Male Hypogonadism, Testosterone, Testosterone Deficiency, Testosterone Replacement Therapy
Conditions
Keywords
testosterone pharmacokinetics, testosterone pharmacodynamics, testosterone pellets
Brief summary
Introduction: Male hypogonadism is a clinical syndrome associated with significant consequences for health and quality of life. In Brazil, approved testosterone replacement therapy options are limited to injectable formulations and transdermal gels, which are often associated with suboptimal adherence. Subcutaneous testosterone implants, already used in the United States and recommended by international guidelines, represent a promising alternative but are not yet available in Brazil. Objective: To evaluate the efficacy, safety, pharmacokinetics, and quality-of-life impact of 200 mg testosterone implants manufactured in Brazil for the treatment of men with symptomatic hypogonadism. Methods: This is a prospective interventional study conducted at the Division of Urology of the Hospital das Clínicas, University of São Paulo School of Medicine (FMUSP). Thirty cisgender hypogonadal men meeting strict inclusion and exclusion criteria will be enrolled. Participants will receive subcutaneous testosterone implants totaling 800 mg and will be followed for six months. Serial blood sampling will be performed to assess hormonal levels (total and free testosterone, LH, FSH, and PSA) and metabolic parameters (lipid profile, body mass index, and waist circumference). Validated questionnaires, including the IIEF-15, ADAM, and WHOQOL-BREF, will be used to evaluate sexual function, hypogonadal symptoms, quality of life, and patient satisfaction. Outcomes: The primary outcome is the ability of the implants to achieve and maintain therapeutic serum testosterone levels (450-800 ng/dL). Secondary outcomes include pharmacokinetic profile (Cmax, half-life, and mean duration), metabolic effects, changes in quality of life, and treatment adherence. Clinical Significance: This study advances the understanding of a testosterone replacement modality that may offer greater convenience for selected patients and for which data on nationally manufactured products are currently lacking. Over a six-month period, the study will investigate laboratory behavior, clinical impact, and patient satisfaction. Relevance and Impact: This is the first study of its kind conducted in Brazil, combining methodological rigor with a robust design to evaluate the safety and efficacy of domestically manufactured testosterone implants. The methodology incorporates detailed ethical and scientific criteria, ensuring high-quality data. The results may support regulatory and clinical decision-making, benefiting patients and potentially contributing to the Brazilian Unified Health System (SUS).
Interventions
DRUGSubcutaneous Testosterone Implants
Subcutaneous Testosterone Implants in Men With Symptomatic Hypogonadism
Sponsors
University of Sao Paulo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Implant of four BIOS testosterone pellets of 200mg in hypogonadal man and followup with pharmacokinetics of the response
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Absence of desire for future fertility. * Two fasting total testosterone measurements ≤ 350 ng/dL obtained between 6:00 and 10:00 a.m. * A positive ADAM questionnaire result (Participants with a prior diagnosis of testosterone deficiency established at this institution who are currently receiving testosterone replacement therapy and wish to participate in the study will be eligible for inclusion after completion of an appropriate washout period of the testosterone formulation in use.)
