The Effects of Testosterone

November 6

by John Connor

One of the most common question I'm asked is "what should I do for a first cycle?" The questions are; "what steroid should I take?" "How long should I take it?" and "What will the effects be?" There are literally dozens of steroids available and that makes it difficult for a first time user to choose. The following information will attempt to provide enough information for a first time user to make an educated decision about anabolic androgenic steroid use.

Testosterone is one of the most effective, safe and available steroids today, therefore I believe Testosterone is the best first cycle choice. The following text outlines the benefits and risks of Testosterone administration based on a clinical human trial of 61 healthy men in 2001. The purpose of the trial was to determine the dose dependency of testosterone's effects on fat-free mass and muscle performance. In this trial 61 men, 18-35years old were randomized into 5 groups receiving weekly injections of 25, 50, 125, 300, 600 mg of Testosterone Enanthate for 20 weeks.

They had previous weight-lifting experience and normal T levels. Their nutritional intake was standardized and they did not undertake any strength training during the trial. The only two groups that reported significant muscle building benefits were the 300 and 600 mg groups so any dose lower than 300mg will not be considered in this essay. 12 men participated in the 300 mg group and 13 men in the 600 mg group.

600mg of Testosterone a week for 20 weeks resulted in the following benefits. Increased fat free mass, muscle strength, muscle power, muscle volume, hemoglobin and IGF-1.

The same 600 mg administration resulted in 2 side effects. HDL cholesterol was negatively correlated and 2 men developed acne.

The normal range for total T in men is 241-827 ng/dl according to Labcorp and 260-1000 ng/dl according to Quest Laboratories. The normal range for IGF-1 is 81-225 according to Labcorp. Total T and IGF-1 levels were taken after 16 weeks and resulted in the following;

Total Testosterone
300 mg group-1,345 ng/dl a 691 ng increase from baseline
600 mg group-2,370 ng/dl a 1,737 ng increase from baseline

IGF-1
300 mg group-388 ng/dl a 74 ng increase from baseline
600 mg group-304 ng/dl a 77 ng increase from baseline

Body composition was measured after 20 weeks.

Fat Free Mass by underwater weighing
300 mg group-5.2kg (11.4lbs) increase
600 mg group-7.9kg (17.38lbs) increase

Fat Mass by underwater weighing
300 mg group-.5kg (1.1lbs) decrease
600 mg group-1.1kg (2.42lbs) decrease

Thigh Muscle Volume
300 mg group-84 cubic centimeter increase
600 mg group-126 cubic centimeter increase

Quadriceps Muscle Volume
300 mg group-43 cubic centimeter increase
600 mg group-68 cubic centimeter increase

Leg Press Strength
300 mg group-72.2kg (158.8lbs) increase
600 mg group-76.5kg (168.3lbs) increase

Leg Power
300 mg group-38.6 watt increase
600 mg group-48.1 watt increase

Hemoglobin
300 mg group-6.1 gram per liter increase
600 mg group-14.2 gram per liter increase

Plasma HDL Cholesterol
300 mg group-5.7 mg/dl decrease
600 mg group-8.4 mg/dl decrease

Acne
300 mg group-7 of the 12 men developed acne
600 mg group-2 of the 13 men developed acne

There were no significant changes in PSA or liver enzymes at any dose up to 600mg. However, long-term effects of androgen administration on the prostate, cardiovascular risk, and behavior are unknown. The study demonstrated that there is a dose dependent relationship with testosterone administration. In other words the more testosterone administered the greater the muscle building effects and potential for side effects.

Given the results of the study and based on years of personal experience I believe the first time user can safely use between 300-600 mg of testosterone enanthate or cypionate per week for 8-12 weeks. Because it is desirable to have even blood androgen levels I advise at least 2 equal injections per week. The following graph demonstrates that testosterone cypionate peaks within 1-2 days after injection and falls off to almost baseline by day 10. Therefore waiting 7 days between injections of cypionate would cause wide fluctuations in blood androgen levels.

Pharmacokinetics of Testosterone cypionate Injection

Source: Schulte-Beerbuhl, 1980 Figure. Pharmacokinetics of 200mg Testosterone cypionate injection. Source: Comparison of Testosterone, dihydrotestosterone, luteinizing hormone, and follicle-stimulating hormone in serum after injection of Testosterone enanthate or Testosterone cypionate. Schulte-Beerbuhl M, Nieschlag E. Fertility and Sterility 33 (1980) 201-3.

If a first time user wanted to use 600 mg of cypionate or enanthate per week he would inject 300 mg on Tuesday and another 300 mg on Saturday each week for 10 weeks. When injecting long heavy esters like cypionate with this frequency I tend to have less acne then 1 injection per week.

There are a number of esters which provide varying release times. Acetate or propionate esters extend the release time of testosterone a couple of days. In contrast, a deconate ester prolongs the release of testosterone about 3 weeks. Testosterone enanthate and cypionate are almost identical esters. The use of an ester allows for a less frequent injection schedule than using a water based testosterone like suspension which has no ester at all and is rapidly in and out of your system after injection. The published release times are not exact and are many times based on a single injection not many multiple injections which can delay the release of the hormone. Other factors affect release times of esters such as scar tissue and the muscle group injected. Only a blood test can confirm when the active hormone has cleared your system.

Esters not only effect release times but also the potency of the Testosterone as esters make up part of the steroid weight. This must be taken into account when calculating dosages. The longer the release time the less free hormone. For example propionate is about 15% more potent mg. for mg. then enanthate so 500mg of propionate would equal about 575 mg. of enanthate. The following chart illustrates the free base equivalents for several compounds.

Although it was not indicated in the trial, during or after the steroid cycle some men are prone to gynecomastia which is the formation of female like breast tissue. This is due to excessive estrogen as the body tries to balance out the sex hormones. A selective estrogen receptor modulator or S.E.R.M. such as Tamoxifen can be used effectively to combat gynecamastia in an emergency as it competes for the estrogen receptor which in turn inhibits estrogen's effects. It is highly recommended that a S.E.R.M. be available during treatment of Testosterone. 10-40mg daily is an effective dose however dosage is dependent on how much testosterone is administered as well as the individual himself.

The decision to use steroids should not be taken lightly and should be the last consideration after implementing a solid nutritional, training and recovery plan. It is advised to get blood work when using these medications.

