Understanding Hormone Replacement Therapy & Low Testosterone

September 11, 2018


Article at a Glance


  • Low testosterone can increase the risk of cardiovascular disease, osteoporosis, metabolic syndrome, obesity, and diabetes.
  • Testosterone deficiency can be treated by oral administration, topical gels, or injections.
  • Patients receiving testosterone replacement therapy should be monitored closely. Each patient absorbs and metabolizes testosterone at vary rates and adjustments may need to be made.

The male hormone testosterone plays a critical role in men’s health: it strengthens bones, builds muscle, and improves brain function and heart health. Testosterone also improves libido and energy levels. Yet, by their middle ages, most men begin to witness a decline in this important hormone. By the age of 30, hormone levels begin to drop by 1% to 3% annually; at age 50, this could amount to a 20% drop. These imbalances can penetrate every aspect of life, from physical wellbeing to personal life, job performance, and business success.

Typically, hormone levels in men decline at a much slower rate than in women. Thus, the effects of testosterone deficiency can come on gradually, which is one of the reasons it is so often mistakenly attributed to general aging. Energy depletion, for instance, is typically attributed to being a “normal” part of aging. In reality, it could point to low testosterone, also known as low T. There are many other similar symptoms which could be going unnoticed.

Yet, while declining testosterone levels are normal to some degree in men, that doesn’t mean they have to live with the symptoms they produce. From low libido to increased risk of mortality, a decline in this critical hormone can lead to a number of frustrating symptoms. The good news is that these challenges can now be addressed through hormone replacement therapy.

In this guide, we’ll explore the topic of low T to help you make informed health decisions tailored to your precise needs and expectations. We’ll begin by looking at some of the common symptoms of testosterone deficiency, and by the end of this guide, you will have a comprehensive understanding of how the condition can be treated effectively through modern medical solutions.

Increased Disease Risk of Low Testosterone

increased risk of diabetes due to low testosterone, man checking blood glucose levels for improvement after hormone replacement therapy

In addition to the tangible effects of low T, there is also some increased risk of serious diseases men face when experiencing a deficiency. As stated in The Textbook of Age Management Medicine: Volume 2, available on Amazonconditions associated with testosterone deficiency include cardiovascular disease, osteoporosis and related bone fractures, metabolic syndrome and obesity, diabetes, and frailty. By addressing the deficiency through medical treatment, men can minimize their risk for these serious conditions, thereby enjoying a better quality of life, as well as reduced healthcare costs as they age.

What Impacts Testosterone Levels?

pharmaceuticals used in hormone replacement therapy, pharmaceuticals used to treat testosterone deficiency

As we’ve established, a gradual and minor decline in testosterone is normal with aging. Yet, that leaves the question: what actually causes abnormally low T levels?

It’s important to understand that there are both primary and secondary causes of hypogonadism, the medical term for “male menopause” or “andropause.” Congenital defects, certain developmental conditions, and even stress could be to blame for low T. Testicular trauma and surgical procedures, radiation treatment or chemotherapy, alcoholism, obesity, and certain types of pharmaceuticals can also hasten the decline of testosterone.

Because there are so many potential causes for low testosterone levels, approaching the issue requires personalized testing to confirm the diagnosis, which brings us to our next section.

What are the Risks of Testosterone Treatment?

Unmonitored testosterone levels during hormone replacement therapy can increase risk of cardiovascular issues

Misinformation tends to circulate surrounding the risks of testosterone treatment. There are certain side effects associated with testosterone replacement therapy, but it’s critically important to put these effects into context. Testosterone treatment can raise red blood cell counts, for instance, but under the care of experienced physicians, any associated risk will be minimized through in-depth screenings and active monitoring. The risk of cardiovascular disease is also low and cannot be determined as a direct contraindication to testosterone replacement therapy. In a 2010 study of men using testosterone gel, some participants experienced serious cardiovascular issues such as heart attacks. [2] Yet, studies have not been able to establish a concrete link between testosterone replacement therapy and heart attack risk, and there are many other contributing factors, which need to be examined more closely any time cardiovascular issues are present. [8] Lifestyle management tactics should therefore be implemented by age management professionals to parallel treatments and effectively minimize any potential risk.

