Testosterone is the primary male sex hormone and an anabolic steroid. In male humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair.[2] In addition, testosterone is involved in health and well-being,[3] and the prevention of osteoporosis.[4] Insufficient levels of testosterone in men may lead to abnormalities including frailty and bone loss.
The hypogonadal-obesity-adipocytokine cycle hypothesis. Adipose tissue contains the enzyme aromatase which metabolises testosterone to oestrogen. This results in reduced testosterone levels, which increase the action of lipoprotein lipase and increase fat mass, thus increasing aromatisation of testosterone and completing the cycle. Visceral fat also promotes lower testosterone levels by reducing pituitary LH pulse amplitude via leptin and/or other factors. In vitro studies have shown that leptin also inhibits testosterone production directly at the testes. Visceral adiposity could also provide the link between testosterone and insulin resistance (Jones 2007).
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Before assessing the evidence of testosterone’s action in the aging male it is important to note certain methodological considerations which are common to the interpretation of any clinical trial of testosterone replacement. Many interventional trials of the effects of testosterone on human health and disease have been conducted. There is considerable heterogenicity in terms of study design and these differences have a potential to significantly affect the results seen in various studies. Gonadal status at baseline and the testosterone level produced by testosterone treatment in the study are of particular importance because the effects of altering testosterone from subphysiological to physiological levels may be different from those of altering physiological levels to supraphysiological. Another important factor is the length of treatment. Randomised controlled trials of testosterone have ranged from one to thirty-six months in duration (Isidori et al 2005) although some uncontrolled studies have lasted up to 42 months. Many effects of testosterone are thought to fully develop in the first few months of treatment but effects on bone, for example, have been shown to continue over two years or more (Snyder et al 2000; Wang, Cunningham et al 2004).
^ Jump up to: a b Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, Lapauw B, Fiers T, Matsumoto AM, Bhasin S (April 2017). "Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe". The Journal of Clinical Endocrinology and Metabolism. 102 (4): 1161–1173. doi:10.1210/jc.2016-2935. PMC 5460736. PMID 28324103.
A large number of trials have shown the positive effects of testosterone treatment on markers of bone formation and increased bone density in hypogonadal men treated with testosterone.1,4,6,8,13 Not surprisingly, the effects may take several years to fully develop. At present no data on the role of testosterone in preventing fracture in men with hypogonadism are available.
Epidemiological studies have also assessed links between serum testosterone and non-coronary atherosclerosis. A study of over 1000 people aged 55 years and over found an inverse correlation between serum total and bioavailable testosterone and the amount of aortic atherosclerosis in men, as assessed by radiological methods (Hak et al 2002). Increased intima-media thickness (IMT) is an early sign of atherosclerosis and has also been shown to predict cardiovascular mortality (Murakami et al 2005). Cross-sectional studies have found that testosterone levels are negatively correlated with carotid IMT in independently living men aged 74–93 years (van den Beld et al 2003), diabetic men (Fukui et al 2003) and young obese men (De Pergola et al 2003). A 4-year follow up study of the latter population showed that free testosterone was also inversely correlated with the rate of increase of IMT (Muller et al 2004).
This is over simplified but should offer you some clarity to what you are experiencing – If you are getting Testosterone Cypionate injections every 2 weeks, then you are on the roller coaster. I have great results with weekly injections and some folks need bi-weekly injections. It’s all how your body reacts but every 2 weeks is just plain too far apart as the product is relatively ineffective after 10 days. Measurable at 10 days? Somewhat but still ineffective at that point.
When you’re under stress (be it from lack of sleep, workplace stress, emotional stress, stress from a bad diet, overtraining etc.), your body releases cortisol. Cortisol blunts the effects of testosterone (47), which makes sense from an evolutionary point of view – if we were stressed as cavemen chances are it was a life or death situation – not running late to a meeting - in this state (i.e. running from a lion) the body wouldn’t care if you couldn’t get it up, there was more to worry about!
