Initiating High-Dose Oral Testosterone Undecanoate Therapy in Hypogonadal Men

Jimmy Vo BS, Grace Yoon BS, and Andrew Y. Sun MD
Urology Partners of North Texas, Arlington, Texas, USA
Introduction
  • Oral testosterone undecanoate is a novel form 
of testosterone replacement therapy.
  • Oral TU is conventionally initiated at 200mg 
BID (Kyzatrex), 237mg BID (Jatenzo), or 225mg 
BID (Tlando).
  • Many patients attain greater symptomatic benefit at higher doses.
  • In our practice we often initiate therapy at a starting dose of 400mg BID.
Results
  • 27 patients met inclusion criteria and had complete data
  • Mean follow up time = 6 months
  • Significant increase in TT (263 to 798 ng/dL).
  • Drop in SHBG (32.4 to 17.83 nmol/L).
  • Increase in calculated fT (7.24 to 26.74 ng/dL).
  • Estradiol modestly increased (20.5 to 24.7 pg/ml).
  • Hematocrit did not significantly increase (44.9% to 47.4%).
Aim
  • Retrospectively report the outcomes of starting hypogonadal men on oral TU at the maximum available dose of 400 mg BID
  • Safety
  • Efficacy
  • Patient satisfaction
  • Adherence
  • FSH and LH were maintained at non-zero levels:
(FSH from 5.7 to 2.9 mlU/mL and LH from 3.3 to 1.9 mlU/mL).
Method
  • Retrospective, single-center chart review
  • Hypogonadal men treated with a starting dose of oral TU at 400mg BID from August 2023 to April 2024.
  • Satisfaction was subjectively recorded
  • Adherence was measured by prescription refill records.
  • Total testosterone (TT)
  • Sex Hormone Binding Globulin (SHBG)
  • Calculated Free Testosterone (fT)
  • Estradiol (E2)
  • Hematocrit (Hct)
  • Follicle stimulating hormone (FSH)
  • Luteinizing hormone (LH).
  • No patients reported testicular atrophy.
  • No patients were initiated on aromatase inhibitors.
  • One patient had a hematocrit rise above 52% (53.2%) and was reduced to 300mg BID with resolution of 
his erythrocytosis.
  • Side effects were rare with 2 patients (7.4°/o) reporting transient GI upset.
  • Subjective patient satisfaction was high, with 26/27 (96%) of patients reporting improvement in symptoms and continuing therapy.
Conclusion
  • Initiating oral TU therapy with Kyzatrex at 400mg BID is safe and effective.
  • The high dose was well-tolerated and resulted in substantial symptom improvement, high patient satisfaction, 
and adherence.
  • These findings support considering a higher starting dose for hypogonadal men considering oral TU therapy.

Combined Clomiphene and High-Dose Oral Testosterone Therapy in Hypogonadal Men: A Case Series

Grace Yoon BS, Jimmy Vo BS, and Andrew Y. Sun MD
Urology Partners of North Texas, Arlington, Texas, USA
Introduction
  • Clomiphene is often used in the treatment of hypogonadal men who wish to preserve endogenous testosterone production
  • However symptomatic responses are often suboptimal.
  • Exogenous testosterone replacement, while effective, typically suppresses the hypothalamic­pituitary-gonadal (HPG) axis.
Results
  • Baseline serum testosterone levels of 303, 223, and 
230 ng/dl.
  • After 3 months of clomiphene 50mg QoD, TT rose to 
418, 680, and 667 ng/dl
  • Add 400mg oral TU QD for 3 months, TT rose to 1001, 
1055, and 1120 ng/dl
  • Patients reported significant improvement in symptoms such as erectile dysfunction, fatigue, libido, and 
exercise tolerance.
  • FSH and LH levels both rose on clomiphene and subsequently dropped after initiation of oral TU, but remained near baseline
Aim
  • This case series investigates the efficacy of combining clomiphene with high­ dose oral testosterone undecanoate (TU) (Kyzatrex ®, Marius Pharmaceuticals).
  • 3 Patient case series
  • SHBG and Estradiol levels rose with clomiphene monotherapy but subsequently decreased after adding oral TU.
  • Hct was unchanged throughout.
  • No significant adverse events were reported.
Method
Three hypogonadal men:
  • Initially received clomiphene therapy (50mg QoD) with poor symptomatic improvement
  • Given oral TU 400mg once daily with lunch.
  • Evaluated after 3 months of clomiphene monotherapy

  • Evaluated again after 3 additional months of clomiphene + Oral TU combination therapy.
  • Total testosterone (TT)
  • Sex Hormone Binding Globulin (SHBG)
  • Calculated Free Testosterone (fT)
  • Estradiol (E2)
  • Hematocrit (Hct)
  • Follicle stimulating hormone (FSH)
  • Luteinizing hormone (LH).
Conclusion
  • SHBG and Estradiol levels rose with clomiphene monotherapy but subsequently decreased after adding oral TU.
  • Hct was unchanged throughout.

Effects of Oral Testosterone Undecanoate on Semen Parameters in Hypogonadal Men: An Interim Analysis of a Prospective Pilot Study

Gal Saffati, Daniela Orozco Rendon, Shane Kronstedt,
David E. Hinojosa-Gonzalez, Mohit Khera.
Baylor College of Medicine, Houston, TX
Introduction
  • Testosterone replacement therapy (TRT), per the AUA guidelines, is indicated for men with hypogonadism who do not want to preserve fertility.
  • While injectable testosterone preparations are widely used, oral testosterone formulations have become an increasingly popular treatment option due to their ease of administration and avoidance of repeated intramuscular injections.
  • However, the effects of oral testosterone on semen analysis (SA) parameters and male fertility potential remain understudied.
Results
Table 1. Baseline and follow-up values
T: testosterone; FSH: follicle stimulating hormone, LH: luteinizing hormone; SA: semen analysis
Aim
  • To evaluate changes in SA parameters, among hypogonadal men receiving oral testosterone undecanoate therapy.
Method
  • Design: A single-arm pilot prospective 
study, unblinded.
  • Inclusion:
    • 18-49 years old who qualify for TRT.
    • TRT naïve.
  • Exclusion:
    • Prior TRT.
    • Prior use of clomiphene citrate or hCG.
    • Demonstrated azoospermia.
Conclusion
  • Despite a substantial increase in total and free testosterone levels after 3 months of therapy, the overall semen analysis parameters—sperm concentration, motility, and volume—remained largely unchanged.
  • The exception of one patient developing azoospermia underscores the potential impact of testosterone therapy on fertility in certain individuals, though this was not a widespread effect in the cohort.
  • While these early results suggest that oral testosterone undecanoate may not universally impair semen parameters in the short term, we highlight the need for larger and longer-term studies to fully elucidate the potential reproductive risks associated with this therapy