Optimising testosterone can lead to a number of considerable structural benefits in the body, particularly in:

• muscle mass
• strength
• body composition
• bone mineral density (BMD)

This article will research into these benefits. In the previous article, we looked at the large numbers of men with low testosterone and the increasing trend of declining testosterone levels. In this article, we will focus on the structural benefits of testosterone optimisation. These benefits cannot be understated particularly in aging men. Considering that loss of muscle mass, strength, body composition, and bone mineral density are some of the leading risk factors for increasing mortality risk as we age.

A meta analysis looked at this in 2017 and found a a 60% increase in the relative risk of death in people with sarcopenia compared to people without. In my own practice as a hospital doctor, I have cared for patients suffering from sarcopenia and osteoporosis presenting with fractures. I’ve witnessed the devastating loss of mobility and the significant decline in health these patients face— often caring for them at the tail end of this decline. These are issues that can often be prevented through maintaining muscles mass, strength, bone mineral density and optimal body composition.

Bone Mineral Density (BMD)

There has long been an impression that testosterone does not significantly impact BMD, as bone density was traditionally thought to be largely established by one’s twenties, with only certain lifestyle and health factors affecting it afterward. Conventional wisdom held that BMD could primarily be preserved by:

• Avoiding factors that decrease BMD, such as long-term corticosteroid use
• Engaging in impact exercises to help maintain existing bone density

However, recent findings challenge this view, revealing that testosterone may, in fact, increase BMD, providing a potential tool for actively strengthening bones. As men age, the risk of osteoporosis and fractures increases due to declines in bone mineral density. Optimising testosterone has been shown to positively impact BMD, providing a significant protective effect against age-related bone loss.

In a study by Amory et al. (2004), older men receiving testosterone therapy exhibited marked increases in BMD across various skeletal sites, including the lumbar spine and hip. This study is noted for its clear focus on a critical question in testosterone replacement therapy: whether the benefits of TRT are driven more by testosterone itself or by its powerful metabolite, dihydrotestosterone (DHT).

Study Design

This study was carried out over 36 months, which is longer than many other similar studies.

• Group One: Receives 200 milligrams of testosterone every two weeks along with a placebo pill, serving as the “testosterone-only” group.
• Group Two: Receives the same dose of testosterone along with five milligrams of finasteride daily. This “testosterone plus finasteride” group maintains testosterone levels comparable to Group One but minimizes DHT due to the enzyme-blocking effects of finasteride.
• Group Three: Receives placebo injections and placebo pills, serving as the control group.

This study used a dosing regimen of 200 milligrams of testosterone administered intramuscularly every two weeks, equating to an average of 100 milligrams per week. This dose is generally considered physiological for TRT.

Due to testosterones half-life of about three to four days, some clinicians prefer more frequent dosing to maintain stable levels. For instance, some patients are prescribed twice-weekly subcutaneous doses, splitting the weekly amount. In some cases, patients even divide the weekly dose into daily administrations, maintaining more consistent testosterone levels without the peaks and troughs associated with less frequent dosing.

Study Findings on Bone Mineral Density

The study measured BMD in several critical bone regions: lumbar spine, total hip, intertrochanteric region (between the upper femur and hip socket) femoral neck and the trochanter.

Results show a consistent and nearly monotonic increase in BMD from baseline through 6, 12, 18, and up to 36 months in both the testosterone and testosterone-plus-finasteride groups, with no significant increase in the placebo group. This trend suggests that testosterone—not DHT—is likely responsible for the observed BMD gains, as both groups with increased testosterone levels saw improved bone density regardless of DHT suppression.

Figure 2: Study findings on bone mineral density (Amory et al. 2004) A statistically significant rise in bone mineral density.

These findings demonstrate the potential of testosterone therapy not only to support muscle strength and vitality but also to protect against age-related bone density loss, helping to reduce the risk of falls and fractures.

Furthermore, the study highlighted that the benefits on BMD were evident in both testosterone-only and testosterone plus finasteride groups, indicating that the primary effects are attributable to testosterone rather than its metabolite, dihydrotestosterone (DHT).

