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

Abstract

IntroductionNumerous testosterone (T) formulations are available, each with differing effects on serum parameters.AimThe aim of this study was to compare the long-term effects of topical, injectable, and implantable pellet T formulations in hypogonadal men.MethodsRetrospective 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 MeasuresEffects of topical, injectable, and pellet T formulations on serum hormone levels, Hgb, Hct, lipid parameters and PSA.ResultsMen 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.ConclusionsAll 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.

Testosterone therapy and prostate cancer

“…Male hypogonadism is defined as the presence of both low serum testosterone levels as well as symptoms that can include decreased libido, erectile dysfunction, loss of vitality, loss of lean muscle and bone density, fatigue, anemia and depression (1). The prevalence of hypogonadism has proven difficult to accurately determine, with the highest reported prevalence reported in 2006 when Mulligan et al found that 40% of men over age 45 had symptomatic hypogonadism (2).…”

Effect of Dose and 5α‐Reductase Inhibition on the Circulating Testosterone Metabolite Profile of Men Administered Oral Testosterone

“…Testosterone replacement therapy (TRT) is the first‐line treatment for testosterone deficiency and has been shown to improve bone density, alleviate depression, and maintain sexual function 5. Currently available options for TRT in the United States include intramuscular injections, transdermal patches, and gels 6, 7. The development of an oral TRT has been extremely challenging because of extensive first pass metabolism.…”

“…The development of an oral TRT has been extremely challenging because of extensive first pass metabolism. As a result, the 2–4 million hypogonadal men in the United States requiring TRT mainly rely on intramuscular or topical testosterone dosage forms,6, 7 both of which are challenging in terms of compliance, and have suboptimal pharmacokinetics (PK) or variable absorption 8. Clearly, the development of a safe and effective formulation of oral testosterone is a major unmet need for these men.…”

“…5 Currently available options for TRT in the United States include intramuscular injections, transdermal patches, and gels. 6,7 The development of an oral TRT has been extremely challenging because of extensive first pass metabolism. As a result, the 2-4 million hypogonadal men in the United States requiring TRT mainly rely on intramuscular or topical testosterone dosage forms, 6,7 both of which are challenging in terms of compliance, and have suboptimal pharmacokinetics (PK) or variable absorption.…”

Enclomiphene citrate for the treatment of secondary male hypogonadism

“…[21] Treatment with exogenous testosterone is associated with several adverse sequelae, the most common of which are erythrocytosis, elevated serum estrogen levels, alterations in serum lipids, and infertility. [2] An increased cardiovascular risk in men using exogenous testosterone has also been proposed, although high quality evidence examining this relationship remains lacking.…”