Contemporary medical science has conclusively demonstrated the negative effects of low testosterone (hypogonadism) on mood (depression, anxiety, irritability, sadness, tiredness/fatigue, anger, friendliness, etc.), sexual performance and interest (libido), and health (general well-being in all life related areas).  It is, however, also quite possible to view the effects of low testosterone on health, mood, and sex from the inverse relationship.  That is to say, one can glean just as much (if not more) from viewing how elevating testosterone levels (either back into normal range, or further into the range of normalcy) improves hypogonadic symptoms, in particular those of health, mood, and sex.  The following studies and descriptive commentary look at this problem from both perspectives.

Low Testosterone Affects Mood

The relationship between declining testosterone levels and increased depressive symptoms is a complex one.  This is largely due to the many associated independent conditions, which include obesity, stress, smoking, alcohol abuse, and medical or genetic disorders.  However, certain conditions more specifically identify low testosterone as an indicator, such age-related gradual decline in testosterone levels which is known to contribute to the rising rate of depression in older men.

In December 2012, U. Aydogan, et al of the Department of Family Medicine, Gulhane School of Medicine, Ankara, Turkey published a study entitled, ‘Increased frequency of anxiety, depression, quality of life and sexual life in young hypogonadotropic hypogonadal males and impacts of testosterone replacement therapy on these conditions’.  The aim of this study was to assess the relationship between low testosterone levels and psychopathological symptoms (anxiety and depression levels, sexual function, and quality of life), which are the most common conditions in young hypogonadal men.  This six-month study was comprised of 39 young hypogonadal male patients, and 40 age-matched healthy males.  Pre- and post-tests were used to assess before and after 6 months treatment period using valid and reliable scales, such as the Beck Depression Inventory (BDI), the Arizona Sexual Experiences (ASEX), the Short Form-36 (SF-36), and the Beck Anxiety Inventory (BAI).  U. Aydogan, et al found that compared to the control group, the experimental group (pre-treatment) had both a greater number of and a higher severity of sexual dysfunction, anxiety, depression symptoms along with a lesser reported quality of life.  Following the 6 months of testosterone replacement therapy, these researchers observed improvements in each of the above parameters, concluding that low endogenous testosterone levels are related to increased incidence of psychological symptoms.

In March of 2012 M. Khera, et al of the Scott Department of Urology, Baylor College of Medicine, Houston, TX published a study in Aging Male ­­­­­­­­­­(the official journal for the International Society of the Aging Male) entitled, ‘The effect of testosterone supplementation on depression symptoms in hypogonadal men from the Testim Registry in the US (TRiUS)’.  The expressed aim of this study was to determine the effect of long-term testosterone replacement therapy on depression symptoms in hypogonadal men.  Although multiple subgroups were broken out for greater detailed analyses, this study was comprised of 849 over the age of 60 hypogonadal men for whom 1% testosterone gel had been recently prescribed.  The study data spanned a total of 12 months, and was taken from an observational multicenter registry known as the Testim Registry in the United States (TRiUS).  Total testosterone measures were assessed at baseline and months 3, 6, and 12, while depression symptoms were gauged using a validated self-report questionnaire called the Patient Health Questionnaire-9 (PHQ-9), wherein a decrease of ≥5 represents clinical improvement.  Based on the significantly improved PHQ-9 scores at 3 months (p < 0.01), and clinically meaningful (actual real world impact on depression) mean improvement of 5.62 points on the PHQ-9 at 12 months M. Khera, et al provided sufficient evidence to verify testosterone replacement therapy’s ability to reduce depression symptoms in hypogonadal men.

In January of 2000 the S. Grinspoon, et al of the Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA published a study in the Journal of Clinical Endocrinology and Metabolism entitled, ‘Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men’.  The expressed aim of this study was to investigate the relationship between depression score and gonadal function of hypogonadism (specifically quality of life and mood disturbances) among human immunodeficiency virus-infected patients.  This double-blind, randomized, placebo-controlled study among a group of hypogonadal HIV/AIDS positive adult men (39 of whom provided complete end of study results) used multiple measurement instruments, among which was the Beck Depression Inventory.  S. Grinspoon, et al found that the Beck score decreased significantly only in the subjects receiving testosterone replacement therapy (-5.8+/-1.3, P< 0.001), but not in subjects randomized to placebo group.

