Home | TESTOSTERONE 2-page summation | high testosterone 40% lower death rate | Prostate cancer not promoted by testosterone | DHEA cheap legal popular steroid | Viagra & Erectal Dysfunction | Why Testosterone is Cardiovascular Protective | TESTOSTERONE-CONCISE NOTES | TESTOSTERONE--EXTENSIVE NOTES | Pharmacology textbook, chapter on TESTOSTERONE | Methods of Testosterone Supplementation | Testosterone for Women? | TTT GOOD FOR THE BRAIN--2 studies | MALE-MENOPAUSE-2ND ARTICLE | MALE MENOPAUSE | DOUBTS ON TTT & ANDROSTENE | OVER-THE-COUNTER-SOLUTION | HOT NUTS: THE CONSEQUENCES | Oral hGH, what works? | HGH-HYPE & FACTS | HGH-POSITIVE FINDINGS--HARVARD | TESTOSTERONE NOT LINKED TO PROSTATE CANCER--latest study shows | Cialis better than Viagra | VIAGRA SAFE | circumcision reduces HIV risk 60% | Prostate Disease | Prostate biopsy, PSA test, prostatectomy--Urology textbook | Prostate cancer and blocking testosterone | LINKS



Quality medical information on Testosterone



The testes produce 95% of the Testosterone (TTT), about 5 mg/day& about 50 to 100 mcg of dihydrotestosterone (DHT) and estradiol.  TTT is 60% bonded to a plasma protein, 38% to albium, and 2% free.  TTT is derived from LH, and TTT is readily metabolized by the liver.  DHT is more potent than TTT.  TTT freely enters target cells and binds to intracellular receptors which then bind to DNA promoting gene transcription.  DHT works is more active at these sites.  DHT is necessary in early development for enlargement of the prostate, penis, and hair growth at the time of puberty.  TTT for muscle mass and sex drive


Androsol, 8 ml, $37, Biotest, Colorado Springs, biotest-online.com, 800-525-1940.  7 sprays = 1 ml contains 50 mg of 4-androstene-3,7-diol


30-35 years old the normal level of free testosterone is 700-900 ng/dl, women 50-70 (only 2% is free.  [Goodman & Gilman list plasma less of less than 20 ng/dl prior to puberty.  And the adult male has a rate of product of 2.5 to 11 mg/day.].  Androgens may be therapeutic value against Alzheimer's disease and male aging.

Journal of Neurochemistry   77(5), 1319-26.



In circulation Androgens serve as prohormones for the formation of two classes of steroids:  5 alpha reduced androgens, which act as the intracellular mediators of most actions of the hormone, and estrogens, which enhance some androgenic effects and block others.  Androgens may be responsible in part for organizational effects in the brain during prenatal or early postnatal life (1442).  "Normal men experience only a transient positive nitrogen balance of a slight degree when exogenous androgens are administered.  A maximally effective dose of 25 mg of testosterone propionate daily causes an average retention of nitrogen of 63 mg/kg daily in hypogonadal men. 




Testosterone Replacement Therapy

Wayne J.G. Hellstrom, M.D.

Tulane University Medical Center
New Orleans, LA



    Transdermal testosterone replacement therapy, in particular, has been linked to positive effects on fatigue, mood, and sexual function, as well as significant increases in sexual activity.20 More specifically, testosterone replacement therapy has been shown to improve positive mood parameters, such as feelings of wellness and friendliness, while reducing negative mood parameters, such as anger, nervousness, and irritability.21 Testosterone replacement is an effective treatment for some depressive symptoms in hypogonadal men and may effectively augment treatment in selective serotonin reuptake inhibitor (SSRI)-refractory major depression.22 Relative to eugonadal men, hypogonadal men in one study were impaired in their verbal fluency and showed improvement in verbal fluency following testosterone replacement therapy.23Testosterone replacement therapy is also associated with potentially positive changes in body composition. In hypogonadal men, testosterone replacement therapy has demonstrated a number of effects, including an increase in lean body mass and decrease in body fat,24 an increase in weight,25 and increases in muscle size.26 Parenteral testosterone replacement in hypogonadal men resulted in improved strength and increased hemoglobin compared to controls.27 In another study by Urban and colleagues,28 testosterone administration also increased skeletal muscle protein synthesis and strength in elderly men.

