Is Testosterone Replacement Therapy Safe? New Study Says Yes
By Steve Blechman
Testosterone replacement therapy (TRT) is the standard treatment for male hypogonadism, low testosterone.
“Testosterone sales increased 12-fold globally from USD $150 million in 2000 to 1.8 billion in 2011,” according to The Lancet Healthy Longevity journal.
“Deficiency of testosterone causes hypogonadism, including diminished secondary sexual characteristics, sexual dysfunction, muscle wasting and weakness, osteoporosis, and reduced quality of life,” according to The Lancet.
The Lancet Healthy Longevity journal also said, “despite the increasing use of testosterone, the USA Endocrine Society, American College of Physicians, and Endocrine Society of Australia have independently concluded that the cardiovascular safety of testosterone has not been adequately established. Furthermore, the European Association of Urology (EAU) and the European Academy of Andrology (EAA) have recommended the assessment of cardiovascular risk before initiation of testosterone therapy.”
Is testosterone replacement therapy safe? New study say yes. A new study published June 1st, 2022 in the prestigious journal The Lancet Healthy Longevity “found no evidence that testosterone increased short-time to medium-term cardiovascular risks in men with hypogonadism.” The study was a most in-depth “meta-analysis of more than 3,000 patients with hypogonadism from randomized placebo-controlled trials done by 17 research groups.” 1,750 patients received testosterone and 1,681 were given a placebo for about 9.5 months. The researchers “found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone.” The study said “there was little available data evaluating the cardiovascular safety of testosterone beyond a 12-month duration of administration.”
The researchers found that “testosterone treatment did not have adverse effects on blood pressure or glycemic markers compared to placebo; furthermore, it did not increase thrombotic events despite increased hematocrit. Testosterone treatment was associated with a modest lowering of total HDL cholesterol and triglyceride concentration compared with placebo.”Currently, a long-term 5-year testosterone clinical trial is being investigated in 5,000 men. Some experts are cautious at this time, and recommend men to wait for results of this new larger and longer study before prescribing testosterone replacement (TRT).
BEST NATURAL TESTOSTERONE SUPPLEMENTS
DHEA is a naturally occurring steroid hormone in the body that can enhance health, vitality, fat loss and improve “free testosterone” levels (the most important kind!) when taken before high-intensity exercise.
DHEA is a prohormone, serving as a precursor to testosterone, which has sparked interest as a potential “Fountain of Youth” supplement. However, just like testosterone, DHEA levels peak in early adulthood and then slowly fall as you age. To combat the effects of aging and declining DHEA, many adults supplement with DHEA.
Low levels of DHEA have been shown to increase storage of abdominal fat! The good news is that supplementing with 50 mg of DHEA per day prevented abdominal fat and improved insulin action, meaning DHEA replacement could play a significant role in the prevention and treatment of the metabolic syndrome. But there’s more.
Additional research into DHEA concluded that it can inhibit fat cell growth, increase metabolic rate and lower cortisol, the catabolic stress hormone that also suppresses brown fat tissue function in humans, lowering energy expenditure and enhancing abdominal fat storage. The exact opposite of what you want when trying to reshape your body.
DHEA can combat cortisol, boost free testosterone and help prevent muscle loss and overtraining. 50 mg of DHEA before exercise can improve free testosterone levels and improve testosterone/cortisol ratio. But here’s the really cool thing about DHEA …
DHEA can increase free testosterone after exercise!
There are two types of testosterone in the body: free testosterone and bound testosterone. Free testosterone is the most biologically active form of testosterone, while bound testosterone is biologically inactive, due to sex hormone-binding globulin (SHBG). In order for your body to use testosterone, it must unbind the testosterone, making it free and usable.
DHEA can do this!
High-intensity interval training (HIIT) increases fitness rapidly but suppresses testosterone, which could increase the susceptibility to overtraining. But, research notes that DHEA supplemented at 50 mg was found to increase circulating DHEA and free testosterone above baseline AND prevented those levels from declining during HIIT. More importantly, this study also showed that oral DHEA supplements can elevate free testosterone!
Another study found that 50 mg of oral DHEA given to men aged 40 to 70 for three months saw an increase in androstenedione (another important anabolic hormone) and a significant increase in the anabolic hormone IGF-1! Moreover, there was no change in circulating levels of sex hormone-binding globulin, estrogen (estrone or estradiol).
Also, more isn’t better when it comes to DHEA, as research shows that taking amounts higher than 50 mg does not provide more effective results and may potentially predispose you to unwanted side effects.
Boron is an ultra-trace element found in humans first introduced in the 1980s as a testosterone booster. Studies reported that when dosed at 10 mg per day boron increased testosterone. One study in particular showed that 10 mg of boron per day for seven days increased free testosterone by 28% and decreased estrogen levels by 39%. Another study in the Journal of Trace Elements Medicine and Biology reported that supplementing 10 mg of boron per day in healthy young males (ages 29 to 50) for a week decreased levels of sex-hormone binding globulin (SHBG) and significantly increased levels of free testosterone, which makes the hormone more biologically active.