I have tried pellets, I went from 5 grams/day gel, to 10 grams, had little change due to work schedule and no energy made it difficult to manage daily. Levels got down to 78 at one point. Testo pellets worked great but it took 10 to make a difference and it brought me up to the 300-400 range. My body rejected 3 pellets and expelled them. Tried axiron, didn’t work, natesto, which the doc never heard off next, a Nasal spray which helped but the bottle ran out 5 days early either by my mistake or dosage problems. Back to 10 grams Testim AG ($360 after deductible) which helps if i could stay consistent but I’m 28. With a job, and health insurance, deductible issues I can not afford 800 dollars a month, 360 after deductible. Recent levels of FSH/LH are .7 and 1.2 (low). Total testosterone 114, free 18.9, and bioavalability at 39.6 (low). I had a MRI of my pituitary gland today, and get results next week. Hoping to start depo T next week as I return to work. If I can recommend anything to anyone, is make sure it’s affordable, you have the time or energy to apply/administer, and understand most people will not understand what you are going through. 2 killers of testosterone are chronic stress and lack of sleep. In 3 years of treatment I wish I came to this man’s article and others and read up prior because I’m on the brink of losing everything I’ve worked for due to hypogonadism. Wish you all results and good health, and thank you for a great article!
Present in much greater levels in men than women, testosterone initiates the development of the male internal and external reproductive organs during foetal development and is essential for the production of sperm in adult life. This hormone also signals the body to make new blood cells, ensures that muscles and bones stay strong during and after puberty and enhances libido both in men and women. Testosterone is linked to many of the changes seen in boys during puberty (including an increase in height, body and pubic hair growth, enlargement of the penis, testes and prostate gland, and changes in sexual and aggressive behaviour). It also regulates the secretion of luteinising hormone and follicle stimulating hormone. To effect these changes, testosterone is often converted into another androgen called dihydrotestosterone. 

I’m 56 and 5 years ago dropped to 270 with all the side effects listed for low test. After trying shots and not liking the roller coaster effect, I switched to gels. Androgel and Axiron had too low a dosage and far too messy. They need to not call them gels but liquids. If it pours like water it’s a liquid. My doctor recommended a compounding Pharmacy that made a cream and it was perfect. It had a click dispenser that looked like a deoderant that would pre-measure the dosage and I could rub it on my arms and shoulders or on my neck, really anywhere not covered in hair but the thinner the skin the better. It dried instantly so I could get dressed in a couple minutes. My totals never got out of the 400’s until I started the 150mg daily cream dosage, then they hovered around 700. The down side was Insurance didn’t cover it and I had to pay $50 a month vs free shots from the doctors office or $10 for the so-called gels. Bad news is it has now doubled in price due to new Federal production regs on compounding Pharms. Now, I am going back on the shots which I now have to buy the vile for $125 for 10 doses and have to take it to my doctor to administer it every 2wks while I am looking into bioidentical pellet implants.
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.
If your levels are indeed low, there are a number of synthetic and bioidentical testosterone products on the market, as well as DHEA, which is the most abundant androgen precursor prohormone in the human body, meaning that it is the largest raw material your body uses to produce other vital hormones, including testosterone in men and estrogen in women.
If you have low testosterone and are prescribed testosterone therapy by your doctor, it does not increase your risk for getting prostate cancer. However, in some patients with existing prostate cancer, adding testosterone hormone therapy can make the cancer grow faster. Men with low testosterone levels are actually more likely to get prostate cancer than men with normal prostate levels. You need to discuss these details with your physician and make the best decision for you.

The researchers found that the dose of testosterone required to produce different effects in the body varied widely. The influence of testosterone and estradiol also differed. As the testosterone gel dose was reduced, the scientists showed, reductions in lean mass, muscle size, and leg-press strength resulted from decreases in testosterone itself. In contrast, increases in body fat were due to the related declines in estradiol. Both testosterone and estradiol levels were associated with libido and erectile function.