Exclusion criteria
* Inability to complete or respond to study questionnaires. * Body mass index (BMI) \> 35 kg/m². * Untreated depression, defined as a Beck Depression Inventory score \> 20. * Personal history of cancer. * Suspicious findings on digital rectal examination or breast examination. * Prostate-specific antigen (PSA) \> 4 ng/mL. * History of thrombosis. * Known thrombophilia. * Erythrocytosis. * Polycythemia. * Elevated liver enzymes (AST or ALT \> 1.5 times the upper limit of normal). * Untreated chronic disease. * Heart failure classified as New York Heart Association (NYHA) class III or IV. * History of cardiovascular disease within the previous 6 months. * Substance use disorder or alcohol dependence. * Use of antiandrogen medications (flutamide, bicalutamide, enzalutamide, apalutamide, spironolactone, cyproterone acetate, abiraterone, ketoconazole, dutasteride, finasteride). * Use of estrogenic medications (estradiol, conjugated estrogens, progestogens). * Use of anabolic androgenic steroids without medical indication. * Untreated hypothyroidism. * Known allergy or hypersensitivity to testosterone or any component of the implant (testosterone, stearic acid).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Testosterone 200mg implants in hypogonadal men pharmacokinetics | 180 days | To evaluate the efficacy of a resorbable subcutaneous testosterone implant (200 mg), administered at a total dose of 800 mg (four 200-mg implants), in achieving and maintaining total serum testosterone concentration between 450 and 800 ng/dL in symptomatic hypogonadal men over a 180-day period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Testosterone Concentration | Up to 180 days | Assessment of the maximum plasma concentration of total testosterone. |
| Time to Maximum Plasma Testosterone Concentration (Tmax) | Up to 180 days | Assessment of the time required to reach the maximum plasma concentration of total testosterone after implantation. |
| Plasma Testosterone Elimination Half-Life (T½) | Up to 180 days | Assessment of the elimination half-life of total testosterone in plasma following implantation. |
| Average Plasma Testosterone Concentration (Cavg) | Up to 180 days | Assessment of the average plasma concentration of total testosterone following implantation. |
| Area Under the Plasma Concentration-Time Curve | Up to 180 days | Assessment of the area under the curve of plasma concentration. |
| To evaluate the safety profile of testosterone implants. | 180 days | Evaluate the incidence of complications in a clavien dindo scale |
| Change in Serum Luteinizing Hormone (LH) Levels | Up to 180 days | Assessment of changes in serum luteinizing hormone (LH) levels during treatment with testosterone implants. |
| Evaluation of sexual outcomes | 180 days | To evaluate the incidence of erectile dysfunction withe the International Index of Erectile Function. |
| Evaluation of coagulation after testosterone implants | 180 days | Evaluate the plasma thromboelastography in men treated with testosterone implants. |
| Change in Hypogonadal Symptoms Assessed by the Androgen Deficiency in the Aging Male Questionnaire | Up to 180 days | Assessment of changes in hypogonadal symptoms using the Androgen Deficiency in the Aging Male questionnaire. |
| To evaluate changes in quality of life in hypogonadal patients undergoing testosterone replacement therapy with implants | 180 days | To evaluate changes in quality of life in hypogonadal patients undergoing testosterone replacement therapy with implants with the World Health Organization Quality of Life - BREF (WHOQOL-BREF) assessment questionnaire score. |
| To evaluate the metabolic effects of testosterone implants using serum lipid profile | 180 days | To evaluate the metabolic effects of testosterone implants on the serum lipid profile |
| To assess patient satisfaction with testosterone implant therapy. | 180 days | To assess patient satisfaction with a numerical Likert scale 1 to 5 |
| To compare patient satisfaction with testosterone implants versus other testosterone replacement therapy modalities previously used by the participants. | 180 days | To compare patient satisfaction with testosterone implants versus other testosterone replacement therapy modalities previously used by the participants, with a qualitative comprehensive questionnaire and a numerical final grade from 1 to 100 |
| Change in Serum Follicle-Stimulating Hormone (FSH) Levels | Up to 180 days | Assessment of changes in serum follicle-stimulating hormone (FSH) levels during treatment with testosterone implants. |
| Change in Prostate-Specific Antigen (PSA) Levels | Up to 180 days | Assessment of changes in serum prostate-specific antigen (PSA) levels during treatment with testosterone implants. |
| To evaluate patient regret with testosterone implant treatment | 180 days | Evaluate the incidence of regret in the use of testosterone implant treatment in a 1-5 Likert scale. |
| To evaluate the metabolic effects of testosterone implants on body mass index (BMI) | 180 days | To evaluate the metabolic effects of testosterone implants on body mass index in kg/m2 (BMI) |
| To evaluate the metabolic effects of testosterone implants on waist circumference. | 180 days | To evaluate the metabolic effects of testosterone implants on the measure of waist circumference in centimeters (cm). |
Contacts
CONTACTBruno N PhD, MD
Outcome results
None listed