The ability to effectively treat the condition of low testosterone depends upon the correct determination of cause, but once the cause has been properly diagnosed the outlook (prognosis) for patients suffering from it is extremely good, as the findings of numerous clinical and meta-analytical studies attest. Low testosterone levels are often accompanied by a diversity of negative life hindering hypogonadic (low testosterone) symptoms in variety of areas. Testosterone replacement therapy (TRT) has been conclusively determined to greatly improve, and often completely reverse, hypogonadic symptoms experienced by low testosterone sufferers including such areas as decreased sexual function, and overall quality of life (mood, depression, muscle strength, body composition, insulin sensitivity, general well-being, etc.).
Outlook with Regard to Improved Sexual Function
Low testosterone can negatively impact one’s ability to have satisfying sex due to a diminished libido (sex drive) and an array of erectile dysfunctions, i.e., sexual problems that can result from low testosterone. However, as evidenced by the studies below, such problems are rapidly remedied with the effective administration of TRT.
In June of 2013 the Journal of Sexual Medicine published a study from Good Hope Hospital, Sutton Coldfield, UK by G. Hackett, et al entitled, ‘Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes’. The study aim was to determine the effects of testosterone replacement using long-acting testosterone undecanoate on sexual function, mood, and quality of life as compared to a controlled placebo group. The primary outcome measure, the International Index of Erectile Function (IIEF), was used to evaluate sexual dysfunction, with secondary outcome measures used to assess self-reported mood and quality of life using the Ageing Male Symptom (AMS), the Hospital Anxiety and Depression Scale, and the Global Efficacy Question. Conducted in a primary care population of men with type 2 diabetes, the male diabetic populations of seven general practices were screened at routine diabetes visits to detect symptomatic men with total testosterone levels of 12 nmol/L or less or with free testosterones of 250 pmol/L or less (with an aim of bringing them back into the optimal range of 700 – 1,100 ng/dl). Although two hundred and eleven men were screened, this placebo-controlled, double-blind study was comprised of 199 men with type 2 diabetes and hypogonadism all of whom were treated for 30 weeks with either 1,000 mg of testosterone undecanoate or a placebo followed by 52-week open-label follow on. Testosterone replacement therapy significantly improved all domains of the IIEF and patient reported quality of life at 30 weeks, and more significantly after the 52-week open-label extension, with initial benefits as early as 6 weeks in. Significant improvement within each domain of sexual function was achieved at the 30-week mark including: erectile function; intercourse satisfaction; sexual desire; orgasm; and overall satisfaction. All responses in sexual function continued to improve significantly up to 18 months, wherein less obese and older patients responded better to testosterone therapy.
In a 2011 study published in the Journal of Sex and Marital Therapy entitled, ‘Testosterone gel replacement improves sexual function in depressed men taking serotonergic antidepressants: a randomized, placebo-controlled clinical trial’, R. Amiaz, et al at the Chaim Sheba Medical Center, Tel Hashomer, Israel studied the effects of testosterone replacement on sexual dysfunction in hypogonadal men. The study was a placebo-controlled, double-blind, 6-week clinical trial of a testosterone gel versus a placebo gel in men taking a serotonergic antidepressant for major depressive disorder while exhibiting low or low-normal testosterone levels. The subjects were enrolled at two study sites, one in Tel Aviv, Israel and one in Boston, Massachusetts and was comprised of 100 men with a final ‘n’ (those for whom complete pre- and post-trial data existed) of 63 subjects who were randomized into two groups of similar age, baseline testosterone levels, and baseline IIEF scores producing a testosterone group (n = 31) and a placebo group (n = 32). After the 6 weeks concluded and data was analyzed using linear regression, the placebo group showed virtually no change from baseline, whereas the testosterone group displayed substantial increase improvements (with adjustments for age and study site). R. Amiaz, et al concluded that treatment with exogenous testosterone was associated with a significant improvement in sexual function, particularly regarding ejaculatory ability. Furthermore, they found that the subgroup (adjusted for change in depression scores on the Montgomery Asberg Depression Rating Scale) showed significant improvement in overall depression (depressive hypogonadic symptom) as well.
