The Guys Guide to Testosterone Replacement Research: 100 Studies Explained
With the complex world of testosterone, low testosterone, and testosterone replacement therapy we put the most comprehensive simple-to-read collection of research and studies from 1940 to present day. The effects, side effects, risks, and benefits are sometimes misinterpreted so this summary gives you real data to better understand this complex hormone. We’ve done the heavy mental lifting for you including almost 100 uniquely creditable research studies.
We deserve a Pulitzer Prize for this piece of work…
The success of TRT dates back to May 23, 1940 as reported by Joseph C. Aub, MD in “Endocrines: The use of Testosterone”
While there is a continuous focus on symptomatic improvement among low T care providers, the wide range of health benefits with testosterone replacement therapy both short and long term seem to be ignored in our instant gratification world we live in today.
Table of Content
Merely asking patients whether they "feel better" after 3-6 months might miss the mark on these important health benefits, which could influence men to stop replacement treatment. We feel it’s important to measure and monitor long-term effects of TRT.
The UK Endocrine Society recommends checking testosterone levels in all men with type 2 diabetes.
Diabetic patients with low testosterone that start TRT should see statistically significant improvement in A1c levels. Patients without depression also showed a significant reduction in waist size, weight, and BMI while on TRT.
In a double bind study of 211 patients show that TRT improves A1c levels, cholesterol levels and waist circumference after 52 weeks.
Researchers found that 3 to 6 months of therapy may be insufficient to achieve optimal response from testosterone replacement therapy. The men reported significant improvements in general health, but let’s look at the long-term benefits of testosterone replacement therapy. Study,Study
In 2011, researchers looked at studies from 1976 to 2011 with the goal to better understand how long it take for the effects of TRT to take effect until max effect is reached.
Consistent with the double-blind study, symptomatic relief showed up as soon as after 3-4 weeks. Noticeable effects on body fat, muscle mass and bone mineral density were present after 6 months and continued 3 years.
Timetable of symptom relief of Low T
- Libido 3-6 weeks (no increase after 6 weeks)
- Sexual function should improve after 6 months.
- Quality of life 3-4 weeks.
- Improvements in mood 3-6 weeks, maximum effect 18-30 weeks.
- Changes in red blood cell production 3 months, peaking at 9-12 months.
- PSA, gradual elevation for the first 12 months. Aging should be assigned to PSA increases after 12 months.
Effects on fat after showed up after 4 weeks, maximum effects after 6-12 months.
Insulin sensitivity should show up within a few days, positive effects on blood sugar control after 3-12 months.
Changes in fat-free mass, lean body mass, and muscle strength occurred within 12-16 weeks and stabilize after 6-12 months.
Reduction in inflammation within 3-12 weeks.
Effects on bone density and strength may show up after 6 months, continuing at least 3 years. Study
In 2001, VA researchers ran a similar study examining 1031 male veterans over the age of 40 years showed that in men with hypogonadism, Testosterone Replacement treatment was associated with a decrease in mortality when comparing data with those who were not treated after 4 years on therapy: 10.3% in the treated group and 20.7% in the untreated group. Study
While previous studies have identified reasons why women live longer than men in terms of sociological factors, more recent research has found that biological factors also have important effects on the body. It is a fact that men are more vulnerable to health issues vs. women, which warrants a more concentrated effort to promote health in an aging men society.
Hypogonadism or low testosterone is medically classified as males with total T of 320ng/dL and Free T of 6.4. Sexual symptoms are also among the first ones to improve with testosterone therapy.
However, improvements in areas of the body take a longer time to manifest, and many of them (e.g. insulin resistance, HbA1c, blood lipids, bone mineral density) need to be closely measured and monitored by professionals, as warning signs or symptoms for more dangerous ailments could surface.
The low adherence rates reported by these studies are in line with previous other reports. For example, it has been found that patients who initiated treatment with testosterone therapy stayed on treatment for a median of 150 days during the 12 months following initiation of treatment, and almost 20% of all new users received treatment for only a maximum of 30 days. Study
Noticeable effects on body fat, muscle mass and bone mineral density may take at least 6 months to years to manifest. Importantly, these long-term improvements keep continuing with continuing testosterone therapy.
“The metabolic syndrome is considered the most important public health threat of the 21st century. This syndrome is characterized by a cluster of cardiovascular risk factors including increased central abdominal obesity, elevated triglycerides, reduced high‐density lipoprotein, high blood pressure, increased fasting glucose, and hyperinsulinemia.”
Eye opening state made in this indepth study run by the Boston University School of Medicine.
