Does Testosterone Therapy Increase The Risk of Heart Disease in Men?

on June 7, 2017 by Chris Kresser

In recent years, advertising campaigns for testosterone replacement therapy have sparked a rapid rise in the use of testosterone gels, patches, pellets, and injections by men of all ages. Despite its popularity, testosterone therapy is not without risk. Research suggests that men who use testosterone may be at increased risk of heart disease. Read on to learn about the dangers of testosterone replacement therapy and why dietary and lifestyle changes are a much healthier approach for restoring optimal levels of this crucial hormone.

Low T: Epidemic or fad?

Testosterone replacement therapy (TRT) is currently a hot topic of discussion in the media and the medical community. Slick TV commercials, persuasive magazine news folds, and attention-grabbing billboards advertising testosterone therapy abound and have not gone unnoticed by men hoping to bolster their masculinity. Not surprisingly, sales of testosterone drugs have increased more than five-fold in the last decade, and the use of testosterone therapy has soared among middle-aged and older men. (1, 2)

Originally, the intended use of TRT in men was for the treatment of hypogonadism, a condition characterized by low testosterone levels (typically less than 300 ng/dL) caused by disease or damage to the testes or endocrine system. (3) However, in the past decade, TRT has become increasingly popular among men who have minimal or no deficits in testosterone but who hope to lessen symptoms of aging such as fatigue, weight gain, lack of sex drive, and muscle wasting. Some health professionals believe that many men suffer from low testosterone (popularly referred to as “low T”) and that this is having a detrimental impact on their health and quality of life.

While there is no doubt that some men do indeed suffer from low testosterone, research indicates that men with normal testosterone levels and ambiguous symptoms are seeking out and being prescribed TRT, and some doctors are writing prescriptions for TRT without even carrying out baseline hormone testing. (4) This may pose a risk to patients’ health. Overall, the topic of TRT is divisive; some healthcare practitioners believe low testosterone is an epidemic, while others think it is a fad designed to sell more drugs and have gone so far as to call it fearmongering. (5) However, the truth regarding low testosterone appears to lie somewhere in between these two extremes.

Low testosterone is a legitimate problem

Adequate levels of testosterone are crucial for the promotion of optimal health in men, including maintenance of muscle mass, bone density, sperm production, optimal lipid profiles, healthy numbers of red blood cells, sex drive, and fertility. Testosterone levels naturally decline with age. However, certain factors such as pharmaceutical drugs, environmental toxins, obesity, and an unhealthy diet can prematurely decrease testosterone.

For example, statins lower testosterone by decreasing cholesterol, an essential building block for testosterone and other steroid hormones, and endocrine-disrupting chemicals such as BPA and phthalates mimic estrogen and block the action of testosterone, respectively. (6, 7) In addition, obesity and a diet high in refined carbohydrates lower testosterone levels by creating insulin resistance and diabetes, which affect the endocrine system. For men experiencing a true testosterone deficiency, the symptoms can be quite distressing and may include fatigue, loss of libido, loss of facial and body hair, excess body fat, and gynecomastia. Testosterone therapy can seem like a beacon of hope to men facing these issues. However, despite the favorable way TRT has been painted by the media, research indicates this therapy may come with a very serious hidden cost—an increased risk of heart disease.

Testosterone therapy increases the risk of heart disease

A growing body of research indicates that testosterone therapy is associated with an increased risk of cardiovascular disease in men. A study conducted by the National Institutes of Health followed 56,000 middle-aged and older men who were prescribed testosterone therapy between 2008 and 2010. It was found that men 65 years of age and older had a twofold increase in risk of heart attack within just 90 days of starting testosterone therapy. In addition, men younger than 65 years of age with a history of heart disease experienced a two- to threefold increased risk of heart attack when taking testosterone. (8)

Another large study published in JAMA: The Journal of the American Medical Association discovered that men with a history of heart disease had a 30 percent increase in mortality, heart attacks, and stroke after commencing testosterone therapy. (9) Several systematic reviews of the medical literature regarding testosterone therapy have further backed up these findings, confirming that exogenous testosterone is strongly associated with an increased risk of cardiovascular events.

