Research
Research

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.

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

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).
  • 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.

Conclusion

  • SHBG and Estradiol levels rose with clomiphene monotherapy but subsequently decreased after adding oral TU.
  • Hct was unchanged throughout.

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

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).
  • 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.

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

Important Safety Information for KYZATREX (testosterone undecanoate)
KYZATREX can increase blood pressure, which can increase the risk of having a heart attack or stroke and can increase risk of death due to a heart attack or stroke.
Your risk may be greater if you have already had a heart attack or stroke or if you have other risk factors for heart attack or stroke.

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