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.

Background: Testosterone deficiency (TD) is a prevalent condition, especially in men ≥45 years old, and testosterone therapy (TTh) can improve the quality of life in these patients. Aim: To evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the efficacy between compounded and market brand testosterone pellets for TTh: E100 (Empower Pharmacy) and Testopel (Food and Drug Administration approved), respectively. Methods: This was a prospective, phase 3, randomized, noninferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 to a market brand group and a compounded pellet group. The patients were implanted with their respective testosterone pellets: Testopel (10 pellets of 75 mg) and E100 (8 pellets of 100 mg). Outcomes: We evaluated adverse events after implantation and followed men at 2, 4, and 6 months for morning laboratory levels (prior to 10 am): serum testosterone, estradiol, hematocrit, and prostate-specific antigen. Results: After randomization, 33 participants were enrolled in the Testopel arm and 42 in the E100 arm. Serum testosterone levels were similar between the groups at 2, 4, and 6 months, with most men (82%) dropping to <300 ng/dL by the end of the trial. Adverse events were also similar, such as elevations in prostate-specific antigen, estradiol, and hematocrit. Most dropouts were related to persistent TD symptoms and serum testosterone <300 ng/dL, with similar rates between the groups in the study. Clinical Implications: Men treated with Testopel and E100 pellets had comparable serum testosterone levels and similar adverse event rates, providing an effective choice of long-term TTh among men with TD. Strengths and Limitations: Strengths include the prospective, randomized, single-blinded study design and adequate follow-up. Limitations include the lack of external validity and the single-institution cohort. Conclusion: E100 compounded testosterone pellets are a noninferior option of TTh as compared with Testopel for men presenting with TD.

Implante de testosterona para la mujer, evaluación de seguridad y efectividad en esta vía de administración / Testosterone implant for women, evaluation of safety and effectiveness in this route of administration

INTRODUCCIÓN Y OBJETIVO: El rol de la testosterona exógena en la función sexual femenina ha sido estudiado durante muchos años, con resultados contradictorios. En el último tiempo se ha promovido el uso de pellets de testosterona como una solución para mejorar la libido femenina, la cognición, la fuerza muscular y los sistemas cardiovascular y óseo, e incluso evitar el envejecimiento. Por ello, revisamos las publicaciones para tratar de responder si esto es una moda o el tratamiento más innovador del último tiempo. MÉTODO: Se analizaron las bases de datos PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct y ResearchGate. RESULTADOS: De acuerdo con la evidencia, la mejor testosterona disponible es la transdérmica y debe ser usada solo en el trastorno del deseo sexual hipoactivo (TDSH). Los trabajos que evalúan los pellets de testosterona tienen sesgos metodológicos importantes. Si bien son útiles para mejorar la función sexual femenina, producen concentraciones plasmáticas suprafisiológicas de testosterona, por lo que no se puede establecer su seguridad a largo plazo. Tampoco hay datos suficientes que avalen su uso para mejorar el rendimiento cognitivo y el bienestar general, en el tratamiento de enfermedades cardiovasculares o en la prevención de enfermedad ósea. CONCLUSIONES: La testosterona solo se recomienda en el tratamiento del TDSH por vía transdérmica. No recomendamos el uso de pellets de testosterona para el tratamiento de la disfunción sexual ni como hormona antienvejecimiento, ya que no hay estudios consistentes sobre su seguridad, eficacia y efectos adversos a largo plazo.

INTRODUCTION AND OBJECTIVE: The role of exogenous testosterone in female sexual function has been studied for many years with contradictory results. In recent times, the use of testosterone pellets has been promoted as a solution to improve female libido, cognition, muscle strength, cardiovascular system, bone and even prevent aging. Therefore, we will review the publications in order to answer whether this is a fad or the most innovative treatment of recent times. METHOD: The databases PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct and ResearchGate were analyzed. RESULTS: So far, the evidence best testosterone available is transdermal testosterone and that it should be used only in hypoactive sexual desire disorder (HSDD). Papers evaluating testosterone pellets have significant methodological biases. While they are useful in improving female sexual function, they produce supra-physiological plasma levels of testosterone, so their long-term safety cannot be established. There is also insufficient data to support their use in improving cognitive performance and general well-being, treatment of cardiovascular disease or prevention of bone disease. CONCLUSIONS: Testosterone is only recommended for the tratment of HSDD via the transdermal route. We do not recommended the use of testosterone pellets for the treatment of sexual dysfunction or as an anti aging hormone, as there are no consistent studies on its safety, efficacy, and long-term adverse effects.

