Low T: Are Testosterone Treatments Safe and Effective for Men?

Nicole Dubowitz, National Center for Health Research

 

There’s nothing new about the search for the fountain of youth. Men and women have experimented with hormonal therapies to reverse aging since the late nineteenth century: In 1889, neurologist Charles Édouard Brown-Séquard announced that guinea pig and dog testicle injections, and later, surgical implantations, could restore physical and mental health to older men.[1]

But today, we have advertisements for testosterone topical gels, patches, and underarm roll-ons that make hormone replacement therapy (HRT) look like it should be part of every aging man’s daily routine. In order to qualify for a prescription, men are advised to go to their doctor and test their testosterone levels. If these levels are below “normal” and “Low-T” symptoms are described, potent hormonal drugs may be yours.

What the ads don’t say is that studies show no agreed-upon “normal”: The range goes from 270 – 1,070 ng/dL for men of all ages. Testosterone (“T”) levels peak in a man’s 20s and decline gradually after age 40, by around 1% every year.[2] They vary widely between men and can change by the hour, depending on factors like sleep, exercise, or if your favorite team just won.

Most important, the most recent research suggests that men who take testosterone don’t usually have any benefit, and they face real risks of heart attacks and stroke.

Too Much Hype?

Ads note that Low-T symptoms overlap with normal aging, but say the “condition” may be to blame. Online surveys warn that Low-T may cause decreased energy or falling asleep after dinner (guilty!). Moreover, the medical literature fails to establish a consistent relationship between testosterone levels and supposed Low-T symptoms.

Pharmaceutical companies know that women tend to be more conscientious of health matters than men are. So, don’t be surprised if you see advertisements in women’s magazines or during female-geared television shows suggesting that your partner may have “lost that loving feeling” or not be able to perform due to Low-T.[3] However, the connection between testosterone levels and libido is inconclusive and testosterone is not a substitute for erectile dysfunction treatments.

Even if T-therapy doesn’t work as advertised, one might wonder what the harm is in trying it. Unfortunately, what we don’t know can hurt us, as demonstrated by HRT for women. In the 1980s and 1990s, women were the target of hormone therapy, which doctors promised would ease menopause and help prevent heart attacks, strokes, and Alzheimer’s disease. Twenty years later, we learned that hormone supplementation actually increased the risk of all of these ailments, in addition to breast cancer.[4]

A study of 308 men reported that 3 years of testosterone replacement therapy did not improve sexual function.[5]

Known Risks

Even if T-therapy doesn’t work as advertised, one might wonder what the harm is in trying it.

Unfortunately, the risks are substantial. A 2013 meta-analysis that combined the findings of 27 studies that included more than 2,900 men found that testosterone replacement therapy increased the risk for serious heart problems by 50%.[6] A 2014 study based on medical records of more than 67,000 men reported that men taking testosterone replacement therapy were 30% more likely to have a heart attack, and that the risk got higher with age. Men 75 years of age and older who were taking testosterone were more than 3 times as likely to have a heart attack. In addition, men under 65 years of age who had a previous history of heart disease were almost 3 times as likely to suffer a heart attack while taking testosterone replacement therapy. [7] As a result of these studies, testosterone products must come with a “black box warning” that they increase the chances of having a heart attack or stroke. [8]

Another side effect of testosterone treatment is infertility.  The testosterone decreases levels of a hormone known as FSH (follicelstimulating hormone), which causes a decrease in sperm production. Even more harmful are the risks of polycythemia, which is a disease characterized by thickening of blood that occurs when the number of red blood cells increases.  This condition has been linked to testosterone treatment, especially with Testosterone Replacement Therapy.

Hormones wreaking havoc is not a novel concept, as naturally occurring excessive hormones are also culprits for cancer in both sexes. Even before these studies were conducted, testosterone had been linked to blood clots, the growth of prostate cancer, and worsening congestive heart failure.[9]

Testosterone creams can affect partners and children of treated men through bodily contact or possibly by sharing sheets and towels. This can result in increased body hair and acne in women and children, and enlarged genitalia, increased aggression, and advanced bone age in children.[10] Prescription labels always say medicines should only be used by the person they were prescribed for, but it’s much easier to inadvertently share cream and ointment medications, which is a popular form of which are currently the main form in which testosterone therapy.

