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How SHBG Genotype Affects Testosterone and What It Means for Your Health

Sex Hormone Binding Globulin or SHBG is a protein that controls how much testosterone circulates in its active, free form. Genetic differences in the SHBG gene change typical SHBG levels, which in turn change the proportion of free, bioactive testosterone available to tissues. Because free testosterone influences energy, mood, sex drive, muscle mass, and metabolic health, knowing your SHBG genotype can help you interpret symptoms and tailor lifestyle choices.

How SHBG Changes Testosterone Availability

SHBG binds testosterone in the blood. When SHBG is high, more testosterone is bound and less is free to act on tissues. When SHBG is low, a greater proportion of testosterone is unbound and active. Men with higher SHBG may feel symptoms of low testosterone even if total testosterone tests as normal. For women, higher SHBG generally protects against excess androgens but very high SHBG may contribute to low energy or libido.

Two effect alleles (TT) — Highest SHBG, lowest free testosterone

Your TT genotype for rs727428 is associated with the highest typical SHBG levels. That translates to the lowest proportion of free, bioactive testosterone in circulation. SHBG binds testosterone in the bloodstream, reducing the amount available in its active form.

What you may notice

  • Men: Possible reduced libido, fatigue, lower mood, difficulty building or maintaining muscle, and symptoms that look like low testosterone even if total testosterone appears normal.
  • Women: Often protected from androgen excess, but very high SHBG can contribute to low energy, low libido, or reduced sexual satisfaction.

Practical steps to consider

  • Ask your healthcare provider to measure free testosterone in addition to total testosterone and SHBG to get a full picture.
  • Focus on a nutrient-rich, higher protein diet to support hormone balance.
  • Limit alcohol and reduce intake of simple sugars and refined carbohydrates.
  • Avoid exposure to hormone-disrupting chemicals where possible, including certain plastics and personal care products.
  • Prioritize regular resistance exercise to support muscle mass and healthy hormone signaling.
  • Discuss targeted blood tests and personalized care with your healthcare provider if symptoms persist.
One effect allele (CT) — Intermediate SHBG, moderately reduced free testosterone

Your CT genotype for rs727428 is associated with intermediate SHBG levels. This typically means moderately lower free testosterone than people without the effect allele. SHBG still binds testosterone, so bioavailable testosterone may be lower than in CC individuals.

What you may notice

  • Men: Possible mild reductions in energy, libido, or strength, sometimes despite normal total testosterone levels.
  • Women: Often protective against androgen excess and usually balanced hormone activity.

Practical steps to consider

  • Measure free testosterone and SHBG if you have symptoms like low energy or low libido.
  • Emphasize adequate protein at each meal and ensure overall nutrient adequacy, especially vitamin D and zinc which support hormone health.
  • Limit binge alcohol use and high sugar intake which can raise SHBG or worsen symptoms.
  • Include regular resistance training and maintain a healthy body composition.
No effect alleles (CC) — Lowest SHBG, highest free testosterone

Your CC genotype for rs727428 is associated with lower typical SHBG levels and therefore a higher proportion of free or bioactive testosterone. Less testosterone is bound, leaving more available to tissues. This is the most common pattern for testosterone bioavailability.

What you may notice

  • Men: Greater baseline free testosterone which supports energy, libido, muscle mass, and recovery.
  • Women: Higher free testosterone can be normal, but if accompanied by symptoms of androgen excess it should be evaluated.

Practical steps to consider

  • Maintain balanced lifestyle habits that support healthy hormone regulation.
  • Continue resistance training and consume adequate protein to maintain muscle and metabolic health.
  • Minimize exposure to hormone-disrupting chemicals and limit excessive alcohol.
  • Monitor symptoms and discuss hormone testing with your healthcare provider if concerns arise.

Diet and Supplements to Support Healthy SHBG and Testosterone Balance

  • High quality protein: Aim for protein at every meal to support muscle, satiety, and hormone production. Lean meats, fish, eggs, dairy, legumes, and soy are good choices.
  • Healthy fats: Include monounsaturated and omega 3 fats from olive oil, avocados, nuts, seeds, and fatty fish. Healthy fat intake supports hormone synthesis.
  • Limit alcohol and simple sugars: Both can negatively affect SHBG and hormone balance when consumed excessively.
  • Vitamin D: Adequate vitamin D status supports overall reproductive health. Consider testing and supplementing if low, under provider guidance.
  • Zinc and magnesium: These minerals support testosterone production and metabolic health. Get them primarily from food; supplements may be considered with provider approval.
  • Fiber and phytonutrients: Whole vegetables, fruits, and whole grains support metabolic health and hormone balance.

Lifestyle Recommendations

  • Resistance training: Regular strength training increases muscle mass and supports healthy testosterone signaling. Aim for at least 2 to 3 sessions per week.
  • Maintain healthy body composition: Excess body fat can alter SHBG and hormone levels. Focus on sustainable weight management strategies.
  • Prioritize sleep: Poor sleep reduces testosterone and interferes with recovery and mood. Aim for consistent, restorative sleep.
  • Stress management: Chronic stress and high cortisol can disrupt sex hormones. Use stress reduction strategies such as mindfulness, breathing, and regular activity.
  • Minimize exposure to endocrine disruptors: Reduce contact with certain plastics, phthalates, parabens, and nonessential chemicals in personal care products and household items.

Monitoring and When to Talk to a Provider

If you have symptoms such as low libido, fatigue, mood changes, trouble building muscle, or signs of androgen excess, consider talking to your healthcare provider about testing. Recommended measurements to discuss:

  • Total testosterone
  • Free testosterone or calculated free testosterone
  • SHBG
  • Other baseline labs as indicated by symptoms such as estradiol, LH, FSH, thyroid tests, and metabolic panels

Interpreting hormone labs in the context of symptoms and your SHBG genotype can provide a clearer picture than total testosterone alone. If labs and symptoms are incongruent, your provider may suggest further evaluation or targeted interventions.

Important Legal and Medical Disclaimer

PlexusDx provides educational information about genetic predispositions only. This content is not medical advice and is not intended to diagnose, treat, or prevent any medical condition. Always consult with your healthcare provider before making changes to your diet, supplements, exercise, or medical care based on genetic information. Your healthcare provider can evaluate your symptoms, interpret lab results, and recommend appropriate testing or treatment.