Questions of a link between prostate cancer and testosterone treatment have also been raised, but these have also been challenged. Evidence shows that risk of prostate cancer in a patient undergoing testosterone treatment is equal to or actually less than that for the general population, with the exception of patients who have a history of prostate cancer. Thus, appropriate patient selection by expert physicians again plays a role in minimizing any risk associated with treatment.

Some testosterone replacement candidates also wonder about the risk of additional side effects, such as breast enlargement and hair loss. Yet, it’s important to understand that genetics, stress, and other factors play a role in many of these side effects. Again, expert physicians can monitor for early warning signs of these potential side effects to take prompt action against them. For breast tissue enlargement, for instance, aromatase inhibitors such as Anastrozole can be implemented to counterbalance this effect. Hair loss can be treated with over-the-counter solutions such as Minoxidil.

What are Symptoms of Low Testosterone?

One of the reasons testosterone deficiency is so infrequently diagnosed is because many of its symptoms imitate those associated with other conditions. Additionally, as mentioned above, some are also simply attributed to aging. As explained in The Textbook of Age Management Medicine: Volume 2, available from Amazon, age and body mass index (BMI) are both directly correlated with testosterone deficiency rates, so it is often difficult to determine whether age or hormones are to blame for increases in body fat. With that said, it is estimated that up to 39% of men aged 40 and older are deficient in testosterone. [3]

According to Harvard Health Publishing, testosterone levels in men decline by roughly 1% to 2% beginning in the 40s. [6] Although these slight decreases are considered normal with aging, noticeable symptoms could point to a testosterone deficiency. Oregon Health and Science University urologist Jason Hedges, MD, PhD, notes that lack of interest in sex, along with many of the other symptoms accompanying drops in testosterone, are often perceived as just a part of aging, “but that’s a misconception.” A gradual decline in testosterone would not account for little to no interest in sex. Many other symptoms may be mirrored by other conditions. Instead of low T, these symptoms were often credited to high blood pressure, depression, and diabetes. Due to the increasing awareness surrounding testosterone deficiencies, medical experts are now beginning to see the condition as the root cause for many of these problems. [5]

Below, we highlight some of the most common symptoms caused by testosterone deficiencies.

It isn’t simply increased BMI that men with testosterone deficiency face. As mentioned in “9 Signs of Low Testosterone,” a Healthline.com article, a deficiency is specifically linked to increased body fat. Some also develop gynecomastia, or enlarged breast tissue, which is suspected to result from a hormonal imbalance between testosterone and estrogen. The article also highlights decreased bone mass, loss of muscle mass, fatigue, hair loss, low semen volume, and difficulties with erections as additional physical indicators of low T. [1]

Beyond the physical impact of low T, men may also experience mood changes relating to the condition. Testosterone plays an important role in many physical processes, but it can also influence mood and mental capacity. According to research, factors such as depression, irritability, and difficulty focusing can all impact men facing testosterone deficiency. Likewise, low sex drive is another indicator of a hormonal issue. [9]

How is Low Testosterone Diagnosed?

physician meeting with patient to discuss low testosterone, physician discussing hormone replacement therapy with testosterone deficient patient

In order for a diagnosis of a testosterone deficiency to be made, a combination of biochemical and clinical diagnostic criteria is required. Clinical symptoms of testosterone deficiency are typically what spur patients to seek medical treatment, thereby prompting physicians to pursue a laboratory investigation.

