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

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          Abstract

          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.

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          Most cited references37

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          Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study.

          We used longitudinal data from the Massachusetts Male Aging Study, a large population-based random-sample cohort of men aged 40-70 yr at baseline, to establish normative age trends for serum level of T and related hormones in middle-aged men and to test whether general health status affected the age trends. Of 1,709 men enrolled in 1987-1989, 1,156 were followed up 7-10 yr afterward. By repeated-measures statistical analysis, we estimated simultaneously the cross-sectional age trend of each hormone between subjects within the baseline data, the cross-sectional trend between subjects within the follow-up data, and the longitudinal trend within subjects between baseline and follow-up. Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data, whereas both free and albumin-bound T declined at about 2%/yr, all significantly more steeply than within the baseline data. Sex hormone-binding globulin increased cross-sectionally at 1.6%/yr in the follow-up data, similarly to baseline. The longitudinal decline within subjects between baseline and follow-up was considerably steeper than the cross-sectional trend within measurement times for total T (1.6%/yr) and bioavailable T (2-3%/yr). Dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, and estrone showed significant longitudinal declines, whereas dihydrotestosterone, pituitary gonadotropins, and PRL rose longitudinally. Apparent good health, defined as absence of chronic illness, prescription medication, obesity, or excessive drinking, added 10-15% to the level of several androgens and attenuated the cross-sectional trends in T and LH but did not otherwise affect longitudinal or cross-sectional trends. The paradoxical finding that longitudinal age trends were steeper than cross-sectional trends suggests that incident poor health may accelerate the age-related decline in androgen levels.
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            Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis.

            The risks of testosterone therapy in men remain poorly understood. The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men. We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies. Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility. Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data. The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes. The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.
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              Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials

              Background Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease. Methods A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. Results Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60). Conclusions The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy.
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                Author and article information

                Journal
                Sex Med
                Sex Med
                sm2
                Sexual Medicine
                John Wiley & Sons, Ltd (Chichester, UK )
                2050-1161
                2050-1161
                September 2015
                12 August 2015
                : 3
                : 3
                : 165-173
                Affiliations
                [* ]Scott Department of Urology, Baylor College of Medicine Houston, TX, USA
                []Center for Reproductive Medicine, Baylor College of Medicine Houston, TX, USA
                []Department of Cell Biology, Baylor College of Medicine Houston, TX, USA
                Author notes
                Corresponding Author: Alexander W. Pastuszak, MD, PhD, Male Reproductive Medicine and Surgery, Scott Department of Urology, Baylor College of Medicine, 6624 Fannin St. Suite 1700, Houston, TX 77030, USA. Tel: 713-798-6163; Fax: 713-798-5553; E-mail: pastusza@ 123456bcm.edu

                Funding: A.W.P. is a National Institutes of Health (NIH) K12 scholar supported by a Male Reproductive Health Research Career (MHRH) Development Physician-Scientist Award (HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program (to Dolores J. Lamb).

                [1]

                These authors contributed equally to the preparation of this manuscript

                Article
                10.1002/sm2.76
                4599554
                26468380
                7b71e4f1-1cb8-4c4c-984b-999606b94310
                © 2015 The Authors. Sexual Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Sexual Medicine.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Categories
                Original Research—Pharmacotherapy

                . testosterone therapy,testosterone pellets,testosterone gel,testosterone injections,erythrocytosis,lipid panel,prostate cancer

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