Remember, in order for the body to use testosterone it must unbind the testosterone, making it free and usable. Boron does this by blocking the sex-hormone binding globulin (SHBG) from binding testosterone, making it unusable by the body.
Additional benefits of boron include decreased biomarkers of inflammation, such as c-reactive proteins (CRP). Lowering the level of CRP has been shown to enhance cardiovascular health.
FENUGREEK SEED EXTRACT
A staple of Ayurveda, fenugreek has a long history of use in traditional medicine. Studies have shown that fenugreek has blood sugar- and cholesterol-lowering properties, and may also improve insulin function and sensitivity, due to the presence of the amino acid 4-hydroxyisoleucine.
The powerful plant also contains glycosides and steroidal saponins that can boost free testosterone and inhibit aromatase. It should be noted that a portion of testosterone is converted to estrogen through a process called aromatization, which increases estrogen levels and decreases testosterone; however, aromatase inhibitors (like fenugreek) prevent the conversion of testosterone to estrogen, thereby reducing estrogen levels and increasing testosterone.
Given the potency of aromatase inhibitors, they’re a favorite for bodybuilders looking to prevent gynecomastia – the development of female-like breast tissue. But many of the pharmaceuticals come with a range of unwanted side effects, putting your health and well-being at risk. Fenugreek is a natural aromatase inhibitor shown to be safe in research trials.
Research published in the International Journal Sports Nutrition Exercise Metabolism (2010) noted that fenugreek supplementation decreased body fat and increased total and biologically available testosterone (compared to a placebo). Subjects in the trial trained four days per week consuming 500 mg of a standardized fenugreek extract.
After the trial, researchers concluded fenugreek “incompletely inhibited aromatase and 5-alpha-reductase activity while significantly increasing total and bioavailable testosterone levels, as well as decreasing percent body fat in conjunction with a resistance-training program.”
A study published in the Journal of Sports and Health Science (2015) reported that an eight-week treatment containing a standardized fenugreek extract (600 mg daily) offered beneficial effects in terms of repetition to failure in leg press and increased free testosterone levels compared to placebo, and it demonstrated significant anabolic and androgenic activity as compared with placebo. Subjects experienced significant improvements in body fat without a reduction in muscle strength or repetitions to failure. Best of all, supplementation with fenugreek came without any clinical side effects.
In short, fenugreek enhances testosterone levels, decreases estrogen levels, improves body composition and comes with absolutely no drawbacks!
Tongkat ali (aka Longjack) is a Malaysian plant used throughout Asia as an aphrodisiac. It’s extracted from the root of the small tree Eurycoma Longifolia, which is typically consumed as a beverage in Southeast Asia.
A study from the National Research Institute of Scientific Medicine found that tongkat ali promoted erection and delayed ejaculations in rats. Researchers determined that tongkat ali promoted penile blood flow while reducing stimulation of smooth muscle in the penis – which enhanced erections without overstimulation that would lead to premature ejaculation, suggesting that longjack might help men with two of the most common sexual disabilities: erectile dysfunction and premature ejaculation (Journal of Sexual Medicine, May 2011).
Tongkat ali has been shown to increase testosterone concentrations, muscle mass and strength in men and women. Studies in humans have demonstrated that 100 mg of tongkat ali extract increased strength and muscle circumference while treatment with 200 mg and 400 mg of tongkat ali increased total and free testosterone concentration.
Additionally, tongkat ali is often referred to as “Malaysian ginseng” for its adaptogenic benefits where it exerts anti-stress properties and restores hormonal balance by improving testosterone/cortisol ratio. Tongkat ali extract also increases free testosterone by inhibiting sex-hormone binding globulin (SHBG), and research demonstrates that supplementation with tongkat ali root extract (200 mg/day) improves stress hormone profile (lower cortisol, higher testosterone) as a result of stresses such as dieting for weight loss, sleep deprivation and intense exercise training.
In two other studies, tongkat ali supplementation (100 mg/day) improved lean body mass, one-repetition maximum (1RM) strength and arm circumference to a significantly greater degree compared to placebo. In men with low testosterone (average age 51), one month of daily supplementation with tongkat ali extract (200 mg/day) resulted in significantly improved serum testosterone levels, and another study using young healthy adult males (average age 25) demonstrated that 100 mg/day of tongkat ali extract, added to an intense strength-training program, improved lean body mass and arm size compared to placebo group. The results demonstrate that tongkat ali extract can enhance muscle mass and strength and enhance fat loss in healthy exercises.