Ancillaries during the cycle

Aromatase Inhibitor

I briefly wrote about using Tamoxifen above for emergency gynecomastia treatment however I'm convinced that there is a better strategy for controlling estrogen during a steroid cycle. Rather than waiting for the side effects of estrogen to present an aromatase inhibitor like Arimidex or Aromasin should be used on cycle to control Estrogen and keep free testosterone levels high. 0.5mg-1mg Arimidex every other day OR 10-25mg Aromasin daily. Start with the lower dose and then see how that controls water retention, blood pressure and libido and make adjustments as needed. A blood test would be the most ideal way to determine the dosage of the AI. Free T needs to be in the high range and estradiol between 10-30 pg/ml.
Human Chorionic Gonadotropin

Testosterone-Induced gonadotropin suppression tends to cause atrophy of the testes and decreases intratesticular testosterone. In other words, when a male administers testosterone his testes shrink because they are suppressed. A simple way to restore ITT levels and maintain the mass of the testes is to administer HCG during testosterone treatment. During a study it was determined that HCG is dose dependent and that approximately 300iu HCG taken every other day restored ITT levels. This is 1,050iu HCG weekly. I recommend 500iu twice weekly while on testosterone treatment. HCG will not only keep ITT levels and the mass of the testes normal but will also aid in keeping the male fertile.
Sample cycle with ancillaries

Sunday 10mg Aromasin
Monday 10mg Aromasin/500iu HCG
Tuesday 10mg Aromasin/300mg Enanthate
Wednesday 10mg Aromasin
Thursday 10mg Aromasin
Friday 10mg Aromasin/500iu HCG
Saturday 10mg Aromasin/300mg Enanthate

For all you guys who want to add multiple compounds to your first course I advise against it because if you have side effects then you will not know which compound is causing the sides. I have gotten a ton of questions over the years and there is always some reason that I'm given for using multiple compounds on the first run but there really is no need. However my cycle sample above may not be for everyone so I am offering an alternative to the flat cycle design. If you want to run a first cycle with a little more horsepower then you may want to consider a modified pyramiding cycle. I have done over 20 pyramid courses and must say they are my favorite way to run aas. The human body is always fighting for homeostasis so the concept is to increase dose before gains plateau. Based on the 2009 myostatin study we can design a cycle that is effective for 10 weeks using this strategy. The following first cycle is for men that want a little more performance with added risk while only using Testosterone. The first 5 weeks a standard dose is administered to evaluate how your body responds and to determine if sides are manageable. If sides are manageable then increase the dose.
Sample first course #2

Week 1-5 600mg Testosterone weekly
Week 6-8 800mg Testosterone weekly
Week 9-10 1 gram Testosterone weekly

10-25 mg Aromasin daily with the goal of keeping Estradiol between 10pg/ml-30pg/ml. Only blood work can confirm if you are in this range.

500iu HCG twice weekly.

Post Cycle therapy

I strongly believe that an AI should be used as long as there is an aromatizing compound being administered. In this case Testosterone and HCG aromatize therefore using an AI until these meds clear is what I'm recommending. Nolvadex has been shown to reduce IGF-1 and GH levels when used alone. This is not a big deal on cycle as testosterone increases IGF-1 in a dose dependent relationship. However off cycle this is may be a problem. PCT is a fragile time and lower IGF-1 and GH levels are not desirable. More advanced users may opt to use Nolvadex and Human Growth Hormone during PCT to counter the HGH lowering effect of Nolvedex. However, I'm recommending AI's that may be used on cycle and during PCT. It's my conclusion that Aromasin or Arimidex are both good choices.

I recommend the following PCT protocol for esters like Cypionate and Enanthate;

While the aas ester is clearing : 2500iu HCG every third day for 2 weeks. (You may use less HCG if your testes are normal in size AND you have been using HCG on cycle, i.e. 1,000iu HCG every third day.)

100/100/100/50 Clomid (50mg taken twice per day weeks 1-3 AFTER the aas ester clears)

20mg/20mg/20mg Aromasin (20mg daily for 3 weeks)

3g Vit C every day split in 3 doses

10g creatine daily

The HCG is administered BEFORE the aas ester clears to increase the mass of the testes and bring back ITT levels. This will allow the testes to sustain output of testosterone sooner.

Clomid is universally accepted as THE testosterone recovery tool. It blocks estrogen from the HPTA and stimulates the production of GNRH then initiates the production of LH, which in turn signals the testis (if not atrophied) to produce testosterone.

Aromasin or a similar aromatase inhibitor is for testosterone recovery and it is used to keep the testosterone/estrogen balance in favor of testosterone. It is also helps to keep any additionally occurring estrogen from HCG low to none.

Cortisol is catabolic. It is the enemy of all anabolism and must be kept in check. While it is blocked when under the influence of AAS, it is free to attach to the Anabolic Receptors (AR) once the steroids leave. Due to this blockage Cortisol tends to accumulate and increase when on. A low level is desirable however since it is important for other vital functions such as control of inflammation. Balance is the key. Vitamin C keeps the exercise induced rise of Cortisol in check.

The use of Creatine has shown to increase ATP metabolism and cellular water storage among many other things. This is beneficial because it provides for heightened nutrient storage and a slight increase in anabolism as well as workout stamina.

Failed Post Cycle TherapySometimes a single post cycle therapy is insufficient to restore healthy testosterone levels and a second post cycle therapy may be needed. In that case I would advise a simple clomid HPTA restart at 50mg daily for 4-6 weeks.

Testosterone dose-response relationships in healthy young men

Shalender Bhasin1, Linda Woodhouse1, Richard Casaburi3, Atam B. Singh1, Dimple Bhasin3, Nancy Berman3, Xianghong Chen4, Kevin E. Yarasheski4, Lynne Magliano2, Connie Dzekov1, Jeanne Dzekov1, Rachelle Bross3, Jeffrey Phillips3, Indrani Sinha-Hikim1, Ruoquing Shen1, and Thomas W. Storer2

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles 90059; 2 Laboratory for Exercise Sciences, El Camino College, and 3 Harbor-University of California Los Angeles Medical Center, Torrance, California 90502; and 4 Biomedical Mass Spectrometric Research Resource, Department of Internal Medicine, Washington University, School of Medicine, St. Louis, Missouri 63110

ABSTRACT

Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.

Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy

Indrani Sinha-Hikim1, Jorge Artaza1, Linda Woodhouse1, Nestor Gonzalez-Cadavid1, Atam B. Singh1, Martin I. Lee1, Thomas W. Storer1, Richard Casaburi2, Ruoquing Shen1, and Shalender Bhasin1

1 Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, 90059; and 2 Division of Respiratory and Critical Care Physiology and Medicine, Harbor-University of California at Los Angeles Medical Center, Torrance, California 90509