M. Khera, et al of the Scott Department of Urology, Baylor College of Medicine, Houston, TX published a November 2011 study in the Journal of Sexual Medicine entitled, ‘Improved sexual function with testosterone replacement therapy in hypogonadal men: real-world data from the Testim Registry in the United States (TRiUS)’. The study’s primary aim was to determine if 12-month TRT (using testosterone gel) significantly improves the sexual function of hypogonadal men as measured by the Brief Male Sexual Function Inventory (BMSFI). This 849 subject, 12-month study of hypogonadal men treated with Testim (a 1% testosterone topical gel),
collected data at suggested visits (baseline, 1, 3, 6, and 12 months). The data measured at each visit included total testosterone, free testosterone, BMSFI scores, physical exam, and body dimension measurements. Regression analysis indicated significant improvements in all measured areas at 6 months, and continued improvements at 12 months. More specifically, total and free testosterone levels and BMSFI scores increased along with improvement in sex drive/libido, erectile function, ejaculatory function, and level of bother.
Outlook with Regard to Improved Quality of Life
Low serum testosterone is associated with several life-hindering symptoms, many of which combine to reduce the quality of life. TRT has been conclusively proven to restore diminished quality of life factors by: reducing body fat; enhancing sleep quality; increasing bone and muscle mass, along with muscular strength; reducing depression, anxiety, and irritability; improving cognitive faculties such as concentration and focus, memory and recall, and the reduction of brain fog; improving sexual performance by restoring libido, reversing erectile dysfunction; reducing insulin resistance; etc. As evidenced by the studies below, such problems are rapidly remedied with the effective administration of TRT.
XW Zhang, et al of the Department of Urology, Peking University People’s Hospital, Beijing 100044, China published a November 2012 study in the Chinese Medical Journal entitled, ‘Androgen replacement therapy improves psychological distress and health-related quality of life in late onset hypogonadism patients in Chinese population’. Conducted to examine the interrelationship among hypogonadic symptoms, this study’s aim investigated the effects of TRT on psychological wellbeing, and quality of life. This 160 male subject study compared initial baseline and end of study (after 6 months) results for total and free testosterone levels, and the measures of four different inventory scales specifically: 1) the short form health survey-12 (SF-12); 2) the perceived stress scale (PSS); 3) the hospital anxiety and depression scale (HADS); and 4) the aging male’s symptoms (AMS) rating scale. Subjects were randomly assigned to treatment and control groups, and administered oral testosterone undecanoate capsules (total of 120 – 160 mg TU orally on a daily basis) or a placebo (vitamin E/C capsules). In the active treatment group, total serum testosterone concentrations before and after intervention were (7.98 ± 0.73) nmol/L and (13.7 ± 1.18) nmol/L. Every single measure (hypogonadic symptom) in the experimental group significantly improved, whereas no significant changes were observed in the control group after 6 months. XW Zhang, et al concluded that testosterone replacement therapy not only improves a diversity of hypogonadic symptoms, but also enhances comprehensive improvement in psychological issues.
In November of 2009, ES. Andrade Jr., et al published a study in the Arquivos brasileiros de endocrinologia e metabologia entitled, ‘Short term testosterone replacement therapy improves libido and body composition’. Their expressed aim was to assess the efficacy and safety of testosterone replacement in males with late-onset hypogonadism as compared to hypogonadal men without replacement and controls. This 6-month study was comprised of 62 subjects, who were also patients, broken out into three groups (one experimental and two controls) wherein subjects were randomly assigned membership to either groups of 17 hypogonadal males who received intramuscular testosterone injections every three weeks, or 14 hypogonadal males, along with 31 non-hypogonadal males all of whom received a placebo of oral vitamins daily. The subjects were assessed, and their profiles were documented through clinical and laboratory examinations, and the employment of four different inventory scales specifically: 1) the short form health survey-36 (SF-36); 2) the aging male’s symptoms (AMS) rating scale; 3) the International Index of Erectile Function (IIEF); and 4) the Androgen Deficiency in the Aging Male (ADAM) questionnaire. ES Andrade Jr., et al findings revealed that testosterone replacement therapy significantly improved sexuality and body composition, with prostatic and hematological safety. More specifically, when compared to the other groups the experimental group returned greater libido improvement, greater sexual potency improvement, and greater decrease in waist circumference after only eight weeks.