Evidence linking androgen (testosterone) deficiency to health risk like obesity, diabetes, hypertension, and high cholesterol, suggests that normalized testosterone play an critical role in the regular physiological bodily functions while low testosterone contributes to many risk factors and markers for heart metabolic diseases. Study
Short answer - Yes. TRT does not cure low testosterone, so your symptoms may return as level return to low, abnormal levels if you stop treatment.
Two-thirds of men with low T who begin TRT will complete at least 12 months of treatment. Treatment benefits were noted in a majority of patients by 3 months. This is an important concern because continuous therapy over a longer period (years, if not indefinitely) is necessary to derive all the benefits of testosterone therapy.
To come up with the approximation, 127 men’s chart were included in the investigation study. 65% of the men had a combination of ED and low sex drive. 70 men were on injections and 57 on topical gel. 63% completed a full year of TRT and the remainder stopped because they did not feel the benefits or stopped coming in for checkups. Study
NOTE: it is important to “dial-in” your treatment to feel your best. The effects of therapy do not start showing up until 6 weeks on average.
In 2018, the International Consultation for Sexual Medicine met to discuss updated recommendations treatment of low testosterone.
Symptoms of low testosterone might be influenced more by free T than total T levels so it is important to look at the total T levels tell you the full picture.
Symptoms + total testosterone = accurate diagnostics.
Symptomatic men with total T <350 ng/dL or free T <65–100 pg/mL should consider testosterone replacement.
The group recommended that 6-month of TRT should be considered in men with strongly symptoms and values above these thresholds.
As per insurance standards, morning blood testing is indicated in men <40 years of age.
Men >40 years may undergo initial afternoon testing, but a follow up morning blood tests are later should be considered. (If you’re clinically low, you’re low regardless of time).
There is tons of evidence that demonstrates TRT in men with low T improves sexual desire and erectile function - The weight of evidence indicates that TRT is not associated with increased risk of prostate cancer, cardiovascular events, or worsening lower urinary tract symptoms.
Bone density and anemia are improved with TRT.
Obesity and type 2 diabetes are associated with low T and TRT is proven to improve these ailments.
Multiple safe and effective FDA approved therapeutic options are available to treat men with low testosterone.
Sex hormone-binding globulin (SHBG) levels vary drastically among older and younger men. Due to the inconsistent readings test results may lead to a misinterpretation of hormones that bind to SHBG (like testosterone).
It is important to look at total, free and SHBG levels along with symptoms to determine hypogonadism. Study
There are multiple proven benefits for sexual symptoms and general health. Recent studies have found compelling evidence that disproves there is an increased risk of prostate cancer or cardiovascular events. Study
Why people don't take their medications?
Here are several reasons why some men might stop treatment.
A group of researchers looked through 102 to determine why some people simply do not stick with therapeutic treatment plans.
Age: studies show middle aged patients are less likely to be compliant with prescribed therapies. The group also found that patients between ages 20-40 years old have other priorities in daily life like work and family and are less willing to spend time waiting at doctor’s offices.
Studies show minorities have poor compliance compared to Caucasians. However, this may also be attributed to financial or social constraints.
Gender and education:
Studies showed inconsistent relationships between compliance to therapy and gender.
Some of the studies revealed a higher compliance rate in married patients (go-figure).
Compliance is better when: The patient feels the effects of the illness
The patient believes that the illness could cause severe consequences to their health
The patient believes that therapy will be effective or is able to see the benefits of therapy
Some negative beliefs affecting compliance are belief the medication will lose effectiveness over the time. Fear of dependence to medication. Lack of motivation. Depression and anxiety can also factor in to non-compliance.
Poor communication on the part of healthcare providers has a negative impact on compliance.
Non-compliant patients often feel that the treating doctors lack concern about the patient’s condition. Having more doctors in the patients’ care team also has a negative impact. Patients that are able to remember their medications, strengths, and dosing instructions are more likely to be compliant as opposed to those who do not know what their meds are. Patient education in their condition, the treatment plan, and the duration of treatment improve compliance. Counseling patients about disease and treatment improves compliance.
A study of 851 people with high blood pressure, 359 (42.6%) that were compliant with therapy showed drastically better blood pressure health. Improvements by roughly 10 mmHg. Study
Patients who smoke and drink are less likely to be compliant.
Forgetfulness is a factor in non-compliance. One study found that meal frequency is effective in reminding patients to take medications. Written instructions are more effective than oral instructions. Ease of medication administration (oral vs injection)
Simple treatment plans vs complex treatment plans (HCG and Clomid vs Testosterone)
Treatment plans that last for a long time are more likely to have compliance issues. But patients that believe that long term treatments are working are more compliant. Side effects can cause non-compliance. Behavioral change affects patient motivation to continue compliance.
