Which testosterone ester has the least dihydrotestosterone (DHT) conversion in a standard adult male patient with hypogonadism?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: January 7, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

DHT Conversion and Testosterone Esters

All testosterone esters convert to testosterone in the body, which is then metabolized to DHT by 5α-reductase enzyme—the ester itself does not determine DHT conversion rates. The route of administration and formulation characteristics, rather than the ester type, influence DHT levels.

Understanding Testosterone Metabolism

  • Once any testosterone ester is cleaved in the body, it releases native testosterone, which undergoes identical metabolic pathways regardless of the original ester 1, 2
  • The conversion to DHT occurs via 5α-reductase enzyme in peripheral tissues and is determined by testosterone exposure patterns, not ester chemistry 2
  • The key differentiator is the pharmacokinetic profile (how quickly testosterone is released and metabolized), not the chemical structure of the ester itself 3

Formulation-Based DHT Differences

Oral Testosterone Undecanoate: Highest DHT Conversion

  • Oral testosterone undecanoate produces supraphysiological DHT levels with a DHT:testosterone ratio of 0.36, nearly double the physiological ratio 1
  • This occurs because oral TU undergoes first-pass hepatic metabolism, generating excessive DHT before reaching systemic circulation 1, 2
  • The DHT:testosterone ratio with oral TU is significantly elevated compared to other formulations 2

Injectable Testosterone Undecanoate: Lower DHT Conversion

  • Injectable testosterone undecanoate (not oral) produces more physiological DHT levels compared to oral formulations 3
  • Injectable TU provides more stable testosterone levels (40-68 nmol/L for 45 days) without the extreme peaks seen with shorter-acting esters 3
  • The avoidance of first-pass metabolism with injectable TU results in more physiological DHT:testosterone ratios 3

Transdermal Testosterone: Most Physiological DHT Conversion

  • Transdermal preparations (gels, patches) provide the most stable day-to-day testosterone levels, avoiding supraphysiological peaks 4, 5
  • The steady-state delivery minimizes fluctuations that could drive excessive DHT conversion 5
  • Transdermal formulations are favored in guidelines specifically for their more physiological hormone profiles 5

Injectable Testosterone Cypionate/Enanthate: Variable DHT Conversion

  • These short-acting esters produce highly supraphysiological testosterone peaks (100-177 nmol/L) within 24-48 hours, followed by rapid decline 3
  • The extreme fluctuations result in periods of both excessive and insufficient DHT conversion 3
  • DHT levels parallel testosterone levels, meaning supraphysiological testosterone peaks drive proportionally elevated DHT 2

Clinical Recommendation Algorithm

For minimizing DHT conversion in hypogonadal men:

  1. First choice: Transdermal testosterone gel (1.62% formulation at 40.5 mg daily) provides the most stable testosterone levels and physiological DHT:testosterone ratios 5, 1

  2. Second choice: Injectable testosterone undecanoate (750 mg initially, repeat at 4 weeks, then every 10 weeks) offers stable levels without oral first-pass metabolism 5, 3

  3. Avoid: Oral testosterone undecanoate due to DHT:testosterone ratio of 0.36 versus the physiological 0.19 seen with native testosterone formulations 1

  4. Avoid: Short-acting injectable esters (cypionate/enanthate) if DHT minimization is the priority, as supraphysiological peaks drive proportionally elevated DHT 2, 3

Critical Caveats

  • The question conflates "ester type" with "formulation route"—it's the delivery method (oral vs. injectable vs. transdermal), not the ester chemistry, that determines DHT exposure 1, 2
  • Newer oral native testosterone formulations (not undecanoate esters) show DHT:testosterone ratios of 0.19, matching physiological levels, but these are not yet widely available 1
  • Injectable testosterone undecanoate avoids the DHT problem of oral TU specifically because it bypasses hepatic first-pass metabolism 1, 3
  • If a patient specifically requires injectable therapy and DHT minimization is critical, testosterone undecanoate injection is superior to cypionate or enanthate 3

References

2
Research

Which testosterone replacement therapy?

Clinical endocrinology, 1984

4
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

5
Guideline

Testosterone Injection Treatment for Male Hypogonadism

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Related Questions

Do testosterone serum levels continue to drop after injection?
Are there testosterone formulations besides injections or topical applications?
What is the recommended dosage comparison between bioidentical testosterone (testosterone) pellets and oral testosterone (testosterone undecanoate) formulations for testosterone replacement therapy?
What is the optimal testosterone level for a female on hormone replacement therapy (HRT)?
What is the recommended next dose of testosterone for a 36-year-old male with obesity, currently on 100 mg every 14 days, with post-treatment total testosterone levels of 242, free testosterone levels of 37.6, and bioavailable testosterone levels of 75.7?
What is the diagnosis and treatment for a patient presenting with a widespread rash, itchiness, and red spots across their body, including arms, back, torso, and legs?
Is hormone replacement therapy (HRT) suitable for a female patient in her 50s with a history of smoking and currently on anticoagulants (blood thinners) for stents?
What are the risks and necessary actions if an adult patient with a history of mental health issues, taking fluoxetine (a selective serotonin reuptake inhibitor) for depression or anxiety, accidentally ingests five times their daily dose?
Is prednisone (a corticosteroid) indicated for an adult patient with a history of inflammatory conditions and back pain, undergoing Magnetic Resonance Imaging (MRI) and L5-S1 spinal fusion surgery?
What is the best course of treatment for a pediatric patient with high Attention Deficit Hyperactivity Disorder (ADHD) questionnaire scores, indicating symptoms of inattention, hyperactivity, and impulsivity, but average cognitive function as indicated by the QB (Quotient Behavioral) test?
What is the management approach for an asymptomatic adult patient with a low neutrophil (white blood cell) count and no significant underlying health conditions?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question