ABSTRACT

Administration of replacement doses of testosterone to healthy hypogonadal men and supraphysiological doses to eugonadal men increases muscle size. To determine whether testosterone-induced increase in muscle size is due to muscle fiber hypertrophy, 61 healthy men, 18-35 yr of age, received monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone secretion and weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate (TE) for 20 wk. Thigh muscle volume was measured by magnetic resonance imaging (MRI) scan, and muscle biopsies were obtained from vastus lateralis muscle in 39 men before and after 20 wk of combined treatment with GnRH agonist and testosterone. Administration of GnRH agonist plus TE resulted in mean nadir testosterone concentrations of 234, 289, 695, 1,344, and 2,435 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Graded doses of testosterone administration were associated with testosterone dose and concentration-dependent increase in muscle volume measured by MRI (changes in vastus lateralis volume, http://ajpendo.physiology.org/math/1...rmal/minus.gif4, +7, +15, +32, and +48 ml at 25-, 50-, 125-, 300-, and 600-mg doses, respectively). Changes in cross-sectional areas of both type I and II fibers were dependent on testosterone dose and significantly correlated with total (r = 0.35, and 0.44, P < 0.0001 for type I and II fibers, respectively) and free (r = 0.34 and 0.35, P < 0.005) testosterone concentrations during treatment. The men receiving 300 and 600 mg of TE weekly experienced significant increases from baseline in areas of type I (baseline vs. 20 wk, 3,176 ± 186 vs. 4,201 ± 252 µm2, P < 0.05 at 300-mg dose, and 3,347 ± 253 vs. 4,984 ± 374 µm2, P = 0.006 at 600-mg dose) muscle fibers; the men in the 600-mg group also had significant increments in cross-sectional area of type II (4,060 ± 401 vs. 5,526 ± 544 µm2, P = 0.03) fibers. The relative proportions of type I and type II fibers did not change significantly after treatment in any group. The myonuclear number per fiber increased significantly in men receiving the 300- and 600-mg doses of TE and was significantly correlated with testosterone concentration and muscle fiber cross-sectional area. In conclusion, the increases in muscle volume in healthy eugonadal men treated with graded doses of testosterone are associated with concentration-dependent increases in cross-sectional areas of both type I and type II muscle fibers and myonuclear number. We conclude that the testosterone induced increase in muscle volume is due to muscle fiber hypertrophy.

Testosterone nduced muscle hypertrophy is associated with an increase in satellite cell number in healthy young men

Indrani Sinha-Hikim,1 Stephen M. Roth,2 Martin I. Lee,1 and Shalender Bhasin1

1Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059; and 2Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvamia 15261
Submitted 22 August 2002 ; accepted in final form 26 March 2003

ABSTRACT

Testosterone (T) supplementation in men induces muscle fiber hypertrophy. We hypothesized that T-induced increase in muscle fiber size is associated with a dose-dependent increase in satellite cell number. We quantitated satellite cell and myonuclear number by using direct counting and spatial orientation methods in biopsies of vastus lateralis obtained at baseline and after 20 wk of treatment with a gonadotropin-releasing hormone agonist and a 125-, 300-, or 600-mg weekly dose of T enanthate. T administration was associated with a significant increase in myonuclear number in men receiving 300- and 600-mg doses. The posttreatment percent satellite cell number, obtained by direct counting, differed significantly among the three groups (ANCOVA P < 0.000001); the mean posttreatment values (5.0 and 15.0%) in men treated with 300- and 600-mg doses were greater than baseline (2.5 and 2.5%, respectively, P < 0.05 vs. baseline). The absolute satellite cell number measured by spatial orientation at 20 wk (1.5 and 4.0/mm) was significantly greater than baseline (0.3 and 0.6/mm) in men receiving the 300- and 600-mg doses (P < 0.05). The change in percent satellite cell number correlated with changes in total (r = 0.548) and free T concentrations (r = 0.468). Satellite cell and mitochondrial areas were significantly higher and the nuclear-to-cytoplasmic ratio lower after treatment with 300- and 600-mg doses. We conclude that T-induced muscle fiber hypertrophy is associated with an increase in satellite cell number, a proportionate increase in myonuclear number, and changes in satellite cell ultrastructure.

Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment

Indrani Sinha-Hikim, Wayne E. Taylor, Nestor F. Gonzalez-Cadavid, Wei Zheng and Shalender Bhasin

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059

Address all correspondence and requests for reprints to: Shalender Bhasin, M.D., Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059. E-mail: sbhasin@ucla.edu.

Abstract

Androgens stimulate myogenesis, but we do not know what cell types within human skeletal muscle express the androgen receptor (AR) protein and are the target of androgen action. Because testosterone promotes the commitment of pluripotent, mesenchymal cells into myogenic lineage, we hypothesized that AR would be expressed in mesenchymal precursor cells in the skeletal muscle. AR expression was evaluated by immunohistochemical staining, confocal immunofluorescence, and immunoelectron microscopy in sections of vastus lateralis from healthy men before and after treatment with a supraphysiological dose of testosterone enanthate. Satellite cell cultures from human skeletal muscle were also tested for AR expression. AR protein was expressed predominantly in satellite cells, identified by their location outside sarcolemma and inside basal lamina, and by CD34 and C-met staining. Many myonuclei in muscle fibers also demonstrated AR immunostaining. Additionally, CD34+ stem cells in the interstitium, fibroblasts, and mast cells expressed AR immunoreactivity. AR expression was also observed in vascular endothelial and smooth muscle cells. Immunoelectron microscopy revealed aggregation of immunogold particles in nucleoli of satellite cells and myonuclei; testosterone treatment increased nucleolar AR density. In enriched cultures of human satellite cells, more than 95% of cells stained for CD34 and C-met, confirming their identity as satellite cells, and expressed AR protein. AR mRNA and protein expression in satellite cell cultures was confirmed by RT-PCR, reverse transcription and real-time PCR, sequencing of RT-PCR product, and Western blot analysis. Incubation of satellite cell cultures with supraphysiological testosterone and dihydrotestosterone concentrations (100 nM testosterone and 30 nM dihydrotestosterone) modestly increased AR protein levels. We conclude that AR is expressed in several cell types in human skeletal muscle, including satellite cells, fibroblasts, CD34+ precursor cells, vascular endothelial, smooth muscle cells, and mast cells. Satellite cells are the predominant site of AR expression. These observations support the hypothesis that androgens increase muscle mass in part by acting on several cell types to regulate the differentiation of mesenchymal precursor cells in the skeletal muscle.

Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men.

Sinha-Hikim I, Cornford M, Gaytan H, Lee ML, Bhasin S.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University, Los Angeles, CA 90059, USA.

Abstract

OBJECTIVE: In this study, we determined the effects of graded doses of testosterone on muscle fiber cross-sectional area (CSA) and satellite cell number and replication in older men.

PARTICIPANTS: Healthy men, 60-75 yr old, received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate im weekly for 20 wk.

METHODS: Immunohistochemistry, light and confocal microscopy, and electron microscopy were used to perform fiber typing and quantitate myonuclear and satellite cell number in vastus lateralis biopsies, obtained before and after 20 wk of treatment.
RESULTS: Testosterone administration in older men was associated with dose-dependent increases in CSA of both types I and II fibers. Satellite cell number increased dose dependently at the three highest doses (3% at baseline vs. 6.2, 9.2, and 13.0% at 125, 300, and 600 mg doses, P < 0.05). Testosterone administration was associated with an increase in the number of proliferating cell nuclear antigen+ satellite cells (1.8% at baseline vs. 3.9, 7.5, and 13% at 125, 300, and 600 mg doses, P < 0.005). The expression of activated Notch, examined only in the 300-mg group (baseline, 2.3 vs. 9.0% after treatment, P < 0.005), increased in satellite cells after testosterone treatment. The expression of myogenin (baseline, 6.2 vs. 20.7% after treatment, P < 0.005), examined only in the 300-mg group, increased significantly in muscle fiber nuclei after testosterone treatment, but Numb expression did not change.

CONCLUSIONS: Older men respond to graded doses of testosterone with a dose-dependent increase in muscle fiber CSA and satellite cell number. Testosterone-induced skeletal muscle hypertrophy in older men is associated with increased satellite cell replication and activation.

