In a man receiving testosterone replacement therapy, what does an LH level of 3 mIU/mL indicate?

LH of 3 mIU/mL in a Man on Testosterone Replacement Therapy

An LH level of 3 mIU/mL in a man receiving testosterone replacement therapy indicates inadequate suppression of the hypothalamic-pituitary-gonadal axis, suggesting either suboptimal testosterone dosing, poor medication adherence, or potentially incorrect diagnosis of hypogonadism.

Understanding Normal LH Suppression on TRT

Expected suppression pattern:

• During testosterone therapy, exogenous androgens inhibit pituitary LH secretion through negative feedback, typically suppressing LH to <1.0 IU/mL in most men 1, 2
• Approximately 73% of men on testosterone therapy will achieve LH <1.0 IU/mL at some point during treatment, though only 22% maintain complete suppression throughout 2
• An LH of 3 mIU/mL falls within the low-normal range for untreated men (normal range 0.9-7.0 IU/mL morning) 3, indicating the axis is not adequately suppressed 1

Clinical Interpretation Algorithm

Step 1: Verify Medication Adherence

• First action: confirm the patient is actually taking testosterone as prescribed 1
• Non-adherence is common and will result in persistently elevated LH despite a prescription for TRT 1

Step 2: Measure Serum Testosterone Level

• Obtain morning total testosterone (8-10 AM) to assess whether therapeutic levels are being achieved 1
• For injectable testosterone, measure midway between injections (days 5-7 for weekly dosing) targeting 500-600 ng/dL 1, 4
• For transdermal preparations, measure any time after 2-3 months of stable therapy 1

Step 3: Interpret Combined LH and Testosterone Results

If testosterone is subtherapeutic (<350 ng/dL) with LH 3 mIU/mL:

• This pattern indicates inadequate dosing—the pituitary is attempting to compensate for low testosterone by maintaining LH secretion 5, 6
• Action: increase testosterone dose and recheck levels in 2-3 months 1

If testosterone is therapeutic (450-600 ng/dL) with LH 3 mIU/mL:

• This unusual pattern suggests either:
  • Laboratory error (repeat both tests) 1
  • Timing issue (testosterone measured at peak rather than steady-state) 1
  • Possible misdiagnosis—the patient may not have had true hypogonadism initially 1, 3

If testosterone is supraphysiologic (>900 ng/dL) with LH 3 mIU/mL:

• This pattern is physiologically implausible and indicates laboratory error 5, 6
• Exogenous testosterone at supraphysiologic levels invariably suppresses LH to <1.0 IU/mL 2, 5

Predictors of Incomplete LH Suppression

Factors associated with higher LH levels during TRT:

• Lower baseline LH before treatment paradoxically predicts better suppression (OR 0.94 per IU/mL increase) 2
• Transdermal testosterone produces less complete LH suppression than intramuscular injections (OR 2.44 for IM route achieving suppression) 2
• Lower estradiol levels during treatment—estrogen receptor signaling contributes significantly to negative feedback (r = -0.39 between LH decline and estradiol) 6
• Younger age—older men show greater LH suppression at equivalent testosterone levels (r = -0.46 between age and LH suppression) 6

Reassessing the Original Diagnosis

Critical consideration: Up to 25-30% of men receiving testosterone therapy do not meet diagnostic criteria for hypogonadism 1, 3

Diagnostic requirements that should have been met before starting TRT:

• Two separate morning testosterone measurements <300 ng/dL (not a single value) 1
• Specific qualifying symptoms: diminished libido or erectile dysfunction (not fatigue, low energy, or mood complaints) 1
• Measurement of LH and FSH to confirm secondary hypogonadism if that was the diagnosis 1

If the patient's pre-treatment LH was already in the normal range (>2 IU/mL):

• This suggests primary hypogonadism (testicular failure) rather than secondary hypogonadism 1, 5
• In primary hypogonadism, baseline LH is typically elevated (>7 IU/mL) due to lack of testicular feedback 1
• An LH of 3 mIU/mL before treatment would be inappropriately normal for someone with true testosterone deficiency, raising the possibility of functional or obesity-related hypogonadism 1

Recommended Management Steps

Immediate Actions:

1. Confirm medication adherence through patient interview and pharmacy records 1
2. Measure morning total testosterone (8-10 AM, fasting) 1
3. Repeat LH measurement to exclude laboratory error 1
4. Review original diagnostic workup—were two morning testosterone values <300 ng/dL documented? 1

Based on Results:

If testosterone is low (<350 ng/dL):

• Increase testosterone dose by 25-50% 1, 4
• Recheck testosterone and LH in 2-3 months 1
• Expected outcome: testosterone normalizes and LH suppresses to <1.0 IU/mL 2, 5

If testosterone is therapeutic (450-600 ng/dL):

• Discontinue testosterone therapy temporarily (2-4 week washout) 1
• Repeat diagnostic workup with two morning testosterone measurements and LH/FSH 1
• If repeat testing shows testosterone >300 ng/dL, the patient does not have hypogonadism and TRT should be permanently discontinued 1

If testosterone is high (>700 ng/dL):

• Reduce dose by 25-50% to target mid-normal range (500-600 ng/dL) 1, 4
• This minimizes erythrocytosis risk while maintaining efficacy 4, 7

Common Pitfalls to Avoid

• Do not ignore an unsuppressed LH on TRT—it always indicates either inadequate dosing, non-adherence, or incorrect diagnosis 2, 5
• Do not assume the original diagnosis was correct—approximately 25% of men on TRT never met diagnostic criteria 1, 3
• Do not measure testosterone at the wrong time—peak levels (days 2-5 post-injection) will be misleadingly high 1
• Do not continue therapy indefinitely without reassessing the diagnosis if LH remains elevated despite adequate testosterone levels 1