Testosterone
Common Questions about Testosterone Testing and Testosterone Replacement Therapy (TRT)
Answers to these questions below are derived from Canadian, American and European Clinical Practice Guidelines. The answers presented here are based on mainstream and clinically accepted practices. TeleTest physicians offers monitoring in accordance with clinical practice guidelines and we do not deviate from accepted mainstream clinical practice.
Background
I'm looking to make a diagnosis of testosterone deficiency or renew my testosterone. Can TeleTest help?
At present time, TeleTest only offers surveillance monitoring for individuals on Testosterone Replacement Therapy (TRT). We do not currently make a diagnosis of testosterone deficiency or provide renewals of testosterone.
What percentage of Canadians have testosterone deficiency?
The prevalence of testosterone deficiency is approximately 4-12% of men aged 50-59 years, 9-23% of men aged 60-69, and 28-49% of men over 70.
What are symptoms of low testosterone?
Sexual: low libido, loss of morning erections, decreased orgasm intensity, reduced ejaculate volume
Cognitive: fatigue, depression, insomnia, poor concentration, irritability
Physical: loss of facial/arm/groin hair, testicular shrinkage, low bone density, breast development, anemia, increased body fat
What's the difference between free and total testosterone values?
Testosterone travels in your bloodstream attached to transport proteins (Albumin and Sex Hormone Binding Globulin) but also travels freely, unattached to any proteins. Total testosterone is the sum of attached (protein-bound) testosterone and free testosterone. Only 2-4% of circulating testosterone is free.
What proteins is testosterone attached to?
Testosterone is attached to Sex Hormone Binding Globulin, Albumin, and Cortisol-Binding Globulin.
What is meant by the term bio-available testosterone?
Bioavailable testosterone refers to the sum total of free testosterone and testosterone that is weakly attached to transport proteins (i.e. testosterone attached to albumin). Sex Hormone Binding Globulin (SHBG) binds most testosterone in the bloodstream and holds it very tightly. Testosterone attached to SHBG is not considered bio-available.
What is the free hormone hypothesis?
The free hormone hypothesis states that the biological activity of testosterone is dependent on the amount of free testosterone in the body, rather than the total or protein-bound testosterone. Current clinical practice guidelines recommend titrating testosterone therapy against total testosterone and do not recommend using free testosterone for this purpose.
Testosterone Monitoring
What is diurnal variation in T levels?
Diurnal variation refers to the natural daily changes in your testosterone (T) levels. For most men, T levels are usually highest in the morning and lowest in the afternoon and evening. However, this can vary based on your age.
How do T levels vary with age?
Young men, around the age of 25, typically have their highest T levels in the morning. These levels drop to their lowest point about 12 hours later, and then they gradually rise again until the next morning. This pattern, though, changes as you get older. For men in their 70s, the difference between morning and afternoon T levels is only about 10%.
Why are morning blood tests recommended for the diagnosis of TD?
Given the natural pattern of T levels being highest in the morning, guidelines from organizations like the Canadian Urological Association recommend getting a blood test in the early morning if there's a suspicion of testosterone deficiency (TD). This helps to capture the peak level of your T for the day.
Do T levels change throughout the day in men with TD?
No, men diagnosed with TD don't show the usual pattern of T levels changing throughout the day. Their T levels are generally much lower than those in healthy men, regardless of the time of day.
How can T levels be increased in men with TD?
pThere are a number of treatment options that can help raise T levels to a normal range in men with TD. These include injections, gels, and oral products, some of which are designed to mimic the natural daily pattern of T levels in younger or older men.
Can any single treatment perfectly match the natural daily variation of T in both young and older men?
No single treatment appears to match perfectly with the daily variation of T levels in both young and older men. However, the goal of these treatments is to keep T levels within the normal range, which can help alleviate the symptoms of TD.
Are there factors other than treatment that can influence T levels?
Yes, other factors such as sleep quality and duration can also influence your T levels. The role of these factors is still being researched, and more information is needed to fully understand their impact.
