A large number of trials have demonstrated a positive effect of testosterone treatment on bone mineral density (Katznelson et al 1996; Behre et al 1997; Leifke et al 1998; Snyder et al 2000; Zacharin et al 2003; Wang, Cunningham et al 2004; Aminorroaya et al 2005; Benito et al 2005) and bone architecture (Benito et al 2005). These effects are often more impressive in longer trials, which have shown that adequate replacement will lead to near normal bone density but that the full effects may take two years or more (Snyder et al 2000; Wang, Cunningham et al 2004; Aminorroaya et al 2005). Three randomized placebo-controlled trials of testosterone treatment in aging males have been conducted (Snyder et al 1999; Kenny et al 2001; Amory et al 2004). One of these studies concerned men with a mean age of 71 years with two serum testosterone levels less than 12.1nmol/l. After 36 months of intramuscular testosterone treatment or placebo, there were significant increases in vertebral and hip bone mineral density. In this study, there was also a significant decrease in the bone resorption marker urinary deoxypyridinoline with testosterone treatment (Amory et al 2004). The second study contained men with low bioavailable testosterone levels and an average age of 76 years. Testosterone treatment in the form of transdermal patches was given for 1 year. During this trial there was a significant preservation of hip bone mineral density with testosterone treatment but testosterone had no effect on bone mineral density at other sites including the vertebrae. There were no significant alterations in bone turnover markers during testosterone treatment (Kenny et al 2001). The remaining study contained men of average age 73 years. Men were eligible for the study if their serum total testosterone levels were less than 16.5 nmol/L, meaning that the study contained men who would usually be considered eugonadal. The beneficial effects of testosterone on bone density were confined to the men who had lower serum testosterone levels at baseline and were seen only in the vertebrae. There were no significant changes in bone turnover markers. Testosterone in the trial was given via scrotal patches for a 36 month duration (Snyder et al 1999). A recent meta-analysis of the effects on bone density of testosterone treatment in men included data from these studies and two other randomized controlled trials. The findings were that testosterone produces a significant increase of 2.7% in the bone mineral density at the lumber spine but no overall change at the hip (Isidori et al 2005). These results from randomized controlled trials in aging men show much smaller benefits of testosterone treatment on bone density than have been seen in other trials. This could be due to the trials including patients who are not hypogonadal and being too short to allow for the maximal effects of testosterone. The meta-analysis also assessed the data concerning changes of bone formation and resorption markers during testosterone treatment. There was a significant decrease in bone resorption markers but no change in markers of bone formation suggesting that reduction of bone resorption may be the primary mode of action of testosterone in improving bone density (Isidori et al 2005).
This paper will aim to review the current evidence of clinical effects of testosterone treatment within an aging male population. As with any other clinical intervention a decision to treat patients with testosterone requires a balance of risk versus benefit. We shall try to facilitate this by examining the effects of testosterone on the various symptoms and organs involved.
As crazy as it seems, it has lately been proven that there is a no relation between cholesterol intake and heart attack as doctors once thought (and many still do). This is slowly becoming common knowledge, regardless of pharmaceutical companies wishes. (Trust me, this billion dollar industry does not want you to know this. You don;t have to be a conspiracy theorist to see this.)
Vitamin D is a fat-soluble vitamin and is obtained from sunlight. In the active form, it acts as a steroid hormone in the body. These days many people suffer from vitamin D deficiency because lacking exposure to sunlight, but taking vitamin D supplements to improve the weakness. Low vitamin D levels also lower the testosterone levels, but with intake of vitamin D, the testosterone levels boost. In typical cases, vitamin D doesn’t show the significant result in testosterone levels but people who are vitamin D deficient shows an increase in testosterone levels.
