Precision Protocols for Hormones: Testing Methods, Case Strategy, and Clinical Pitfalls

The fourth episode of the Precision Protocol Series from Biocanic, hosted by Jeremy Malecha with co-host Brendan Vermeire of Metabolic Solutions, brought a clear, clinically grounded look at hormone testing. Host Jeremy Malecha and co-host Brendan Vermeire unpacked how to choose the right test for the question at hand, why timing and methodology matter, and how to translate hormone data into practical protocols that move outcomes.

This discussion focused on the intersection of blood, urine, and saliva testing, the importance of circadian biology for cortisol, and the role of thyroid and metabolism in shaping hormone expression. It also explored how to layer lifestyle, nutraceuticals, and hormone replacement therapy in a way that is both trackable and sustainable.

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Why Hormones Still Matter Most for How Clients Feel

Hormones drive cognition, mood, energy, motivation, recovery, and metabolic capacity. For many clinical presentations in mental health and metabolism, restoring healthy hormone signaling can move the needle faster than any other lever. The challenge is selecting the right testing method, aligning it to the clinical question, and tracking with consistency over time.

Blood, Saliva, and Urine: What Each Method Does Best

Serum blood testing

Best for absolute concentrations, especially for monitoring hormone replacement therapy.
Allows assessment of SHBG and albumin, which helps contextualize free versus bound hormones.
Practical and cost effective for routine markers like AM cortisol, DHEA, testosterone, estradiol, progesterone, and thyroid panels.

Saliva testing

Best for diurnal cortisol mapping and the cortisol awakening response, which reflects circadian biology and stress system engagement.
Recommended for four to six point mapping to assess daily rhythm, behavior, and intervention efficacy.

Urine testing

Best for hormone metabolism and downstream pathways, including estrogen hydroxylation and methylation and androgen conversion patterns.
Offers a functional read on tissue level processing and clearance that serum alone cannot detect.
Full 24-hour collections remain the gold standard for some panels, while dried urine methods offer convenience with growing validation.

In practice, serum provides the absolute number, saliva provides the rhythm, and urine provides the map of metabolism. When budgets allow, pairing blood and urine on the same day gives a superior picture.

The Timing Problem: Context Drives Interpretation

For women, cycle timing determines whether results are useful or confusing. Without knowing where a patient is in their cycle, estradiol, progesterone, and LH/FSH data are difficult to interpret. When possible:

Use luteal window collections for standard blood panels, typically days 19 to 21 in a 28 day cycle.
Use cycle mapping if cycles are irregular or perimenopausal patterns are suspected.
Encourage menstrual tracking through an app to align labs and symptoms.

For men, diurnal timing still matters for cortisol and testosterone. Collect AM fasting serum and align saliva cortisol collections with consistent wake times.

Free vs Total Testosterone, SHBG, and Direct vs Calculated Methods

For many cases, the clinical question is how much bioavailable testosterone is actually getting into tissues. Consider:

Measuring SHBG and albumin alongside total testosterone to contextualize free fractions.
Favoring direct free testosterone using the most sensitive technology available when possible. Liquid chromatography with mass spectrometry is preferred although not always practical due to cost.
Using calculated free testosterone formulas when direct methods are not available, while noting the limitations introduced by SHBG variability, albumin, hydration status, and inflammatory conditions.

What Urine Metabolites Reveal That Serum Cannot

Urine metabolite testing can clarify:

Estrogen pathways including 2, 4, and 16 hydroxy conversions and 2 and 4 methoxy metabolites.
Trends toward quinone formation and DNA reactivity that indicate a need for Phase 1 and Phase 2 support.
Androgen metabolism and five alpha reductase activity that explains patterns like oily skin, hair changes, and androgenic symptoms despite normal serum values.
Progesterone estimated via pregnanediol isomers, providing context for luteal function.

Use urine when the clinical question involves metabolism, detoxification, adverse reactions to HRT, or persistent symptoms that do not match serum values.

