In a postmenopausal woman with elevated estradiol, suppressed follicle‑stimulating hormone (FSH) and luteinizing hormone (LH), and low thyroid‑stimulating hormone (TSH) with normal free thyroxine (free T4), what is the likely cause and recommended work‑up?

Elevated Estradiol with Suppressed Gonadotropins in a Postmenopausal Woman

This hormone pattern—elevated estradiol with suppressed FSH, LH, and TSH—is inconsistent with true menopause and suggests either an exogenous estrogen source, an estrogen-secreting tumor, or misclassification of menopausal status; the priority is to identify the estrogen source and evaluate for thyroid pathology.

Understanding the Paradoxical Pattern

This presentation contradicts the expected postmenopausal hormone profile, where FSH should be >35 IU/L, LH >11 IU/L, and estradiol consistently low 1. The elevated estradiol is actively suppressing gonadotropins through negative feedback, indicating ongoing significant estrogen exposure 2.

Key Diagnostic Considerations

Exogenous Estrogen Exposure:

• Systematically review all medications, supplements, and topical preparations for estrogen-containing compounds 3
• Ask specifically about hormone replacement therapy, compounded bioidentical hormones, and over-the-counter products 3
• Estrogen from any source will suppress FSH and LH through hypothalamic-pituitary feedback 2

Estrogen-Producing Pathology:

• An ovarian tumor (granulosa cell tumor, thecoma) can autonomously secrete estradiol and must be excluded 4
• Obtain pelvic ultrasound to evaluate ovarian morphology and identify masses 2
• Some postmenopausal ovaries retain residual estrogen-secreting capacity, though this typically produces only modest elevations 5

Thyroid Dysfunction:

• The low TSH with normal free T4 suggests either subclinical hyperthyroidism or central hypothyroidism 1
• Measure TSH receptor antibodies and consider pituitary imaging if central hypothyroidism is suspected 1
• Thyroid disease can mimic menopausal symptoms and must be definitively excluded 1

Recommended Work-Up Algorithm

Immediate Steps:

1. Medication and exposure history:

   • Document all prescription medications, supplements, creams, and patches 3
   • Discontinue any potential estrogen sources and retest in 4-6 weeks

2. Pelvic imaging:

   • Transvaginal ultrasound to evaluate ovarian size, morphology, and masses 2
   • If ovarian mass identified, obtain tumor markers (inhibin, CA-125) and gynecologic oncology referral

3. Thyroid evaluation:

   • Complete thyroid panel including TSH receptor antibodies 1
   • If central hypothyroidism suspected, obtain morning cortisol and consider pituitary MRI 6

4. Serial hormone measurements:

   • Repeat FSH, LH, and estradiol in early morning, ideally three times at 20-minute intervals and average the results 1
   • Single measurements are unreliable; serial testing over weeks is required for accurate classification 1, 7

Critical Pitfalls to Avoid

Do not assume menopausal status based on age alone. Even women ≥60 years can have this pattern if exposed to exogenous estrogen or harboring estrogen-secreting tumors 7.

Do not overlook perimenopause misclassification. During the menopausal transition, transient episodes of elevated estradiol with high gonadotropins can occur, though this pattern (suppressed gonadotropins) is more concerning 8. True perimenopause shows fluctuating but generally elevated FSH, not suppressed FSH 8, 9.

Do not ignore the thyroid abnormality. The combination of low TSH with normal free T4 requires explanation independent of the reproductive hormone findings 1.

Special Circumstances

If the patient has a history of breast cancer or is on tamoxifen/toremifene, FSH results are unreliable and alternative assessment strategies are needed 1, 7. However, elevated estradiol in this context would be particularly concerning and warrants immediate oncology consultation 2.

If chemotherapy-induced amenorrhea occurred, ovarian function may recover over time, but this would typically show rising (not suppressed) gonadotropins as ovarian function wanes 2.

Referral Indications

• Gynecologic oncology: Any ovarian mass or persistently elevated estradiol without identified source 2
• Endocrinology: Confirmed pituitary dysfunction or complex thyroid abnormalities 2, 6
• Reproductive endocrinology: If fertility preservation or definitive menopausal status determination is needed 2