Testosterone therapy with Testopel® and the Esoterix Laboratory assay: A CASE study.

We present a patient receiving Testopel® implants whose serum testosterone levels, as measured by a CDC certified assay, were accurately predicted by a multi-compartmental model. This is the first time a model has predicted measured serum testosterone levels within 4% of values calculated. To our knowledge, it was also the first time a pharmacokinetic model allowed patient targeted serum levels (peak/trough/average) to be reached within three months.

Failure of testosterone replacement therapy to improve symptoms correlates with burden of systemic conditions.

BACKGROUND: The symptoms of hypogonadism are non-specific and restoring testosterone (T) to physiologic levels may not lead to clinical improvement. In men with a high burden of systemic illness, it is difficult to assess whether hypogonadism is a primary contributing factor of their symptoms. Given that testosterone replacement therapy (TRT) is not without risk, it is important to understand which patients will benefit from treatment. Therefore, we hypothesize that men with a higher burden of systemic illness would be less likely to continue with TRT. METHODS: We performed a retrospective review of our men's health registry for men who started TRT and adhered to follow up labs and visits within the first year. We restricted treatment to Testopel pellets due to reliable early T levels. Men were classified as yes/no for continued TRT based on whether they felt their presenting symptoms improved on therapy and they chose to continue TRT. The previously validated ACTIONS men's health phenotype was calculated as a composite systemic disease score grading severity [0-2] for each of anxiety, cardiovascular disease, low testosterone, diabetes, obesity, neurologic disease and obstructive sleep apnea (total score 0-14). RESULTS: Sixty men were identified with a mean age of 59.5 (range, 33-81) years and mean starting total testosterone of 215 [48-332] ng/dL. Thirty-nine men (65%) felt symptomatic benefit and continued therapy for a median of 40.4 (20.5-76.4) months vs. 21 men without benefit treated for a median of 4.1 months (2.9-10.7, P<0.0001). Those who stopped TRT had a higher ACTIONS score than those who continued (8±2.5 vs. 4.1±1.6, P<0.0001). Age weakly correlated with total ACTIONS score (r=0.28, P=0.03) but age had no impact on continuing TRT and the relationship between continuing TRT and ACTIONS score held true regardless of age. CONCLUSIONS: Patients with a greater burden of systemic disease were less likely to have symptomatic improvement with TRT and more likely to stop therapy within a year. As several hypogonadal symptoms are non-specific, it is imperative that patients be counseled on the likelihood of success with TRT, particularly if they have multiple comorbidities. Ideal outcomes may come from multimodal therapy that includes lifestyle modification, and optimization of conditions such as diabetes, cardiovascular disease and sleep apnea.

Testosterone Pellet Implantation Practices: A Sexual Medicine Society of North America (SMSNA) Member Questionnaire.