Perhaps not surprisingly, it has been found that conclusions regarding the relationship between testosterone and heart disease risk vary within the medical literature based on the source of funding for the research. A comprehensive systematic review found that studies funded by pharmaceutical companies with a large stake in testosterone sales typically concluded that testosterone therapy is entirely safe or poses only minimal risk, while studies not funded by the industry almost unanimously determined that testosterone increases the risk of cardiovascular events. (10)

Up until recently, prescription testosterone lacked any sort of warnings about associations with cardiovascular disease risk. However, in 2015 the FDA finally released a report cautioning that prescription testosterone products have only been approved for men with low testosterone due to hypogonadism and that the benefits and safety of testosterone have not been established from the treatment of low T due to aging. (11)

Risk-free ways to raise testosterone without replacement therapy #testosterone #hearthealth

Testosterone therapy thickens the blood

Testosterone is involved in red blood cell production, and exogenous testosterone has been found to substantially increase hematocrit, which is the ratio of red blood cells to the total volume of blood in the body. This is the mechanism by which testosterone therapy appears to raise cardiovascular disease risk. When hematocrit is increased, red blood cells can clump together, thickening the blood. In older men and men with pre-existing cardiovascular problems, such as atherosclerosis, thickened blood poses a serious health risk and may precipitate a cardiovascular event. (12)

Testosterone therapy raises blood pressure and reduces HDL cholesterol

In addition to thickening the blood, exogenous testosterone has also been found to increase blood pressure and reduce HDL cholesterol, two other risk factors that play a role in the pathogenesis of heart disease. (13, 14) Given the number of adult males who are struggling with high blood pressure and lipid abnormalities, adding TRT into the mix may prove to be a dangerous combination for their heart health.

What about bioidentical testosterone?

The jury is out when it comes to the safety of bioidentical testosterone in comparison to prescription synthetic testosterone; we do not yet know if bioidentical testosterone has detrimental effects on the cardiovascular system similar to prescription testosterone. Nonetheless, it is important to keep in mind that there is a difference between providing the body with testosterone from exogenous sources (whether synthetic or bioidentical) and boosting the body’s production of testosterone naturally. Considering the concerning research regarding testosterone replacement therapy and heart disease risk, it appears that dietary and lifestyle interventions that encourage the body’s own production of testosterone may be the healthier and safer long-term option for restoring testosterone levels.

Low endogenous testosterone is associated with cardiovascular disease

While exogenous testosterone replacement appears to increase cardiovascular disease risk, low endogenous testosterone (testosterone produced naturally within the body) is also positively associated with cardiovascular events. Thus, effects of exogenous and endogenous testosterone may differ. This evidence provides further support for the notion that naturally increasing the body’s testosterone production is preferable to TRT as a method of treatment. (15, 16)

Alternatives for raising testosterone

There are many dietary and lifestyle modifications that can help to naturally raise testosterone levels. The side benefit of these natural interventions is that in addition to raising testosterone, they may also improve blood sugar control, insulin resistance, and liver health and strengthen the immune system.

Lose weight

Low testosterone is associated with obesity, and weight loss has been found to lead to a sustained increase in testosterone levels. Undertaking dietary and lifestyle changes to promote fat loss may be one of the most important steps a man can take to raise his testosterone levels. (17, 18)

Eat a nutrient-dense, whole foods diet

Losing excess weight is an essential step in raising testosterone levels, and cleaning up one’s diet can serve as the impetus for healthy weight loss. A nutrient-dense, whole foods diet that includes plenty of protein, zinc, magnesium, and healthy fats is crucial for maintaining optimal testosterone levels.

  • Protein
    Consuming adequate amounts of high-quality protein is crucial for maintaining muscle mass and promoting fat loss, two factors that can impact testosterone levels. (19) When selecting sources of animal protein, opt for organic and pastured options as much as possible; these sources of animal protein do not contain the endocrine-disrupting growth hormones that are often found in conventionally raised animals.
  • Zinc and magnesium
    Zinc and magnesium are two crucial nutrients for promoting healthy testosterone levels. Zinc deficiency is associated with low testosterone levels and infertility in males. (20, 21) Zinc is abundant in red meat, poultry, and pumpkin seeds. Magnesium is another key testosterone-boosting nutrient; magnesium supplementation has been found to increase the serum level and biological activity of testosterone. (22) Magnesium can be found in leafy green vegetables, almonds, avocados, and dark chocolate.
  • Healthy fats
    A healthy intake of fat is essential for maintaining testosterone levels. Cholesterol, found in saturated fat, is needed to produce steroid hormones such as testosterone. An inadequate intake of fat may therefore deprive the body of the building blocks it needs to produce testosterone. (23) For healthy sources of fats, try grass-fed butter, pastured animal fats, coconut oil, olive oil, avocado, and moderate amounts of nuts.
  • Cut out refined carbohydrates
    To optimize testosterone production, refined carbohydrates should be removed from the diet. Refined carbohydrates disrupt insulin sensitivity, and insulin regulation is closely linked to hormonal balance, including the maintenance of healthy testosterone levels. Research has found that men with metabolic syndrome and diabetes frequently have low testosterone. (24, 25) A reduced-carbohydrate diet is strongly associated with improved insulin sensitivity and may also help to raise testosterone levels.