Diagnosis
What is the definition of testosterone deficiency?
The definition of testosterone deficiency is reduced testicular production of testosterone by the testes.
How can I be diagnosed with testosterone deficiency?
Step 1: Symptom Review
The symptoms of testosterone deficiency are non-specific (i.e. fatigue, low stamina, excess abdominal weight), meaning they apply to many conditions. Your doctor will first ask you if your symptoms might be related to other conditions or lifestyle issues (i.e. lack of exercise, poor dietary choices, sleep apnea, stress etc).
Step 2: Routine Bloodwork and Examination
Initially, your doctor may order routine bloodwork to screen for other conditions like anemia, and kidney and liver disease. S/he will likely also screen for other conditions like diabetes or sleep apnea.
Your doctor will complete an examination for things like blood pressure, and cardiovascular and respiratory fitness and look for physical signs of testosterone deficiency (i.e. hair loss, loss of muscle bulk and testicular shrinkage).
Step 3: Normal Examination & Test Results
If you have normal bloodwork and no other identifiable causes of your symptoms, your doctor will order a fasting morning 7-10AM total testosterone level.
Some guidelines recommend a repeat morning testosterone level if your initial level is low to confirm a diagnosis.
The "Testosterone Therapy in Men With Hypogonadism: An Endocrine Society* Clinical Practice Guideline" lists a straightforward algorithm to diagnose low testosterone function in men (reference page 7).
What exam should my doctor perform before prescribing TRT?
Physical examination includes an assessment for:
The presence and distribution of body hair (i.e. loss of pubic or under-arm hair)
Looking for signs of insulin resistance ('acanthosis nigricans')
Signs of breast development or gynecomastia
Testicular size
Prostate examination in older men (i.e. age > 40) to look for prostate nodules or irregularity
Weight, height and Body Mass Index
Medication
How long does it take to feel an improvement in symptoms after starting on TRT?
We typically see an improvement in testosterone levels before we see an improvement in symptoms.
3 months: libido, energy, sexual function
6 months: muscle mass, body composition, bone density
What are the types of testosterone available?
TRT therapy is available in short and long acting injectable formulations, along with topical variations (i.e. gel, patch and nasal spray).
Short Acting Injection: Testosterone Cypionate (Depo-testosterone)
Long-Acting Injection: Testosterone Enanthate (Delatestryl)
Oral capsule: Testosterone Undecanoate (Andriol)
Topical (gel): Androgel, Testim
Topical (patch): Androderm
Nasal (gel): Natesto 4.5%
What's the difference between Intramuscular (IM) and Subcutaneous (SC) testosterone?
IM testosterone has a faster time to peak blood testosterone level compared to SC testosterone
The half-life for IM testosterone is shorter than SC testosterone.
How frequently should my doctor dose testosterone?
Generally speaking, smaller doses and more frequent dosing (i.e. weekly) reduces trough testosterone levels (i.e. time spent outside of the normal range). For example, 100mg given once weekly is preferred over 200mg given every 2 weeks.
How frequently should I have monitoring after starting or changing my testosterone dosing?
We typically wait for 5 half-lives to check your testosterone levels. The expected time frame to re-check your levels after a dose change is provided below.
Topical (gel): Androgel, Testim - 24 hours
Topical (patch): Androderm - 24 hours
Nasal (gel): Natesto 4.5% - 24 hours
Oral capsule: Testosterone Undecanoate (Andriol) - 24 hours
Short-Acting Injection: Testosterone Cypionate (Depo-testosterone) - 4 weeks
Long-Acting Injection: Testosterone Enanthate (Delatestryl) - 10 weeks
Family Planning
I'm planning on having children. Will TRT affect my ability to have children?
Absolutely. Testosterone therapy causes decreased testicle size and loss of sperm production. We typically see loss of sperm production 10 weeks after beginning therapy.
How long does it take to recover sperm levels?
Sperm levels typically return to your baseline levels ~6-18 months after stopping therapy.
