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How SHBG and the rs6259 Variant Affect Testosterone and Your Health

Sex hormone binding globulin or SHBG is a protein made by the liver that binds testosterone and other sex hormones in the blood. The amount of SHBG determines how much testosterone is bound and how much is free and active. The rs6259 variant in the SHBG gene influences SHBG levels. Different genotypes at rs6259 are linked to higher or typical SHBG, which can change free testosterone availability and influence energy, mood, libido, body composition, and metabolic health.

Why free testosterone matters

Total testosterone measures all testosterone in the blood. Free testosterone is the small portion that is not bound to SHBG and can enter tissues to exert effects. Two people with the same total testosterone can have different free testosterone if SHBG levels differ. Symptoms such as low energy, reduced libido, decreased muscle mass, difficulty building strength, or mood changes can be related to low free testosterone even when total testosterone looks normal.

What to watch for

  • Low energy, persistent fatigue, or decreased motivation
  • Reduced sexual desire or erectile changes in men
  • Loss of muscle mass or difficulty gaining strength
  • Mood changes such as increased low mood or irritability
  • In women, less androgen excess symptoms like acne or unwanted hair may occur with higher SHBG

Genetic interpretation for rs6259

2 effect alleles (AA) — highest SHBG, lowest free testosterone

The AA genotype is associated with the highest SHBG levels. More testosterone will be bound in the blood and less will be free and active. This may protect against androgen excess symptoms like acne or hirsutism. However, it can also contribute to symptoms related to low free testosterone such as low libido, low energy, reduced muscle mass, and mood changes. Because total testosterone may appear normal, consider testing both total and free testosterone if you notice symptoms.

Considerations

  • Request both total and free testosterone tests when discussing symptoms with your provider
  • Focus on lifestyle supports that help maintain healthy free testosterone
  • Monitor symptoms over time and recheck labs as directed by your clinician
1 effect allele (AG) — intermediate SHBG, reduced free testosterone relative to typical

The AG genotype is linked to intermediate SHBG levels. You may have somewhat less free testosterone compared to typical levels. This can contribute to milder forms of the same symptoms seen with the AA genotype, including fatigue, lower libido, and modest reductions in muscle mass. In women, modestly higher SHBG can reduce androgen excess symptoms but may affect energy or mood if free testosterone is low.

Considerations

  • Test both total and free testosterone if symptoms arise
  • Support hormone balance with targeted lifestyle strategies
  • Talk with your clinician about whether further evaluation is needed
0 effect alleles (GG) — typical SHBG, normal free testosterone availability

The GG genotype is associated with typical SHBG levels. You are likely to have a normal proportion of testosterone circulating in its unbound, active form. That supports standard energy, mood, muscle mass, and metabolic function. Maintain healthy habits to preserve optimal hormone balance.

Considerations

  • Routine monitoring only as clinically indicated
  • Maintain lifestyle habits that support healthy hormone levels
  • See your healthcare provider if you develop symptoms

Practical steps to support healthy free testosterone

Diet and nutrition

  • Prioritize adequate protein intake to support muscle mass and hormone production. Aim for a protein source at each meal.
  • Include healthy fats such as olive oil, avocados, nuts, seeds, and fatty fish to support steroid hormone synthesis.
  • Keep carbohydrate intake balanced around activity to support training and recovery. Whole grains, legumes, and vegetables are good choices.
  • Maintain a nutrient-dense diet including zinc rich foods like oysters, beef, pumpkin seeds and selenium sources such as Brazil nuts, which support reproductive hormones.
  • Avoid highly processed foods and excessive alcohol, both of which can negatively affect hormones and liver function.

Supplements to consider discussing with your provider

  • Vitamin D if levels are low. Low vitamin D has been linked to lower testosterone in some people.
  • Zinc when dietary intake is insufficient. Zinc plays a role in testosterone production.
  • Magnesium for sleep and recovery support which can indirectly benefit hormone balance.
  • Omega 3 fatty acids for overall metabolic and inflammatory support.
  • Only start supplements after checking labs and discussing safety and dosing with your healthcare provider.

Exercise and body composition

  • Resistance training 2 to 4 times per week helps preserve or increase muscle mass and can support testosterone function.
  • Include compound movements like squats, deadlifts, presses and rows for maximal hormonal and strength benefits.
  • Moderate intensity aerobic activity supports metabolic health. Avoid chronic excessive endurance training without adequate recovery as that can lower testosterone.
  • Maintain a healthy body composition. Both excess body fat and very low body fat can negatively affect hormones.

Sleep and stress management

  • Aim for consistent sleep of 7 to 9 hours per night. Poor sleep lowers testosterone and increases SHBG in some people.
  • Practice stress reduction techniques such as mindfulness, breathing exercises or short walks to reduce chronic cortisol elevation which can disrupt hormones.

Limit exposure to hormone-disrupting chemicals

  • Reduce use of plastics for food storage especially when heating. Prefer glass or stainless steel.
  • Choose personal care products and cleaning items with fewer synthetic fragrances and known endocrine disruptors.
  • Avoid unnecessary exposure to known pesticide residues by washing produce and choosing organic where feasible.

Testing and monitoring

If you experience symptoms suggestive of low free testosterone, discuss testing with your healthcare provider. Useful tests may include total testosterone, free testosterone or calculated free testosterone, SHBG, luteinizing hormone, prolactin, thyroid tests, vitamin D, and basic metabolic panels. Results should be interpreted in the context of symptoms, health history, and other lab values.

Final notes and disclaimer

PlexusDx provides educational information about genetic predispositions. This content is not medical advice. Always consult your healthcare provider before making medical decisions, starting new supplements, or changing your treatment plan.