone health independently, making bone-protective hormone therapy even more important 5