How should a woman with premature ovarian insufficiency who has a levonorgestrel‑releasing intrauterine device (Mirena) in place and does not desire pregnancy be treated?

Treatment of Premature Ovarian Insufficiency with Mirena IUD in Place

A woman with premature ovarian insufficiency who has a Mirena IUD in place and does not desire pregnancy should receive systemic estrogen replacement with transdermal 17β-estradiol 50-100 μg daily, while the Mirena IUD remains in place to provide endometrial protection. 1

Core Treatment Strategy

The Mirena (levonorgestrel-releasing IUD) already provides adequate endometrial protection through local progestogen delivery, eliminating the need for additional systemic progesterone therapy. 2 This creates an ideal treatment scenario where:

• Add transdermal 17β-estradiol 50-100 μg daily as the sole additional therapy, which addresses the systemic estrogen deficiency that causes cardiovascular disease, osteoporosis, and premature mortality in POI. 1

• The Mirena IUD serves dual purposes: it provides contraception (though spontaneous pregnancy odds are modest in POI) and delivers continuous local progestogen for endometrial protection without the need for cyclic oral progesterone. 3

• Transdermal estradiol is strongly preferred over oral formulations because it provides physiological serum concentrations and has a superior cardiovascular and metabolic profile compared to oral conjugated estrogens or combined oral contraceptives. 1, 2

Why This Combination is Optimal

The levonorgestrel IUD eliminates the need for systemic progestogen, which simplifies the regimen and avoids potential adverse effects of oral progestogens on cardiovascular risk and breast tissue. 2 This approach is particularly advantageous because:

• Women with POI face significantly increased cardiovascular disease risk due to prolonged estrogen deficiency, and the transdermal estradiol route minimizes additional thrombotic risk. 1, 3

• The local progestogen delivery from Mirena provides adequate endometrial protection without systemic progestogen exposure. 2

• This regimen avoids withdrawal bleeding that would occur with cyclic progesterone, which many young women prefer. 2

Treatment Duration and Monitoring

Continue this combined therapy until at least age 50-51 years (the average age of natural menopause) to control future cardiovascular disease risk and prevent osteoporosis. 1, 3

Annual clinical review should focus on:

• Compliance with transdermal estradiol application 1
• Blood pressure and weight monitoring 1
• Smoking status assessment 1
• Adequacy of estrogen replacement based on symptom control 4

Baseline bone mineral density measurement at diagnosis is recommended, especially if additional risk factors exist, with repeat measurement if symptoms of estrogen deficiency persist despite treatment. 1, 5

Critical Contraindications to Assess

Avoid estrogen replacement entirely if the patient has:

• Personal history of breast cancer 1
• Active venous thromboembolism 1

These are absolute contraindications that override the benefits of hormone replacement therapy. 1

Common Pitfalls to Avoid

Do not use combined oral contraceptives as first-line therapy unless the patient specifically prioritizes highly reliable contraception over optimal cardiovascular protection, as COCs contain ethinyl estradiol rather than physiological 17β-estradiol and carry higher thrombotic risk. 2

Do not add systemic progesterone when the Mirena IUD is already in place, as this provides redundant endometrial protection and unnecessary systemic progestogen exposure. 2

Do not discontinue estrogen replacement at menopause age without reassessing bone density and cardiovascular risk, as some women may benefit from continuation beyond age 51. 4

Ensure the Mirena IUD is replaced every 5-8 years (depending on formulation) to maintain adequate endometrial protection throughout the treatment period. 2