Direct To Consumer Platforms

Testosterone therapy and related treatments are increasingly promoted through online direct-to-consumer (DTC) platforms. From 2017 to 2019, there was a 1500% increase in online visits to DTC platforms related to erectile dysfunction. [12] Although access to healthcare is important, online promotions of treatments can be dangerous. In a study of seven online companies that offered testosterone therapy, researchers used a script to portray a secret shopper as a hypothetical man with normal testosterone levels who wanted children and was asking for T-therapy. Even though the secret shopper had normal testosterone levels and desire of fertility, which medical guidelines say would disqualify a person from testosterone treatment, 6 out of 7 platforms still offered the man testosterone therapy and only 1 out of 7 asked the shopper about his cardiac health and fertility. Every platform also offered a range of off-label medications.[13] Many online direct-to-consumer platforms don’t align with guideline-based criteria for treatments, nor discuss the risks and benefits of therapy, and in some cases non-medically licensed providers suggest  treatment. This study illustrates the importance of consulting with a trusted physician before using prescription treatments promoted on any online direct-to-consumer platforms.

Should Anyone use Testosterone Therapy?

Testosterone therapy was developed for good reason. It was first FDA-approved for hypogonadism, which is lack of testes or damage to a male’s testes that leads to extremely low natural testosterone production. But companies that make Low-T drugs want to sell it much more, and prescribing rates tripled between 2001 and 2013.[11] Nevertheless, hormones should not be taken lightly in an effort to stave off aging — hormones are powerful drugs that should be used only when we know that benefits outweigh the harms.

The story of the misuse of Low-T drugs is very similar to the widespread misuse of hormone therapy for women. In the 1980s and 1990s, women were the target of hormone therapy, which doctors promised would ease menopause and help prevent heart attacks, strokes, and Alzheimer’s disease. Twenty years later, we learned that hormone supplementation actually increased the risk of all of these ailments, in addition to breast cancer.[4] If men use testosterone drugs for many years, as women did with estrogen therapy, we may eventually learn it is even more dangerous than the recent studies have shown.

All articles on our website have been approved by Dr. Diana Zuckerman and other senior staff.

  1. Brown-Séquard CE. (1889). “The Effects Produced on Man by Subcutaneous Injections of a Liquid Obtained From The Testicles of Animals.” The Lancet. Available at http://www.usrf.org/news/TRT/Brown-Sequard,%20Lancet,%201889.pdf
  2. Myers, J. and Meacham, R. “Androgen Replacement Therapy in the Aging Male.” Rev Urol. 2003 Fall; 5(4): 216–22W6.
  3. Jio, S. “8 Reasons He Doesn’t Want to Have Sex.” Women’s Day. Available at http://www.womansday.com/sex-relationships/sex-tips/8-reasons-he-doesnt-want-to-have-sex-91131. Accessed December 5, 2013.
  4. Women’s Health Initiative. (2004). “Questions and Answers About the WHI Postmenopausal Hormone Therapy Trials.” Accessed November 25, 2013. Available at http://www.nhlbi.nih.gov/whi/whi_faq.htm.
  5. Basaria S, Harman S, Travison TG, et al. Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial. JAMA. 2015;314(6):570-581.
  6. Xu L, Freeman G, Cowling BJ, Schooling CM (2013). Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med, 11, 108.
  7. Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, et al. (2014) Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men. PLoS ONE 9(1): e85805.
  8. FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use.
  9. Abbott Labs. (2011). Androgel®. FDA/Center for Drug Evaluation and Research. Accessed August 13, 2012.
  10. Landau, E. (2009) “Testosterone gel effects in children spur FDA warning.” CNN Health. Available at http://www.cnn.com/2009/HEALTH/05/07/testosterone.gel.children/.
  11. end O’Connor, A. “Men’s Use of Testosterone on the Rise.” The New York Times “Well” blog. June 3, 2013. Available at http://well.blogs.nytimes.com/2013/06/03/mens-use-of-hormone-on-the-rise/.
  12. Wackerbarth  JJ, Fantus  RJ, Darves-Bornoz  A,  et al.  Examining online traffic patterns to popular direct-to-consumer websites for evaluation and treatment of erectile dysfunction.   Sex Med. 2021;9(1):100289. doi:10.1016/j.esxm.2020.100289
  13. Dubin JM, Jesse E, Fantus RJ, et al. Guideline-Discordant Care Among Direct-to-Consumer Testosterone Therapy Platforms. JAMA Intern Med. 2022;182(12):1321–1323. doi:10.1001/jamainternmed.2022.4928