INTRODUCTION: There has been renewed interest in the use of subcutaneous testosterone pellets for the treatment of hypogonadism since the introduction of Testopel in 2008 by Slate Pharmaceuticals (Durham, NC, USA). Manufacturer guidelines recommend using two to six pellets; however, in the clinical setting, this is deemed insufficient. This has produced a wide variety of testosterone pellet usage that is not fully understood. AIM: To better understand subcutaneous testosterone pellet implantation practices among members of the Sexual Medicine Society of North America (SMSNA). METHODS: A 19-item questionnaire was emailed to the 687 members of the SMSNA. Of the 19 questions, 17 were multiple choice and two required write-in responses. Usage patterns, satisfaction rates, and complication rates were investigated. MAIN OUTCOME MEASURES: Data regarding indications for initiating treatment with Testopel, initial dosage, follow-up of testosterone levels and dose titration, patient tolerance and satisfaction, technique of implantation, and procedural complications were collected. RESULTS: Eighty-seven survey responses were received (12.9%). At initiation of Testopel therapy, 80.5% of respondents would implant at least 10 pellets, whereas only 4.6% would place six to seven pellets and 3.4% would implant fewer than six pellets. Many respondents would determine the starting dose based on some combination of baseline testosterone level and weight, although 24.1% described using a standard starting dose for all patients. All respondents would check testosterone levels within 3 months of initiating therapy, with the vast majority (72.4%) doing so at 1 month. Subsequent dosing of Testopel was not changed in most patients, with 41.4% and 26.4% of respondents reporting that 60% to 80% and 80% to 100% of patients, respectively, remained on their initial dose. Most respondents would re-implant pellets at a 3-month (21.8%) or 4-month (43.7%) interval. High patient satisfaction was described by respondents, with 56.3% finding patients to be satisfied "most times" and 34.5% "almost always." CONCLUSION: This study provides insight into the usage of Testopel among members of the SMSNA. We found that the vast majority of specialists use at least 10 pellets at initial implantation, with limited need for subsequent dose adjustments, good durability of response, and high patient satisfaction and tolerability.

Comparison of the Effects of Testosterone Gels, Injections, and Pellets on Serum Hormones, Erythrocytosis, Lipids, and Prostate-Specific Antigen.

INTRODUCTION: Numerous testosterone (T) formulations are available, each with differing effects on serum parameters. AIM: The aim of this study was to compare the long-term effects of topical, injectable, and implantable pellet T formulations in hypogonadal men. METHODS: Retrospective review of hypogonadal men treated with a single T formulation was performed: 47 men on T gels, 57 on injectable T, and 74 on T pellets were identified. Total T (TT), calculated free T (FT), estradiol (E), hemoglobin (Hgb), hematocrit (Hct), prostate-specific antigen (PSA), total cholesterol (Tchol), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were evaluated at baseline and every 3-6 months for 3 years. Serum parameters were compared using a mixed model linear regression for repeated measures. MAIN OUTCOME MEASURES: Effects of topical, injectable, and pellet T formulations on serum hormone levels, Hgb, Hct, lipid parameters and PSA. RESULTS: Men in the injectable T group were younger (42.5 ± 12.3 years) than in the gel (54.1 ± 9.8 years) or pellet groups (53.8 ± 13.0 years), and baseline FT, Hgb, and Hct were higher in the injectable T group than in gel or pellet groups. Increases in TT and FT were observed throughout follow-up in all groups. Increases in E were observed at in all T groups and throughout follow-up in injectable and gel groups. No PSA increases were observed. Erythrocytosis (Hct > 50%) was more common with injectable T (66.7%) than with T gels (12.8%) or pellets (35.1%, P < 0.0001). Transient changes in cholesterol, TG, and LDL were observed, and no significant changes were seen in HDL for any group. CONCLUSIONS: All T formulations increase serum T and FT. More significant increases in E occur with injectable T and T gels. Changes in Hgb and Hct are most significant with injectable T, and effects on lipids are variable and inconsistent. Selection of T formulations must account for individual patient preferences and the effects of each formulation.

Coadministration of anastrozole sustains therapeutic testosterone levels in hypogonadal men undergoing testosterone pellet insertion.

