Clinical Evaluation of Subcutaneous Testosterone Implants in Men With Symptomatic Hypogonadism

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Male Hypogonadism; Testosterone Deficiency; Testosterone; Testosterone Replacement Therapy
• Intervention / Treatment: Drug: Subcutaneous Testosterone Implants

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bruno N PhD, MD; Phone Number: +5511999686655; Email: bruno.nascimento@hc.fm.usp.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subcutaneous Testosterone Implants; Subcutaneous Testosterone Implants in Men With Symptomatic Hypogonadism	Drug: Subcutaneous Testosterone Implants; Subcutaneous Testosterone Implants in Men With Symptomatic Hypogonadism

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Testosterone 200mg implants in hypogonadal men pharmacokinetics	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	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Testosterone Concentration	Assessment of the maximum plasma concentration of total testosterone.	Up to 180 days
Time to Maximum Plasma Testosterone Concentration (Tmax)	Assessment of the time required to reach the maximum plasma concentration of total testosterone after implantation.	Up to 180 days
Plasma Testosterone Elimination Half-Life (T½)	Assessment of the elimination half-life of total testosterone in plasma following implantation.	Up to 180 days
Average Plasma Testosterone Concentration (Cavg)	Assessment of the average plasma concentration of total testosterone following implantation.	Up to 180 days
Area Under the Plasma Concentration-Time Curve	Assessment of the area under the curve of plasma concentration.	Up to 180 days
To evaluate the safety profile of testosterone implants.	Evaluate the incidence of complications in a clavien dindo scale	180 days
Change in Serum Luteinizing Hormone (LH) Levels	Assessment of changes in serum luteinizing hormone (LH) levels during treatment with testosterone implants.	Up to 180 days
Evaluation of sexual outcomes	To evaluate the incidence of erectile dysfunction withe the International Index of Erectile Function.	180 days
Evaluation of coagulation after testosterone implants	Evaluate the plasma thromboelastography in men treated with testosterone implants.	180 days
Change in Hypogonadal Symptoms Assessed by the Androgen Deficiency in the Aging Male Questionnaire	Assessment of changes in hypogonadal symptoms using the Androgen Deficiency in the Aging Male questionnaire.	Up to 180 days
To evaluate changes in quality of life in hypogonadal patients undergoing testosterone replacement therapy with implants	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.	180 days
To evaluate the metabolic effects of testosterone implants using serum lipid profile	To evaluate the metabolic effects of testosterone implants on the serum lipid profile	180 days
To assess patient satisfaction with testosterone implant therapy.	To assess patient satisfaction with a numerical Likert scale 1 to 5	180 days
To compare patient satisfaction with testosterone implants versus other testosterone replacement therapy modalities previously used by the participants.	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	180 days
Change in Serum Follicle-Stimulating Hormone (FSH) Levels	Assessment of changes in serum follicle-stimulating hormone (FSH) levels during treatment with testosterone implants.	Up to 180 days
Change in Prostate-Specific Antigen (PSA) Levels	Assessment of changes in serum prostate-specific antigen (PSA) levels during treatment with testosterone implants.	Up to 180 days
To evaluate patient regret with testosterone implant treatment	Evaluate the incidence of regret in the use of testosterone implant treatment in a 1-5 Likert scale.	180 days
To evaluate the metabolic effects of testosterone implants on body mass index (BMI)	To evaluate the metabolic effects of testosterone implants on body mass index in kg/m2 (BMI)	180 days
To evaluate the metabolic effects of testosterone implants on waist circumference.	To evaluate the metabolic effects of testosterone implants on the measure of waist circumference in centimeters (cm).	180 days

Collaborators and Investigators

• Sponsor: University of Sao Paulo

Publications and helpful links

General Publications

• Smith RP, Khanna A, Coward RM, Rajanahally S, Kovac JR, Gonzales MA, Lipshultz LI. Factors influencing patient decisions to initiate and discontinue subcutaneous testosterone pellets (Testopel) for treatment of hypogonadism. J Sex Med. 2013 Sep;10(9):2326-33. doi: 10.1111/jsm.12226. Epub 2013 Jul 16.
• McMahon CG, Shusterman N, Cohen B. Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency. J Sex Med. 2017 Jul;14(7):883-890. doi: 10.1016/j.jsxm.2017.04.734.
• Kaminetsky JC, Moclair B, Hemani M, Sand M. A phase IV prospective evaluation of the safety and efficacy of extended release testosterone pellets for the treatment of male hypogonadism. J Sex Med. 2011 Apr;8(4):1186-96. doi: 10.1111/j.1743-6109.2010.02196.x. Epub 2011 Jan 26.
• Cavender RK, Fairall M. Subcutaneous testosterone pellet implant (Testopel) therapy for men with testosterone deficiency syndrome: a single-site retrospective safety analysis. J Sex Med. 2009 Nov;6(11):3177-92. doi: 10.1111/j.1743-6109.2009.01513.x. Epub 2009 Sep 29.
• Kresch E, Lima TFN, Molina M, Deebel NA, Reddy R, Patel M, Loloi J, Carto C, Nackeeran S, Gonzalez DC, Ory J, Ramasamy R. Efficacy and safety outcomes of a compounded testosterone pellet versus a branded testosterone pellet in men with testosterone deficiency: a single-center, open-label, randomized trial. Sex Med. 2023 Mar 17;11(2):qfad007. doi: 10.1093/sexmed/qfad007. eCollection 2023 Apr.
• McCullough A. A Review of Testosterone Pellets in the Treatment of Hypogonadism. Curr Sex Health Rep. 2014;6(4):265-269. doi: 10.1007/s11930-014-0033-7.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 24, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: testosterone pharmacokinetics; testosterone pharmacodynamics; testosterone pellets
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Eunuchism
• Other Study ID Numbers: 88009225.0.0000.0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No