What is the diagnosis and management for a 40-year-old woman with irregular menses, using a levonorgestrel‑releasing intrauterine device (Mirena), who now has elevated follicle‑stimulating hormone and luteinizing hormone, low estradiol and progesterone, and normal thyroid function and prolactin?

Diagnosis: Premature Ovarian Insufficiency (POI)

This 40-year-old woman has premature ovarian insufficiency, confirmed by two elevated FSH measurements (initial high FSH and now 67.8 IU/L) with elevated LH (31.7 IU/L), low estradiol (34.1 pg/mL), and low progesterone (0.1 ng/mL), meeting diagnostic criteria for POI. 1

Diagnostic Confirmation

The laboratory findings definitively establish POI:

• FSH >40 IU/L on two separate occasions (initial measurement and current 67.8 IU/L) confirms the diagnosis, as POI requires two elevated FSH values obtained at least four weeks apart 1
• LH elevation to 31.7 IU/L in the postmenopausal range further supports ovarian failure 1
• Low estradiol of 34.1 pg/mL confirms the hypoestrogenic state characteristic of POI 1
• Normal TSH (2.03), free T4 (0.92), prolactin (11.2), and TPO antibodies (12) appropriately exclude thyroid dysfunction and hyperprolactinemia as alternative causes 1

The Mirena IUD is not causing these findings—while levonorgestrel can suppress ovulation and cause amenorrhea through local endometrial effects, it does not elevate FSH or cause systemic ovarian failure 2, 3.

Immediate Management: Hormone Replacement Therapy

Initiate physiologic estrogen replacement therapy immediately to prevent the devastating long-term complications of prolonged hypoestrogenism 4, 1, 5, 6:

Preferred HRT Regimen

• Transdermal estradiol 100 μg patch applied twice weekly (preferred over oral estrogen for better bone protection and lower thrombotic risk) 1
• Add cyclic micronized progesterone 200 mg daily for 12 days per month since she has an intact uterus (the Mirena provides local progestin but systemic progesterone is needed with systemic estrogen) 1
• Continue HRT until at least age 50-51 years (the natural menopause age) to maintain bone health and reduce cardiovascular risk 4, 1, 6

Critical Rationale for Immediate Treatment

• Without prompt estrogen replacement, she faces decades of estrogen deficiency during the period when peak bone mass should be preserved, markedly increasing osteoporosis risk 1
• The hypoestrogenic state is the primary mechanism driving accelerated bone loss in POI 1
• Women with POI have a 2-fold increased risk of fractures compared to healthy women 1
• One-third of POI patients develop endothelial dysfunction, indicating increased cardiovascular disease risk 1
• The benefit of HRT vastly outweighs minor side effects in this population, unlike older postmenopausal women 5

Bone Health Assessment

Order a DXA scan immediately to establish baseline bone mineral density, as prolonged hypoestrogenism significantly increases osteoporosis risk 1:

• Add calcium and vitamin D supplementation unless contraindicated 1
• Repeat DXA scanning every 1-2 years to monitor response to HRT

Additional Workup Required

Screen for associated conditions that frequently accompany POI 1:

• Fragile X premutation testing (FMR1 gene)—POI is commonly associated with premutation carriers
• Autoimmune antibody panel: 21-hydroxylase antibodies, adrenal cortex antibodies, thyroid antibodies (though TPO already normal)
• Consider karyotype if not previously done to exclude Turner syndrome mosaicism

Fertility Counseling

• POI does not mean absolute infertility—intermittent ovarian function occurs in 5-10% of cases 6
• If she desires future pregnancy, refer to reproductive endocrinology for discussion of oocyte donation or potential spontaneous conception
• The Mirena IUD can remain in place for contraception if she does not desire pregnancy, as spontaneous ovulation remains possible

Common Pitfalls to Avoid

• Do not attribute the amenorrhea solely to the Mirena IUD—the markedly elevated FSH/LH and low estradiol indicate true ovarian failure, not progestin-induced amenorrhea 2
• Do not prescribe combined oral contraceptives instead of physiologic HRT—oral contraceptives provide supraphysiologic doses and do not protect bone density as effectively as transdermal estradiol 1
• Do not delay HRT initiation—every month of untreated hypoestrogenism causes irreversible bone loss during her premenopausal years 1
• Do not stop HRT at an arbitrary age—continue until at least age 50-51 to replace what her ovaries should have been producing 4, 6

Multidisciplinary Referral

Refer to gynecology or reproductive endocrinology for ongoing POI management, as this condition requires specialist expertise 4:

• Coordinate HRT optimization
• Monitor for rare spontaneous ovarian function recovery
• Provide psychological support for the diagnosis
• Discuss fertility preservation options if applicable