PMID: 16705073 [PubMed - indexed for MEDLINE]

Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis.

Ferna¡ndez-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos-Orozco JF, Wang AT, Erwin PJ, Bhasin S, Montori VM.

Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.

Abstract

CONTEXT: The risks of testosterone therapy in men remain poorly understood.

OBJECTIVE: 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.

DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies.

STUDY SELECTION: 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.

DATA EXTRACTION: Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data.

DATA SYNTHESIS: 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.

CONCLUSIONS: 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.

PMID: 20525906 [PubMed - indexed for MEDLINE]

Pharmacokinetic properties of testosterone propionate in normal men.

Fujioka M, Shinohara Y, Baba S, Irie M, Inoue K.

Abstract

The pharmacokinetic characteristics of testosterone propionate were studied in normal men after a single im dose of 25 mg testosterone propionate-19,19,19-d3. Plasma levels of testosterone propionate-19,19,19-d3, its active metabolite testosterone-19,19,19-d3, and endogenous testosterone were measured by gas chromatography-mass spectrometry. Testosterone propionate-19,19,19-d3 was gradually transferred from the im injection site to the systemic circulation. The plasma levels of testosterone propionate-19,19,19-d3 were maintained at 2-4 ng/ml between 3 and 36 h after administration. Plasma testosterone-19,19,19-d3 levels were maintained above the physiological testosterone level for 48 h, while plasma levels of endogenous testosterone changed little.

PMID: 3782423  [PubMed - indexed for MEDLINE]

The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to Estradiol and Dihydrotestosterone in Young and Older Men

Kishore M. Lakshman, Beth Kaplan, Thomas G. Travison, Shehzad Basaria, Philip E. Knapp, Atam B. Singh, Michael P. LaValley, Norman A. Mazer 1 and Shalender Bhasin 1

ivision of Endocrinology, Diabetes, and Nutrition, and Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies (K.M.L., T.G.T., S.Ba., P.E.K., S.Bh.), Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts 02118; Lahey Clinic Medical Center (B.K.), Burlington, Massachusetts 01805; Charles Drew University (A.B.S.), Los Angeles, California 90059; Department of Biostatistics (T.G.T., M.P.L.), Boston University School of Public Health, Boston, Massachusetts 02118; and Hoffman LaRoche (N.A.M.), CH-4070 Basel, Switzerland

Address all correspondence and requests for reprints to: Kishore M. Lakshman, M.D., M.P.H., Division of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Medical Center, 670 Albany Street, Second Floor, Boston, Massachusetts 02118. E-mail: Kishore.Lakshman@bmc.org.

Abstract

Background: During testosterone (T) therapy, T is partly converted to 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT). Effects of age, testosterone dose, and body composition on total and free E2 and DHT levels are unknown.

Objective: We evaluated age and dose-related differences in E2 and DHT levels in response to graded doses of testosterone enanthate in young and older men.

Methods: Fifty-one young (aged 19–35 yr) and 52 older (aged 59–75 yr) men completed treatment with monthly injections of a GnRH agonist plus randomly assigned weekly doses of testosterone enanthate (25, 50, 125, 300, or 600 mg) for 5 months.
Results: During testosterone administration, total and free E2 levels increased dose-dependently (dose effect, P < 0.001) in both young and older men. Total and free E2 levels and E2:T ratios during T administration were higher in older than young men, but age-related differences in free E2 and free E2:T ratios were not significant after adjusting for testosterone levels, percentage fat mass, and SHBG. DHT levels and DHT:T ratios were dose-related but did not differ between young and older men. Mechanistic modeling of free hormone data revealed that the conversions of T to E2 and DHT were both consistent with saturable Michaelis-Menten kinetics. The in vivo Km values were estimated to be 1.83 nm for aromatase and 3.35 nm for 5α-reductase, independent of age. The Vmaxparameter for E2 was 40% higher in older men than younger men, but Vmax for DHT was not significantly different between age groups.

Conclusions: During im testosterone administration, E2 and DHT levels exhibit saturable increases with dose. The rate of whole body aromatization is higher in older men, partly related to their higher percentage fat mass, SHBG, and testosterone levels.

References:

1.Testosterone dose-response relationships in healthy young men;
2.Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males
3.Low-Dose Human Chorionic Gonadotropin Maintains Intratesticular Testosterone in Normal Men with Testosterone-Induced Gonadotropin Suppression
4.Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse.
5.Changes in the Endocrinological Milieu After Clomiphene Citrate Treatment for Oligozoospermia: The Clinical Significance of the Estradiol/Testosterone Ratio as a Prognostic Value
6.Testicular steroidogenesis after human chorionic gonadotropin desensitization in rats.
7.Effect of tamoxifen on GH and IGF-1 serum level in stage I-II breast cancer patients
8.Treatment of gynecomastia with tamoxifen: A double-blind crossover study
9.Role of testosterone/estradiol ratio in predicting the efficacy of tamoxifen citrate treatment in idiopathic oligoasthenoteratozoospermic men.

Drugs of the Future

November 8

by Blane Morton

Who doesn’t love fantasizing about what will be the next latest and greatest drug to hit the black market? You know, it wasn’t too long ago that growth hormone wasn’t readily available. Those Andro pills in Mark McGuire’s locker look more like chewable vitamins than a congressional problem next to the prohormones we have available today. You would have to have absolutely no imagination at all not to be curious as to what’s next? It’s the hope that keeps many guys training. If science can just crack the superhuman code it could eventually be in the hands of the guys on the streets. So what is it?

By now we’ve all seen the Belgium Blue bull with a myostatin resistant gene. Lucky cow! An all-natural, hormone free animal that’s bigger and stronger than anything we’ve seen before including those animals jabbed in the ear with tren pellets. The magical drug administered is Follistatin and right now it costs an arm and a leg to afford and it’s even trickier to obtain. Many conspiracy theorists in bodybuilding believe mega freaks like Ronnie and Big Ramy should credit Follistatin as the cause of their abnormally dense and massive bodies. Hard to argue when you look like the side-by-sides of them and the cow.

What if Follistatin became as easy to buy as growth hormone? Would that make steroids and growth hormones obsolete? And would that make for better sports and better bodybuilding or just a bigger version of what we already have?

Obviously there are a lot of questions to be answered. Has it already been manufactured at a low cost to the consumer, but is not being released for fear of it getting out of control? The thought of it makes me think of the movie The Incredible Hulk, an injection that could make our soldiers as big as Ronnie Coleman, as athletic as Georges St. Pierre, and as fast as Usain Bolt. Maybe I’m getting ahead of myself, but maybe not, after all I’m fantasizing about the drugs of the future.

Not only do I think releasing a true myostatin blocker to the masses would all but crush just about everything shy of HRT doses of testosterone and growth hormone, I think it would make for a real moral and ethical debate for athletes who previously never had a problem with using hormones. In other words, you’re not concealing your use with gene therapy. This stuff could make Miley Cyrus look like Serena Williams—well, only if she used Melanotan II along with it.