     Improvements in bone density have also been shown with testosterone replacement therapy. Increases in spinal bone density have been realized in hypogonadal men,31 with most treated men maintaining bone density above the fracture threshold.32 Testosterone replacement in hypogonadal men improves both trabecular and cortical bone mineral density of the spine, independent of age and type of hypogonadism.33

    Lipid Abnormalities

Physiologic testosterone replacement is known to reduce total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL) levels,24 but the extent to which these parameters are affected by treatment varies considerably between studies. While reductions in HDL did not reach significance in a study by Tenover24 and testosterone replacement was not associated with unfavorable changes in lipid profiles in a separate study by Tan and colleagues,38 research by Anderson and colleagues39 suggests testosterone replacement therapy may result in significant reductions in HDL and elevations in blood viscosity. Some authorities recommend that lipid values be followed closely in men receiving testosterone replacement therapy.


     There appears to be little association between testosterone replacement therapy and the development of prostate cancer. The etiology of prostate cancer is apparently multifactorial, and dietary, geographic, genetic, and other influences are all thought to play a role in the development of the disease. Recent studies indicate that testosterone levels have no apparent systematic relationship to the incidence of prostate cancer.45,46



20. Meikle, A.W., Arver, S., Dobs, A.S., Sanders, S.W. and Mazer, N.A.: Androderm: A permeation-enhanced, non-scrotal testosterone transdermal system for the treatment of male hypogonadism. In: Pharmacology, Biology, and Clinical Applications of Androgens. Edited by S. Bhasin. New York, NY: Wiley Liss, Inc., pp. 449-457, 1996.

21. Wang, C.W., Alexander, G., Berman, N., Salehian, B., Davidson, T., McDonald, V., Steiner, B., Hill, L., Callegari, C. and Swerdloff, R.S.: Testosterone replacement therapy improves mood in hypogonadal menóa clinical research center study. J Clin Endocrinol Metab, 81:3578, 1996.

22. Seidman, S.N. and Rabkin, J.G.: Testosterone replacement therapy for hypogonadal men with SSRI-refractory depression. J Affect Disord, 48:157, 1998.

23. Alexander, G.M., Swerdloff, R.S., Wang, C., Davidson, T., McDonald, V., Steiner, B. and Hines, M.: Androgen-behavior correlations in hypogonadal men II. Cognitive abilities. Horm Behav, 33:85, 1998.

24. Tenover, J.S.: Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab, 75:1092, 1992.

25. Wang, C., Eyre, D.R., Clark, R., Kleinberg, D., Newman, C., Iranmanesh, A., Veldhuis, J., Dudley, R.E., Berman, N., Davidson, T., Barstow, T.J., Sinow, R., Alexander, G. and Swerdloff, R.S.: Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, increases bone formation markers in hypogonadal menóa clinical research center study. J Clin Endocrinol Metab, 81:3654, 1996.

26. Bhasin, S., Storer, T.W., Berman, N., Yarasheski, K.E., Clevenger, B., Phillips, J., Lee, W.P., Bunnell, T.J. and Casaburi, R.: Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab, 82:407, 1997.

27. Sih, R., Morley, J.E., Kaiser, F.E., Perry, H.M., Patrick, P. and Ross, C.: Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab, 82:1661, 1997.

28. Urban, R.J., Bodenburg, Y.H. and Gilkison, C.: Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol, 269 (Endocrinol Metab 32): E828ñE826, 1995.

31. Finkelstein, J.S., Klibanski, A., Neer, R.M., Dopplet, S.H., Rosenthal, D.I., Segre, G.V. and Crowley, W.F.: Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab, 69:776, 1989.

32. Behre, H.M., Kliesch, S., Leifke, E., Link, T.M. and Nieschlag, E.: Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab, 82:2386, 1997.

33. Leifke, E., Korner, H.C., Link, T.M., Behre, H.M., Peters, P.E. and Nieschlag, E.: Effects of testosterone replacement on cortical and trabecular bone mineral density, vertebral body area and paraspinal muscle area in hypogonadal men. Eur J Endocrinol, 138:51, 1998.

34. Burstein, S., Grumbach, M.M. and Kaplan, S.L.: Early determination of androgen-responsiveness is important in the management of microphallus. Lancet, 2:983, 1979.