Type 2 diabetes patients having difficulty managing disease with diet due to habits, for example. Patients may not be able to take time off work for treatment. Patients who live closer to healthcare facility are more likely to be compliant. White collar workers tend to place other priorities before treatment. Low income patients are more likely to be non-compliant due to expenses. Emotional support from family, friends, and care team increase likelihood of compliance. Availability and accessibility to treatment, wait times for treatment, ease of getting prescriptions filled help compliance. Patients that have unhappy clinic visits and patient’s overall satisfaction with clinic visits are more non-compliant. Study
Men with low Testosterone show lower muscle mass, bone mineral density, and have poorer general health than men with normal testosterone levels. Study
In 2011, 456 men with low total testosterone or free testosterone. The researchers found that the men were more likely to report slow walking speed, difficulty climbing stairs, or weakness and diabetes than those with normal testosterone levels. Study
A Study in 2009 showed that a large proportion of patients tend to stop and restart therapy every 2 to 3 months.
Reasons for poor adherence are not fully understood but possible explanations, as reported for other therapies, may be cost of therapy, preference for different preparations (e.g., topical, injectable) that they are not getting from their doctor, perceived low efficacy, concerns about therapy safety, inadequate patient education, and unrealistic patient expectations for alleviation of symptoms. Study
Estradiol is a form a estrogen and play a huge role in men from a physiologic functional level. Estradiol helps bone metabolism, mediates cardiovascular health, and testicular function.
With that, it is important for our providers to monitor these levels to help treat hypogonadism. Study
Our magnificent bodies naturally want to maintain a comfortable testosterone-to-estrogen balance in the body. This naturally occurring process is trigged by an enzyme called aromatase located in multiple tissues in the body. The more aromatase circulating in the body, the more testosterone will be converted into estrogen. Study
Aromatase activity becomes more active with age similar to how testosterone levels begin to decrease.
As aromatase stay active, studies show that this increases with the amount of fat deposit throughout the body.
- A bad diet and weight gain increases the aromatase process. Study
- High stress and little to no exercise also cause increases in aromatase. Study
- Estradiol plays a critical role in regulating the bodies food intake.
- Too much estradiol can impact mood and cause ED.
If you current have, borderline, or have a family history of diabetes, extensive research shows that you can benefit from Testosterone Replacement Therapy.
Testosterone Replacement may improve survival in men with low testosterone and type 2 diabetes.
HbA1c, glycated hemoglobin, is used to monitor diabetes. Alc reflect the average blood sugar level over the preceding 60 days.
- A level below 5.7% is considered normal. An A1c between 5.7 to 6.4% signals prediabetes. Type 2 diabetes is diagnosed when the A1c is over 6.5%.
- When diabetes, the goal is to lower the Alc blood sugar percentage to around 5.7%.
A study that followed 1709 men aged 40–70 years for almost 10 years. Researchers found that low testosterone plays a role in the development of type 2 diabetes. Study
The Division of Urology at the University of Toronto ran a massive population-based study covering 5 years between 2007-2012.
The study included follow-ups with 10,311 men that were on long term testosterone replacement. They compared those findings with a control group of 28,029 (!!!) and found decreased risk in all-cause mortality, heart issues, and prostate cancer - all-cause mortality is any cause of death.
Researchers show a small increase for risk of heart problems in the first 6 months of TRT, but they believe the increased risk was triggered by low testosterone before the men reached therapeutic targets. Study, Study
In a 6-year study by the UK’s Robert Hague Centre for Diabetes and Endocrinology, 581 men with Type 2 Diabetes had their T levels checked. During the follow up at year 6, they found survival rates improved with men on TRT:
The clear connection between hypogonadism in type 2 diabetes men raises important issues about its possible consequences on sexual function (desire and erectile dysfunction), healthy muscle, abdominal body fat, bone density, mood, and cognition.
Boston University’s School of Medicine ran a study of 656 men with an average age of 57 years to investigate the risks and benefits of testosterone replacement in men with low T treated for up to 8 years and compare these benefits with those in men with low T who were untreated for the same amount of time.
The estimated reduction in mortality for the testosterone replacement group was between 66% and 92%.
- A1c decreased from 6.9% to 5.6% in the testosterone replacement group.
- Alc increase ever-so-slightly (+0.3%) in the untreated group.
Blood Pressure decreased by almost 14 mm Hg (both systolic & diastolic) Optimal blood pressure is 120 mm Hg systolic - heart beats - over 80 mm Hg diastolic - heart relaxes.
- A good resting heart rate, the target is between 60 and 100 beats per minute (BPM).
