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How SHBG Gene Variation Affects Testosterone, Free Testosterone, and Health

Testosterone is a key hormone that supports muscle mass, libido, mood, energy, and reproductive health. A big part of how testosterone works is whether it is bound to carrier proteins in the blood or free and available for tissues. Sex hormone binding globulin, or SHBG, is a liver-produced protein that binds testosterone and reduces the amount that is free. Variations in the SHBG gene change how much SHBG you make, which shifts the balance between bound and free testosterone and affects downstream hormones such as dihydrotestosterone (DHT).

This article explains what the rs727428 variant in the SHBG gene means for testosterone availability, how that might influence health and wellness, and practical diet, supplement, and lifestyle steps you can use to support healthy hormone balance. PlexusDx provides this educational information about genetic predispositions only. This is not medical advice. Always consult your healthcare provider before making changes to treatments, supplements, or lifestyle based on genetic information.

Why free testosterone matters

Total testosterone measures both bound and free hormone. Free testosterone is the biologically active portion that can enter cells and trigger responses like muscle growth, sex drive, energy, and mood regulation. SHBG binds testosterone tightly; higher SHBG lowers free testosterone and lower SHBG raises free testosterone. DHT is a potent metabolite formed from testosterone and is linked to androgenic effects like facial and body hair growth but can also contribute to acne and pattern hair loss in susceptible people.

Genetic influence: rs727428 in the SHBG gene

The rs727428 variant is a single-letter difference in the DNA sequence near the SHBG gene. The presence of the T allele at this position is associated with lower circulating SHBG levels and therefore higher free testosterone and higher DHT compared with the C allele. Below are plain-language interpretations for each genotype and practical steps to support healthy hormonal balance.

Two effect alleles — TT (lower SHBG, higher free testosterone and DHT)

If you have the TT genotype for rs727428, you carry two copies of the effect allele. This pattern is linked to lower SHBG levels and increased free testosterone and DHT compared with other genotypes. That can translate into stronger libido, easier muscle gain, higher energy, and improved mood for some people.

Potential considerations

  • Increased DHT can raise the risk of androgen-driven effects such as acne or male pattern hair thinning in those who are genetically susceptible.
  • Monitor skin and hair changes, and discuss concerns with your healthcare provider if they appear.

Practical steps

  • Strength training 3 to 5 times per week to support muscle health and healthy testosterone signalling.
  • High-protein meals spread across the day to support muscle repair and hormone factory function.
  • Ensure zinc (from foods like oysters, beef, pumpkin seeds) and magnesium (leafy greens, nuts, whole grains) intake to support testosterone synthesis and sleep quality.
  • Consume healthy fats such as olive oil, avocados, and fatty fish to support steroid hormone production.
  • Prioritize 7 to 9 hours of quality sleep and aim for morning sunlight exposure to support circadian rhythm and hormone regulation.
  • Limit alcohol and avoid endocrine-disrupting plastics and BPA-containing items to reduce interference with hormone metabolism.
  • If acne or hair loss emerge, consult your clinician to evaluate options such as topical or systemic therapies, or to measure hormone levels if indicated.
One effect allele — CT (likely lower SHBG, higher free testosterone and DHT)

If you have the CT genotype for rs727428, you carry one copy of the effect allele. This is associated with moderately lower SHBG levels and higher free testosterone and DHT compared with the CC genotype.

Potential considerations

  • Generally favorable for libido, muscle maintenance, and mood, but DHT-related side effects such as acne or hair thinning are possible in susceptible individuals.
  • Effects are usually intermediate compared with TT and CC genotypes.

Practical steps

  • Follow a balanced, protein-forward diet with adequate essential fats and micronutrients to support testosterone production.
  • Include resistance and high-intensity interval training to maximize anabolic signalling and preserve muscle.
  • Make zinc and magnesium a regular part of your diet; supplement only after discussing with your clinician if dietary intake is insufficient.
  • Prioritize sleep hygiene, morning light exposure, and stress reduction techniques such as mindfulness or breathing exercises to keep hormone regulation steady.
  • Monitor for skin or hair changes and consult a healthcare professional if you notice concerning symptoms.
Zero effect alleles — CC (typical SHBG, normal testosterone balance)

If you have the CC genotype for rs727428, you carry two copies of the non-effect allele. This is associated with typical SHBG levels and a standard balance of bound and free testosterone.

Potential considerations

  • Your genetic pattern represents the more common baseline for SHBG and testosterone availability.
  • You can still experience variations in hormone levels due to age, body composition, sleep, medications, and lifestyle factors.

Practical steps

  • Support healthy testosterone through consistent resistance exercise and a diet that provides adequate protein, healthy fats, zinc, and magnesium.
  • Include foods rich in omega-3 fats such as fatty fish to support overall hormone balance and inflammation control.
  • Avoid excess alcohol, manage body fat, and limit exposure to potential endocrine disruptors like BPA and certain plastics.
  • Prioritize regular sleep, morning sunlight, and stress management to maintain steady hormonal rhythms.

Diet, supplements, and lifestyle recommendations

  • Diet: Emphasize lean proteins, whole grains, vegetables, and healthy fats. Aim for balanced meals that include protein at each meal to support muscle and hormone production.
  • Micronutrients: Ensure adequate zinc and magnesium intake through diet or supplementation after discussing with your clinician. Vitamin D status is also relevant to hormone health; consider testing and repletion if low.
  • Exercise: Prioritize regular resistance training and include short bouts of high-intensity work. Maintain an active lifestyle to support lean mass and metabolic health.
  • Sleep and light exposure: Aim for consistent sleep of 7 to 9 hours and get morning sunlight to reinforce circadian cues that influence hormone release.
  • Substances and environment: Limit alcohol, avoid smoking, and reduce exposure to BPA and plastic containers for food and drinks where possible.
  • Monitoring: Track changes in libido, energy, muscle, acne, and hair. If you notice concerning changes, discuss them with your healthcare provider who may recommend blood testing for total testosterone, free testosterone, SHBG, and other relevant markers.

When to see a healthcare provider

If you experience significant changes in mood, sexual function, muscle mass, unexplained acne, or hair loss, speak with your clinician. They can evaluate symptoms in context, order appropriate lab tests, and recommend safe, evidence-based interventions. PlexusDx provides genetic education only and does not give medical advice. Always consult a healthcare professional before starting medications, hormone therapies, or supplements based on genetic results.

Understanding your SHBG genotype gives insight into one piece of the complex puzzle that determines hormone balance. Lifestyle, nutrition, sleep, exercise, and medical history all interact with genetics to shape your hormonal health. Use this information to guide informed conversations with your healthcare provider and to take practical steps that support your wellbeing.