"I went from 230 pounds down to 192. When my son got married, I went for the suit fitting, and I was a size 48. When I went back to do the final fitting, I was a 44! I want to keep getting it for the weight loss; I lost 4 inches around my belly, and I want to get rid of the rest of the weight around my belly. I’m 57, and my wife says I look like I’m back in my 30s. I have more energy for sure, and I’m going to participate in one of those Savage races where they have the obstacle courses with one of our kids."
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Vitamin D3: Vitamin D3 is actually more hormone than it is a vitamin. Vitamin D is taken in by around 10% of our diets and D3 is mostly absorbed from the sun, which can be linked to greater testosterone production. The link between the two is a result from the luteinizing hormone playing its role. Read more about how vitamin D3 effects testosterone — the evidence is staggering.
Epidemiological evidence supports a link between testosterone and glucose metabolism. Studies in non-diabetic men have found an inverse correlation of total or free testosterone with glucose and insulin levels (Simon et al 1992; Haffner et al 1994) and studies show lower testosterone levels in patients with the metabolic syndrome (Laaksonen et al 2003; Muller et al 2005; Kupelian et al 2006) or diabetes (Barrett-Connor 1992; Andersson et al 1994; Rhoden et al 2005). A study of patients with type 2 diabetes using measurement of serum free testosterone by the gold standard method of equilibrium dialysis, found a 33% prevalence of biochemical hypogonadism (Dhindsa et al 2004). The Barnsley study demonstrated a high prevalence of clinical and biochemical hypogonadism with 19% having total testosterone levels below 8 nmol/l and a further 25% between 8–12 nmol/l (Kapoor, Aldred et al 2007). There are also a number longitudinal studies linking low serum testosterone levels to the future development of the metabolic syndrome (Laaksonen et al 2004) or type 2 diabetes (Haffner et al 1996; Tibblin et al 1996; Stellato et al 2000; Oh et al 2002; Laaksonen et al 2004), indicating a possible role of hypogonadism in the pathogenesis of type 2 diabetes in men. Alternatively, it has been postulated that obesity may be the common link between low testosterone levels and insulin resistance, diabetes and cardiovascular disease (Phillips et al 2003; Kapoor et al 2005). With regard to this hypothesis, study findings vary as to whether the association of testosterone with diabetes occurs independently of obesity (Haffner et al 1996; Laaksonen et al 2003; Rhoden et al 2005).

Epidemiological data has associated low testosterone levels with atherogenic lipid parameters, including lower HDL cholesterol (Lichtenstein et al 1987; Haffner et al 1993; Van Pottelbergh et al 2003) and higher total cholesterol (Haffner et al 1993; Van Pottelbergh et al 2003), LDL cholesterol (Haffner et al 1993) and triglyceride levels (Lichtenstein et al 1987; Haffner et al 1993). Furthermore, these relationships are independent of other factors such as age, obesity and glucose levels (Haffner et al 1993; Van Pottelbergh et al 2003). Interventional trails of testosterone replacement have shown that treatment causes a decrease in total cholesterol. A recent meta-analysis of 17 randomized controlled trials confirmed this and found that the magnitude of changes was larger in trials of patients with lower baseline testosterone levels (Isidori et al 2005). The same meta-analysis found no significant overall change in LDL or HDL cholesterol levels but in trials with baseline testosterone levels greater than 10 nmol/l, there was a small reduction in HDL cholesterol with testosterone treatment.
However, an important peculiarity of testosterone boosting products is their inability to cause addiction. Also, as opposed to steroids, the natural supplements don’t disturb the bodily functions. It means that these products don’t destroy the men’s hormone balance and don’t suppress the natural testosterone synthesis. Instead, the high-quality boosters successfully and safely eliminate the hormone imbalance issues in the men’s body.
Most men report being able to lose body fat and gain lean muscle more easily when they take testosterone boosters. These supplements can also raise a man’s mood and make him feel more confident. You might notice that your libido gets a boost, too. They make workouts more effective and, in some cases, easier. Testosterone boosters are also great for men with low testosterone levels, as they will combat the low energy and fatigue that go along with low levels. Other supplements to consider are energy-boosting supplements and pre-workout supplements.