Low Testosterone Affects Sex 

There appears to be a direct correlation (relationship) between declining testosterone levels and reduced sexual function, i.e., diminished libido/sexual desire, and a variety of erectile dysfunctions such as impotence or the ability to achieve erection, inability to sustain erection, low semen volume, sterility, etc.  While this correlation is still being examined with regard to exactly how low testosterone levels negatively impact sexual function, the majority of studies have concluded that they indeed do, and that testosterone replacement therapy improves the symptoms of sexual dysfunction. 

In June of 2013 G. Hackett, et al of Good Hope Hospital, Sutton Coldfield, UK published a study in the Journal of Sexual Medicine 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 therapy on sexual function, mood, and quality of life while using long-acting testosterone undecanoate (also known as the testosterone preparation Nebido).  The International Index of Erectile Function (IIEF) served as the primary outcome measure, and was used to evaluate sexual dysfunction.  The secondary outcome measures used to assess self-reported mood and quality of life included the Hospital Anxiety and Depression Scale, the Global Efficacy Question, and the Ageing Male Symptom (AMS).  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 a 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 improvements became even more significant 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 both older and less obese patients responded better. 

In 2011 R. Amiaz, et al at the Chaim Sheba Medical Center, Tel Hashomer, Israel published a study 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’.  The aim of this study was to investigate the effects of testosterone replacement on sexual dysfunction in hypogonadal men.  This was a double-blind, placebo-controlled, 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 study was comprised of 100 men of who 63 provided complete data and 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).  The subjects were enrolled at two study sites, one in Tel Aviv, Israel and one in Boston, Massachusetts.  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 improvements (with adjustments for age and study site).  R. Amiaz, et al concluded that treatment with exogenous testosterone was associated with significant improvement in sexual function, particularly regarding ejaculatory ability. 

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 main focus of this study was to determine if 12 months of testosterone replacement therapy using testosterone gel significantly improved sexual function in hypogonadic male subjects.  Sexual function was measured using the Brief Male Sexual Function Inventory (BMSFI).  Comprised of 849 subjects, this 12-month study of hypogonadal men receiving a 1% testosterone topical gel (Testim), collected data during routinely suggested visits which included a baseline measure and intervals of 1, 3, 6, and 12 months.  Data collected during visits included a physical exam, body dimension measurements, free testosterone, total testosterone, and BMSFI scores.  A Regression analysis revealed significant improvements in all measured areas were found at 6 months, with continued improvements at 12 months.  Furthermore, both free and total testosterone levels, as well as BMSFI scores, increased along with improvement in ejaculatory function, level of bother, sex drive/libido, and erectile function. 

Low Testosterone Affects Health

Low serum testosterone has been correlated with a variety of quality of life diminishing symptoms.  Testosterone replacement therapy has been conclusively proven to reverse these adverse symptoms through:  improving cognitive faculties such as concentration and focus, memory and recall, and the reduction of brain fog; improving sexual performance by restoring libido; increasing bone and muscle mass, along with muscular strength; reducing depression, anxiety, and irritability; reversing erectile dysfunction; reducing insulin resistance; reducing body fat; enhancing sleep quality; etc.  As evidenced by the studies below, such problems are routinely reversed by effective testosterone replacement therapy administration.

In November of 2012 the Chinese Medical Journal published a study by XW. Zhang, et al of the Department of Urology, Peking University People’s Hospital, Beijing, China entitled, ‘Androgen replacement therapy improves psychological distress and health-related quality of life in late onset hypogonadism patients in Chinese population’.  The aim of this study was to investigate the effects of testosterone replacement therapy on psychological well-being and quality of life, which was defined as the interrelationship among hypogonadic symptoms.  This 6-month, double blind, 160 male subject study compared initial baseline and end of study results for both total and free testosterone levels, along with the measures of four separate inventory scales which included:  1) the perceived stress scale (PSS); 2) the aging male’s symptoms (AMS) rating scale; 3) the short form health survey-12 (SF-12); and 4) the hospital anxiety and depression scale (HADS).  Randomly assigned to treatment and control groups, the subjects were administered either oral 120 – 160 mg of testosterone undecanoate capsules on a daily basis, or placebo capsules containing vitamin E and vitamin C.  Total experimental (treatment) group serum testosterone concentrations before and after the intervention were (7.98 ± 0.73) nmol/L and (13.7 ± 1.18) nmol/L.  XW Zhang, et al found that each of the hypogonadic symptom measures within the experimental group had significantly improved, with no significant changes in the control group.  They concluded that testosterone replacement therapy both improved a variety of hypogonadic symptoms, and comprehensively enhanced the improvement of psychological issues as well.