Does taking TRT therapy result in permanent fertility loss?
No, fertility loss is related to the period on TRT therapy and the 'wash-out' period while coming off the medication.
Are there alternatives to TRT to increase testosterone levels while preserving fertility?
Yes. There are other categories of medications that regulate testosterone levels without compromising fertility. These include
SERMS: clomiphene, tamoxifen
Aromatase inhibitors: anastrozole, letrozole, testolactone
Benefits of Testosterone
Does testosterone improve body composition and muscle mass and strength?
In aging men, testosterone therapy decreases fat mass and increases lean body mass. It has been demonstrated to improve grip strength and muscle strength in upper and lower extremities. There isn't enough evidence to suggest routine use in older men who are frail.
Does testosterone improve mood, energy and quality of life (QOL)?
There are some studies which support improvement in mood, energy and QOL with TRT therapy, and others which show no change. Each study has limitations and is applicable only to a specific population (i.e. men above 65, HIV + men, etc). Currently, the American Urological Association reports there is inconclusive evidence of whether TRT improves cognitive function, energy and quality of life.
However,
In some studies, in men who have low testosterone (low levels and symptoms), replacement has been associated with an improvement in mood and well-being.
In some studies, in men who have normal testosterone (normal levels but symptoms), replacement has not been associated with an improvement in mood and well-being.
Potential Risks of Testosterone
Prostate
Does TRT increase the size of your prostate and cause BPH?
Benign Prostatic Hypertrophy (BPH) is an enlargement of the prostate. It can cause urinary symptoms including a feeling of incomplete emptying, frequent nighttime urination and reduced urinary flow.
TRT does not increase the risk of BPH and does not increase prostate volume. In fact, in several studies, TRT has been found to improve urinary symptoms in men resulting in stronger urinary flow and improved bladder emptying. Testosterone seems to improve bladder muscle function in men.
Can I take TRT if I have a diagnosis of BPH?
Yes, you can safely take TRT if you have a history of BPH. If you have a significant increase in your PSA level while on testosterone, it should be investigated and not assumed to be related to testosterone therapy.
Can testosterone therapy cause prostate cancer?
Contrary to popularly held beliefs, testosterone therapy does not increase the risk of developing prostate cancer. In fact, there is no association between prostate cancer and testosterone levels.
Can men with prostate cancer be on TRT?
Yes, men with low testosterone levels and a current or previous diagnosis of prostate cancer can be managed with TRT. These include men who have had a radical prostatectomy, or radiation therapy or those are who actively monitored by a urologist (this means having quarterly PSA testing). Testosterone therapy does not significantly increase the risk of PSA increases or lead to local or metastatic progression of cancer.
Is there a subset of men who have had prostate cancer who should avoid TRT?
Men with locally advanced prostate cancer, or metastatic prostate cancer should not be on TRT, as it can stimulate prostate cancer growth and aggravate symptoms in these cases.
Heart
Does testosterone therapy cause heart disease?
There is a lack of evidence to suggest that testosterone therapy increases the risk of heart attacks, strokes or cardiovascular disease in men. Why then did the FDA and Canadian regulators add a black-box warning to testosterone in 2014? This was based on a review of 5 observational studies and 2 meta-analyses of RTCs.
Two studies and one meta-analysis suggested an increased risk, two demonstrated no increased risk and one was 'neutral'. The second meta-analysis showed no increased risk. The Committee reviewing the available study data reported there was not enough evidence to conclude TRT increased major cardiovascular events, but the warning was added nonetheless.
The Canadian Urological Association officially states "To date, there are no large, long-term, placebo-controlled trials to help make definitive statements on testosterone therapy and cardiovascular risk."
Does testosterone therapy prevent heart disease?
Yes, men who are testosterone deficient and remain untreated are at an increased risk of heart disease, cardiovascular events and death.
Hemoglobin
Can TRT increase my hemoglobin count?