Cross-sectional studies have not shown raised testosterone levels at the time of diagnosis of prostate cancer, and in fact, low testosterone at the time of diagnosis has been linked with more locally aggressive and malignant tumors (Massengill et al 2003; Imamoto et al 2005; Isom-Batz et al 2005). This may reflect loss of hormone related control of the tumor or the effect of a more aggressive tumor in decreasing testosterone levels. One study found that 14% of hypogonadal men, with normal digital rectal examination and PSA levels, had histological prostate cancer on biopsy. It is possible that low androgen levels masked the usual evidence of prostate cancer in this population (Morgentaler et al 1996). Most longitudinal studies have not shown a correlation between testosterone levels and the future development of prostate cancer (Carter et al 1995; Heikkila et al 1999; Stattin et al 2004) but a recent study did find a positive association (Parsons et al 2005). Interpretation of such data requires care, as the presentation of prostate cancer could be altered or delayed in patients with lower testosterone levels.
Another recent development is the production of adhesive tablets which are applied twice daily to the buccal mucosa on the gum above the incisor teeth. The tablets gradually release testosterone into the systemic venous circulation and steady state physiological concentrations are achieved in most patients within two days (Ross et al 2004). Some patients do not like the feeling of the tablet in the mouth or find that there is an abnormal taste in the mouth, but local adverse effects are usually mild and transient (Wang, Swerdloff et al 2004).
The testosterone booster pills are effective from 4 to 8 hours. To maintain testosterone levels high during the whole day, you need a multiple daily dosing regimen. 2-times daily dosing still not always can improve hormone production to the greatest extent. 3-4-times daily dosing is the best solution to make your body normalize testosterone synthesis and prevent it from decreasing before you take another pill. Don’t forget that the regularity of daily supplement intake is crucial if you really aspire to give a boost to hormone production.

Started HRT in my early 50’s as I had all the low-T symptoms and Type 2 Diabetes, which was hammering my body. My total T was about 100 (not sure about Free at that point). First started with Androgel, and was getting decent symptomatic improvement, but didn’t like the residue from the cream, and traveling with the creams was a problem. I’ve gone to pellet implants for the past 7 years. Every 4-5 months, very happy with results to date.
It also had a purpose. It turns out posing in powerful stances causes your testosterone to increase within 20 minutes [13,14]. In those two studies, power posing for just a few minutes also dropped cortisol and boosted confidence. It’s a great way to start your day, or to give yourself an edge before a job interview or a big presentation. They don’t call it “warrior pose” for nothing!
I had been on testosterone cyperonate 250-300 mg every 2 weeeksfor one year when diagnosed as having hypercythemic. I was cut of treatments immediately. Scanned from head to toe side to side. All clear. My urologist refuses to resume any HRT as my total testosterone is 701 immunoassay. However, he never mentions my Free % T value of 1.3. The labs range is 1.6-2.9. SHGB =70.6. Albumin 4.1. Is not the Free T we should be concerned with? Do I not need to go “Uologist Hunting”????
“However, the parallels don’t necessarily follow logically, creating a real need to bring more evidence to this area so that physicians and patients would be able to make more  informed decisions based on the best possible evidence,” said Dr. Gill, a professor of medicine and the lead investigator at the Yale study site, the largest site participating in the TTrials, and coauthor of all 4 TTrials. 
I have been on both pills and gel.While the pills were much more convenient, the gel seems to work better for me. I feel more focused and clear of mind with gel therapy. I’ve also noticed more sexual interest (closer to levels when younger – now 65) and get ‘harder’ when I do get an erection. The therapy has been good for me emotionally and physically. I’ll stay on it until and if negative signs/symptoms arise.

The participants were seen every 4 weeks. Blood was taken to measure hormone levels, and questionnaires were given to assess physical function, health status, vitality, and sexual function. Body fat and muscle measurements were also taken at the beginning and end of the 16 weeks. The study was funded in part by NIH’s National Institute on Aging (NIA) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results appeared in the September 12, 2013, issue of the New England Journal of Medicine.
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