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Testosterone Replacement Therapy- Men

Optimizing the health and quality of life for men of all ages

Testosterone plays an important role for men and women, influencing not just physical characteristics but also cognitive functions and emotional well-being. Research indicates that by the age of 80, nearly half of men may experience testosterone levels below the normal range (1).

What is testosterone and why is it important?

Testosterone is known as an androgen, it plays a critical role in various aspects of male growth, reproductive development, and the manifestation of masculine characteristics. From the emergence of body hair to the maintenance of muscle mass and sexual function, testosterone is the driving force behind many male traits. Testosterone is not exclusive to men either, women actually have higher levels of testosterone then they do estrogen. 

However, this article is focusing on testosterone function, levels and replacement in men (we will have another blog about testosterone replacement for women in the future). 

What happens when this vital hormone dips below optimal levels? And how can we navigate the complexities of testosterone replacement therapy (TRT) to harness its benefits while mitigating potential risks?

Understanding Testosterone 

As men age, their testosterone levels naturally decline. Various factors, including obesity, chronic illnesses, and certain medications, can exacerbate this decline, leading to a cluster of symptoms associated with low testosterone, or hypogonadism.

The Prevalence of Low Testosterone

As men age, their testosterone levels naturally decline. Research indicates that by the age of 80, nearly half of men may experience testosterone levels below the normal range (1). Various factors, including obesity, chronic illnesses, and certain medications, can exacerbate this decline, leading to a cluster of symptoms associated with low testosterone, or hypogonadism.

Signs and Symptoms

Low energy, diminished libido, erectile dysfunction, and muscle loss or difficulty gaining muscle are hallmark signs of low testosterone.

However, the manifestations of hypogonadism extend beyond the physical realm, encompassing mood disturbances and even infertility in severe cases.

Causes of Low Testosterone

 

Low testosterone in males is referred to as hypogonadism. Primary causes of low testosterone is when there is an issue with testicular function itself. Examples of this include: genetic conditions, physical trauma, and radiation exposure. Indicators of primary hypogonadism is high LH/FSH and low testosterone on bloodwork. Secondary causes of hypogonadism are when there is an issue with signaling to the testes from the brain (hypothalamus or pituitary). Causes of this include: malnutrition/anorexia, hypothyroidism, hyperprolactinemia, type 2 diabetes, hemochromatosis, and certain medications (ex. opioids, steroids). In secondary hypogonadism, LH/FSH are often normal and testosterone is low. 

Age-Related Decline and Its Ramifications

The decline in testosterone levels with age, termed late-onset hypogonadism, poses intriguing questions regarding its clinical significance. Supporting evidence shows that testosterone levels decline with age in all men, regardless of symptoms, at an estimated rate of 1%–3% per year starting age 40 (2,3). Additionally, several cross-sectional studies show a decline of serum total testosterone concentration with increasing age (3,4). While some studies link low testosterone to other related illnesses, including decreased bone density and mood disorders, the precise implications remain debated.

Diagnostic Dilemmas and Treatment Modalities

Diagnosing hypogonadism necessitates comprehensive evaluation, including morning testosterone measurements. Treatment options range from testosterone gels and injections to pellets, each tailored to individual needs and preferences.

Weighing the Benefits and Risks of Testosterone Replacement Therapy

TRT has emerged as a promising intervention for mitigating the symptoms of low testosterone. TRT is typically reserved for older males as it can decrease sperm count and potentially affect fertility.

To further evaluate the benefits and risks of TRT, there have been several trials done that are worth reviewing.  In 2003, the TTrials were done to assess the efficacy of TRT in men aged 65 years or older with low testosterone. This was a set of seven placebo controlled trials over the span of one year. The main findings of the trials were that TRT was helpful for sexual function, mood/depression, walking, bone mineral density and anemia. Notably, they didn’t find an increased association with benign prostatic hyperplasia (BPH), prostate cancer or cardiovascular events (5). 

The Traverse trial was another placebo controlled study that evaluated men aged 45-80 years old with preexisting or high risk cardiovascular disease and low testosterone. They found that over a 22 month time span, the group who received TRT was similar to placebo in respect to the occurrence of major adverse cardiac events. However, concerns still persist regarding potential adverse effects like erythrocytosis which could lead to increased risk of blood clots (6).

Navigating the Complexities: A Call for Informed Decision-Making

As with any medical intervention, informed decision-making is paramount when considering TRT. While the benefits of testosterone replacement may be substantial, careful consideration of individual risk/ benefits and preferences is essential to optimize outcomes.

Questions? Let us know below. 

Citations: 

  1. Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86:724–31.

  2. Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002;87:589–98. 

  3. Wu, Frederick C W et al. “Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study.” The Journal of clinical endocrinology and metabolism vol. 93,7 (2008): 2737-45. doi:10.1210/jc.2007-1972

  4. Handelsman, D J et al. “Age-specific population centiles for androgen status in men.” European journal of endocrinology vol. 173,6 (2015): 809-17. doi:10.1530/EJE-15-0380Millar, A.C., et al. “Predicting low testosterone in aging men: a systematic review.” CMAJ vol. 188,13 (2016): E321-E330.

  5. Snyder, Peter J., et al. "Effects of testosterone treatment in older men." New England Journal of Medicine 374.7 (2016): 611-624.

  6. Lincoff AM, Bhasin S, Flevaris P, et al., on behalf of the TRAVERSE Study Investigators. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med 2023

  7. Moon, D.G., and Park, H.J. “The Ideal Goal of Testosterone Replacement Therapy: Maintaining Testosterone Levels or Managing Symptoms?” Journal of clinical medicine vol. 8,3 (2019): 362.

  8. Krakowsky, Y., and Grober, E.D. “Testosterone Deficiency - Establishing A Biochemical Diagnosis.” EJIFCC vol. 26,2 (2015): 105-13.

  9. Dhindsa, S., et al. “Testosterone concentrations in diabetic and nondiabetic obese men.” Diabetes care vol. 33,6 (2010): 1186-92.

  10. Wu, F.C.W., et al. “Identification of late-onset hypogonadism in middle-aged and elderly men.” The New England journal of medicine vol. 363,2 (2010): 123-35.

I started testosterone replacement therapy and within three weeks I saw a huge change. I am sleeping better, my energy has improved, I’m less moody, and I’m way more motivated to go to the gym. In general, I just feel younger.”

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