TRT can increase your hemoglobin levels above the normal range because TRT therapy stimulates the formation of new red blood cells. High hemoglobin levels are called polycythemia. The greatest risk of polycythemia is when your testosterone levels are well above the normal lab-defined range. Current guidelines recommend monitoring your hemoglobin levels while on therapy.
Which TRT formulations are more likely to increase my hemoglobin levels?
Injection formulations of testosterone vs. oral/transdermal routes have been shown to have a higher risk of Polycythemia.
Are high hemoglobin levels dangerous?
Elevated hemoglobin levels may increase the thickness (i.e viscosity) of your blood. In individuals with heart disease, or plaque buildup in arteries in their brain (cerebrovascular disease) or arms and legs (peripheral vascular disease), high hemoglobin levels can lead to blood clots which can be life-threatening and fatal in some instances.
What is my hematocrit?
Your hematocrit is the percentage of hemoglobin that makes up your blood volume. If your hematocrit is greater than 55%, it warrants any of the following:
A dose reduction of your testosterone
Temporarily stopping your testosterone
Changing the type of testosterone (i.e. changing from injection to gel)
Donating blood
Monitoring while on TRT
What should I have monitored before I start TRT?
A doctor should review your current symptoms (i.e. libido, fatigue, mood)
Measure a fasting morning Total Testosterone
Measure a Complete Blood Count (Hematocrit)
Measure your Prostate Specific Antigen (PSA)
Do I need an annual prostate exam while on TRT?
The Canadian Urological Association recommends an annual digital rectal exam while on TRT. Other guidelines state annual examination is not necessary. TeleTest currently recommends annual DREs while on TRT based on Canadian Guideline recommendations, even though different practitioners may advise differently.
Is monitoring estrogen required while on TRT?
If men develop breast discomfort, or enlargement (i.e. gynecomastia) while on TRT therapy, it is reasonable to measure their estrogen level. Your provider may reduce your TRT dose to lower your estrogen levels if your testosterone levels are in the upper/normal range.
Should I have my Prolactin levels or TSH monitored while on TRT?
The Canadian Urological Association does not recommend routine monitoring of prolactin or TSH while on TRT. Prolactin may be ordered before the initiation of TRT to ensure no secondary causes of low testosterone exist (i.e. a prolactinoma or pituitary tumour).
What is the best time to monitor my levels on TRT injection therapy?
There is no universally agreed on time in between injections to monitor your total testosterone levels. Some doctors assess peak levels (18-36 hours after an injection), while others assess trough levels (the morning prior to the injection day) when your levels are lowest in their cycle.
Adverse events (i.e. high hematocrit, elevated estrogen levels) may be related to high peak levels and monitoring for peak levels might advise the physician to lower your overall dose if you have very high testosterone levels. If you have a history of high hematocrit or have breast discomfort, a doctor might order a peak level and then recommend reducing your testosterone dose if it is in the 'high-normal' range.
Measuring trough levels would be useful if are experiencing symptoms of a 'testosterone crash' related to low testosterone levels close to the end of your cycle. Having low levels might prompt your doctor to raise your TRT dose if your testosterone levels are in the 'normal range'.
What is the best time to monitor my levels on TRT topical (gel) therapy?
You can monitor your testosterone levels at any time in your cycle, provided you're consistently using your medication as directed.ex
What tests should my doctor order for routine monitoring?
Your doctor should order a fasting morning Total Testosterone, Complete Blood Count (Hematocrit), and Prostate Specific Antigen (PSA) 3 and 6 months after starting TRT. If your dose is not adjusted, your levels should be monitored annually.
Do I need liver enzyme testing while on TRT?
The Canadian Urological Association in their Testosterone Replacement Guidelines does not reference the need to monitor liver function on TRT.
Oral 17-alkylated testosterone (methyltestosterone) has been associated with liver toxicity but is no longer sold in Canada. If you are on oral 17-alkylated testosterone, please let your provider know. We understand many patients obtain their testosterone through non-traditional means and liver testing is warranted on methyltestosterone.
Oral Andriol (testosterone undecanoate) is not associated with any liver toxicity.