INTRODUCTION: Current U.S. Food and Drug Administration-approved therapies for hypogonadism involve testosterone (T) replacement. Testosterone pellets (TP) require a minor office procedure every 3 to 4 months. The need for repeated insertions increases the likelihood of a complication. Anastrozole (AZ) is an aromatase inhibitor that has been used off-label for the treatment of male hypogonadism. AZ increases T levels by lowering serum estradiol (E2) levels and increasing gonadotropin (GTP) levels. AIM: We hypothesized that the concomitant use of AZ with TP insertions would sustain therapeutic T levels and increase the interval between TP insertions. METHODS: Men treated with TP for hypogonadism at an academic center were offered AZ (1 mg/day) at the time of TP reinsertion as a way of potentially decreasing the frequency of TP insertions. Total T (TT), free T (FT), sex hormone binding globulin, E2, luteinizing hormone (LH), and follicle-stimulating hormone FSH levels were obtained prior to T replacement and at 6 and 15 weeks from TP insertion. Men were re-implanted at 16 weeks if their TT levels were less than 350 ng/dL and their symptoms recurred. We retrospectively reviewed our records of men who underwent TP, TP, and AZ from 2011 to 2012. Demographics, TT, FT, LH, FSH, and E2 levels were recorded. Data were analyzed with anova and a Tukey's test. MAIN OUTCOME MEASURE: TT level at 6, 15, or >15 weeks from TP insertion. RESULTS: Thirty-eight men with 65 insertions were analyzed. The TP AZ group had significantly higher TT and FT levels than the TP group at >120 days (P < 0.05). The TP group had significantly higher E2 levels at all time points (P < 0.01). GTP levels remained stable in the TP AZ group. Average time to reinsertion in TP AZ was 198 days vs. 128 days in the TP group. CONCLUSION: Men on TP AZ maintain therapeutic T levels longer than men on TP alone and have significantly less GTP suppression.

A Review of Testosterone Pellets in the Treatment of Hypogonadism.

Currently, the most popular form of testosterone replacement is the topical gels that require daily applications and incur a risk of transfer of testosterone to partners and family. One of the problems with testosterone replacement is the short half-life of testosterone. A long-acting formulation is appealing to patients and physicians. In 1972, fused crystalline testosterone pellets were approved in the USA by the FDA but they were not marketed until 2008. Pharmacokinetics studies were available on a different formulation from which much can be learned and applied to the current formulation, Testopel®. The decay kinetics, pituitary suppression, and effect on other sex steroids are reviewed as well as the short-term complication rates. This review should provide the testosterone pellet implanter a better understanding of the physiology of testosterone pellet supplementation for hypogonadism.

Factors influencing patient decisions to initiate and discontinue subcutaneous testosterone pellets (Testopel) for treatment of hypogonadism.

INTRODUCTION: A variety of modalities for testosterone replacement therapy (TRT) are available, including topical gels, injections, and Testopel subcutaneous testosterone pellets (STP). STP are becoming more commonly utilized in the United States; however, patient preferences, expectations, and usage patterns regarding this therapy remain poorly characterized. AIM: To identify factors influencing patients' decisions to initiate or discontinue STP. METHODS: A total of 175 men from an academic urology clinic who were currently using or who had previously used STP for hypogonadism received a 32-item electronic survey. MAIN OUTCOME MEASURES: Assessment of the impact of convenience, efficacy, side effects, cost, and symptom relief on initiation and discontinuation of STP. RESULTS: One hundred and thirteen men (64.6% response rate) of mean age 51.4 years who previously underwent a mean of 2.8 STP implant procedures completed the survey. Fifty-nine (52.2%) and 40 (35.4%) men had switched to STP from topical gel and injection therapy, respectively, whereas 14 (12.4%) men initially started TRT with STP. Convenience (68.8%) was the most important factor in patients' decision to start STP, while cost of the previous form of TRT (14.7%) was least important. At the time of the survey, 32 men (28.3%) had discontinued STP therapy. Cost of therapy (50%) was the primary factor in discontinuing STP. There was no difference in serum testosterone levels between men who continued STP and those who discontinued therapy (642.8 vs. 629.0 ng/dL, P = 0.83). Overall, 68.1% of patients continued STP therapy at the time of survey completion. CONCLUSIONS: Convenience is the most important factor in a patient's decision to initiate STP; however, physician recommendation also plays a substantial role. Cost was the primary reason for discontinuation. Upon survey completion, greater than two-thirds of respondents elected to continue STP therapy. STP are a viable treatment option for hypogonadal men seeking a convenient and efficacious alternative modality of TRT.