39. Anderson, F.H., Francis, R.M. and Faulkner, K.: Androgen supplementation in eugonadal men with osteoporosis(effects of 6 months of treatment on bone mineral density and cardiovascular risk factors). Bone, 18:171, 1996.

40. Arver, S., Meikle, A.W., Dobs, A.S., et al.: Hypogonadal men treated with the Androderm testosterone transdermal system had fewer abnormal hematocrit evaluations than those treated with testosterone enanthate injections. In: Program and Abstracts of the 77th Annual Meeting of the Endocrine Society, Washington DC, June 14-17, 1995, Abstract P1-327.


45. Ebling DW, Ruffer J, Whittington R, Vanarsdalen K, Broderick GA,
Malkowicz SB, Wein AJ. Development of prostate cancer after pituitary dysfunction: A report of 8 patients. Urology 1997;49:564-568.

46. Gustafsson O, Norming U, Gustafsson S, Eneroth P, Astrom G, Nyman CR. Dihydrotestosterone and testosterone levels in men screened for prostate cancer: a study of a randomized population. Br J Urol 1996;77:433-440.




  • Normal sexual function requires conversion of testosterone into other hormones!
  • Early sexual dysfunction can be reversed easily with proper hormone replacement.
  • Hormone replacement with estrogen alone fails to normalize sexuality without adequate testosterone.
  • Most specialists feel that only 5% of impotence is due to hormonal deficiency. In my experience they are way off the mark.
  • Hormonal mechanisms play a part in every major element in normal erectile function.
  • When the first signs of sexual difficulty appear, they may reflect risk for major diseases.
  • Most hormonal treatments have been wrong for many individuals.


AndroGel, a newly approved topical drug which is administered in 5 to 10 gms. daily (1%) to yield 50 to 100 mgs. of which an unknown fraction enters the body.  It compared quite favorable to the testosterone patch--which caused skin irritation in 66%.




from rxlist.com  ("Clinical Pharmacology") 



No age related effects on testosterone pharmacokinetics were observed in clinical trials of Androderm in men up to 65 years of age. In a group of 9 elderly testosterone deficient men (65-79 years of age, average baseline testosterone level 184±50 ng/dL). a single application of two Androderm 2.5 mg systems to the back resulted in an average testosterone level of 591±121 ng/dL with a Tmax of 14.2±4.2 hours. The total testosterone delivered over the 24-hour application time was 3.8±0.6 mg, approximately 20% less than the average amount delive


Table 1

Steady-state serum testosterone pharmacokinetic parameters in hypogonadal men measured during continuous Androderm (testosterone transdermal system) treatment.







ng/ dL





ng/ dL





ng/ dL









T 1/2






L/ day






Mean serum testosterone concentrations (ng/dL) measured during single-dose applications of two Androderm 2.5 mg systems applied at night to different sites in 34 hypogonadal men.





Upper Arm

Time (hr)































































In a steady-state study of 12 hypogonadal men, nightly application of 1. 2, or 3 Androderm 2.5 mg systems resulted in increases in the mean morning serum testosterone concentrations. These concentrations averaged 424, 584, and 766 ng/dL with the application of 1, 2, and 3 systems, respectively. The mean baseline serum testosterone concentration was 76 ng/db.

Normal range morning serum testosterone concentrations are reached during the first day of dosing. There is no accumulation of testosterone during continuous treatment.

In a study of 20 hypogonadal patients, two Androderm 2.5 mg systems and a single Androderm 5 mg system produced equivalent serum testosterone concentration profiles. Average steady state concentrations over 24 hours (Cssavg) were 613±169 and 621±176 ng/dL for the two 2.5 mg and single 5 mg systems, respectively. Cmax values were 925±340 ng/dL for the two 2.5 mg systems and 905±254 ng/dL for the single 5 mg system.


In serum, testosterone is bound with high affinity to sex hormone binding globulin (SHBG) and with low affinity to albumin. The albumin bound portion easily dissociates and is presumed to be bioactive. The SHBG-bound portion is not considered to be bioactive. The amount of SHBG in serum and the total testosterone concentration determine the distribution of bioactive and nonbioactive androgen. Bioactive serum testosterone concentrations (BT) measured during Androderm (testosterone transdermal system) treatment paralleled the serum testosterone profile (Figure 2) and remained within the normal reference range.


