Next Step: Measure LH, FSH, and Estradiol
With normal prolactin and thyroid function confirmed (recognizing the low TSH is iatrogenic from levothyroxine suppression therapy with normal free T4), the next critical step is to measure LH, FSH, and estradiol (E2) levels to differentiate between the major causes of amenorrhea. 1
Rationale for This Approach
The 2017 Endocrine Society guideline on functional hypothalamic amenorrhea provides clear direction: after excluding pregnancy and ruling out hyperprolactinemia and thyroid dysfunction, measuring FSH, LH, and E2 is essential to distinguish between functional hypothalamic amenorrhea (FHA), ovarian insufficiency, and other causes 1.
Key Diagnostic Patterns to Identify
The hormone pattern will guide your diagnosis:
Functional Hypothalamic Amenorrhea (FHA): Low or low-normal LH (<10 IU/L), normal FSH (<10 IU/L), LH/FSH ratio ~1, E2 <50 pg/mL, progesterone <1 ng/mL 1
Ovarian Insufficiency/Menopause: Elevated FSH and LH (>15 IU/L), FSH > LH, E2 <50 pg/mL, progesterone <1 ng/mL 1
PCOS: LH <15 IU/L, FSH <10 IU/L, LH > FSH ratio, E2 <50 pg/mL, progesterone <1 ng/mL 1
Organic Hypothalamic Amenorrhea: Very low or undetectable LH and FSH, suggesting pituitary/hypothalamic tumors or infiltrative lesions 1
Additional Testing to Consider
Add AMH (anti-Müllerian hormone) to your panel 1. The guideline specifically recommends AMH as part of the initial endocrine evaluation, as it helps assess ovarian reserve (low <0.5 ng/mL in ovarian insufficiency, normal or elevated in PCOS).
If Clinical Hyperandrogenism Present
Only if there are signs of androgen excess (hirsutism, acne, male pattern alopecia), add:
- Total testosterone
- DHEA-S
- 8 AM 17-hydroxyprogesterone (if suspecting late-onset CAH) 1
Important Caveat About the Low TSH
Your patient's low TSH with normal free T4 is expected and appropriate if she's on levothyroxine for thyroid cancer suppression or other indication requiring TSH suppression 2. This is iatrogenic, not pathologic. The guideline notes that in true FHA, TSH would be in the lower range of normal, not suppressed 1. Don't let the suppressed TSH distract from the amenorrhea workup—the normal free T4 confirms adequate thyroid hormone replacement.
Why This Pattern-Based Approach Matters
The pattern of hormone levels is more critical than absolute values 1. A single hormone abnormality rarely provides the diagnosis. For example, normal LH and FSH can be confusing in FHA since E2 is low, but this combination is characteristic of the condition 1. Very low gonadotropins suggest organic hypothalamic disease requiring brain imaging, while elevated gonadotropins indicate ovarian failure requiring different management entirely.
Clinical Implications Drive Testing
- FHA patients need evaluation for eating disorders, excessive exercise, stress, and bone density assessment 1
- Ovarian insufficiency patients may maintain unpredictable ovarian function and need hormone replacement until average age of menopause
- PCOS patients require metabolic screening for glucose intolerance and dyslipidemia 1
The next laboratory draw should include: LH, FSH, estradiol, and AMH as the core panel 1.