Cortisol, Circadian Biology, and the Impact of Light

Cortisol is not just a stress hormone. It is the get-work-done hormone that surges after waking to drive focus, output, and energy. The pattern matters:

Healthy rhythm includes a strong cortisol awakening response in the first 60 to 90 minutes, followed by a gradual decline toward bedtime.
Blunted or delayed patterns correlate with fatigue, apathy, cognitive slowdown, and sleep disturbance.
Blue light at night disrupts melatonin and elevates nighttime cortisol. Standardize light hygiene, especially for patients with poor sleep and flat cortisol curves.
Shift workers commonly show misaligned cortisol rhythms that match their schedule rather than the light cycle. Behavioral cues and light strategies can help realign.

Serum AM cortisol is cost effective for a snapshot. Saliva is better for mapping rhythms and confirming clinical suspicion.

Case Strategy: Foundations First, Then Modulate

Common strategy across use cases:

Establish foundations before therapy. Protein-rich, nutrient dense diet, resistance training, sleep hygiene, stress reduction, and light management are prerequisites for effective HRT. An inflamed, oxidized terrain will often aromatize and mis-metabolize exogenous hormones.
When needed, layer targeted nutraceuticals to support mineral cofactors, methylation capacity, estrogen metabolism, and five alpha modulation.
If using HRT, monitor through consistent methodology. Many patients benefit from small, adjustable dosing via non-pellet delivery with close tracking and symptom correlation.

For men with low free testosterone and high SHBG, investigate inflammation, liver function, and metabolic contributors. For women with irregular cycles, consider cycle mapping to time interventions. For PCOS or cortisol dysregulation, expect sex hormone suppression or relative estrogen dominance until circadian and inflammatory drivers are addressed.

Thyroid Integration is Non-Negotiable

Thyroid status changes the entire hormonal landscape. Assess a full thyroid panel rather than TSH alone:

TSH, free and total T4, free and total T3, reverse T3, and antibodies when indicated.
Low thyroid function will blunt metabolism, reduce hormone potency, slow clearance, and mimic low sex hormone symptoms.
For many patients, small adjustments in T3, alongside progesterone support, can meaningfully improve outcomes.

Test Design, Frequency, and Consistency

Baseline: comprehensive serum panel with sex hormones, SHBG, DHEA, thyroid panel, AM cortisol. Add urine metabolite mapping when metabolism, detox, or adverse reaction questions are on the table.
Frequency: retest 8 to 12 weeks after major interventions or HRT adjustments. Maintain the same modality and timing to track trend lines.
Consistency: collect blood and urine on the same day when possible. Align saliva collections to consistent wake times. Document cycle timing.

What to Avoid

Overreliance on a single specimen type for complex cases. Pair absolute values with metabolism data when symptoms and labs are not aligned.
Running tests without cycle timing or clear cortisol collection windows. Context determines interpretability.
Chasing numbers without addressing terrain. Inflammation, circadian disruption, and poor recovery undermine protocols and HRT efficacy.
Switching methodologies during monitoring. Keep the same test type, lab, and timing for accurate comparisons.

The Future of Hormone Testing

The field is moving toward higher frequency, higher fidelity monitoring. Real-time or near real-time hormone tracking integrated with adjustable micro-dosing would allow true precision care. Until then, the strongest model uses:

Absolute values from blood
Rhythms from saliva
Metabolic mapping from urine
Consistent timing and methodology across retests

Key Takeaways

Match the test to the question. Serum for absolute values, saliva for rhythm, urine for metabolism.
Timing matters. Align to cycle phase and waking schedule for reliable interpretation.
Treat the terrain before escalating therapy. Sleep, light, nutrition, movement, and stress inputs determine hormone utilization.
Integrate thyroid. Optimize thyroid status to unlock hormone effects downstream.
Monitor with consistency. Use the same modality and timing when tracking changes.
Use HRT intelligently. Start with foundations, use the minimum effective dose, and monitor closely.

This was only a fraction of the insight shared in the Precision Protocol Series episode with Brendan Vermeire. In the full conversation, we dive deeper into hormone testing, which tests are worth your time with clients, the truth behind the results and how to use these tests effectively within your practice.

📅 RSVP for upcoming episodes and catch the replays on YouTube.

Watch the Full Interview

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