Maintain optimal levels of vitamin D

Vitamin D is intrinsically involved in male reproductive health, including regulation of testosterone. Vitamin D helps regulate aromatase, an enzyme involved in the biosynthesis of estrogens. Sufficient levels of vitamin D in males prevent the conversion of testosterone into estrogens by the aromatase enzyme. (26, 27) Thus, a low level of vitamin D may lead to decreased testosterone by increasing the conversion of testosterone into estrogen. (28, 29, 30)

Reconsider use of statins

The use of statin drugs is associated with significant decreases in testosterone in men. Cholesterol is needed for the synthesis of steroid hormones such as testosterone, and statins lower cholesterol, thus limiting the amount available for hormone synthesis. Physicians working with patients who have low testosterone and are on statins may want to consider recommending dietary and lifestyle changes for managing cholesterol, rather than the use of statin drugs. (31, 32)

Avoid endocrine-disrupting chemicals

Endocrine-disrupting chemicals such as phthalates, pesticides, and BPA have been found to lower testosterone levels in men. This occurs due to a process called aromatization, in which testosterone is converted into estrogen. Avoid body care products filled with synthetic chemicals, since many of these are estrogenic. In addition, plastic water bottles, a common source of BPA, should also be avoided. (33)

Exercise regularly

Exercising regularly has many positive effects on health, including testosterone regulation. However, the type of exercise performed appears to play a significant role in testosterone levels. Moderate and high-intensity exercise such as weight lifting and high-intensity interval training boost long-term testosterone levels, whereas chronic aerobic exercise and overtraining may moderately decrease testosterone levels. (34, 35)

Get enough sleep

Sleep quality affects testosterone levels, and chronic sleep deprivation can significantly decrease testosterone levels. Aim for eight hours per night of sleep, and practice sleep hygiene before bed, such as powering down electronics and eating your last meal of the day at least two hours before bed. (36, 37)

Address chronic stress

Cortisol increases sex hormone-binding globulin and can thus lower free testosterone levels. Chronic psychological stress raises cortisol, thus lowering testosterone. (38) Stress management should therefore be a key part of any protocol designed to naturally raise testosterone levels.

Now I’d like to hear from you. Have you ever tried testosterone replacement therapy? Would you consider trying the dietary and lifestyle interventions outlined here for naturally raising your testosterone levels? Share your experiences and thoughts in the comments!

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  1. I don’t know where the spurious information that so many studies showed an increased risk of cardiovascular disease with TRT comes from. In fact, there were only 4 studies that showed this and these were so flawed that the Androgen Study Group – a “multidisciplinary group of clinicians and researchers dedicated to the accurate reporting on the science of testosterone deficiency and it’s treatment” – encouraged JAMA to retract the main one stating that the failure to do so constituted ‘ Medical Journal Malpractice” (see AndrogenStudyGroup.org and click on “initiatives” . BTW the other 3 studies had serious flaws as well.)

    In addition, the urology department of Baylor College of Medicine has conducted an meta-analysis of studies on cardiovascular disease and testosterone looking at every single study from 1939 to 2015 and concluded that TRT not only posed no increased risk of cardiovascular disease but that it was, in fact, protective against cardiovascular disease (see https://www.youtube.com/watch?v=kLAnsdocmKY) The section on this video on sexual wellness conducted by urologist Mohit Khera MD of Baylor University is at 50:07.

    I hope you will review these sites. Just like JAMA I really feel you need to retract the section of this article that states that TRT increases the risk of cardiovascular disease. There is no reliable data to support that statement and a lot of studies that refute it. You can do a lot of damage by publishing misinformation like this.

  2. I am 55 with very low cholesterol, but dad has heart dz. My MD is a Biote practitioner so I am using T pellet therapy over the last 6 months. I think there are some positive benefits from having my level higher. He feels strongly that T around 900-1000 provides less risk of heart disease. He has looked at all the studies and feels some of the negative results are not trustworthy. Sadly, in the medical community, the only strategy ever discussed is statins plus BP meds. The docs don’t even have enough concern to add EFA’s or CoQ10 for their patients.

  3. I’m a female who had a total hysterectomy (ovaries and uterus) at the age of 50. I’m now 78. I’ve been using testosterone cream daily since the ovaries are needed after menopause to produce small amounts of testosterone. Women without ovaries and not using testosterone cream have a much greater risk for heart disease and weight gain I just wanted to put this in perspective for all those lovers and haters of testosterone out there.

  4. Thanks Chris,

    Very informative as usual. I am curious, who what do you think of the use of natural aromatase inhibitors and how effective are they to help maintain healthy “T” levels.

