In April 2015, the government introduced controversial changes to the PBS criteria for prescribing testosterone.1
Under the restrictions, men diagnosed as androgen deficient by a GP need the input of a specialist – an endocrinologist, urologist, or registered member of the Australasian Chapter of Sexual Health Medicine – before they can gain access to PBS subsidised treatment. This applies to newly identified and existing patients.
Under the new rules, the patient must either be referred for a specialist consultation, or the GP can seek an authority prescription from the Federal Department of Health after consulting with a specialist, which could be by phone, email or fax.
At the time of the changes, critics said this highlighted a misunderstanding of the GP’s role in the health system, where traditionally they were the first port of call for the diagnosis of and treatment for hypogonadism, a relatively straightforward condition that previously had not required the intervention of a specialist.1
Consistent with this, a survey of 250 GPs showed that three-quarters of them found this to be more inconvenient for their patients and an unnecessary burden on specialists.1 Other criticisms of the testosterone restrictions included the additional cost of the specialist consultation, and the costs of travel for those living in rural and remote areas.
In a survey of 208 men who are current or potential users of testosterone replacement therapy, cost and personal inconvenience associated with the new treatment protocols were important issues. Nearly half of these potential users decided not to receive treatment.1 The majority of GPs in the survey believe that these new rules have had a detrimental impact on patients with testosterone deficiency.1
The other major PBS change made last year was to lower the cutoff for testosterone levels for the purpose of subsidy in those men aged over 40 who do not have an established pituitary or testicular disorder. Now, these men must have a serum testosterone of less than 6 nmol/L, down from the 8 nmol/L limit established in 1999.1
Furthermore, there was no grandfather clause, so if a man previously had two serum testosterone levels below 8 nmol/L, but above 6 nmol/L, they no longer qualified for PBS subsidised testosterone.
“The government’s decision was tough”, said Dr Michael Lowy, Sexual Health Physician at Sydney Men’s Health and a Lecturer in Men’s Health at the University of Sydney, of last year’s threshold change.
“The rules about the level of testosterone that can be treated with a PBS authority were based on the evidence that most cases of low testosterone are due to other causes that are ‘potentially correctable’ such as obesity and diabetes”, he said.
“However the change last year from 8 to 6nmol/L excluded some men who were doing well on treatment and now lost the subsidy, and had to pay privately for the medication as their initial level was between 6 and 8,” Dr Lowy said.
“Assuming the chronic disease is maximally treated yet the level remains between 6 and 8 nmol/L, then there is a case for testosterone replacement therapy as no other action can be taken. But these men will have to pay privately for this medication.”
By way of comparison, in the United States, hypogonadism is diagnosed as a testosterone level below 6.9nmol/L.2 In some parts of the UK, reference levels as high as 8.7nmol/L and 10 nmol/L are used.1 The new Australian threshold is therefore one of the most conservative in the world.
Why the changes?
Over recent years, treatment with testosterone has increased due to greater awareness about the benefits of treatment, the launch of new and improved forms of therapy and growth in the patient population.
In October 2012, PBAC’s Drug Utilisation Sub-Committee (DUSC) – which monitors government spending on medicines – reported that the use of testosterone replacement had doubled in the preceding five years.3
In strict monetary terms over two decades, PBS expenditure on testosterone products had risen nine-fold to $12.7 million in 2010,4 and to $14.6 million in 2011.3 It now sits at around $15 million – in context, about 0.2% of total PBS spending.1
According to the DUSC report, GPs were initiating testosterone replacement therapy at an increasing rate, and the authors expressed concern at the number of patients between 40-79 years receiving therapy.3
“This large group of men may not have pathologically-based androgen deficiency”, the sub-committee stated.3
“The principles of cost-minimisation may not be realised and dose relativities may need to be reconsidered,” the report concluded.3
Despite the rise in testosterone prescribing, Andrology Australia believes hypogonadism remains an underdiagnosed and undertreated condition.5
The prescribing increase was steep because it came off a very low base, and new testosterone formulations were introduced along with greater awareness of the benefits of treatment and growth in the patient population.1
In Australia, it is estimated that only one in five affected men currently receive care. And using the Europe as a benchmark, there could be around 100,000 Australians who could benefit from treatment.1
Furthermore, at an International Expert Consensus Conference on testosterone deficiency last October, which brought together top medical minds from around the world, it was concluded there was “no T concentration threshold that reliably distinguishes those who will respond to treatment from those who will not.” 6
The interpretation of testosterone concentration can be confounded by a number of factors: inter-individual variation, variation in serum SHBG, and genetic variation in androgen sensitivity due to androgen receptor polymorphisms.