Total Cholesterol/High Density progressively decrease from 5.6 to 2.6 in the TRT group and from 6.2 to 5.6 in the untreated group. The improves in HDL shows us that TRT may improve cardiovascular issues. Study
In 2019, a study from the Heart of England Foundation showed that a third of men with type 2 diabetes have low testosterone and run the risk of heart disease. They also confirmed that men with low testosterone are at a higher risk of developing type 2 diabetes. To confirm this, the researchers studied data from 2005 to 2017 (1800+ trails and articles). Study
A study of 181 men over five years showed that normalizing testosterone levels in obese men or diabetics with low testosterone drastically can improve their metabolic state. Study
Another study watched 561 men with “diabesity” (diabetes and obesity) and low testosterone but receiving testosterone replacement therapy for up to 6 years showed marked improved in fasting glucose (declined by 2 points); A1c decreased by 6.14%; Systolic and diastolic blood pressure, lipid profiles including total cholesterol + liver enzymes all greatly improved. Study
Short answer is NO. You want to feel horny and a desire to have sex.
In 2010, the European Male Aging Study Group surveyed a random population sample of 3369 men between the ages of 40 and 79 years across the EU.
They found that men with low T have a higher chance of experiencing physical dysfunction, sexual dysfunction, and diabetes.
One of the main signs of low testosterone is a decrease in frequency of morning erections, sexual thoughts, and erectile dysfunction.
They determined that late-onset low t can be defined by the presence of at least three of the above sexual symptoms with a total testosterone level of less than 317 ng/dL and a free testosterone level of less than 220 pmol per liter (64 pg per milliliter).
In one of the groups, which included 1610 men, the team found that inability to perform vigorous activity, depression, and fatigue were significantly related to the testosterone level. This was then validated by comparing the first group to the other half of 1609 men. Study
In a study of 1,413 men, those with the lowest levels of testosterone were four times more likely to have diabetes. Study
There is a clear associate between get older and duration of TRT as it impacts the likelihood of recovery of sperm.
Our providers are cautious when discussing testosterone replacement therapy, more so in men that still want to remain fertility.
- As the study suggests, our providers counsel with the men about the recovery of sperm at 6 and 12 months.
If you are younger and HCG does not relieve your symptoms and you decide to start testosterone replacement therapy, you may still be able to restore fertility by stopping treatment.
According to research most men should return to baseline sperm production in 6 to 9 months depending on age. A 2006 study executed by UCLA and LA Biomedical Research institute showed that 90% of patients were expected to return to baseline sperm concentration values 12 months after cessation of treatment and 100% after 24 months.
TRT trends over the course of a decade shared that 20% of men ages of 18-45 who were on TRT did not get a baseline testosterone level prior to starting TRT…
Some didn’t even know that TRT impacted fertility. This is problematic. We require blood work to start and continue TRT treatment regardless of age, but if you are in the reproductive age range and you are symptomatic, we have treatment options available. Study, Study
The Department of Epidemiology and Statistics, Boston University ran a study of 261 men aged 32–84 years old. The men had sought consultation in a single clinic for erectile dysfunction.
Hypogonadism (Low Testosterone) is associated with an increase in body fat, decreased muscle mass, weak bones, and reduced libido.
Treatment of low testosterone men with testosterone has been shown proven to the reverse the effects of low testosterone on bone, muscle, erythropoiesis (red blood cell production) and the prostate. Study
A published study in The Journals of Gerontology testosterone replacement showed bone mass density improves at a “much more impressive” rate than the untreated control group. Normalizing testosterone levels in men and women has shown effects on bone metabolism. Study
A group of researchers observed 45 men with osteoporosis over 6 years. This group confirmed that testosterone levels, when normalized with testosterone replacement treatment not only gradually improved bone mineral density but benefited also their metabolic state, mood and sexual functioning as confirmed in other studies throughout this page. Study
Hemoglobin is the iron rich molecule that gives blood its red color and ships oxygen throughout the body. Hemoglobin is a protein in red blood cells and hematocrit is the volume percentage of red blood cells when compared to the overall blood count total (red/white). Sometimes referred to as “H&H.”
Testosterone and other androgens naturally stimulate red blood cell production (hemoglobin and Hematocrit).
We monitor H&H very closely - 51-52% hematocrit is when our providers begin to recommend regular blood donation. Above that is when our providers order a Therapeutic Phlebotomy.
Sometimes, an increase in hemoglobin might be beneficial in men with diagnosed low testosterone (hypogonadism) or anemic. Our providers monitor these levels to manage the risks of cerebrovascular events and hypertension. Study
55 men with clinically and biochemical confirmed hypogonadism were randomly assigned to 4 groups receiving different forms of androgen substitution:
In an analysis of data among men on testosterone pellet therapy between 2009 and 2014, 97 patients were analyzed.