Diagnosis of Testosterone Deficiency by Measurement of Free Testosterone Levels

The Textbook of Age Management Medicine: Volume 2, explains that testosterone is measured in multiple ways. First, there is free testosterone (FT), which refers to the fraction of testosterone that actually enters cells. It accounts for roughly 1% to 2% of testosterone available. It can be measured via equilibrium dialysis, a process that takes place following the patient’s blood draw. Average total testosterone (TT) levels are 723.8 according to the Framingham Heart Study, with a standard deviation of 221.1. [3] Thus, the “normal” range is not within the 95% confidence interval of average as standard medicine and lab ranges suggest. We’ll address these substantial differences below.

Diagnosis of Testosterone Deficiency by Measurement of Total Testosterone

In addition to FT, there is also total testosterone (TT). This figure measures both FT and the amount of hormone bound to the protein albumin, which is active and therefore bioavailable in the body. In other words, while FT floats around independently in the blood, roughly half of the remaining testosterone is attached to the albumin protein. TT measures both the FT and the testosterone attached to proteins. This, too, can be measured via a blood draw. [7] While the average level of FT is 141.8, this, too, can vary widely from one patient to the next.[3]

The challenge with getting an accurate reading lies in the fact that even TT tests leave 40% to 70% of testosterone unaccounted for, because it is traveling with a protein called sex hormone binding globulin (SHBG). It is tightly bound to this protein and therefore is unavailable in the cells. Thus, a large portion of TT could be biologically inactive, and results of tests may be misleading. TT levels that are borderline low could represent a true deficiency; or, it could be a variation in SHBG levels. For this reason, FT is the most essential measurement in making the biochemical diagnosis of a testosterone deficiency.

Another problem with diagnosing testosterone deficiency is that there are some limitations in measuring the hormone. First, there are technical limitations: the quality of tests may vary among laboratories, especially since there are multiple ways to measure testosterone. While equilibrium dialysis for measuring FT is considered the gold standard of testing, calculated free testosterone is considered an adequate measure. However, it must be understood that the different approaches for measuring testosterone levels can account for variability in patient results.

In addition to technical limitations, there is also a host of inherent variations in testosterone levels that can impact a patient on a daily, or even hourly, basis. Total testosterone fluctuates significantly throughout the day, for example. For this reason, blood is typically drawn for testosterone tests between 7 and 10 a.m. Still, we must consider daily intra-patient variations in levels according to health status, age, fasting state, and sleep, among other factors.

Lastly, there is still no single consensus on the definition of “low” testosterone. The criteria depend on the standards adopted by the doctor and/or lab.

The factors described above present significant challenges to making an initial diagnosis. Thus, while FT and TT measurements are necessary for managing patients with symptoms of low T, as well as monitoring treatments, reference ranges should be used as guidelines – not absolute inclusion or exclusion criteria for a diagnosis. Signs, symptoms, and patients known to have high risk factors for low T should be heavily weighted in diagnosing a deficiency. The most effective way to get a diagnosis is therefore to seek input from expert physicianssuch as those trained in age management medicine. Test results should be interpreted in light of identifiable symptoms, and the physician should therefore be able to form a “big picture” view of the condition.

Men who are ideal candidates for seeking help from a specialist could have the symptoms described in the previous section, along with loss of body hair, hot flashes, insomnia, decreased energy, poor concentration and memory, reduced muscle bulk and increased body fat, and diminished physical or work performance.

How is Testosterone Deficiency Treated?

Luckily, testosterone treatments are available to combat the symptoms described above. Patients tend to notice significant improvements within just a few weeks. Yet, many understandably have questions before beginning treatment. Here are some of the most commonly addressed points regarding testosterone replacement therapy.

Is Testosterone Replacement Therapy Safe?

physicians review and monitor progress of hormone replacement therapy for low testosterone, physicians monitor changes in testosterone during hormone replacement therapy

In an article for WebMD, urologist Jason Hedges, MD, Ph.D. confirms that testosterone treatment is safe, as long as patients are monitored carefully by specialists. Appropriate patient selection, safe administration, and expert supervision are all essential for minimizing potential risks. Patients will be closely monitored during the initial six months of treatment to adjust dosing to their specific absorption rate. Absorption rates for testosterone can vary dramatically, which is why frequent lab work is performed and reviewed by expert physicians in age management medicine.