Additional studies showed that 50-100 mg/day of tongkat ali extract helped improve normal testosterone levels in supplemental dieters (compared to a drop in testosterone among non-supplemental dieters). For many dieters, it would be expected for cortisol to rise and testosterone to fall following several weeks of dieting. Also, in one trial, endurance cyclists’ cortisol levels were 32% lower and testosterone levels were 16% higher in supplemental subjects compared to placebo, creating an anabolic state.
Basically, tongkat ali is a very effective compound that has been shown to increase total and free testosterone concentrations, muscle mass and strength in men!
RED WINE POLYPHENOLS
Red wine is a rich source of polyphenols, bioflavonoids that serve as potent antioxidants. Studies have shown that red wine polyphenols may help promote cardiovascular health.
The polyphenols, anthocyanins and procyanidins in red wine provide the most cardiovascular health benefits. One of the most popular polyphenols is resveratrol, which also has many health benefits, and a big reason behind the push to consume red wine these days. However, we currently don’t know which polyphenols are best, so, it’s good to take a mixture found in red wine.
Research studies have shown that red wine polyphenols are potent, natural aromatase inhibitors that decrease estrogen and increase testosterone levels. They’re also potent nitric oxide boosters that enhance vasodilation and blood flow, meaning they’re great for getting a muscle pump!
Red wine polyphenols can also raise free testosterone by reducing sex-hormone-binding globulin (SHBG), a carrier protein that protects testosterone from being metabolized while in the bloodstream.
Additionally, researchers found that red wine polyphenols might reduce the amount of testosterone excreted by the body, leading researchers to believe that if further studied, it’s possible that the “compounds in red wine can reduce the amount of testosterone in urine and give a boost to testosterone levels.”
Low levels of vitamin D are linked to low blood testosterone. An Austrian study showed that supplementation with vitamin D (3,332 IU) daily for one year increased testosterone by 20% and the biologically active free testosterone by 17% via lowering sex-hormone binding globulin (SHBG). Vitamin D also decreases the breakdown of testosterone into estrogen by reducing the expression of the aromatase enzyme, and has been shown to raise IGF-1 levels.
Vitamin D is produced by the body via exposure sunlight and through the diet. It is critical for bone health but also important for immune system function. The increased incidence of colds and flu during the winter may be due to reduced levels of vitamin D.
Vitamin D can also increase muscle strength. A review of vitamin D concluded that supplementation with the vitamin (4,000 IU per day) increased upper and lower strength. The review included 310 adults, average age 21 to 31. The authors wrote, “This review has found that vitamin D3 supplementation improves upper and lower muscle strength in a healthy adult, athletic and non-athletic population between ages of 18 and 40.” This was the first finding that vitamin D can increase muscle strength in young, healthy adults.
As if that wasn’t reason enough to use vitamin D, consider this: Vitamin D supplementation can also cut body fat!
Vitamin D supplements combined with 12 weeks of weight training improved and increased power output in overweight young adults – according to a study led by Andres Carrillo from Purdue University. Researchers supplemented 4,000 IU of vitamin D per day. They found improvements in peak power output and waist-to-hip ratio.
WHAT WORKS AND WHAT DOESN’T
D-Aspartic acid, Tribulus terrestris, stinging nettle, saw palmetto, maca root extract, damiana leaf extract, indole 3-carbinol and 3,3-diindolylmethane (DIM) are not reviewed in the report because of lack of published, scientific human research supporting increased free or total testosterone in humans. Also, purified supplements of indole-3-carbinol and DIM are shown to be phytoestrogens, anti-androgens (blocking androgen receptors) and endocrine disruptors. They shouldn’t be taken as dietary supplements if you want to maximize testosterone function! If you want to get your health benefits from these compounds, then play it safe and eat your cruciferous vegetables such as broccoli, cauliflower, Brussels sprouts or asparagus.
For example, the latest research has shown that D-aspartic acid decreases testosterone! Australian scientists from the University of Western Sydney, led by Geoffrey Melville, found that daily supplementation of either 3 or 6 grams of D-aspartic acid decreased total and free testosterone in resistance-trained men and had no effect on related hormones such as estrogen or sex-hormone binding globulin (Nutrition Research, 2013 & Journal of the International Society of Sports Nutrition, 2015).
Another example is Tribulus terrestris, often recommended for increasing testosterone. Tribulus terrestris is an herb that was fist cultivated on the Steppes of Georgia (the country, not the state). East Bloc athletes used it to boost testosterone production and improve performance. Russian scientists theorized that the herb acts like the pituitary hormone (LH) to stimulate testosterone release in the testes. The supplement has been extremely popular with bodybuilders and powerlifters for increasing performance and non-athletic men for improving sexual performance, even though little research supports its effectiveness. Well-controlled studies have found that Tribulus has no effect on strength, body composition, or testosterone. (Journal of Human Kinetics, 2014).
