Roll up Roll up! Welcome one and all. Do YOU want increased muscle mass, sharper memory, better concentration, much stronger libido, harder erections? Do you want to stop ageing, have more energy, cure depression, and also solve world hunger? Then Testosterone therapy could be for you!
Or is it?
We commonly see testosterone discussed in the media and a good example of this is a recent article by the ABC in 2013 on the use of testosterone as an anti-ageing hormone – Link
Testosterone replacement use has significantly “bulked up” in America over the last 20 years but also in Australia testosterone prescribing rates have doubled between 1992 and 2010 (Anzac Research Institute).
I get asked every few weeks by gentlemen patients about testosterone replacement. So what do I say? Well to be honest I generally have told patients that we can test their testosterone levels but they do not necessarily correlate to certain symptoms. I generally talk down the concept and, subsequently, have not done many testosterone levels.
But this is based on second hand information from other doctors and from medical school. What should I be doing though? What is the evidence?
Here’s what you need to know –
Question 1: What does testosterone do in the normal male body?
A great refresher summary of Testosterone’s role in male physiology is available on a Medscape article on testosterone therapy found here.
As a very quick summary, testosterone is a cholesterol based hormone produced in the Leydig cells of the male testes. Production is triggered by GNRH leading to LH surge and then production of testosterone. This is controlled by a HPA feedback loop.
At puberty, testosterone exerts effects over secondary sexual characteristics leading to an adult male. Once physical maturity has been achieved, testosterone has a more homeostatic function. It sustains spermatogenesis, maintains muscle bulk, maintains secondary sex characteristics, and aids in erectile function.
Question 2: What are normal testosterone levels doing as we age? How common is testosterone deficiency?
In the normal healthy male, testosterone levels will drop approximately 1% per year after age 30. The Endocrine Society of Australia suggests low levels of testosterone is a condition that affects 1 in 200 men.
Question 3: Who do I suspect may have low levels of testosterone?
Some specific patients are at significantly higher risk of clinical testosterone deficiency. These occur in approximately 1 in 200 men (Link).
Certain high risk groups include: Klinefelter’s syndrome, chemo/radiotherapy patients, alcoholics, hypothalamic or pituitary lesion issues, and patients with anosmia (from Kallman’s syndrome).
Presenting symptoms in the general population are often non-specific and often overlap with normal ageing. Reduced energy, depressed mood, poor concentration and memory, sleep disturbance, increased body fat, and diminished physical and work capacity (which includes the majority of my male patients from time to time!)
Question 4: Are there any specific symptoms or signs I should check for to increase my suspicion?
Certain clinical symptoms and signs do suggest a more significant testosterone deficiency. Incomplete sexual development, reduced libido/sexual activity, decreased spontaneous erections, breast discomfort/gynaecomastia, loss of body hair, small or shrinking testes (tested with an orchidometer), infertility, height loss (low bone mineral density), reduced muscle bulk and strength, and hot flushes/sweats.
An AFP article in 2009 goes through this in good detail – Link.
Question 5: Are there any negative outcomes if I don’t diagnose it?
Yes. Obviously if you miss it in children it can lead to delayed or failed puberty with its significant connotations. Long term untreated hypogonadism can also cause quite severe osteoporosis and early fracture. (J Adv Pharm Technol Res. 2010 Link). There is also conjecture in the literature about cardiovascular risk of hypogonadism. Data is conflicting but suggests there is a worsening metabolic profile with hypogonadism (hypertension, hypercholesterolaemia, T2DM, and obesity – J Clin Lipidol. 2008 – Link). Because of this, it is suggested there is also worse cardiovascular outcomes but research is ongoing – (Eur J Endocrinol. 2011 – Link).
Question 6: So how do I work out whether my patient has low testosterone levels?
The Endocrine Society of Australia in their latest consensus document in 2000 recommended:
To help with the diagnosis there is a “Androgen Deficiency in the Ageing Male” (ADAM) questionnaire which identifies patients who may be at risk. Feel free to have a look at the link but I think it would include a large group of males which you would likely have thought of anyway – Link.
Here is a great table from MJA which explains interpreting different LH/FSH/Testosterone levels and their use in indentifying the cause or pathology – Link
95% of testosterone is bound to both SHBG and albumin. Different levels of these binding proteins will lead to different levels of circulating testosterone. Testosterone levels also alter with time – being highest in the mornings and lowest at night. Because of this, blood should be drawn between 0800 and 1000.
There are problems with interpreting the result. Direct measurement of free testosterone, which gives the most accurate value, is a difficult test which requires significant validation. Because of this, it is often poorly correlated between different laboratories.
Alternatively, indirect measurements of free testosterone such as FAI correspond poorly with the more accurate direct measurement. Subsequently there is ongoing debate over the best way to test physiologically active free testosterone.
Testosterone levels are reduced in several disorders eg. chronic renal, liver, cardiac, or respiratory disease. Certain drugs will also reduce testosterone levels including: opiates, thiazides, psychotropic agents, amiodarone etc. treating the cause of these May be a better approach than replacing testosterone.
There are several other tests that you should consider doing as well as a testosterone level. You can consider Fe levels (haemochromatosis), genetic testing (klinefelters) and even possibly a CT of the pituitary (pituitary adenomas or empty sella).
Question 7: So who SHOULD I treat?
Firstly, remember if you start testosterone replacement therapy it is likely to be lifelong! This is a big step so think it through and make this clear in your discussion with your patient.