In November of 2009, the Arquivos Brasileiros de Endocrinologia e Metabologia published a study by ES. Andrade Jr., et al entitled, ‘Short term testosterone replacement therapy improves libido and body composition’.  The aim this study was to investigate the safety and efficacy of testosterone replacement in adult male subjects with late-onset hypogonadism.  This double blind, placebo controlled, 6-month study was comprised of 62 patients who were divided into three randomly assigned groups (one experimental and two controls), of either 17 hypogonadal males who received intramuscular testosterone injections every three weeks, 14 hypogonadal males who received no treatment, or 31 non-hypogonadal males all of whom were given a daily oral vitamin placebo.  Each subject was assessed, profiles were documented through clinical and laboratory examinations, and four diverse inventory scales were used to assess quality of life, specifically the:  4) Androgen Deficiency in the Aging Male (ADAM) questionnaire; 2) International Index of Erectile Function (IIEF); 3) short form health survey-36 (SF-36); and 4) aging male’s symptoms (AMS) rating scale.  ES Andrade Jr., et al found that testosterone replacement therapy had significantly improved both body composition and sexuality.  As compared to the control groups (after only eight weeks), the experimental group returned a greater decrease in waist circumference, greater sexual potency improvement, and greater libido improvement.

In June of 2006 D. Kapoor, et al of the Centre for Diabetes and Endocrinology, Barnsley NHS Foundation Trust Hospital, Gawber Road, Barnsley S75 2EP, UK published a study in the European Journal of Endocrinology entitled, ‘Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes’.  The aim of this study was to investigate the effect of testosterone replacement therapy on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes.  This was a placebo-controlled, double-blind, crossover study was comprised of 24 hypogonadal men with type 2 diabetes over 30 years of age, ten of which were treated with insulin.  Throughout the three month duration, the experimental group received 200 mg of injectable testosterone every 2 weeks.  Based on their findings, D. Kapoor, et al concluded that testosterone replacement therapy was responsible for both reducing insulin resistance, and improving glycaemic control in hypogonadal men with type 2 diabetes.  Additionally, this study revealed marked improvements in cholesterol and visceral adiposity (loss of between organs body fat), all of which together represent a reduced risk of cardiovascular disease.

In September 2003 The Journal of North American Menopause published a study by R. Goldstat, et al of the Jean Hailes Foundation Research Unit, Clayton, Victoria, Australia entitled, ’Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women’.  The expressed aim of this study was to examine the effects of transdermal testosterone replacement therapy on testosterone deficient women suffering from premenopausal physiological decline, specifically defined as mood, well-being, sexual function, and libido.  This placebo-controlled, randomized, crossover, efficacy study was comprised of 34 low libido presenting women, of whom 31 had a mean age 40.  The experimental group received 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.  Composite scores from the Sabbatsberg Sexual Self-Rating Scale, Beck Depression Inventory, and Psychological General Well-Being Index were compared with those of the placebo group.  R. Goldstat, et al found that testosterone replacement therapy significantly improved sexual function, well-being, and mood in premenopausal women with low libido and low testosterone.

As clearly demonstrated by the presented clinical studies low testosterone definitively affects mood, sexual performance, and general well-being (health) in both males and females.  Fortunately, as also demonstrated, the inverse is indeed true, i.e., testosterone replacement therapy does effectively reverse these same hypogonadal symptoms.  Additionally, as cited in several of the studies above, this reversal of symptoms occurs rapidly meaning low testosterone sufferers can expect a quick recovery.

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