A group of researchers out of Charles R. Drew University (LA, had to look it up) examined 7 men with low testosterone and found that testosterone replacement has substantial effects on healthy, lean body composition. After 12-week “washout” from existing testosterone replacement treatment, the men were treated for 10 weeks with intermuscular T injections – 100mg per week.
- The men did not exercise.
- Did not show change in hemoglobin & hematocrit.
- The men progressively gained fat-free weight throughout the first 6 weeks. 3.4% on average.
- The triceps muscle area increased by 12% and quadriceps area increased by 8%.
UCLA School of Medicine looked at patient response to TRT at various doses. Weekly injections were give ranging from 25, 50, 125, 300, or 600 mg of testosterone 20 wk. Study
Note: 300 and 600mgs is A LOT of testosterone. Too much to reach physiologically normal testosterone levels.
Some aspects of sexual function and spatial cognition, and PSA levels, were maintained by relatively low doses of testosterone and did not increase further with administration of higher doses.
125mg+ dose of testosterone showed changes in fat mass and muscle volume.
Hemoglobin levels changed significantly in relation to testosterone dose and concentration.
Note: 300 and 600mgs will definitely spike your H&H at those excessive doses…
Normal ranges 500-1000 ng/dL can be reached and managed with a median dose, less aggressive mg dose over a period of time. Study
It is well published that men with low testosterone levels run a higher risk of coronary artery heart disease.
Extensive studies have provided evidence to support the association between low testosterone and cardiovascular / heart disease and other heart complications. In 2011, 21 studies related to testosterone and CVD 28,015 men with an average age of 61 years and testosterone level of 487 ng/dl were reviewed - There was a clear connection between low testosterone and heart related deaths. Study
A study out of Germany in 2010 recruited 1954 men between 20-79 years of age. The results showed that men with low testosterone were over much more likely to pass away from heart disease when compared to men with normal levels of testosterone.
Shockingly, this ratio removed all other factors like weight, smoking / alcohol, physical activity, etc. Study
A long-term data driven study from 2001 to 2004 of 3690 older men was reviewed in 2010 showed that men was optimal testosterone levels had the lowest death rates among the group. Of the 974 deaths a majority of the group had low testosterone levels. Study
A group of 1104 of men and women over 40 revealed that low testosterone predicted heart attack risks in men with type 2 diabetes.
Researchers found “statistically significant” connections between low T + type 2 diabetes + heart attacks. Study
The American Heart Association Annual Statistics report that Men are more than twice as likely as women to die from coronary heart disease. And the numbers are not improving. Study
As mentioned in our Diabetes section, the anti-inflammatory effect of normal physiological levels of testosterone may provide the heart and arteries important lube to prevent clotting and plaque buildup.
Studies have shown that low testosterone is linked to concerning heart conditions. In connection with the heart, healthy physiological hormone levels have a healing affect. This bodily function happens at the cell level where “Cytokine activation” fires off growth cells called on by the immune system to heal broken cells.
Androgen (testosterone) signals room-service like cells to keep the vascular process pumping clot-free and smooths out muscle healing. Study
In 2007, the University of Tokyo found that low free testosterone level was associated with vascular disorder in men, suggesting a protective effect of testosterone on tissue lining the blood vessels and heart. These finding provides the functional role of testosterone and how it reduces the risks of cardiovascular disease in men. Study
According to a validation study including 154 men, men with Erectile Dysfunction (ED) are likely to have metabolic issues like diabetes, high blood pressure, etc and insulin resistance.
The study validated that early detection of metabolic disease in men with ED may help correct vascular disorders and identify heart disease risks. Early studies showed that:
- 56% of an ED population have undiagnostic heart risk symptoms.
- 75% of men with heart disease have symptoms of ED.
- 91% of our ED patients have cardiovascular risks.
In 2014, 8,709 men with low testosterone were tested for Coronary artery disease, the most common type of heart disease. They split them into two groups: TRT and untreated.
The researchers originally showed that there was higher risk in the TRT; However, other researchers questioned the exclusion of 1,132 patients who experienced events because they were prescribed testosterone therapy after the event.
These men should have been included in the untreated group for purposes of study consistency, which increased the events by 70%. Data tells a different story in this case. Study
In 2015, the VA and University of Kansas evaluated 83,010 men with documented low testosterone.
Divided into 3 groups, those on TRT with normalized testosterone levels had a significantly lower risk of stroke vs. the other TRT group below normal testosterone levels. (the third group did not receive any TRT).
The TRT group with normalized levels included 25,701 men with an average age of 66 years. Study
Testosterone behavior shows 24-hour fluctuation patterns during the day and night (what’s called circadian). During sleep, an increase of testosterone is linked with the first REM cycle and 3 hours of deep sleep.