According to Halis Akturk and Todd Nippoldt from the Mayo Clinic (JAMA, 2016), “The symptoms linked to low testosterone levels can often be improved through exercise, fat loss, improved diet, reduced stress and better sleep habits.”
When it comes to diet, low-fat diets lower testosterone levels. Saturated and monounsaturated fatty acids have been shown to directly and systematically boost testosterone while polyunsaturated fats, by and large, inhibit testosterone production. Arachidonic acid, an omega-6 derived polyunsaturated fatty acid, does support testosterone production, but I do not recommend it as a dietary supplement because it is a substrate for the inflammatory cascade and inflammation in the body. You get all the arachidonic acid you need from the diet. No need to take supplemental arachidonic acid, as it may increase inflammation and the risk of heart disease and other degenerative diseases. The best and healthiest fats for boosting testosterone are monounsaturated fats, which are found preferably in extra-virgin olive oil, avocados and nuts. Not saturated fats, which can increase the risk of cardiovascular disease. Nuts are high in zinc and magnesium. Diets deficient in zinc can lower testosterone levels. Zinc supplements have also been shown to increase testosterone in zinc-deficient adults. Also, oral zinc supplements increase total and free testosterone levels in elite athletes after exhaustion exercise (Neuro Endocrin, 2006).
Studies have shown that oleuropein, a polyphenol in olive oil, has aromatase-inhibiting properties, which might enhance testosterone levels. Also, the polyphenols found in red wine are natural aromatase inhibitors that decrease serum estrogen levels. Don’t overdo the red wine – it contains alcohol, which can lower testosterone and increase aromatase and estrogen levels! Red wine polyphenol supplements might be an alcohol-free alternative. Alcohol can act as an aromatase stimulator and increase estrogen levels. I have personally found that moderate consumption of red wine, one to two glasses per day, has a favorable effect on testosterone, unlike other alcoholic beverages, because of red wine’s polyphenol content.
The polyphenol content is one of the reasons why I’m a big advocate of the Mediterranean diet. A breakthrough study in the American Heart Association journal Circulation, conducted at Ben-Gurion University of the Negev and Harvard University, compared body fat. Researchers compared a low-fat diet to a low-carb Mediterranean diet. The low-carb Mediterranean diet is more effective for reducing body fat, particularly visceral (abdominal) body fat. The diet study used magnetic resonance imaging (MRI) technology for the first time, measuring changes in body fat and organ fat during 18 months on a Mediterranean low-carb diet with moderate physical exercise. This is the best approach to date for measuring body fat compared to weighing people, as opposed to diet and exercise.
The scale, skinfold calipers and underwater weighing aren’t giving you the whole picture. The Mediterranean diet is significantly superior to a low-fat diet in decreasing fat storage including visceral (deep abdominal) liver and heart fat. High visceral fat has been shown to increase metabolic syndrome, inflammation, cardiovascular disease and diabetes. Losing deep subcutaneous visceral fat as well as hepatic (liver) fat was shown to improve lipid sensitivity and lipid profiles.
The low-carb Mediterranean diet is higher in monounsaturated fats from olive oil that can raise testosterone, while low-fat diets lower testosterone production. So not only is the low-carb Mediterranean diet ideal for weight loss, but you get healthier fats from monounsaturated fats such as olive oil and nuts, which can boost testosterone. According to a study in the prestigious New England Journal of Medicine (June 13, 2018), for persons at high cardiovascular risk, the incidents of major cardiovascular events was lower among those on a Mediterranean Diet supplemented with extra-virgin olive oil or nuts compared to a reduced-fat diet.
So, if you want to boost testosterone and enhance fat loss, follow the low-carb Mediterranean diet. A study published in JAMA on April 25, 2018 found that the Mediterranean diet fights against frailty. It’s just another study that supports the Mediterranean diet to preserve lean body mass and health during aging. It’s also especially important to follow a high-intensity resistance training program for maintaining testosterone and enhancing lean body mass. Don’t overdo long periods of cardiovascular, aerobic exercise as it can lower testosterone and encourage overtraining. Overtraining can lower testosterone and raise cortisol. Rest and recovery are important in maintaining normal, healthy testosterone levels.
Coffee is also good for boosting testosterone. A Harvard University study led by Nichole Wedick showed that men who drink caffeinated coffee show increases in total testosterone and decreases in free estradiol (estrogen). Coffee is loaded with phenolic antioxidants that act as natural aromatase inhibitors, which prevent the conversion of testosterone to estrogen (Nutrition Journal, 2012). Among men, consumption of caffeinated coffee has been shown to raise testosterone levels and decrease total estrogen and estradiol levels.
© Published by Advanced Research Media, Inc., 2022
© Reprinted with permission from Advanced Research Media, Inc.
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