Which Forms of Testosterone Replacement Therapy Are Available?

Testosterone therapy options have come quite a long way since they were first introduced in the 1930s. Patients currently have a comprehensive range of choices with small clinical differences in each. Here are some of the most common options available for testosterone replacement therapy.

Testosterone Replacement Therapy by Oral Administration

Man orally ingesting testosterone pill as part of low testosterone hormone replacement therapy, treating testosterone deficiency orally

Oral administration was one of the earliest forms of testosterone therapy. However, it was rendered ineffective when researchers realized that orally ingested testosterone was metabolized in the liver before reaching systemic circulation, resulting in zero bioavailability. The earliest forms of oral testosterone were also linked to liver toxicity. Since then, sublingual (under the tongue) applications were made available, but due to side effects such as change of taste and gum irritation, they are not recommended.

Testosterone Replacement Therapy with Topical Gels

Testosterone administration with gels and topical products during hormone replacement therapy, Addressing low testosterone with gel and topical product

Testosterone gels and topical products, in general, are not recommended for a number of reasons. They require daily use and it is, therefore, easier for patients to mistakenly miss doses. They are also notoriously unreliable because it can be difficult to administer the proper dose and adequate levels are therefore hard to obtain. They are gooey on the skin and can therefore be easily transferred to family members and other individuals with whom the patient regularly comes into contact. They may also lead to skin irritation.

Testosterone Replacement Therapy with Injections

Addressing low testosterone with testosterone injection during hormone replacement therapy, testosterone injected as hormone replacement therapy treatment

Intramuscular injections of testosterone are typically administered on a weekly basis. Like other forms of treatment, patients undergoing testosterone injections should be monitored closely, as it could be linked with an increase in red blood cell count. With that said, they are a preferred option because they are among the least expensive forms of treatment and are hailed for their reliable delivery.

Testosterone Replacement Therapy with Under-the-Skin Implants

Injected microspheres, or under-the-skin implants, release testosterone into the body over both a steady-state, as well as a transient accelerated initial “burst” release. Also sometimes referred to as “pellets,” this form of treatment must be carefully monitored because each patient has a significantly different absorption rate. Pellets can also be relatively painful and expensive. Additionally, because they are implanted beneath the skin, they may cause infection and scarring.

Is Testosterone Therapy the Right Solution for You?

One of the most significant benefits of testosterone replacement therapy is the significant reduction in all-cause mortality. Hypogonadal men treated with testosterone therapy experience reductions by as much as 50% compared with untreated men. Beyond being healthier overall, however, there are many specific benefits men can experience when opting to receive hormone replacement therapy.

For one, muscle strength improves among hypogonadal men across most age groups, and reduction in fat mass is also achieved with the help of testosterone therapy. Certain treatments may also help enhance fertility in couples trying to get pregnant.[4] Typical benefits increasingly supported by clinical science can include improved body composition, greater bone strength, a healthier cardiovascular system, and better sexual function.

happy couple sitting on couch at home, hormone replacement therapy can increase sex drive due to optimal testosterone levels

If you’ve experienced issues like lethargy, increased body fat, declining sex drive, reduced muscle strength, or any of the other symptoms described herein, you could be an ideal candidate for testosterone replacement therapy. Cenegenics physicians are thoroughly trained and experienced in identifying hormone imbalances and are the premier choice for treatment among men who qualify for this powerful form of therapy.

Based on an extensive, full-day initial evaluation with extensive lab panels, Cenegenics physicians who are highly trained experts in age management medicine can offer customized, tailored hormone therapy, if needed. Treatments are administered as part of a comprehensive program of nutrition, exercise, and vitamin and hormone supplementation for each patient to achieve optimal health as they age. The result is not only a better quality of life, but also lowered disease risk and increased vitality through the middle-ages and beyond.

