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).

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).