Testosterone levels are highest during the night and lowest in the evening (5-7pm). Interestingly, every 90 minutes, our bodies release pulse, which essentially stimulates our pituitary glands to secrete (moves) testosterone throughout our bodies; A natural phenomena called “superimposed ultradian rhythm.” Our bodies are incredible. Study
When that process is not working as it should you may have hypogonadism (low T).
Sleep disruption including:
- Poor sleep quality
- Sleep-disordered breathing (snoring, coughing on tongue)
All may result in a decrease in testosterone levels.
When you miss deep sleep and REM, your body cannot naturally fire off a new round of testosterone pulse, which may lead to low testosterone (hypogonadism).
Data shows that there is no clear connection between Obstructive sleep apnea (OSA) and its effects on testosterone; however, there is certainly an impactful and influencing relationship between OSA and T levels.
Tons of studies do show a clear connection between Sleep Apnea and Obesity.
It must be said that treatment of OSA with CPAP aka Continuous Positive Airway Pressure does not increase naturally testosterone levels in most studies.
The data shows that combining sleep apnea treatment and testosterone replacement does indeed improve quality of life.
Low testosterone can affect overall sleep quality which is improved by testosterone replacement if done the right way. Our providers get you to optimal therapeutic T levels to improve quality of life.
Large doses of testosterone and anabolic/androgenic steroid abuse are directly correlated with disruption of sleep duration and normal sleep patterns.
Listen up, untreated sleep disorders coupled with TRT may actually worsen obstructive sleep apnea. It is important to talk with our providers about your quality of sleep and we can review your Epworth Sleepiness Scale. Study, Study, Study
Prostate cancer is an androgen (testosterone) - dependent tumor.
Although prostate cancer diagnostic rates have not been significantly different between placebo‐and testosterone‐treated men in studies dating back to the 80’s on the effects of testosterone replacement in older men, it is important to note that the sheer mass of numbers to gain solid findings with a complex disease like prostate cancer has proven difficult.
According to researchers, it’s difficult to establish a baseline between the prevalence of benign and malignant tumors and testosterone replacement.
There has been no concreate relationship made between serum testosterone levels and the risk of prostate cancer, but as mentioned above – prostate tumors grow by way of testosterone.
In 2014, The European Urology ran an analysis to “identify all original and review articles assessing the effect of androgens on the prostate and the use of testosterone in men with a history of treated and untreated Prostate Cancer.” Their findings showed increase Prostate Cancer rates. Study
Prostate-Specific Antigen (PSA) is a protein produced a small gland that sits below the bladder in men.
PSA levels increase with age in men even in men who do not have cancer markers. Study
Some men with evaluated PSA levels in their blood run the risk of developing clinical prostate cancer. Study
Patients in remission from Prostate Cancer after treatment with previous surgery or radiation could consider TRT.
In a 2014, a database of 149,354 men diagnosed with prostate cancer was studied. Researchers found 1,181 men started testosterone replacement following their cancer diagnosis.
As of recent, the perception on TRT and Prostate Cancer has changed.
More doctors that study the larger studies run in the 2000’s have realized that the smaller studies from the 80’s and 90’s can be disposed by data analytics and modern research technics. Study
Our Rise protocol includes regular screening to monitor PSA levels. We recommend rectal examination, and (if necessary) prostate imaging such as color Doppler ultrasound or multiparametric MRI.
Our Rise Providers set criteria for monitoring PSA changes during testosterone even if they are not the primary care provider. There is a fine line to understand on biopsy + PSA. Study
In a 2016 chart review, 28 men with hypogonadism where identified who underwent TRT while on active surveillance for prostate cancer.
Comparing the active surveillance group with 96 men with untreated low testosterone but on active surveillance, the TRT group conveyed no significant increase in the development of cancer over 3 years review.
These findings should be considered interesting only – these groups are not equal and there was no control to moderate findings. Study
Androgen Deprivation Therapy (ADT) is used to treat Prostate Cancer. As you might expect, the goal of ADT is to reduces levels of androgens in circulation. We won’t get into the how ADT works, but there is some interesting points to be made about ADT.
First a few positives: After two or three years of ADT plus external-beam radiation – has been proven to cure cancer in tons of men. In men with metastatic cancer cells, ADT can dramatically improve quality of life.
According to the Prostate Cancer Foundation, some men have been on ADT for 20 years and are still going strong. https://www.pcf.org/c/adt-what-you-really-need-to-know/
Along with ADT comes low testosterone direct and indirect ailments. There is currently no connection between heart issues and ADT and some studies actually suggest a Cardiologist skip the Stress test before ADT.