Figure 3. Effects of Testosterone or Placebo Treatment for 12 Months on Volumetric Bone Mineral Density (BMD) and Estimated Bone Strength, as Assessed by QCT. (Snyder et al., 2017)

The above graphs are from another study Snyder et al., 2017, which backs up these findings. showed that men over 65 years or older with testosterone concentrations averaging less than 275 ng/L, who were treated with testosterone gel to the normal range for young men, significantly increased bone mineral density and estimated bone strength, more in trabecular than peripheral bone and more in the spine than hip. In this study, participants were not given finasteride.

Testosterone and DHT

When testosterone is introduced into the body, it can be converted by the enzyme 5-alpha reductase into DHT, a hormone three to six times more potent than testosterone. DHT is especially significant because of its impact on tissues sensitive to androgen. For example, in individuals prone to androgenic hair loss, elevated DHT levels are a primary factor driving this process. Additionally, DHT is a major contributor to prostate growth, specifically benign prostatic hyperplasia (BPH), a condition where the prostate enlarges and can cause severe urinary symptoms.

To manage these effects, medications such as finasteride are used to inhibit the 5-alpha reductase enzyme, reducing the conversion of testosterone to DHT. A daily dose of five milligrams of finasteride is known to reduce DHT levels almost entirely, helping to control prostate growth and alleviate BPH symptoms. In fact, finasteride has long been used for this purpose, as shrinking the prostate can reduce symptoms like frequent or difficult urination. At lower doses—typically one milligram daily—finasteride can still lower DHT effectively enough to benefit those experiencing hair loss.

Figure 1: Serum hormone levels in the 3 groups. It is noted that the testosterone and finasteride group in this study achieved at best a 50% reduction in serum DHT levels. Both this group and the testosterone only group increased bioavailable testosterone, testosterone and estrogen levels. (Amory et al. 2004)

Potential cost of suppressing DHT

Inhibiting DHT production can also come at a risk of many side effects including sexual dysfunction. It is suggested that men treated with these drugs may experience androgen deficiency and face a risk of developing erectile dysfunction (ED), non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR), type 2 diabetes (T2DM), dry eye disease, possible kidney dysfunction, and other metabolic and psychiatric disorders (Hackett, et al 2023) . However, the data is ambiguous and it is not clear whether in the context of TRT, these risks remain. As we will see, optimising testosterone came with significant benefits including improving both metabolic and structural outcomes even in the presence of suppressing DHT. This study sought to measure the effect on men administered testosterone with or without finasteride, plus a placebo group. This will be discussed in more detail in another article.

Protective effects of estrogen on bone tissue

The positive effects of testosterone therapy on bone mineral density may be influenced by its conversion to estrogen. In this study, T therapy led to substantial increases in serum E2 levels from baseline. The role of estrogen in maintaining BMD in men has been illustrated by a case involving a man with aromatase deficiency, who exhibited high serum T levels but low BMD; treatment with E2 led to epiphyseal closure and an increase in BMD. Similarly, a second case involving a man with an estrogen receptor mutation showed unfused epiphyses and low BMD. Additional research suggests that bioavailable estrogen may be the strongest predictor of BMD in older men.

The exact way androgens and/or estrogens improve bone mineral density (BMD) isn’t fully understood, though androgen receptors have been found in osteoblasts. In the discussed srudy, most markers of bone formation remained unchanged, but urinary deoxypyridinoline, the most sensitive marker of bone resorption, showed a significant decrease. This indicates that testosterone therapy primarily works by reducing bone resorption rather than boosting bone formation. Interestingly, this finding aligns with a study in younger men. It’s worth noting that this “antiresorptive” effect of T likely involves estrogen, which is believed to play a key role in increasing BMD in postmenopausal women.

Muscle Mass

There isn’t much needed to introduce the positive effects of testosterone on muscle mass. Unhelpfully, the most commonly perceived biological association of testosterone is on muscle mass. Whilst traditionally testosterone has been abused by bodybuilders, maintaining muscle mass in men as they age is one of the key benefits of testosterone replacement. Therefore, one of the most significant effects of optimal testosterone levels is its ability to increase muscle mass and strength, vital for physical function and overall health. Testosterone functions as a powerful anabolic hormone, facilitating muscle protein synthesis, which is crucial for muscle repair and growth.