The European Journal of Endocrinology published a June 2006 study by D. Kapoor, et al of the Centre for Diabetes and Endocrinology, Barnsley NHS Foundation Trust Hospital, Gawber Road, Barnsley S75 2EP, UK entitled, ‘Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes’. The researcher investigated the effect of testosterone replacement therapy on insulin resistance and glycemic control in hypogonadal men with type 2 diabetes. This was a double-blind, placebo-controlled crossover study of 24 hypogonadal men with type 2 diabetes (ten of which were treated with insulin) over 30 years of age. The subjects were treated with 200 mg of injectable testosterone every 2 weeks, or with placebo, for a duration of 3 months in random order. TRT was then followed by a washout period of one month before the alternate treatment phase. D. Kapoor, et al concluded that testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Furthermore, there were marked improvements in glycaemic control, visceral adiposity, cholesterol, and insulin resistance, all of which combined to represent an overall reduction in the risk of cardiovascular disease.
In June of 2003, C. Steidle, et al of the Northeast Indiana Research, Fort Wayne, IN published study in the Journal of Clinical Endocrinology and Metabolism entitled, ‘AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function’. Their aim was to assess the effects of testosterone replacement therapy in hypogonadal men with special interest in the improvement of body composition, mood, and sexual functioning. Comprised of 406 hypogonadal men, this 90-day study compared the pharmacokinetics and treatment effectiveness of a topical testosterone gel (AA2500) at two separate concentrations of 50 mg/d and 100 mg/d, to the effects of a testosterone patch, and a placebo gel. C. Steidle, et al developed pharmacokinetic profiles, and measured body composition, mood, and sexual function. They found that topical testosterone gel treatments delivered dose-dependent improvements in each of their pharmacokinetic parameters, as compared to both the testosterone patch and the placebo receiving control groups. More specifically, C. Steidle, et al reported that significant improvements in sexual desire, sexual motivation, and spontaneous erections were found in the experimental group when compared with the other two. Furthermore, they deemed the topical testosterone gel to be well tolerated, as opposed to the testosterone patch’s a high rate of application site reactions.
In October of 1996, the Journal of Clinical Endocrinology and Metabolism published a study by C. Wang, et al of the Department of Medicine, Harbor-UCLA, Torrance, CA entitled, ‘Testosterone replacement therapy improves mood in hypogonadal men–a clinical research center study’. They investigated the effects of testosterone replacement therapy on changes in mood. This two month (60-day) study was comprised of 51 hypogonadal men, all of whom were patients withdrawn from their prior testosterone replacement therapy for a time period of at least six weeks prior to enrollment. The experimental groups consisted of 18 subjects who received intramuscular testosterone enanthate injections of 200 mg every 20 days, and 16 subjects who received sublingual testosterone cyclodextrin (SLT) at a dose of 2.5 mg three times per day, and 17 subjects who received sublingual testosterone (SL) at a dose of 5.0 mg three times per day. Baseline measurements consisted of patient responses to a questionnaire on 7 consecutive days prior the start of treatment, and subsequent measures included responses on 7 consecutive days before scheduled treatment visits to the clinic on days 21, 41, and 60 of the study. These measures included mood parameters assessed using a 7-point Likert rating scale which included: friendly, nervous, irritable, full of pep (energy), angry, alert, sad/blue, tired, and well/good. In comparison to the baseline measures, the testosterone replacement therapy groups returned statistically significant decreases in, sadness (P = 0.0033), tiredness (P = 0.0035), anger (P = 0.0045), irritability (P = 0.0009), and nervousness (P = 0.0291). These same groups also returned statistically significant improvement in friendliness (P = 0.0072), sense of wellbeing (P = 0.024), and energy level (P = 0.0020). Additionally, baseline serum testosterone levels (those prior to testosterone replacement therapy) showed statistically significant positive correlations between serum testosterone and sense of wellbeing (r = 0.27, P < 0.05) and friendliness (r = 0.29, P < 0.05), and statistically significant negative correlations between tiredness (r = -0.28, P < 0.05), nervousness (r = -0.27, P < 0.05), and irritability (r = -0.29, P < 0.05). Furthermore, C. Wang, et al cited that these results were corroborated in a subsequent study consisting of 30 hypogonadal men. They concluded that testosterone replacement therapy in hypogonadal men improves positive mood parameters among which are friendliness, energy, and well/good feelings, while decreasing negative mood parameters such as anger, nervousness, and irritability.