Hormone Replacement Therapy to Treat Low Testosterone – In Conclusion

Testosterone deficiency can cause men and women to experience lethargy, increased body fat, declining sex drive, reduced muscle strength & loss of muscle mass, and many other symptoms. These symptoms often go unnoticed in correlation to testosterone deficiency as it is viewed as a normal “sign of aging”.

Though there are many treatments to address testosterone deficiency including oral administration, topical gels, intramuscular injections and under-the-skin implants, it is important to find a program in which you will be monitored. How a patient metabolizes or absorbs testosterone differs significantly from patient to patient.

Cenegenics individualized programs address hormone replacement therapy, only when clinically indicated by your comprehensive blood analysis. Your therapy is individualized to meet your specific needs. And patients are monitored to ensure adjustments are made when necessary.

Get Started Now and See If You Are a Candidate for Hormone Replacement Therapy

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We hope the information above assisted you in your research.

Key Resources for Hormone Replacement Therapy to Treat Testosterone Deficiency

This guide was produced with contributions from the following key resources:

The Cenegenics Education and Research Foundation

The Textbook of Age Management Medicine Volume 2: Mastering Healthy Aging Nutrition, Exercise and Hormone Replacement Therapy

Available for purchase here

Textbook Authors:

Jeffrey Park Leake, M.D., CPT

Dr. Jeffrey Park Leake is a Partner and Director of Education at Cenegenics Elite Health specializing in age management and wellness. Having trained hundreds of physicians worldwide, Dr. Leake is also the Director of Education for the Clinical Strategies for Healthy Aging course at AMM Education Foundation.

Todd David Greenberg, M.D., CSCS

Dr. Todd Greenberg is a practicing physician with a broad range of expertise, including wellness, exercise, sports injuries, and MRI of sports injuries. He is a Radiology Clinical Associate Professor at the University of Washington.

Additional Information about Hormone Replacement Therapy at Cenegenics

What is Age Management Medicine?

What is Cenegenics?

Defy Your Age™ With Cenegenics

Anti-Aging vs. Age Management

Cenegenics Elite Health Now Offers State-of-the-Art Genetic Testing

Sources on Hormone Replacement Therapy

[1] “9 Signs of Low Testosterone.” Healthline. 24 July 2018. Retrieved from URL: https://www.healthline.com/health/low-testosterone/warning-signs

[2] Basaria, et al. “Adverse Events Associated with Testosterone Administration.” The New England Journal of Medicine. 08 July 2010. Retrieved from URL: https://www.nejm.org/doi/full/10.1056/NEJMoa1000485

[3] Bhasin et al. “Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham heart study and applied to three geographically distinct cohorts.” Journal of Clinical Endocrinology and Metabolism. 2011 Jun 22.

[4] “Female Fertility: What’s Testosterone Got To Do With It? University of Rochester Medical Center. 03 March 2014. Retrieved from URL: https://www.urmc.rochester.edu/news/story/4022/female-fertility-whats-testosterone-got-to-do-with-it.aspx

[5] McMillen, Matt. “Low Testosterone: How Do You Know When Levels Are Too Low?” WebMD. 31 Aug. 2016. Retrieved from URL: https://www.webmd.com/men/features/low-testosterone-explained-how-do-you-know-when-levels-are-too-low#1

[6] Sloan, Matthew. “Treating low testosterone levels.” Harvard health Publishing. 25 July 2018. Retrieved from URL: https://www.health.harvard.edu/mens-health/treating-low-testosterone-levels

[7] “Testing your testosterone: It’s tricky.” Harvard Health Publishing. Oct. 2012. Retrieved from URL: https://www.health.harvard.edu/mens-health/testing-your-testosterone-its-tricky

[8] “Testosterone and the heart.” Harvard Health Publishing. March 2010. Retrieved from URL: https://www.health.harvard.edu/heart-health/testosterone-and-the-heart

[9] Tsujimura, Arika. “The Relationship between Testosterone Deficiency and Men’s Health.” The World Journal of Men’s Health. 31 Aug. 2013. Retrieved from URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770847/

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