So given this wide variability of testosterone rates in men, a strict cut off may not be appropriate. Accurate assays are required and mass spectrometry is preferred, says the recent Endocrine Society of Australia position statement on male hypogonadism.7 The lower range of the reference interval is 10.4 nmol/L in healthy young men with proven normal testes, with it declining to 6.4 nmol/L in very healthy mean aged 70–89 years.7 Thus, there is a population of hypogonadal men who have testosterone levels over 6 nmol/L.
When it’s all boiled down, this is an important question – can some men with testosterone levels over 6 nmol/L have symptoms that are relieved by androgen therapy, and if so, should it be rebateable?
Or in other words, have the new restrictions gone too far?
In September this year, DUSC reviewed testosterone therapies again to assess the impact of the changes. The outcome is not yet available, but there is the possibility of some change for those clinicians and patients who believe the restrictions are too tight.
Hypogonadism management in general practice
“Hypogonadism refers to a disorder of the hypothalamic – pituitary – testicular (HPT) axis that results in the testes being unable to produce both physiological levels of testosterone (androgen deficiency) and adequate numbers of functional sperm for paternity (male infertility)”, says the Endocrine Society of Australia position statement.7
Most commonly, it is due to congenital or acquired testicular defects (primary testicular failure), such as Klinefelter syndrome. Less commonly, men may suffer hypogonadatropic hypogonadism due to abnormalities of the pituitary gland or hypothalamus.7
The diagnosis of androgen deficiency starts with careful clinical assessment. Testosterone deficiency can be flagged by a raft of symptoms: mood swings, reduced libido, tiredness and lethargy, sudden fat gain, sleep disturbance and muscle loss. Even a presentation with fracture may hint at low testosterone levels, which are associated with reduced bone mass.7
Gynaecomastia, hot flushes and loss of body hair, reduced sperm count and small (<5mL) or shrinking testes also suggest low testosterone.7,8
Physical examination includes height, weight, hair growth and distribution, and the size of the testes.7,8
If the findings on physical examination are consistent with androgen deficiency, the diagnosis can be confirmed with hormone assays. A fasting serum total testosterone (TT) level, taken between eight and 10 o’clock in the morning is the first step.
To ensure accuracy, where possible the test should be performed in a laboratory that offers mass spectrometry, and it should be noted that up to 30% of men of any age who have an isolated initial low serum testosterone will have a normal level on repeat testing.7
For confirmatory testing, a second total testosterone and luteinising hormone (LH), prolactin, and follicle stimulating hormone (FSH) levels should be measured. Measurement of sex hormone-binding globulin (SHBG) can also be informative.7
In the case of a testicular cause, testosterone will be low and gonadotropins will be elevated, whereas if the problem is pituitary in nature, gonadotropins tend to be low, or normal.
Under the current criteria, men with a testosterone level 6 nmol/L and over and normal LH don’t meet the PBS criteria for testosterone therapy.9 However, men whose TT levels are between 6 and 15 nmol/L but have a high LH, do meet the current PBS criteria, as do symptomatic men with TT levels less than 6 nmol/L as long as a specialist is involved.9
For patients with symptoms and signs suggestive of low testosterone levels, but who fail to meet the PBS criteria, a private script for testosterone can be issued (See pathway diagram above).