In August of 2004 Heart (from the British Cardiac Journal) published a study by CJ. Malkin, et al of the Department of Cardiology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK entitled, ‘Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life’. The aim of this single blind, randomized, placebo controlled crossover study was to compare testosterone replacement therapy using the hybrid (short and long ester) testosterone preparation Sustanon 100, with a placebo. The study consisted of 10 adult male subjects with ischaemic heart disease and hypogonadism. After the first month of testosterone replacement therapy, a delta value analysis between the testosterone and placebo groups demonstrated that mean (SD) trough testosterone concentrations increased significantly, the mood scores assessed with validated questionnaires all improved, and that there was a significant reduction in total cholesterol and serum tumor necrosis factor alpha with delta values. CJ. Malkin, et al concluded that testosterone replacement therapy is effective in delaying time to ischaemia (local deficiency of blood supply produced by vasoconstriction or local obstacles to the arterial flow), elevating mood, and is associated with potentially beneficial reductions of total cholesterol and serum tumor necrosis factor alpha in hypogonadal men.
R. Goldstat, et al of the Jean Hailes Foundation Research Unit, Clayton, Victoria, Australia published a 2003 study in Menopause entitled, ’Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women’.
The study aim was to investigate the effects of transdermal testosterone replacement therapy on testosterone deficient women suffering from premenopausal physiological decline, more specifically in the areas of sexual function, libido, mood, and wellbeing.
Comprised of 34 low libido presenting women who completed the study per protocol, 31 of whom with a mean age 39.7 +/- 4.2 years and serum testosterone 1.07 + 0.50 nmol/L provided complete data, this placebo-controlled, randomized, crossover, efficacy study used 10 mg per day dosages of topical testosterone cream with two double-blind, 12-week, treatment periods separated by a single-blind, 4-week, washout period. Using the composite scores of the Psychological General Well-Being Index, the Beck Depression Inventory, and the Sabbatsberg Sexual Self-Rating Scale, as compared with the placebo group, R. Goldstat, et al demonstrated that testosterone replacement therapy significantly improves mood, well-being, and sexual function in premenopausal women with low libido and low testosterone.
As evidenced by the above valid, reliable, and well-performed studies testosterone replacement therapy is highly effective at rapidly improving hypogonadal symptoms in both men and women. Consequently, the outlook for a patient with low testosterone is extremely promising, when properly diagnosed and managed by a physician who employs testosterone replacement therapy.
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- Androgen replacement therapy improves psychological distress and health-related quality of life in late onset hypogonadism patients in Chinese population.
- Zhang XW, Liu ZH, Hu XW, Yuan YQ, Bai WJ, Wang XF, Shen H, Zhao YP.
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- Improved sexual function with testosterone replacement therapy in hypogonadal men: real-world data from the Testim Registry in the United States (TRiUS).
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- Short term testosterone replacement therapy improves libido and body composition.
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- AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function.
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- Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes.
- Kapoor D, Goodwin E, Channer KS, Jones TH.
- Eur J Endocrinol. 2006 Jun;154(6):899-906.
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- J Sex Med. 2013 Jun;10(6):1612-27. doi: 10.1111/jsm.12146. Epub 2013 Apr 3.
- Effects of short-term testosterone replacement on areal bone mineral density and bone turnover in young hypogonadal males.
- Deb P, Gupta SK, Godbole MM.
- Indian J Endocrinol Metab. 2012 Nov;16(6):947-51. doi: 10.4103/2230-8210.102997.
- Testosterone replacement in hypogonadotropic hypogonadal young male improves insulin sensitivity.
- Mao JF, Wu XY, Li NS, Lu SY, Jing ZM, Shi YF.
- Zhonghua Yi Xue Za Zhi. 2008 Sep 23;88(36):2550-2. Chinese.
- Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men.
- Wang C, Swerdloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G, Matsumoto AM, Weber T, Berman N; Testosterone Gel Study Group.
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- Testosterone replacement therapy improves mood in hypogonadal men–a clinical research center study.
- Wang C, Alexander G, Berman N, Salehian B, Davidson T, McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS.
- J Clin Endocrinol Metab. 1996 Oct;81(10):3578-83.
- Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life.
- Malkin CJ, Pugh PJ, Morris PD, Kerry KE, Jones RD, Jones TH, Channer KS.
- Heart. 2004 Aug;90(8):871-6.
- Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women.
- Goldstat R, Briganti E, Tran J, Wolfe R, Davis SR.
- Menopause. 2003 Sep-Oct;10(5):390-8.