Two of the immediate metabolites of testosterone, 5α-DHT and estradiol, are biologically important and can be formed both in the liver and in extrahepatic tissues. Approximately 5 to 7% of testosterone is converted by 5α-reductase into 5α-DHT, with circulating levels of 5α-DHT about 10% of those of testosterone, and approximately 0.3% of testosterone is converted into estradiol by aromatase. 5α-Reductase is highly expressed in the male reproductive organs (including the prostate gland, seminal vesicles, and epididymides), skin, hair follicles, and brain and aromatase is highly expressed in adipose tissue, bone, and the brain. As much as 90% of testosterone is converted into 5α-DHT in so-called androgenic tissues with high 5α-reductase expression, and due to the several-fold greater potency of 5α-DHT as an AR agonist relative to testosterone, it has been estimated that the effects of testosterone are potentiated 2- to 3-fold in such tissues.
The reasons for considering such therapy become evident from the many associations, indicated above, that reduced testosterone has with a variety of both physiological functions (bone metabolism, muscle mass, cognitive function, libido, erectile function) and pathophysiological states (metabolic syndrome, diabetes mellitus, obesity, insulin resistance, autoimmune disease). Although a definitive long-term, large scale placebo-controlled double-blind study of testosterone therapy in the aging male has not yet been carried out, multiple shorter-term trials have suggested improvement by testosterone with a resultant enhancement of muscle mass, bone density, libido, erectile function, mood, motivation and general sense of well-being.
Testosterone is a steroid from the androstane class containing a keto and hydroxyl groups at the three and seventeen positions respectively. It is biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites. It exerts its action through binding to and activation of the androgen receptor. In humans and most other vertebrates, testosterone is secreted primarily by the testicles of males and, to a lesser extent, the ovaries of females. On average, in adult males, levels of testosterone are about 7 to 8 times as great as in adult females. As the metabolism of testosterone in males is more pronounced, the daily production is about 20 times greater in men. Females are also more sensitive to the hormone.
Few examples: In this 2014 study, a bunch of researchers tested multiple different diets with added Lactobacillus Reuteri on male rodents. In every single case, the addition of L.Reuterii to the feed increased testosterone levels, increased luteinizing hormone levels, increased testicular size & weight, prevented age-related testicular shrinkage, improved semen parameters, and even increased markers of social domination.
Testosterone is a vital hormone for men, but just like estrogen in women, it goes down as you age. This is a natural process that has many drawbacks. In men, testosterone is responsible for hair growth, bone density, proper weight distribution, sex drive, muscle mass, red cell production, and so much more. But did you know that you can actually increase your testosterone levels as opposed to letting them dwindle?
Zaima, N., Kinoshita, S., Hieda, N., Kugo, H., Narisawa, K., Yamamoto, A., ... Moriyama, T. (2016, September). Effect of dietary fish oil on mouse testosterone level and the distribution of eicosapentaenoic acid-containing phosphatidylcholine in testicular interstitium. Biochemistry and Biophysics Reports, 7, 259–265. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613343/
One of the most important nutrients that can help boost testosterone levels is vitamin D3. In 2011, the results of a study published in the journal Hormone and Metabolic Research announced that vitamin D supplementation boosts testosterone naturally in overweight men by up to 30 percent. (12) This is pretty exciting because research has shown that vitamin D3 is also linked to helping to prevent and treat cancer! (13)
Puberty occurs when there is an “awakening” of the hypothalamic-pituitary axis. The hypothalamus increases its secretion of gonadotropin releasing hormone (GnRH) which in turn stimulates the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). This leads to a significant increase in the production of testicular testosterone and the induction of the well-known secondary sex characteristics associated with puberty: growth spurt, increased libido, increased erectile function, acne, increased body hair, increased muscle mass, deepening of the voice, spermatogenesis, gynecomastia (usually transient).
A 2010 study published in the journal Hormones and Behavior first suggested this when researchers evaluated the “dual-hormone hypothesis” clinically. (11) They discovered that when cortisol is elevated, testosterone responds by elevating as well but soon after bottoms out at a much lower level than before cortisol kicked in! That means you want to find ways to relieve stress to keep your testosterone levels up.