For men with hypogonadal hypogonadism, additional investigation is warranted to identify rare but treatable underlying disorder; these include thalassemia, haemochromatosis and pituitary adenoma.7
Hypogonadism is treated by administering testosterone in a formulation individualised to the patient. Testosterone therapy comes in various forms, including injectable, oral and transdermal preparations. One transdermal testosterone option is Testogel, this is administered once daily and achieves steady testosterone levels from the second day of treatment.11
Once a patient is on treatment, monitoring for efficacy and side-effects is essential.
The best indicator that testosterone has been adequately replaced is whether primary symptoms and signs are relieved.9
The government’s changes to subsidised testosterone replacement therapy last year have seen a reduction in the number of patients receiving treatment of about 50%.1
It has been estimated that 5,400 Australian men are now missing out on PBS-subsidised testosterone replacement therapy, when compared to the number receiving subsidised therapy before the changes.1
While testosterone deficiency was already under-diagnosed in Australia, this research shows it’s now harder than ever for patients to access treatment.1
In the survey of 250 GPs, respondents said one in 10 of their hypogonadal patients had complained they were deterred from testosterone therapy because of the cost of a specialist consultation, and a further one in twenty failed to start therapy because of the cost of a private script.1
Seventy-two per cent of the GPs reported the changes were distressing to patients no longer eligible for support, and 70% said this was an unnecessary burden for specialists.1
“This reduction in patients receiving subsidised treatment is adding to the impact of a condition that was already significantly under-diagnosed and under-treated,” the report concludes.
“A decreased quality of life, increased risk of osteoporosis and cardiovascular disease, and higher chance of rehospitalisation are some of the long-term effects of untreated hypogonadism in older, male Australians,” the authors said.
“This is likely to have a long-term impact on the broader health system in Australia as the knock-on effects of untreated hypogonadism result in adverse outcomes, such as increased hospitalisation of affected patients.”
1. The Burden of low testosterone on patients, healthcare professionals and government: an Australian perspective. A Frost and Sullivan White Paper 2016. 331 E. Evelyn Ave., Suite 100 Mountain View, CA 94041
2. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position Statement: Utility, limitations, and pitfalls in measuring testosterone: An Endocrine Society position statement. J Clin Endocrinol Metab 2007; 92:405-13
3. Drug utilisation sub-committee (DUSC). Testosterone: utilisation analysis. October 2012. Available at https://www.pbs.gov.au/industry/listing/participants/public-release-docs/testosterone/testosterone-dusc-prd-2012-10.docx.
4. Handelsman DJ. Pharmacoepidemiology of testosterone prescribing in Australia, 1992¬–2010. MJA 2012;196:642-45
5. Andrology Australia. Androgen deficiency: a guide to male hormones. 5th edition, December 2015. Available at https://www.andrologyaustralia.org/booklets/androgen-deficiency/
6. Morgentaler A, Zitzmann M, Traish AM et al. Fundamental concepts regarding testosterone deficiency and treatment: international expert consensus resolutions. Mayo Clin Proc 2016;91:881-9
7. Yeap BB. Grossmann M, McLachlan RI et al. Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy. MJA 2016; 205:173-8
8. Bhasin S, Cunningham GR, Hayes FJ et al. Testosterone therapy in men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 95:2536-59
9. Australian Government Department of Health Pharmaceutical Benefits Scheme. Available at http://pbs.gov.au/medicine/item/8830R
10. Yeap BB. Grossmann M, McLachlan RI et al. Endocrine Society of Australia position statement on male hypogonadism (part 2): treatment and therapeutic considerations. MJA 2016; 205:228-31
11. Product Information Testogel. Available at http://www.pbs.gov.au/medicine/item/10380H
Please review Product Information before prescribing. To have a copy of Product Information sent to you, telephone 1800 237 467.