Bodybuilders would still likely dive right in and still pound away at grams of test and tren without batting an eye. Other athletes might follow suit as well or at least until the drug testers finally caught on. And side effects, bodybuilders and athletes don’t care about side effects; well, most of them. It’s all about the money baby!

As for other drugs in the future, I’d love to see a fast acting endurance drug. Nothing archaic like EPO, but something straight to the point: a guy off the street who never jogged in his life could swallow the pill or take the shot and go run a 6 minute mile. Or how about a joint pill that actually worked? Enough with this glutamine and chondroitin nonsense – go eat your shark cartilage you hippies.

Science has been researching for decades on a cure for cancer to no avail. Yet sport science seems to be doing laps around just about every other scientific advancement. Is this form of muscle mutation chemistry really that much easier? I hope I live long enough to see what comes out in 50 years – a 400lb bodybuilder; a 3 minute mile runner; a 1000lb raw bench presser? Let’s do it!

13 Grams of Anabolic Steroids per Week

http://www.ironmagazine.com/2013/13-grams-of-anabolic-steroids-per-week/


November 12, 2013 

by Mike Arnold

Yes, that’ not a typo. I said 13 grams of gear per week. Does this type of abuse really take place? If so, what kind of man would take such a dose? Surely, a BB’r like this must be shattering our preconceived limits of muscular development. If not, then at least we have another Big Ramy on our hands, right? I wish this were the case, but unfortunately the truth is a bit less impressive. Let me put it this way. He is in his early 20’s, looks like he has been training his legs for about 6 months, and if I am not mistaken, competes on a state or possibly regional level.

Before I get accused of misrepresentation, in fairness I should also state that he is using insulin, GH, IGF-1, a small pharmacy worth of ancillaries, and good ole’ Synthol to top things off. Ohhh…and to his credit, he has built a decent upper-body, which is comparable to other BB’rs at the state level. Lest you think I might be betraying this man’s confidence, let me assure you that he has taken every opportunity to publically proclaim his drug use from rooftops, so there is nothing being said here that others haven’t heard 1000 times over.

As disturbing as some may find this to be, it is not the habits of one man I want to talk about. Rather, spectacles such as this serve to bring awareness of just how far this generation has fallen when it comes to the proper place of drugs in BB’ing. Over the last decade and especially the last few years our community has experienced a shift in consciousness, in which many have come to believe that drugs are the be-all and end-all to BB’ing success. The more is better philosophy and has now become the more is necessary philosophy.

Being that we currently know more than ever about performance enhancing drugs and their effects on the body, how did we ever arrive at this juncture? Doesn’t it seem a little ass-backwards that the BB’rs from the 70’s and 80’s, despite possessing inferior overall knowledge in nearly every aspect of this sport, had a more accurate understanding of the role PEDs play in BB’ing than most BB’rs do today? They understood full well that drugs were only one part of the greater whole; a compliment to one’s hard work in the gym and dedication at the dinner table, while BB’rs today seem to think that drugs are 90% responsible for building a great physique. Somehow, our community’s knowledge in this area has regressed over the last decade.

Make no mistake about it, drugs are absolutely essential for success in this sport on the pro-level. Drug use is mandatory…and using a few d-bol here and there isn’t going to cut it. Unless you are one of the rare genetic freaks, you will need to use plenty of drugs. Most pros today use a combination of AAS, GH, and insulin, among others. So, while we can all agree that large dosages are usually necessary, not everyone holds the same opinion as to what constitutes a “large” dose and this is where the conflict lies.

What is a “large dose”? It wasn’t long ago that 2 grams of total steroids per week was considered a massive dose of steroids. A fully grown adult male will produce roughly 50-100 mg of testosterone per week. A 2 gram per week steroid cycle provides a BB’r with roughly 20-40X the amount of steroid that his body would produce naturally, yet many of today’s younger generation have been brainwashed into thinking that this dose of drugs is insufficient for building pro-level muscle mass…and many believe one can’t even make it to a national stage without using at least this amount of gear or more. The truth is that the human body can build and support a massive amount of muscle tissue with 2 grams of AAS per week…and many pros have built their body on that dose or less, but more on that in a minute. Just a single 200 mg injection of testosterone cypionate has been shown to increase protein synthesis by over 200%! Although 200 mg is now considered nothing more than a TRT dose, it will still double the rate of muscle growth in the average person. Now think about what 5-10X that dose is capable of doing?

In my opinion, the #1 reason for the massive influx of ignorance into our sport is due to the internet. Today, anyone with a computer and an internet connection has a world-wide platform from which they can spout off any amount of nonsense they wish without consequence. I estimate that of all the people we see regularly frequenting BB’ing boards and other social media, maybe 1% of them have any real-world connection to the BB’ing industry or the BB’rs that define it. Very few of these people know the truth through personal experience. Nearly all of their knowledge is obtained from reading and hearing what other people have to say, most of whom are simply repeating what they have heard from other ignorant people…and the pattern repeats itself. So, when we hear people say what “all” the pros are using (which is a completely ignorant statement in itself), we can be rest assured that in nearly every case, this information did not come from the pros themselves, nor anyone who knows them. It is all speculation and guesswork with these people…and they are usually wrong.

You may be wondering how many times I am going to type the word “ignorant”…and the answer is as many times as it takes to convince you that there is very little reliable information posted by those who communicate via social media. Even worse, when accurate information is provided, it is almost always laughed off as being bullshit…or the individual providing the information is called a liar. It seems that if anyone claims to have built their physique on anything other than absolutely monstrous amounts of drugs, the automatic assumption is one of disbelief. This has caused most pros to forgo any type of honest discussion about their PED use, as they don’t want to be subjected to the same type of abuse and ridicule so often encountered by those pros that do.

Consider the following. Back in the 80’s, during the days of Lee Haney, growth hormone usage was basically non-existent, as was insulin. Even if someone did want to use GH, the price was astronomical and availability was so low it was next to impossible to obtain. For this reason GH was not a significant part of pro BB’ing scene in the 1980’s. While insulin was available (only Humulin R) at that time, it was not yet regarded as the potent muscle building drug it is today. Most BB’r didn’t give a second thought to this drug. Hell, most BB’rs did not even realize insulin was anabolic in nature. Most simply viewed it as a medication designed to help diabetics manage their disease. It would be several more years before Dan Duchaine brought the hormone to the forefront of BB’ing drug culture.

The point here is that the pros of the 80’s, in almost every case, built their physiques on steroids and steroids alone. There was no insulin, no GH, and certainly no IGF-1 or myostatin inhibitors available to this generation of great competitors. Despite these limitations, we saw BB’rs like Lee Haney, Rich Gaspari, Mike Christian, Lee Labrada, Jeff King, Matt Mendenhall and others build extremely impressive physiques. Some might say “OK, but they still used a ton of steroids to reach that level of development”…and to that I will say, how do you know how much they used? In reality, the amounts used by the pros of that era were as diverse as they are today. Some used more and some used less, but by and large the dosage employed by the average pro back then were a mere fraction of what they are today.