Next, while testosterone levels do decline with age, this may simply be because the older that men get, the less they take care of themselves – they stop exercising, start putting on weight, and don’t pay as much attention to their diet. A recent study suggests that age-related T decline is not inevitable, and that if you keep living a healthy lifestyle, you can maintain healthy testosterone levels. So if you’re an older guy, try to do all you can as far as lifestyle changes before you get on the prescription T. I don’t mean doing a little cardio a few times a week, using the machines at the gym, and eating “pretty” healthy. Follow the guidelines above, and see what happens first.
Because of inconclusive or conflicting results of testosterone treatment studies reported in the literature, Rabkin and colleagues (2004) undertook a comparison study among testosterone, the anti-depressant, fluoxetine, and placebo in eugonadal HIV positive men. They found that neither fluoxetine nor testosterone were different from placebo in reducing depression, but that testosterone did have a statistically significant effect in reducing fatigue. It is note-worthy that fatigue was reduced with testosterone treatment even though virtually all the men in the study had testosterone levels within the reference range.
Trials of testosterone treatment in men with type 2 diabetes have also taken place. A recent randomized controlled crossover trial assessed the effects of intramuscular testosterone replacement to achieve levels within the physiological range, compared with placebo injections in 24 men with diabetes, hypogonadism and a mean age of 64 years (Kapoor et al 2006). Ten of these men were insulin treated. Testosterone treatment led to a significant reduction in glycated hemoglobin (HbA1C) and fasting glucose compared to placebo. Testosterone also produced a significant reduction in insulin resistance, measured by the homeostatic model assessment (HOMA), in the fourteen non-insulin treated patients. It is not possible to measure insulin resistance in patients treated with insulin but five out of ten of these patients had a reduction of insulin dose during the study. Other significant changes during testosterone treatment in this trial were reduced total cholesterol, waist circumference and waist-hip ratio. Similarly, a placebo-controlled but non-blinded trial in 24 men with visceral obesity, diabetes, hypogonadism and mean age 57 years found that three months of oral testosterone treatment led to significant reductions in HbA1C, fasting glucose, post-prandial glucose, weight, fat mass and waist-hip ratio (Boyanov et al 2003). In contrast, an uncontrolled study of 150 mg intramuscular testosterone given to 10 patients, average age 64 years, with diabetes and hypogonadism found no significant change in diabetes control, fasting glucose or insulin levels (Corrales et al 2004). Another uncontrolled study showed no beneficial effect of testosterone treatment on insulin resistance, measured by HOMA and ‘minimal model’ of area under acute insulin response curves, in 11 patients with type 2 diabetes aged between 33 and 73 years (Lee et al 2005). Body mass index was within the normal range in this population and there was no change in waist-hip ratio or weight during testosterone treatment. Baseline testosterone levels were in the low-normal range and patients received a relatively small dose of 100 mg intramuscular testosterone every three weeks. A good increase in testosterone levels during the trial is described but it is not stated at which time during the three week cycle the testosterone levels were tested, so the lack of response could reflect an insufficient overall testosterone dose in the trial period.
Testosterone boosters are a class of herbal supplements aimed at naturally increasing your testosterone levels. Usually, they contain micronutrients that men are commonly deficient in, such as zinc, and which have been connected in research to healthy testosterone levels. They also may contain adaptogens, which are a class of supplement that are thought to help the body adapt to stress, or ingredients which have been connected to improved sleep. Sleep restriction has been shown to reduce testosterone in healthy young men, and as Chris Lockwood, Ph.D., notes, disturbed sleep is a common symptom of low T-levels.
Few of the most often asked questions I get are: what do I eat to maintain high testosterone levels, and if I have a specific list of recommended foods that increase testosterone naturally. While there are many food related posts scattered around this blog, I’ve never really made an all-around post about what I would put into a high T pantry. Until now.
The normal development of the prostate gland is dependent on the action of testosterone via the androgen receptor, and abnormal biosynthesis of the hormone or inactivating mutations of the androgen receptor are associated with a rudimentary prostate gland. Testosterone also requires conversion to dihydrotestosterone in the prostate gland for full activity. In view of this link between testosterone and prostate development, it is important to consider the impact that testosterone replacement may have on the prevalence and morbidity associated with benign prostatic hypertrophy (BPH) and prostate cancer, which are the common conditions related to pathological growth of the prostate gland.