Inactivation of testosterone occurs primarily in the liver. Testosterone (T) is metabolized to various 17.keto steroids through two different pathways, and the major active metabolites are estradiol (E2) and dihydrotestosterone (DHT). DHT binds with greater affinity to SHBG than does testosterone. In reproductive tissues, DHT is further metabolized to 3-alpha and 3-beta androstanediol.

In many tissues, the activity of testosterone appears to depend on reduction to DHT, which binds to cytosol receptor proteins. The steroid-receptor complex is transported to the nucleus, where it initiates transcription events and cellular changes related to androgen action.

During steady-state pharmacokinetic studies in hypogonadal men treated with Androderm, the average DHT:T and E2:T ratios were comparable to those in normal men, approximately 1:10 and 1:200, respectively. Upon removal of the Androderm systems, serum testosterone concentrations decrease with an apparent half-life of approximately 70 minutes. Hypogonadal concentrations are reached within 24 hours following system removal.

Androderm therapy suppresses endogenous testosterone secretion via the pituitary/gonadal axis, resulting in a reduction in baseline serum testosterone concentrations compared to the untreated state.


Approximately 90% of a testosterone dose given intramuscularly is excreted in the urine as glucuronide and sulfate conjugates of testosterone and its metabolites; about 6% is excreted in the feces, mostly in unconjugated form.

Special Populations


No age related effects on testosterone pharmacokinetics were observed in clinical trials of Androderm in men up to 65 years of age. In a group of 9 elderly testosterone deficient men (65-79 years of age, average baseline testosterone level 184±50 ng/dL). a single application of two Androderm 2.5 mg systems to the back resulted in an average testosterone level of 591±121 ng/dL with a Tmax of 14.2±4.2 hours. The total testosterone delivered over the 24-hour application time was 3.8±0.6 mg, approximately 20% less than the average amount delivered in younger patients.


There is insufficient information available from Androderm trials to compare testosterone pharmacokinetics in different racial groups.

Renal Insufficiency

There is no experience with use of Androderm in patients with renal insufficiency.

Hepatic Insufficiency

There is no experience with use of Androderm in patients with hepatic insufficiency.

Drug-Drug Interactions


Clinical Studies

In clinical studies using the Androderm 2.5 mg system, 93% of patients were treated with two systems daily, 6% used three systems daily, and 1% used one system daily. The hormonal effects of Androderm (testosterone transdermal system) as a treatment for male hypogonadism were demonstrated in four open-label trials that included 94 hypogonadal men, ages 15 to 65 years. In these trials, Androderm produced average morning serum testosterone concentrations within the normal reference range in 92% of patients. The mean (SD) serum hormone concentrations and percentage of patients who achieved average concentrations within the normal ranges are shown in Table 3 below.

Table 3

Individual morning serum hormone concentrations (ng/dL) and percent of patients with mean concentrations within the normal range during continuous Androderm treatment (n=94).






Normal Range















% Normal





% High





% Low





A physiological suppression of the pituitary/gonadal axis occurs during continuous Androderm treatment leading to reduced serum LH concentrations. In clinical trials, 10 of 21 (48%) of men with primary (hypergonadotropic) hypogonadism achieved normal range LH concentrations within 6 to 12 months of treatment. LH concentrations may remain elevated in some patients despite serum testosterone concentrations within the normal range. Twenty-nine patients, previously treated with testosterone, completed 12 months of Androderm treatment. Following an 8-week androgen withdrawal period, Androderm treatment produced positive effects on fatigue, mood and sexual function. The percent of patients complaining of fatigue decreased from 79% to 10% during treatment (p<0.001). The average patient depression score (Beck Depression Inventory) decreased from 6.9 to 3.9 (p<0.001). Nocturnal penile tumescence and rigidity monitoring showed an increase in mean duration of erections 0.23 to 0.39 hours per night (p=0.01) and an increase in penile tip rigidity from 18% to 50% (p<0.001). The total number of self-reported erections reported increased from 2.3 to 7.8 per week (p<0.001). Comparison with intramuscular testosterone: Sixty-six patients, previously treated with testosterone injections, received Androderm or intramuscular testosterone enanthate (200 mg every 2 weeks) treatment for 6 months. The percent of time that serum concentrations measured throughout the dosing interval remained within the normal range were as follows:




p value










76 %




81 %



Sexual function was comparable between groups.

