Genes Associated with Hormone Balance.

Hormones are made, activated, used, and cleared. Genes affect every step. Understanding your genetics helps you support the whole system.

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Beyond hormone levels.

Hormone imbalances aren't just about production—they're about metabolism, clearance, and receptor sensitivity. Two people with identical hormone levels can have completely different symptoms based on how they process those hormones.

The genes.

Hormone genes cluster into estrogen metabolism, thyroid function, stress response, androgens, and fertility.

Estrogen Metabolism

How estrogen is made, used, and cleared determines balance. These genes affect the entire lifecycle.

CYP19A1 (Aromatase)

Cytochrome P450 19A1

Converts testosterone to estrogen

Variant: Variants affect estrogen production levels

Body fat produces aromatase—more fat, more estrogen conversion

CYP1A1

Cytochrome P450 1A1

Phase I estrogen metabolism (2-hydroxylation pathway)

Variant: Affects which estrogen metabolites are produced

2-OH pathway is considered 'safer' than 4-OH

CYP1B1

Cytochrome P450 1B1

Phase I estrogen metabolism (4-hydroxylation pathway)

Variant: Leu432Val affects enzyme activity

4-OH metabolites can damage DNA if not properly cleared

COMT

Catechol-O-Methyltransferase

Methylates and deactivates estrogen metabolites

Variant: Val158Met (fast/slow variants)

Slow COMT = slower estrogen clearance; needs methylation support

SULT1A1

Sulfotransferase 1A1

Sulfates estrogens for excretion

Variant: Affects Phase II estrogen clearance

Part of the Phase II detox system for hormones

Thyroid Function

Thyroid hormones control metabolism. These genes affect production, conversion, and sensitivity.

DIO1/DIO2

Deiodinase 1 and 2

Convert T4 (inactive) to T3 (active thyroid hormone)

Variant: DIO2 Thr92Ala may reduce T4-to-T3 conversion

Some people convert T4 poorly—may benefit from T3

TSHR

Thyroid Stimulating Hormone Receptor

Receives TSH signal in the thyroid

Variant: Variants affect thyroid sensitivity to TSH

Explains some TSH-symptom disconnects

TPO

Thyroid Peroxidase

Essential enzyme for thyroid hormone synthesis

Variant: Target of TPO antibodies in Hashimoto's

Autoimmune thyroid disease is the most common cause of hypothyroidism

MCT8 (SLC16A2)

Monocarboxylate Transporter 8

Transports thyroid hormone into cells

Variant: Rare mutations cause severe neurological issues

Thyroid hormone must get INTO cells to work

Adrenal & Stress Hormones

Cortisol and DHEA affect energy, immunity, and resilience. These genes affect the stress response.

CYP17A1

Cytochrome P450 17A1

Key enzyme in cortisol and androgen synthesis

Variant: Affects DHEA and androgen production

Determines the balance between cortisol and DHEA

HSD11B1

11-Beta Hydroxysteroid Dehydrogenase 1

Reactivates cortisol in tissues

Variant: Higher activity = more tissue cortisol

Active in fat tissue—links stress and visceral fat

NR3C1

Glucocorticoid Receptor

Receives cortisol signal in cells

Variant: BclI and ER22/23EK affect cortisol sensitivity

Some people are more sensitive to cortisol's effects

FKBP5

FK506 Binding Protein 5

Regulates glucocorticoid receptor sensitivity

Variant: Risk variants affect HPA axis feedback

Associated with PTSD, depression, and stress resilience

Androgen Metabolism

Testosterone and DHT affect muscle, mood, and more in both sexes.

SRD5A2

5-Alpha Reductase Type 2

Converts testosterone to DHT

Variant: Affects DHT production and sensitivity

Target of finasteride for hair loss and prostate

AR

Androgen Receptor

Receives testosterone and DHT signals

Variant: CAG repeat length affects sensitivity

Shorter repeats = more sensitive to androgens

CYP11B1

Cytochrome P450 11B1

Final step in cortisol synthesis

Variant: Affects cortisol/androgen balance

Part of the adrenal steroidogenesis pathway

SHBG

Sex Hormone Binding Globulin

Binds and transports sex hormones in blood

Variant: Variants affect free vs. bound hormone levels

Low SHBG = more free (active) testosterone and estrogen

Progesterone & Fertility

Progesterone balances estrogen and supports pregnancy.

PGR

Progesterone Receptor

Receives progesterone signal

Variant: PROGINS variant affects receptor function

Affects progesterone sensitivity in target tissues

CYP21A2

Cytochrome P450 21A2

Key enzyme in cortisol and aldosterone synthesis

Variant: Mutations cause congenital adrenal hyperplasia

Can affect fertility and androgen levels

MTHFR

Methylenetetrahydrofolate Reductase

Methylation affects hormone clearance

Variant: C677T and A1298C reduce function

Impaired methylation = slower hormone metabolism

Estrogen isn't one thing.

Estrogen metabolism produces different metabolites. Which ones you make—and how you clear them—matters more than total estrogen levels.

The three pathways:

✓2-OH pathway (CYP1A1): Generally protective. Produces 'good' metabolites.
⚠4-OH pathway (CYP1B1): Can produce DNA-damaging quinones if not properly methylated.
⚠16-OH pathway: Highly estrogenic metabolites. Can promote growth.

Key insight: COMT methylates these metabolites to make them safe. Slow COMT + 4-OH pathway = higher need for methylation support.

The reframe.

The incomplete view

✗Hormone problems are just genetic
✗You need HRT to fix hormone imbalances
✗Testing hormones once tells you everything
✗Genes determine your hormone levels

The systems view

✓Genes affect metabolism, not just production
✓Lifestyle profoundly affects hormone balance
✓Hormone levels fluctuate—context matters
✓The same genes can produce different outcomes based on environment

What actually matters.

These factors profoundly influence hormone balance—often more than genetics alone.

Liver function

The liver metabolizes hormones. Poor liver function = hormone accumulation. Support Phase I, II, and III detox.

Gut health

The gut microbiome (estrobolome) affects estrogen recirculation. Dysbiosis can cause estrogen dominance even with normal production.

Body composition

Fat tissue produces estrogen via aromatase. More body fat = higher estrogen, lower testosterone in men.

Sleep quality

Growth hormone, testosterone, and cortisol follow circadian patterns. Poor sleep disrupts the entire hormonal cascade.

Stress management

Chronic stress steals pregnenolone from sex hormone production ('pregnenolone steal'). Cortisol takes priority.

Nutrient status

Zinc, magnesium, B vitamins, and vitamin D are essential cofactors for hormone synthesis and metabolism.

Why thyroid affects everything.

Thyroid hormone is the master metabolic regulator. When it's off, other hormones follow.

Estrogen and thyroid

Estrogen increases thyroid-binding globulin, reducing free (active) T3 and T4. Birth control and pregnancy can trigger hypothyroid symptoms.

Cortisol and thyroid

High cortisol inhibits TSH and T4-to-T3 conversion. Chronic stress causes 'low T3 syndrome' even with normal TSH.

Progesterone and thyroid

Thyroid hormone is needed for progesterone synthesis. Low thyroid often means low progesterone—and menstrual issues.