    Thanks, Ned

  5. Love your teaching!
    Overwhel.ing majority of testosteronecstudies in literature show testosterone to be safe and efficacious.
    Average testosterone level in males in 1950’s was 1200, now is 400’s.

    Problem with VA study approx 2013 and wonder about these sited did NOT measure estradiol levels, thus got presumed excess estradiol effects of weight gain. Edema etc. One must measure estradiol levels and use sonic or another aromatase inhibitor to keep it in safe range (20-35).

    Bio-identical testosterone is a vasodilator, thus not causing hypertension. See European Journal of Cardiology (Nov 2015 or 2016) study on testosterone replacement. Crazy good. Totally agree with your toxins and endocrine disrupters.

    Thanks for all your excellent materials!

  6. Do you offer online courses in functional medicine. I have done the ifmcp course and attended metagenics seminars but would like to do a course. Not too intense!

  7. Once again, there is no valid evidence for increased risk of cardiovascular disease in men on testosterone replacement therapy. The following is an exert taken from the Medscape CME activity: New Perspectives on Hypogonadism and Testosterone Replacement in Clinical Practice found at http://www.medscape.org/viewarticle/859399_2 Please check this out for yourself.

    “Some studies on the effect of TRT on the CV system have suggested that it leads to an increased risk for myocardial infarction and stroke. However, these studies were flawed due to selection bias, statistical analysis manipulation, etc., and the evidence is therefore unreliable.[114-116]

    Furthermore, the US Food and Drug Administration requirement for a labeling change regarding a possible increased CV risk with testosterone products was challenged and refuted by the American Association for Clinical Endocrinology and the American College of Endocrinology.[117] Currently, a significant body of evidence indicates that TRT does not increase the risk for CV disease and that TRT in men with stable CV disease is safe.[2,118] For example, a notable 3-year-long RCT demonstrated that the occurrence of adverse events or serious adverse events did not differ between testosterone and placebo groups.[119] This same RCT showed that in men not taking statins, the annual rate of change in coronary artery calcium (a marker of atherosclerosis) was significantly lower in the testosterone group than in the placebo group.[119] Three RCTs in men with known angina demonstrated an increase in time to ischemia.[120-122] Four RCTs of TRT in patients with congestive heart failure found significant functional improvements in the 6-minute walk test, incremental shuttle walk test, and/or peak oxygen consumption, as well as an increased overall exercise capacity, compared with placebo.[123-126] No significant adverse CV events were noted in these RCTs.

    Conclusion

    The importance of hypogonadism in men’s health is firmly established; and, if left untreated, the condition has many detrimental health effects. It is therefore very important that men with suspected hypogonadism undergo diagnostic evaluation and, if a diagnosis is confirmed, are treated and monitored. The management of hypogonadism remains an area of debate among physicians, but evidence-based recommendations are available to guide physicians in managing patients with suspected or confirmed testosterone deficiency.

    The benefits of TRT for men with hypogonadism are well established and have been shown to outweigh the risks for the majority of patients, in particular those who are obese or have T2DM. In spite of suggestions that TRT is associated with an increased risk for prostate cancer and CV disease, evidence from trial data does not support this. Therefore, patients without contraindications should be offered TRT. A variety of formulations are available that have been shown to improve quality of life and reduce mortality among men with hypogonadism.”

  8. I started using TRT 5 months ago and it has been a miracle although I don’t want to stay on it for ever. My question regarding heart disease is around no normal levels of Testosterone. If your body was tested and measured as having well below normal levels and prescribed an amount that maintains normal levels is this still bad for your heart and if so why?

  9. Wonderful information, however I think it is very important for those managing TRT to be educated in the research and recognize that each patient is different. I believe there is danger in global statements including assuming that a natural approach is best for all as well as bio-identical is the way to go. We all know it is complicated and understanding the research seems to be the key. Those with CHF and known heard disease should be treated as such according to the literature. Thank you for your wonderful presentation of the literature as we desperately need consistent updates and summaries as providers in order to deliver the best care. Let’s all get it together and provide care to the best of our knowledge.

    Thank you Chris

  10. Hello Chris,

    Thanks a lot for this fantastic information. I was wondering though, do you think that a dietary and lifestyle change is the proper solution for everyone? I mean, everyone is a little different and what may work for some may not work for another. Perhaps TRT may work wonders for someone and only cause them minimal side effects. Yet, for this same person, exercise and healthy eating habits might just not be enough on their own. Is there any time where you would actually recommend TRT over a healthy diet? Or should everyone that is using TRT just drop it cold turkey and replace it with more natural alternatives?

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