Testosterone Enanthate (Delatestryl) at high doses for prolonged duration has been associated with hepatic adenomas. However, hepatic adenomas do not cause abnormal liver function testing, unless the adenomas are very large.
Oral and injectable anabolic steroids carry significant liver risk and warrant regular liver function testing.
Why is PSA testing not free on TRT, when the Canadian Urological Association recommends monitoring with PSA testing?
OHIP rules only allow for insured (free) PSA testing if a man has an abnormal prostate examination, has prostate cancer and/or is receiving treatment. It is also insured (free) if a man has lower urinary tract symptoms (weak stream, getting up at nighttime to urinate, a feeling of incomplete urinary emptying).
Uninsured Testing
Why are there separate lab fees for some tests?
Doctors are permitted to order lab testing under OHIP insurance which is accepted as medically indicated. Most tests required for drug monitoring or based on symptoms are covered by OHIP insurance. Some tests are not covered, even if medically necessary for monitoring.
Examples
Total Testosterone is covered (OHIP insured) as guidelines recommend monitoring total testosterone levels to target TRT.
Free Testosterone is not covered (OHIP insured) as guidelines do not recommend monitoring free testosterone levels to target TRT.
Estradiol monitoring is not covered (OHIP insured) unless a man develops breast symptoms on TRT, as testosterone dosing is adjusted in response to breast symptoms on the basis of elevated estrogen levels in some men.
PSA Testing, although required for screening purposes, is not covered (OHIP insured) unless a man has urinary symptoms (i.e. weak urinary stream, a feeling of incomplete emptying, etc) on TRT.
Some of the tests that are marked as OHIP uninsured have been marked as insured by other doctors in the past. Why is that the case?
In the past, you may have had a doctor order what should have been an uninsured test (private-pay) as an insured test (paid by OHIP). Doctors are subject to auditing requirements under OHIP to ensure they are using OHIP resources judiciously.
Doctors who work with TeleTest cannot be compelled to order tests the same way as your previous physicians, as we would fail strict auditing requirements from the Ministry of Health and would no longer be able to provide care or screening testing.
We operate within a framework defined by OHIP, and these are not our rules. We hope you understand.
What are the approximate costs for some uninsured tests?
These are approximate costs for some uninsured tests, but are subject to change and vary between the independent laboratories. TeleTest does not control or influence fees charged by Life Labs, Dynacare or Alpha Labs.
Estradiol - $25
Free Testosterone - $25
Sex Hormone Binding Globulin - $30
Prostate Specific Antigen - $40
References
Pastuszak AW, Gittelman M, Tursi JP, Jaffe JS, Schofield D, Miner MM. Pharmacokinetics of testosterone therapies in relation to diurnal variation of serum testosterone levels as men age. Andrology. 2022 Feb;10(2):209-222. doi: 10.1111/andr.13108. Epub 2021 Oct 8. PMID: 34510812; PMCID: PMC9293229.
Grober ED, Krakowsky Y, Khera M, et al Canadian Urological Association guideline on testosterone deficiency in men: Evidence-based Q&A. Can Urol Assoc J 2021;15(5):E234-43. http://dx.doi.org/10.5489/cuaj.7252
Mulhall JP, Trost LW, Brannigan RE et al: Evaluation and management of testosterone deficiency: AUA guideline. J Urol 2018; 200: 423.
Grober ED, Krakowsky Y, Khera M, Holmes DT, Lee JC, Grantmyre JE, Patel P, Bebb RA, Fitzpatrick R, Campbell JD, Carrier S, Morgentaler A. Canadian Urological Association guideline on testosterone deficiency in men: Evidence-based Q&A. Can Urol Assoc J. 2021 May;15(5):E234-E243. doi: 10.5489/cuaj.7252. PMID: 33661092; PMCID: PMC8095276.
General Questions
How do I check my testosterone levels before starting steroids?
Our doctors order these tests for those already using steroids. We don’t adjust or advise on dosing but can help if you're using testosterone.
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