Level: practical · Topic: endocrinology, nutrigenomics, preventive health
In the podcast we described how ancient Egyptians performed a pregnancy test 3,500 years before the discovery of hormones — by having women urinate on wheat and barley seeds. In 1963, American researchers replicated the experiment and found it worked in roughly 70% of cases: oestrogens in the urine of a pregnant woman genuinely stimulate grain germination. That is not magic — it is biochemistry. And it worked long before anyone had a name for it.
This material is a practical navigator through hormonal analysis. Not 'test everything at once,' but a structured approach: which markers to check, when to check them, what deviations mean, and how your genotype affects interpretation.
These five markers are worth testing every six months — regardless of how you feel. Together, they cover the majority of causes behind chronic fatigue, reduced libido, sleep disruption, and mood swings in adults.
Cortisol is the body's primary stress hormone and its primary energy regulator. Levels should be highest in the morning (activation, waking) and taper off toward evening (preparing for sleep). A disruption of this rhythm — so-called 'inverted cortisol' — is characteristic of chronic stress and often precedes burnout by several months.
How to test: Saliva testing at four time points — immediately on waking, at noon, at 16:00, and before sleep. A single blood draw is of limited value: the pattern matters, not one number.
Optimal morning value: 400–600 nmol/L in blood (or the equivalent salivary level per your lab's reference range).
Genetic context: Polymorphisms in the FKBP5 gene affect the sensitivity of glucocorticoid receptors — in other words, how strongly your body 'hears' cortisol. Carriers of certain variants respond more intensely to stress and take longer to return to baseline.
The thyroid gland is the conductor of metabolism. TSH is the brain's signal to the gland: 'work harder' or 'ease off.' A high TSH means the gland is underperforming and the brain is calling for greater effort — a sign of hypothyroidism. A low TSH signals overactivity.
Subclinical hypothyroidism — TSH within the 'normal' range but toward the upper end (2.5–4.5 mIU/L) — affects 10–15% of adult women and frequently goes undetected. Symptoms including fatigue, puffiness, hair loss, and difficulty concentrating are attributed to stress or ageing.
Optimal range: 0.5–2.0 mIU/L for an active adult (not to be confused with the laboratory 'normal range,' which is often stated as 0.4–4.0).
Additional testing: If TSH is abnormal, add free T4 and anti-TPO antibodies to rule out autoimmune thyroiditis (Hashimoto's disease).
Ferritin is the body's iron storage protein. Do not confuse it with haemoglobin: it is possible to have normal haemoglobin while iron stores are depleted. This is called latent iron deficiency, and it manifests as fatigue, reduced endurance, and impaired cognitive function well before anaemia develops.
Lab 'normal' vs. optimum: Many laboratories mark ferritin normal from 12–15 µg/L. For an active person, the functional optimum is no lower than 50–70 µg/L. Below 30 µg/L, symptoms of fatigue are statistically significantly more frequent.
Genetic context: Polymorphisms in the HFE gene — particularly the C282Y variant — are associated with hereditary haemochromatosis, a condition in which the body accumulates excess iron. If unexplained liver disease appears in your family history, HFE testing is warranted.
Vitamin D is more accurately described as a hormone: it is synthesised in the skin under UV radiation and acts through nuclear receptors. Its deficiency is associated with immune dysfunction, depressive states, reduced muscle strength, and — in older adults — elevated fracture risk.
Large European studies find that vitamin D deficiency (below 50 nmol/L) affects 40–60% of adults in temperate latitudes during winter months.
Optimal level: 75–150 nmol/L (30–60 ng/mL). Values above 250 nmol/L enter the zone of potential toxicity — more is not always better.
Genetic context: The VDR gene encodes the vitamin D receptor. Its variants determine how effectively your cells 'hear' this hormone. With certain VDR polymorphisms, a person needs to maintain higher blood levels to achieve the same cellular effect.
Testosterone is not only a 'male' hormone. It plays a critical role in energy, libido, muscle mass, and cognitive sharpness in people of all sexes. Total testosterone often remains within the normal range while free testosterone — the biologically active fraction, unbound to proteins — is low. This is why both forms are worth testing.
In men: Free testosterone below 225 pmol/L produces symptoms commonly attributed to 'ageing' — fatigue, reduced motivation, erectile difficulties, and increased body fat.
In women: Testosterone deficiency (normal total range approximately 0.5–2.4 nmol/L) presents as reduced libido, chronic fatigue, and difficulty building muscle mass, especially after 35.
Additional testing: Test SHBG (sex hormone-binding globulin) simultaneously — it is needed to calculate free testosterone and reveals whether your testosterone is being bound and rendered unavailable to cells.
If you are not sure where to start, find your experience in the left column.
One of the most common sources of confusion when reading blood tests is the difference between a laboratory 'reference range' and the functional optimum for a specific person.
A reference range is a statistical construct: values found in 95% of the sample population tested by that laboratory. That sample includes people with subclinical conditions, elderly individuals, and people across a wide range of lifestyles. It does not represent 'a healthy, active adult.'
A practical rule: if you have symptoms — even with 'normal' results — discuss a functional interpretation with your doctor, not just a comparison to the reference range.
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In the Premium material we examine the mechanics of the hypothalamic–pituitary–gonadal (HPG) axis: how stress blocks libido at the molecular level, why antidepressants can lower testosterone, and what 'stress-induced functional hypogonadism' is — a condition most clinicians miss.
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