For one, testosterone wasn’t nearly as popular then as it is today. Many BB’rs used no testosterone at all and if they did, it was more often small dosages of 200-300 mg/week. Sure, there was a small contingent of BB’rs who relied more heavily on testosterone than the rest of their peers, but this segment of the population did not reflect the majority. The typical Deca & D-bol stack ruled the day when it came to off-season mass-building. It was nearly unheard of for a BB’r to use a gram of Deca and 100 mg of D-bol in the same cycle, like we see today. Your typical dosages were around 500-600 mg of Deca per week combined with 40-50 mg of D-bol per day…and this was for pro BB’rs. Of course, as a contest approached, many BB’s would begin leaning more heavily on drugs such as Winstrol, Anavar, and Primo, but in many cases drugs like Deca & D-bol remained part of the cycle right up until competition day.

If I BB’r really wanted to get crazy he might combine 2 injectables and maybe 2 orals (most BB’rs in that day used only one oral at a time)…and the total dosage might reach 1,500 mg weekly. However, this was not the norm and was considered excessive by most. I am sure at least a few people reading article this will call bullshit because they know of someone who used more, but like I said, there have always been guys who have pushed the dosing envelope in their generation. However, these men do not adequately represent the average BB’r of their era. They are the exception, not the rule.

Believe it or not, these doses remained pretty normal even into the early 90’s, although more and more BB’rs were beginning to go beyond previously conceived limits. In my own person experience, I was taught quite a lesson early on regarding the drug habits of serious competitive BB’rs. The place was Powerhouse gym and the time was 1990. Even though the 1st Anabolic Steroid Control Act had just been passed, many BB’rs were still quite open about their use. It was all too common to find BB’rs injecting each other in the locker rooms or elsewhere. Syringes would be left in the trash bins and empty pill bottles on benches. A few decades ago most serious gyms were BB’r oriented. It was nothing to see a few national level competitors, multiple state & regional competitors, and a handful of state level guys all training at the same gym.

It was under these circumstances that I was first introduced to the reality of steroids in BB’ing. I was not completely ignorant regarding the use of steroids in the sport, but I had no clue how much or what BB’rs were using. After speaking in depth with most of the BB’s that trained there over the years, they did not hold back about their drug use when I inquired. Remember, this was 1990. Lee Haney was about to win his 7th Olympia title and Dorian Yates was about to make his mark on the scene, so we were already witnessing the arrival of some big guys on the pro & national circuit. Of all the high-level BB’rs who trained at my gym…several were 5’10-6’3 and weighed between 250-310 lbs. I regularly saw these men benching 500 lbs or more and behind the neck pressing 3 plates for reps. The average dosing range for these men was about 1 gram of gear per week…sometimes slightly more. NONE of them used GH or insulin.

As we moved into the 90’s the doses grew to the point where roughly 2 grams was considered a massive dose. Many, many pros built massive muscle size by topping out at around 2 grams weekly or less. Yes, some went higher, but there were plenty of BB’rs who did not. As we moved into the 2000’s and beyond, the definition of what constituted a “massive” dose continued to evolve. At this point in 2013 two grams is considered by many to be a minimalist approach, while 3-4 grams weekly is seen as more suitable for maximizing muscular development.

Now, being a BB’r at heart and a drug enthusiast, I do not judge anyone’s decision to use larger dosages, so long as the decision makes sense and by makes sense, I mean they body is actually able to use the gear that is being put into it. You see, the human body has a limit regarding the amount of gear it can use for recovery & growth, beyond which point results will level off and side effects will increase. Surpassing this point is flat-out stupid, as it provides no further benefit while simultaneously increasing the potential for health problems. How can anyone justify such a decision to exceed those limits in light of these circumstances? Unfortunately, most of the people who walk this road and advise others to do the same are acting in ignorance. They lack a fundamental understanding of these drugs and their effect on the human body. Often, they have been brainwashed into thinking that more is always better and that every pro BB’r today is secretly using monstrous dosages of every PED imaginable. Therefore, they believe that they must do the same thing if they want to get to the same place.

So, how much gear can the body actually use? We cannot say for certain, as there are several factors which can impact an individual’s ability to use AAS, but science has still provided us with a ballpark figure. According to medical research, the average human being will reach the point of receptor saturation at about 3,500 mg per week. That means at 3,500 mg per week, every single available androgen receptor site will be filled up! While AAS are also capable of inducing a growth response through non-genomic mechanisms (non-AR mediated muscle growth), AR activation is the primary mechanism through which steroids stimulate muscle protein synthesis. We do know that AAS themselves are capable of directly increasing AR count, so it is very likely this number will rise at least slightly beyond 3,500 mg in heavy steroid users, but we do not know exactly how much. In situations like this, the best we can do when attempting to come to a conclusion is to evaluate the available anecdotal evidence in light of scientific fact. Often, this will help us to fill in the blanks…and in this case we have more than enough anecdotal evidence to draw from.

Based on the personal response of BB’rs over the last 15 or so years (since the mega-dosing started in earnest), it appears that most BB’rs reach the point of diminishing returns somewhere between 3.5-5 grams per week. Among those BB’rs who do appear to receive additional benefit by increasing their dose to the 5 gram per week mark, most will readily confess that their gains barely improved by adding that extra 1,500 mg….and many BB’rs will notice no improvement in growth rate at all. Therefore, real-world experience appears to confirm what science has been telling us for years; that 3,500 mg per week is about the limit for the average person. Personally, I have never known a single BB’r who claims to have experienced measurably better gains when using 7, 8, 9 or more grams of gear per week than when using a more modest, but still massive dose of 3-5 grams weekly.

No matter how you slice it, absolutely no justification whatsoever can be found for using 13 grams of gear per week, as purported by a certain BB’r. I can understand why a serious competitive BB’r might want to reach receptor saturation; at least the body is able to find a place for all that gear, but finding a place for it and actually being able to use it to stimulate additional muscle growth are two different things altogether. You see, just because the body may have enough androgen receptors to accommodate 3,500 mg of gear or slightly more, it does NOT mean the body will necessarily be able to take advantage of all that gear. There are numerous factors involved in the muscle growth process and the body will only grow as fast as the weakest link allows it to. For example, you can take all the gear you want…fill up every receptor site available…and inject enough GH & insulin to put a pharmacy out of business, yet never gain an ounce of muscle if you are following a starvation diet. This is only one factor of many which have the potential to drastically alter our growth rate, regardless of how many drugs we take. Reaching receptor saturation only increases one’s potential for growth…it does not guarantee that growth rate will increase or that growth will even take place at all.

In 2013 just as many BB’rs are ignorant regarding the basic rate limiting factors which govern the muscle growth process, as they are regarding the amount of gear the body can potentially use. No wonder our sport is a mess. These are two separate subjects that every BB’r should have a working knowledge of before he even contemplates using AAS. Otherwise, he will never be able to extract maximum benefit from his gear use and will likely end up jeopardizing his health just to look remotely decent. Why do you think we are now seeing so many low-level amateur and recreational BB’rs use an amount of PED’s that would fell a horse, yet they don’t look half as impressive as the average pro from the 80’s, who used ½ to 1/3rd the dose? If this doesn’t start to raise some questions, then nothing will.