Indirectly speaking, if one has low testosterone and low testosterone is associated with heart issues, diabetes, hypertension, high cholesterol, and obesity then we suggest screening for heart disease periodic.
An advisory group from the American Heart Association, American Cancer Society and the American Urological Association recommends that all patients receiving ADT should have periodic follow-ups for the assessment of cardiovascular risk factors and those existing heart issues should have their own treatment plan. Study, Study
The primary concern with the relations between TRT and Prostate Cancer stems from the use of androgen deprivation (ADT) for the treatment of prostate cancer. Current data fails to demonstrate a clear connection between androgen and prostate cancer.
One of the studies mentioned above included 3886 men with prostate cancer and 6438 undiagnosed of the same demographic found no associations between prostate cancer risk and strength of Testosterone levels. Study
A review of 19 studies revealed no greater risk of prostate cancer in men diagnosed with low testosterone who received placebo versus men who received testosterone replacement therapy. Study
Finasteride is used to prevent or delay the appearance of prostate cancer and may stop balding.
Over the course of 52 weeks, 60 men (less than 60 years old) with clinically low testosterone showed an increase in strength by 8–14%, increase in bone density, and total fat loss of 8.5 pounds without prostate enlargement during a protocol of testosterone replacement and finasteride.
Without getting too complex, finasteride is used clinically to treat BPH and baldness with their ability to reduce circulating DHT.
DHT (Dihydrotestosterone) stimulates the growth for certain part of the body including prostate cells. In older men excess production of DHT contributing to benign prostatic hyperplasia (BPH) aka enlarged prostate.
Finasteride blocks an enzyme called “Type II 5α-reductase” responsible for producing DHT.
Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5α-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer. Study
- Testosterone may elevate PSA, and finasteride reduced PSA. Study
- TRT has been shown to improve A1c levels in patients with type 2 diabetes.
- TRT improves bladder capacity and allows more normal bladder function (improving Lower Urinary Tract Symptoms LUTS, for example)
Symptoms of LUTS include frequency (peeing a lot), urgency (feeling like you have to pee, even if your bladder is not full), incomplete voiding (not completely emptying the bladder when you pee), and reduced stream.
One study showed that men low T levels show increased nighttime urination
The current understanding is that TRT does not cause prostate enlargement. Study
A 2004 study of 70 men aged 65 year or older sought to determine whether bones benefit with no effect on PSA/Prostate, the investigators compared a placebo with a group on testosterone replacement given with finasteride.
After 3 years, there was a 9–10% increase in BMD at the lumbar spine and a 2–3% increase in bone mass density at the hip when compared to the placebo group. Study
It's important to mention that a prostate cancer prevention trial (from the New England Journal of Medicine) showed a 25% reduction in new cases of prostate cancer in older men treated with finasteride therapy alone.
A study that included 3,029 TRT and 2,049 untreated men concluded that TRT was associated with reduced fat mass and increased lean healthy muscle. The group also suggested that TRT improved insulin resistance and blood sugar control. Study
70% of the body's insulin sensitivity taken up by muscles. Low testosterone has shown to effect insulin resistance via anabolic or metabolic effects on muscle. Study
Body insulin and the liver plays an important role in normal testosterone levels. Overeating or overindulging in diets high in fat and carbohydrate coupled with little to no exercise leads to a snowball effect, almost like a clogging effect in the liver because it is unable to process fats/carbs into energy to fuel the muscle.
Excess fatty acids that are not processed into energy kill your insulin and your metabolism. Lipolysis is a process where the liver creates new tissue for our liver and muscles.
Normal insulin and liver function will help fight inflammation, which is another part of getting fat. If your body is constantly inflamed, bloated, and trying to “burn” off pizza and pie, then you will start to become insulin resistant. Study, Study
In 2013, 255 men (aged 33-69) were observed over 5 years. The team at the Germany and Gulf Medical University School of Medicine found that normalizing testosterone levels produced consistent loss of body weight, waist size, and BMI.
- Body weight dropped by 35 pounds after 30 weeks of treatment with injectable testosterone.
- Waist size dropped by 7 inches
- BMI decreased by 4 points
- Weight loss progressively increased year to year with the most drastic drop in years 4 and 5.
This 12-month study of 102 sedentary men ages 40–75 were randomly assigned into an exercise or no change (sedentary) group.
SHBG is a protein produced by the liver (lipoB) that sends important androgen hormones like testosterone, dihydrotestosterone (DHT), and estradiol (an estrogen) in the blood as biologically inactive forms. Study
10.8% improvements in heart and lung fitness (VO2max).
When pairing quality exercise and normalizing testosterone replacement therapy, they found that enhancement DHT levels by 14.5% in middle-aged and elderly obese men through exercise may offer another approach for improved health.