Effect on plasma lipids: In 67 men treated for 6 to 12 months, the average (SE) serum total cholesterol and HDL concentrations were 199 (7.6) ng/dL and 46 (2.3) ng/dL.

Compared to baseline values during a hypogonadal state actfieved by 8 weeks of androgen withdrawal in 29 patients, the following changes in lipids were observed during 1 year of Androderm treatment: Cholesterol decreased 1.2%; HDL decreased 8%; Cholesterol/ HDL ratio increased 9%. In these patients, lipids measured during Androderm treatment were not significantly different from those measured during prior IM injection treatment.

Effects on the prostate: Prostate size and serum prostate specific antigen (PSA) concentrations during treatment were comparable to values reported for eugonadal men. One case of prostate carcinoma occurred during Androderm treatment; two cases were detected during IM treatment.




AndroGel is a clear, colorless topical gel that men apply once daily to the shoulders, upper arms and/or abdomen. Upon application, this testosterone gel dries within a few minutes. The skin absorbs the testosterone and serves as a reservoir for the hormone, which slowly enters the bloodstream. Normal testosterone levels are restored soon after application. The U.S. Food and Drug Administration approved AndroGel in February 2000 for replacement therapy in men for conditions associated with low testosterone.

Harbor--UCLA REI Study Shows Testosterone Gel Improves Sexual Function, Mood, Muscle Strength and Body Composition in Testosterone-Deficient Men 




ANDROGENS:   CHAPTER 62         Goodman & Gilman's The Pharmacological Basis of Therapeutics,  Seventh Edition.


It was the popular belief that failure of testicular function was the cause of the symptoms of old age in men that stimulated many attempts to isolate an active testicular principle [not the successful reversal of the reversal of typical signs of castration in rooster, published in 1849] (1440)."  15 mg of androsterone (a metabolite of testosterone) was obtain in 1931 by Butenandt from 15,000 liters of male urine.  Testosterone was first isolated in 1935 (David) and its structure and synthesis followed in that year.  "In many target tissues for androgens, testosterone is reduced at the 5 position to dihydrotestosterone, which serves as the intracellular mediator of most actions of the hormone (1441)."  It binds about 10 times more tightly than testosterone.  A variety of other naturally occurring weak androgens have ben described, including the adrenal androgen dehydroanhdrostenedione, androstane-3, 17-diol and androsterone.  "However, these steroids bind so weakly to the androgen receptor that it is unlikely that they can act directly as androgens at physiological concentrations, and it is now believed that they are androgens only to the extent that they are converted to testosterone and /or dihydrotestosterone in vivo (1441)." 

          Three general types of modification of testosterone are clinically useful: (1) esterification of the 17 -hydroxyl group with any of several carboxylic acids decreases the polarity of the molecule and thus makes it more soluble in the lipid vehicle used for injection.  "Most esters must be injected, ubt two such compounds, methenolone acetate and testosterone undercanoate, have features that make oral administration possible.  The methyl group on the 1 position of methenolone acetate slows hepatic inactivation and hence allows effective concentrations to be achieved in the blood.  (2) Alkylation of the 17 position (as in methyltestosterone and fluoxymesterone) allows androgens to be effective orally because the alkylated derivatives are slowly catabolized by the liver.  (3) Other alterations of the ring structure have been made with varying effects, examples include fluoxymesterone, and 19-nortestosterone.  Testosterone injected as a solution in oil is so quickly absorbed, metabolized, and excreted that the androgenic effect is small--orally less effective (1446).  The cypionate and enanthate esters are fully effective when given at 1- or 2- week intervals in proportionately larger doses (1446).  Testosterone half life in the blood is 10 to 20 minutes (1446). 

                   The concentration of testosterone in women is about 15 to 65 ng/dl, and the daily rate of production is .25mg. (1443)--the testes produce 20 times as much.  {The book comes to the anti-emperical conclusion that "use of androgens by male athletes in the hope that muscle development may be enhanced has no physiological rationaleindeed normal men experience only a transient positive nitrogen balance of a slight degree when exogenous androgens are administered  (1445).}  Not all target tissues require the conversion of testosterone. 





Enter content here

Enter supporting content here