^ Southren AL, Gordon GG, Tochimoto S, Pinzon G, Lane DR, Stypulkowski W (May 1967). "Mean plasma concentration, metabolic clearance and basal plasma production rates of testosterone in normal young men and women using a constant infusion procedure: effect of time of day and plasma concentration on the metabolic clearance rate of testosterone". The Journal of Clinical Endocrinology and Metabolism. 27 (5): 686–94. doi:10.1210/jcem-27-5-686. PMID 6025472.
So, how does one ensure that testosterone levels remain in balance? Some doctors suggest that monitoring testosterone levels every five years, starting at age 35, is a reasonable strategy to follow. If the testosterone level falls too low or if the individual has the signs and symptoms of low testosterone levels described above, testosterone therapy can be considered. However, once testosterone therapy is initiated, testosterone levels should be closely monitored to make sure that the testosterone level does not become too high, as this may cause stress on the individual, and high testosterone levels may result in some of the negative problems (described previously) seen.
Kostic TS, Stojkov NJ, Bjelic MM, Mihajlovic AI, Janjic MM, Andric SA: Pharmacological doses of testosterone upregulated androgen receptor and 3-Beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase and impaired leydig cells steroidogenesis in adult rats. Toxicol Sci. 2011 Jun;121(2):397-407. doi: 10.1093/toxsci/kfr063. Epub 2011 Apr 6. [PubMed:21427060]
A number of research groups have tried to further define the relationship of testosterone and body composition by artificial alteration of testosterone levels in eugonadal populations. Induction of a hypogonadal state in healthy men (Mauras et al 1998) or men with prostate cancer (Smith et al 2001) using a gonadotrophin-releasing-hormone (GnRH) analogue was shown to produce increases in fat mass and decreased fat free mass. Another experimental approach in healthy men featured suppression of endogenous testosterone production with a GnRH analogue, followed by treatment with different doses of weekly intramuscular testosterone esters for 20 weeks. Initially the experiments involved men aged 18–35 years (Bhasin et al 2001) but subsequently the study was repeated with a similar protocol in men aged 60–75 years (Bhasin et al 2005). The different doses given were shown to produce a range of serum concentrations from subphysiological to supraphysiological (Bhasin et al 2001). A given testosterone dose produced higher serum concentrations of testosterone in the older age group (Bhasin et al 2005). Subphysiological dosing of testosterone produced a gain in fat mass and loss of fat free mass during the study. There were sequential decreases in fat mass and increases in fat free mass with each increase of testosterone dose. These changes in body composition were seen in physiological and supraphysiological treatment doses. The trend was similar in younger versus older men but the gain of fat mass at the lowest testosterone dose was less prominent in older patients (Bhasin et al 2001; Bhasin et al 2005). With regard to muscle function, the investigators showed dose dependent increases in leg strength and power with testosterone treatment in young and older men but there was no improvement in fatigability (Storer et al 2003; Bhasin et al 2005).
Overall, few patients have a compelling contraindication to testosterone treatment. The majority of men with late onset hypogonadism can be safely treated with testosterone but all will require monitoring of prostate parameters HDL cholesterol, hematocrit and psychological state. It is also wise to monitor symptoms of sleep apnea. Other specific concerns may be raised by the mode of delivery such as local side effects from transdermal testosterone.
Acne and Allergic Reactions: The testosterone is universally regarded as one of the triggering factors for acne. It stimulates the activity of oil glands making the skin more oily and vulnerable to acne. This body hormone might also cause allergic reactions, such as hives, rash, difficulty breathing, itching, chest tightness, and big swelling of the facial parts.
Low testosterone levels can cause mood disturbances, increased body fat, loss of muscle tone, inadequate erections and poor sexual performance, osteoporosis, difficulty with concentration, memory loss and sleep difficulties. Current research suggests that this effect occurs in only a minority (about 2%) of ageing men. However, there is a lot of research currently in progress to find out more about the effects of testosterone in older men and also whether the use of testosterone replacement therapy would have any benefits.