They saw that those who had the greatest improvements in V̇O2max experienced the greatest increases in SHBG. This again suggests that other physiologic pathways exist for exercise to affect SHBG than simply altering fat mass. Study
“Testosterone is well known to regulate a host of metabolic functions in liver, adipose tissue, muscles, coronary arteries and the heart” Study
Testosterone replacement therapy for men with low testosterone improves lipid profile and lowers cholesterol, blood sugar and insulin resistance. Study
Normal levels testosterone kick-start rapid turnover of fatty acids by reducing lipoprotein processed through the liver in turn mobilizing lipids from fat depot around the body and contributing to healthy fat loss (think: fat semi-trucks hauling payload). Study
Emotional health in men is extremely important and should not be underestimated. According to the World Health Organization, depression is one of the largest contributors to shorten life in me (increasing 18% over the last decade). Why is that if we are living longer and happier lives?
Perhaps work/life balance or burn-out is to blame.
Another possibility points to the fact that depression is very linked to lifestyle issues, sleep issues, reduced physical activity and poor diet. The high carb, fast food filled American diet could be to blame.
As mentioned in the liver section, body inflammation and insulin imbalances disrupt the critic mechanisms to create energy and distribute testosterone throughout the body.
In a 6-week study out of the University of Washington, 57 men were split into several groups including a placebo. Results showed that physiological increases in testosterone levels gave the men a positive effect on verbal and spatial memory (remembering things, objects around you).
Interestingly, larger doses of testosterone levels did not result improvements in cognition ability. Study
One test measured the ability to navigate a short route within a room (spatial memory).
- Points before: 42.9 Points during treatment: 49.0
Another test asked the me to recall a list of 12 words from the same category (verbal).
- Recognized Words before: 12. Words during: 13.5
A USC review from 2009 confirmed that there is a decline in testosterone levels in men with either Alzheimer or Parkinson disease.
Past studies confirmed that low testosterone levels and frontal lobe dysfunction in normal aged men. With these findings from USC tells us that that the low testosterone and hormone deficiency may cause a "second hit" to impaired cognitive function in neurodegenerative disease; possibly intensifying severity. Study, Study
In 2019, researchers found that normalized levels of circulating testosterone is positively associated with impulsivity.
The study observed the effect of testosterone replacement and impulsive behavior in choice task program, where men are given a choice between “smaller-sooner rewards and larger-later rewards.”
With a treated and untreated (control) group the study showed that testosterone replacement increased impulsive choice. This finding supports the hypothesis that normal levels of testosterone increases impulsivity among males. Study
Many men hope that supplements will increase Testosterone “naturally” and free from risks without medical prescription and care.
In a study out of USC’s School of Medicine and Urology, 90% of the 109 “T booster” supplements claimed to boost Testosterone.
Only 24% of these boosters had data to support their claims. Better yet, over half of the 24% actually presented conflicting data showing no change or a decrease in T with supplementation. Troubling to see boosting sups actually some decreasing T levels…
What’s odd is that 10.1% contained ingrediencies with data suggesting a negative effect on testosterone.
None of the supplements studied were FDA approved.
The objective of the USC study was to “evaluate the composition of “T booster” supplements, their advertised claims, and we compared this with the published literature and RDA.”
A majority of the products included “supra-therapeutic doses of vitamins and minerals”
Supplements contained a median 1,291% of the RDA for vitamin B12.
- 807.6% of vitamin B6
- 272% of zinc
- 200% of vitamin B5
- 187.5% of vitamin B3.
Two supplements had greater than or equal to the UL of zinc (40 mg), 2 had greater than the UL of vitamin B3 (35 mg), and 9 were greater than the UL of magnesium (350 mg).
Too much zinc over a long period of time has shown to interfere with the body’s natural utilization of copper, iron to create healthy blood cells. Over zinc’ing can decrease HDL cholesterol (the “good” cholesterol) leading to a higher risk of heart disease and damage to our immune system. Study, Study
Consider three things before you purchase these OTC supplements:
- Consider the ingredients. The sup company includes energy boosting “feelers” to make feel the pills when they may not be providing any benefit at all.
- Our body can only absorb so many vitamins and minerals. You will pee out the 200-1000% excess without seeing any benefit.
- Note: Our LipoB and B12 injections are intermuscular, which bypasses the “First-Pass Metabolism” Digestion process. Don’t pee away your cash.
There are natural ways to improve testosterone health, but if you are low T symptomatic, TRT or low T treatment (HCG, Clomid) are proven method to feeling better. Low T care is covered by insurance AND cash options are much cheaper than a ‘cycle’ of T boosters.
We recommend that you stay away from the Prime, Alpha, Black Panther, Zeus T Boosters.
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