Testosterone Replacement Therapy (TRT) in Testosterone Deficient men

November 14, 2013  

by Monica Mollica

Testosterone deficiency in men, aka hypogonadism, is associated with increased total and abdominal fat mass, and reduced muscle mass, which negatively impacts body composition.[1, 2] This contributes to development of risk factors like insulin resistance, chronic inflammation, and atherogenic dyslipidemia (a triad of increased blood levels of small, dense LDL particles and triglycerides, and decreased levels of HDL particles), which increase the risk for cardiovascular disease, metabolic syndrome and diabetes.[1, 3-16]

Previous studies have shown that testosterone replacement therapy ameliorates these risk factors in testosterone deficient (hypogonadal) men; it increases insulin sensitivity [17-20] and HDL (the “good” cholesterol)[9, 10, 20, 21], and reduces waist circumference [9, 20, 22], fasting blood glucose [9, 20] triglycerides (blood fats)[9], LDL (the “bad” cholesterol) [19, 22-24], and several inflammatory markers.[17, 25]

A 2011 meta-analysis concluded that testosterone replacement therapy improves metabolic control, as well as reduces abdominal obesity.[9] Many studies have shown that testosterone replacement therapy in hypogonadal men increases muscle mass and reduces fat mass.[19, 26-32] Further, adding testosterone (50 mg/day for 1 year, administered as a transdermal gel) to a diet and exercise program results in greater therapeutic improvements of glycemic control and reverses the metabolic syndrome.[20]

Testosterone also has direct (non-obesity mediated) beneficial effects on many metabolic and cardiovascular risk factors [12, 33-37], and reduces death risk independently of body fat status.[38] In line with all these effects, low testosterone levels are associated with increased risk of cardiovascular complications [39], and all-cause and cardiovascular disease death [40-42]. Low testosterone may thus be a predictive marker for men at high risk of cardiovascular disease.[41] In a group of men aged 50-91 who were followed for 20 years, it was found that men whose total testosterone levels were in the lowest quartile (241 ng/dl or lower) were 40% more likely to die than those with higher levels, independent of age, adiposity, lifestyle or presence of cardiovascular risk factors.[38]

Thus, treatment of testosterone deficient men with testosterone has demonstrated considerable health benefits. Despite this, critics state that most of the studies on testosterone replacement therapy were too small. They also argue that the studies were of too short duration (most of them lasting 6-12 months), and that the long-term effects of testosterone on body composition are not known.

Two 5 year long studies were just published that addressed the duration and small study size shortcomings in previous research…

Effect of testosterone replacement therapy on body fat and waist circumference

This was a registry study of 255 men, aged between 33 and 69 years (mean age 58), who had sought consultation in an urologist’s office for various medical conditions, e.g. erectile dysfunction, decreased libido, questions about their testosterone status or a variety of urological complaints. [43] Upon clinical and laboratory investigation, the subjects were found to have subnormal total testosterone levels, mean 223 ng/dl. All men received treatment with testosterone undecanoate injection (a long acting form of testosterone [44, 45]) at a dose of 1000 mg administered at baseline and 6 weeks and thereafter every 12 weeks for up to 5 years (60 months). Body weight and waist circumference were measured at baseline and yearly.

* The testosterone treatment resulted in a significant increase in total testosterone levels, which increased from a baseline level of 223 ng/dl to 467 ng/dl within the first 12 months, and thereafter stabilized between 519-548 ng/dl for the remainder of the observation period.

* Waist circumference declined from 42.4 in (107.7 cm) to 39 in (99 cm), with a mean reduction of 3.7 in (9.4 cm). The reduction in waist circumference was significant at the end of each year compared to the previous year over the full 5-year observation period.

* Body weight decreased from 221 lb (100.1 kg) to 204 lb (92.5 kg), with a mean loss of 24.5 lb (11.1 kg).
As for the waist circumference reductions, the weight loss was significant at the end of each year compared with the previous year over the full 5-year observation period.

* Of 261 patients treated with testosterone for 5 years, only 6 patients (2.3 %) got diagnosed with prostate cancer.
Effect of testosterone replacement therapy on metabolic syndrome components
The same research group performed another study investigating the effects of the same 5 year long testosterone replacement therapy on metabolic syndrome components [46]. In this study, the testosterone deficient (hypogonadal) men had baseline total testosterone levels of 286 ng/dl (mean value), range 170-350 ng/dl. As in the above mentioned study, all men received treatment with testosterone undecanoate injection, 1000 mg administered at baseline and 6 weeks and thereafter every 12 weeks for up to 5 years (60 months). Blood lipids, glucose, liver enzymes and haemoglobin A1c (HbA1c) were measured at baseline and yearly.

* The testosterone treatment resulted in a marked and significant gradual decrease in LDL “bad” cholesterol levels from approximately 164 mg/dl (4.2 mmol/L) to approximately 110 mg/dl (2.8 mmol/L).
The reduction in LDL level was significant within the first year of treatment and remained low over the course of 5-year treatment period.

* HDL “good” cholesterol levels increased slightly but significantly and remained elevated over the 5-year period of treatment. The increase was gradual and significant within the first year of treatment.

* The total cholesterol/HDL ratio, which gives an indication of cardiovascular disease risk [47, 48], improved considerably from 5.44 to 3.49, suggesting a favorable change in the lipid profile and a potential reduction in cardiovascular disease risk.

* Triglyceride levels decreased from 276 mg/dl (3.1 mmol/L) to 190 mg/dl (2.2 mmol/L), and remained low throughout the 5-year treatment period. The reduction in triglyceride level was significant within the first year of treatment and remained low over the course of 5-year treatment period.

* Systolic blood pressure was reduced from about 154 to 138 mmHg and diastolic blood pressure was reduced from 93 to 80 mmHg. The decreases in blood pressure were significant and gradual over the first 2 years and remained low over the entire course of the 5 years of treatment.

* Fasting blood glucose dropped from 103.4 mg/dl (5.74 mmol/L) to 97.6 mg/dl (5.74 mmol/L). The decrease was significant after 12 months and further declined after 24 months and then reached a plateau.

* The decrease in fasting blood glucose was paralleled by a marked decrease in glycated hemoglobin (HbA1c), from 7.06 % to 6.16%. In contrast to fasting glucose, the decrease in HbA1c was statistically significant after 12 months, between 24 and 12 months, between 36 and 24 months, between 48 and 36 months, and between 60 and 48 months.

* The inflammatory marker CRP was markedly and significant decreased from 6.29 to 1.03 U/L), with a plateau after 36 months.

* The liver enzymes aspartate transaminase (AST) dropped from 43 to 20 U/L) , with a plateau after 24 months), and alanine transaminase (ALT) from 44 to 21 U/l , with a plateau after 36 months).

* Prostate volume increased from 28.51 ml to 30.04 ml, reaching a plateau after 3 years. PSA (prostate specific antigen increased from 1.77 to 1.83 ng/ml, with a plateau after 2 years. There were no occurrences of urinary retention or other problems related to benign prostatic hyperplasia (BPH). Only 3 patients were diagnosed with prostate cancer. This represents an incidence of 1.2% (3 patients out of 255).