Numerous studies have consistently shown that exogenous testosterone administration results in substantial increases in lean muscle mass. For example, in the Amory study cited above, older men receiving TRT exhibited an average increase in lean mass of approximately four kilograms (about nine pounds) (Amory et al., 2004). This is a significant amount of muscle mass for men above 65.

The gains in muscle strength are not merely superficial; they have profound implications for physical performance and functional ability. Improved muscle strength enhances mobility, balance, and the capacity to perform daily activities, which is particularly important for older adults who seek to maintain their independence. Testosterone promotes muscle hypertrophy by enhancing the activation and proliferation of satellite cells—precursor cells necessary for muscle repair—and modulating key signaling pathways such as the mTOR pathway, which is instrumental in muscle growth (Snyder et al., 2017). Although activating the mTOR pathway has traditionally gained a bad rep in longevity circles, the key takeaway is that we do not want mTOR chronically activated. Chronic activation, like we can see in diabetes pathogenesis and obesity leads to accelerated aging. Acute activation promotes muscle protein synthesis.

The benefits of increased muscle mass extend beyond physical appearance. Enhanced muscle strength contributes to metabolic health by increasing resting energy expenditure and improving insulin sensitivity. We will go on to discuss this in a later article. This is particularly relevant for aging men, as maintaining an active lifestyle becomes more challenging with declining muscle mass.

Body Composition

In addition to its effects on muscle mass, TRT significantly alters body composition by promoting a decrease in fat mass alongside an increase in lean mass. Clinical trials have shown that older men undergoing testosterone therapy can experience a loss of approximately ten pounds of fat while gaining about 8.5 pounds of lean mass over three years. This results in a net reduction in total body weight, demonstrating how TRT can positively reshape body composition without affecting overall weight (Amory et al., 2004).

Figure 1: Change in body composition in older men with low T treated with testosterone (T), testosterone and finasteride(T + F), or placebo for 36 months. (Page et al., 2005)

What we can see in the above graph on the left is that those treated with testosterone increased lean muscle mass by up to a whopping 4kg. Whilst on the right above, the same treated groups lost around 4kg in fat mass. What we can take away from these graphs is that optimal testosterone levels led to a significantly positive body recomposition. Participants were aged 65 yr and older.

These changes in body composition have substantial implications for metabolic health. A reduction in fat mass—particularly visceral fat—is associated with lower risks of metabolic disorders such as type 2 diabetes and cardiovascular disease. Visceral fat, which accumulates around internal organs, is known to be metabolically active and can contribute to insulin resistance, inflammation, and various cardiovascular risks. By promoting fat loss and muscle gain, TRT helps to mitigate these risks and improve overall metabolic health.

Additionally, TRT can influence the distribution of body fat. Studies have shown that testosterone therapy can lead to reductions in abdominal fat, which is particularly harmful due to its association with metabolic syndrome. These favorable changes not only enhance physical appearance but also have important health implications, reinforcing the idea that TRT is a crucial intervention for aging men.

Clinical Implications

The structural benefits of TRT emphasise its role as a vital therapeutic intervention for aging men experiencing declines in muscle mass, strength, and bone density. By counteracting the effects of sarcopenia (age-related muscle loss) and osteoporosis, TRT not only enhances physical capabilities but also improves overall health and quality of life. Maintaining muscle strength and bone density is crucial for reducing the risk of falls and fractures, which can lead to significant morbidity in older adults.

Moreover, the positive effects of TRT on muscle mass, body composition, and bone density can have broader implications for healthcare systems. As the population ages, the prevalence of sarcopenia and osteoporosis will likely increase, leading to greater healthcare costs associated with fractures, hospitalizations, and long-term care. By implementing TRT as part of a comprehensive health management strategy, healthcare providers can help mitigate these risks and improve the longevity and quality of life for their patients.

In summary, the structural benefits of testosterone replacement therapy are profound and multifaceted, encompassing significant gains in muscle mass, strength, body composition, and bone mineral density. These changes are essential for promoting functional health, improving the quality of life for aging individuals, and reducing the risk of age-related comorbidities. As research continues to shed light on the benefits of TRT, it becomes increasingly clear that this therapy is an essential component of health management for aging men.