Secondly, testosterone therapy has been known to cause a significant placebo affect when first used, which unfortunately wanes over time and this can lead to dissatisfaction with diagnosis and treatment (MJA – Link)
When assessing whether a patient needs testosterone replacement, actual deficient levels have been controversial! – Link. Testosterone levels at individual labs can also vary so check with your local “normal” ranges.
As a general guide from the MJA article:
Testosterone <8nM = deficiency
Testosterone 8-15nM and LH high (1.5 times normal) = deficiency
Anything 8-15+nM with LH normal is NOT classed as androgen deficient for replacement (may be low/normal but no evidence of treatment benefit).
The American Association of Endocrinology in their last guidelines suggested the primary aims of treating lowered testosterone is to:
Restore sexual function and behaviour, ensure virilisation and restore fertility, optimise bone density, normalise growth hormone levels, and alter cardiovascular profile.
Firstly, there are alot of advertisements for different alternative therapies for replacing testosterone. These are generally not regulated and are not to be advised (eTG).
Secondly, if you are giving replacement to adolescents or to the elderly (for which you should have a strong indication), you should start at half the dose and titrate up over several weeks (eTG)
Thirdly, in men over 50 consider prostate disease before starting testosterone therapy. The Australian Society of Endocrinology states that previous or current prostate cancer or breast cancer are absolute contraindications to androgen therapy.
The options for treating are varied and will depend on patient preference and availability. I will not give brands here – consult your local pharmacy for available products and dosing.
1. Testosterone gels applied daily onto the skin
2. IM injections lasting anywhere from 2 weeks to 6 months
3. Testosterone patches daily
4. Testosterone orally.
Long term options include a testosterone implant that lasts 4-6 mths
Symptoms of low testosterone should begin to improve by 1-2 months. If no significant improvement sometimes retesting levels of testosterone can help titrate the dosing.
Question 9: Are there any absolute contraindications to treatment?
As stated prior, breast cancer or prostate cancer are absolute contraindications.
Precautions include lower starting doses may be required for older men and induction of puberty, avoiding parenteral administration for men with bleeding disorders, warning competitive athletes about risks of disqualification, and androgen-sensitive epilepsy, migraine, sleep apnea, polycythemia or fluid overload.
Question 10: Are there any NEGATIVES to treatment?
This is an area of increasing research. Recent studies have suggested increased cardiovascular risks, enlarged prostate growth, suppression of spermatogenesis, acne, weight gain, gynaecomastia, male-pattern hair loss, changes in mood, sleep apnoea, migraines, and polycythaemia! – (Andrology Australia Article 2014 – Link)
Erectile dysfunction – “Normal adult testosterone levels are NOT required for normal erections and decreased levels at older ages is thought NOT to be low enough to induce ED”
A great discussion on the possible patients where their ED may be affected by testosterone levels is in Urology 2000 – Link
The article concludes that a normal decline in testosterone levels in men is normal as we age but ED and low levels of testosterone may not be causally related. Low levels of testosterone is the most common ENDOCRINE cause of ED but endocrine causes are the LEAST common cause. Normal adult testosterone levels are NOT required for normal erections and decreased levels at older ages is thought NOT to be low enough to induce ED. If hypogonadism (low testosterone) is confirmed and the patient has ED and other causes have been excluded then treatment with exogenous androgens can be considered weighing up possible adverse effects.
DESPITE THIS the Endocrine Society of Australia (Consensus 2000) recommends that all patients with ED are tested for testosterone deficiency – Link
So when my next 53yo M comes into my room asking whether he could be testosterone deficient and if he should go on testosterone replacement therapy there are a few things I think I will do. Firstly, I want to find out what his main symptoms are and what his specific reason for coming in today is. I will try and clarify what he knows about testosterone replacement therapy and where he gained this information. Then, I will take a full history addressing the wide possible other differential reasons for his main symptoms.
I will gently ask about sexual function as this may be the real reason he has presented but patients often do not want to tell us! I will enquire as to any red flag symptoms and address his other general health features (e.g. alcohol consumption, smoking etc). If, in spite of all this, he would still like his testosterone checked and I have not found any other reason for his symptoms then I will discuss with him what the testing involves (two separate days morning blood tests) and also explain that the treatment, if he is truly deficient, will likely be life long and may not settle all his aches and pains. I will then organise the testing (probably with some other general blood tests depending on history eg. TSH, Iron studies etc.)
If he returns with a low reading as per the local laboratory on the two mornings then I will start him on a replacement based on the therapy of his choice. I will then repeat his testosterone levels in 6 weeks to see if their has been improvement. I will then ask him, if his testosterone levels are normalised, whether it has solved any of his symptoms which we attributed to testosterone deficiency, and if not, readdress his health and keep looking. Whether or not he stays on therapy then will be on a decision between the two of us.
Finally, will I be bringing up testosterone deficiency and routinely screening my patients for it. No. I don’t think the evidence is strong enough of significant benefits and I think the harms are still being investigated. It is likely I will only discuss this with the high risk groups (as above) or if a patient specifically asks me. I currently remain unconvinced.
Patient information sheets: Better Health Channel has a good patient information handout – Link
Disclaimer: All information given on this website is for educational purposes and written by a GP. All clinical decisions should be done on a patient by patient basis. Every effort is made to give correct and up to date information however all information used from this page should be correlated with expert sources or the links to which the information has originated from.