Commentary

These two studies provide compelling data on the benefits and safety of testosterone replacement therapy, and confirm the results of previous smaller and shorter duration studies. Here are my comments on the findings:

Prostate

The 1.2-2.3% incidence of prostate cancer in these studies is far lower than the 9.6% incidence reported in the general population.[49] Another 5 year long safety study has also found that testosterone treatment didn’t change neither the Prostate Symptom Score (IPSS), post-void residual (PVR) volume, maximum urinary flow (Qmax) rate nor prostate size in obese testosterone deficient men with metabolic syndrome and moderate lower urinary tract symptoms at baseline.[50] Additional support for prostate safety with testosterone replacement therapy comes from meta-analysis of 19 studies, which revealed no greater risk of prostate cancer in men with testosterone deficiency who received testosterone therapy versus men who received placebo.[51] Another 6-year long study confirmed the prostate safety of testosterone replacement therapy.[52] Further, a large international study comprising 3886 men with prostate cancer and 6438 age-matched controls found no associations between prostate cancer risk and blood levels of total testosterone, free testosterone, or dihydrotestosterone.[53, 54] In the to date largest worldwide sample of hypogonadal men, testosterone replacement was found to be safe, effective and well tolerated.[55]

As I discussed in a previous article “Testosterone Replacement Therapy – why is it so controversial?”, there is no compelling evidence that testosterone is the driving factor in the development or progression of prostate cancer.[56] Evidence accumulated over the last 15 years strongly indicates that beyond the near-castrate range there is little, if any impact of changes in testosterone levels on prostate cancer growth.[57]

Testosterone levels

It should be noted that the baseline total testosterone levels is these two studies were in the low normal range, and that testosterone dose was low and given over an extended period of time. Also, the final level of 520-550 ng/dl is still probably suboptimal for most men.

Although there is no consensus as to what is a desirable range of testosterone, clinical data suggest that the normal range of testosterone in adult men is between 346-1154 ng/dl (12-40 nmol/L).[58] A threshold of 349 ng/dl (12.1 nmol/L) representing the lower end of the normal range was confirmed in an analysis of a number of well-known studies such as Framingham Heart Study generations 2 and 3, European Male Aging Study and the Osteoporotic Fractures in Men Study.[59] The large normal reference range of testosterone levels in adult men underscores the importance of contrasting the low end with the high end.

This was illustrated in a study showing that testosterone levels have to exceed 550 ng/dl in order to cut cardiovascular disease risk.[39] Also, triglyceride levels can respond differently in the low end vs. high end of the normal reference range.[60] Additionally, both supplementation dose and age will influence the outcomes.[12, 61] I will cover this more in-depth in an upcoming article.

HDL – the “good” cholesterol

Studies on the effect of testosterone on HDL have been inconsistent, showing increase [10, 21], decrease [62-66] or no changes [22-24, 26] in HDL levels in testosterone deficient med treated with testosterone. One analysis showed, counter intuitively, that larger doses of testosterone were associated with smaller declines in HDL.[66] These discrepancies in the various studies may relate to use of varying formulations of testosterone, dosage administered, duration of the studies, co-morbidities of subjects enrolled in the various studies. The decrease in HDL in response to testosterone supplementation was seen mostly in studies with supra-physiological testosterone doses.[28, 67, 68] Recently studies have shed light on the importance of HDL quality and function, as opposed to just HDL levels (quantity) [34], which is the commonly measured HDL parameter. Accumulating data is showing that testosterone beneficially might affect several aspects of HDL composition and functionality [69-71]. The link between testosterone levels and HDL quality and quantity is subject of intense research and debate, which I will go over in an upcoming article.

Triglycerides (blood fats) and the Triglyceride/HDL ratio – LDL particle size and Insulin Resistance
Another interesting finding in the second of the above outlined studies is the marked reduction in triglyceride levels.[46] This will lower the triglyceride/HDL ratio (especially when combined with an HDL elevation), which in turn reduces insulin resistance and increases LDL particle size.[72]

An increased LDL particle size indicates an improvement of atherogenic dyslipidemia, and can convert a person from the dangerous “pattern B” to the healthier “pattern A”. For more on the LDL particle size and patterns A and B.
“Blood Cholesterol Testing – don’t let the simple numbers fool you!”

A decreased triglyceride/HDL ratio also indicates improved insulin sensitivity [72-76]. Thus the reduction in triglyceride/HDL ratio seen in the 5-year long testosterone replacement study [46] confirms previous research showing that testosterone improves insulin sensitivity. [17, 18]

Total cholesterol/HDL ratio

The total cholesterol/HDL ratio (like the just mentioned triglyceride/HDL ratio) gives an indication of cardiovascular disease risk [47, 48]. A decrease in the total cholesterol/HDL ratio from 5.44 to 3.49 with testosterone therapy [46] therefore indicates improvement in another aspect of the blood lipid profile, and a reduction in cardiovascular disease risk.

Bottom Line

In the long-term studies outlined in this article [43, 46], subjects were told to keep their habitual lifestyle, so the results are not due to any major other intervention. The remarkable effects of testosterone replacement therapy seen in these two studies, even at low dosages, shows how powerful testosterone therapy can be, and how greatly it can contribute to combat expanding waistlines, obesity, metabolic syndrome, cardiovascular disease and diabetes.

www.trainergize.com

About the Author:
————————————–

Monica Mollica has a Bachelor’s and Master’s degree in Nutrition from the University of Stockholm, Sweden, and is an ISSA Certified Personal Trainer. She works a dietary consultant, health journalist and writer for www.BrinkZone.com, and is also a web designer and videographer.

Monica has admired and been fascinated by muscular and sculptured strong athletic bodies since childhood, and discovered bodybuilding as an young teenager. Realizing the importance of nutrition for maximal results in the gym, she went for a BSc and MSc with a major in Nutrition at the University.

During her years at the University she was a regular contributor to the Swedish bodybuilding magazine BODY, and she has published the book (in Swedish) “Functional Foods for Health and Energy Balance”, and authored several book chapters in Swedish publications.

It was her insatiable thirst for knowledge and scientific research in the area of bodybuilding and health that brought her to the US. She has completed one semester at the PhD-program “Exercise, Nutrition and Preventive Health” at Baylor University Texas, at the department of Health Human Performance and Recreation, and worked as an ISSA certified personal trainer. Today, Monica is sharing her solid experience by doing dietary consultations and writing about topics related to health, fitness, bodybuilding, anti-aging and longevity.

References:

1. Wang, C., et al., Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care, 2011. 34(7): p. 1669-75.
2. Cattabiani, C., et al., Relationship between testosterone deficiency and cardiovascular risk and mortality in adult men. J Endocrinol Invest, 2012. 35(1): p. 104-20.
3. Traish, A.M., et al., The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl, 2009. 30(5): p. 477-94.
4. Corona, G., et al., Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol, 2011. 165(5): p. 687-701.
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