Practical aspects of testosterone therapy (TTh) in general practice

Description

Dr. David underscores the importance of general practice as a gateway to men’s health. General practice is by far the most common entrance point into the healthcare system for preventative health strategies and management of acute and chronic disease in men. There is a large disparity in primary care visits among the sexes; while women start using primary care services in their 20s, men commonly don’t start visiting primary care regularly until their mid-40s. Unsurprisingly, men receive delayed diagnoses and treatments compared to women, even for the same conditions, such as melanoma.

Treatment seeking for testosterone deficiency among men is often delayed. In a survey, 55% of all respondents waited between 3 and 24 months, with 35% waited for more than 2 years before seeking advice. Common reasons cited for delay in treatment seeking include:

  • I didn't think it was a serious problem
  • I thought it was just part of life
  • I assumed it had to do with my age
  • I was embarrassed
  • I didn't want to waste the doctor's time
  • I didn't think it could be treated
  • I was too busy/ didn't have time

Sexual health problems (erectile dysfunction and low libido) were the key drivers of treatment-seeking in the majority of men with testosterone deficiency, but for half of the men other symptoms, including tiredness, mood swings, irritability, lack of energy, body fat gain/redistribution, loss of muscle mass and weakness were also important reasons for seeking medical treatment.

HCPs need to be aware of all the conditions beyond sexual dysfunction that are associated with testosterone deficiency, such as obesity, metabolic syndrome, diabetes, reduced muscle mass, weakness, depression, anemia, fatigue, loss of energy and medication use (especially opioids).

In the UK, the National Institute for Health and Care Excellence (NICE) provides national guidance and advice to improve health and social care. Problem is, while all UK doctors are aware of the NICE guidelines, there are no NICE guidelines on hypogonadism and testosterone therapy. Other societies, such as the BSSM (British Society for Sexual Medicine) and AACE (American Association for Clinical Endocrinologists) have published great guidelines on hypogonadism and testosterone therapy; unfortunately, almost no physicians are aware of those.

To find out what is happening in the real world in general practice, Dr David conducted the REVITALISE audit, which assessed the prevalence of men with type 2 diabetes and erectile dysfunction, or who were potentially at risk of erectile dysfunction and/or testosterone deficiency across 13 practices in the UK. It also investigated how often erectile dysfunction and testosterone deficiency were discussed, and how many men with diagnosed hypogonadism were actually receiving testosterone therapy. 43,633 men were reviewed; the prevalence of type 2 diabetes was 7.3%. Nearly 40% of men with type 2 diabetes had testosterone levels <12 nmol/L. However, one third of men were not asked about erectile dysfunction or other sexual problems. Over two-thirds of men with type 2 diabetes and erectile dysfunction had not had a testosterone blood test within the past 2 years. Among those who have had their testosterone level checked and found to have testosterone levels < 12 nmol/L, 73% were not receiving testosterone therapy. A similar situation prevailed among men with erectile dysfunction but without type 2 diabetes; 60% had not had a testosterone blood test within the past 2 years. Among those who have had their testosterone level checked and found to have testosterone levels < 12 nmol/L, 93% were not receiving testosterone therapy. Among men with hypogonadism but without erectile dysfunction and without type 2 diabetes, 57% were not receiving testosterone therapy.

The REVITALISE audit concluded:

  • Men who had been diagnosed with ED and/or low testosterone were often not receiving the necessary screening and/or treatment in line with current evidence-based guidelines.
  • A proactive approach to screening and management of erectile dysfunction and low testosterone is needed.
  • Primary care providers should be aware of the common cluster of type 2 diabetes, erectile dysfunction and low testosterone, and a diagnosis of one of these conditions should prompt inquiry about the others.

Who should be initiating & monitoring patients?

The ISSM (International Society for Sexual Medicine) has pointed out that the great majority of men with testosterone deficiency can be effectively assessed and managed by the generalist.

The BSSM guidelines recommend the following prior to initiating testosterone therapy:

  • Confirm Diagnosis
    • Signs/Symptoms & Biochemical Evidence
    • Physical Examination
  • Consider Etiology
    • Primary or Secondary (Check LH/FSH)
    • Reversible (Opioids, Glucocorticoids, Anti-Psychotics)
  • Consider Contraindications & Cautions
    • Prostate cancer, Abnormal DRE, Breast Cancer
    • Fertility requirement, Hematocrit <54%

BSSM recommendations for follow-up:

Assess the response to therapy at 3, 6, and 12 months and every 12 months thereafter.

Aim for a target total testosterone level of 15-30 nmol/L to achieve optimal response.

Monitor hematocrit before treatment, at 3-6 months, 12 months, and every 12 month thereafter; decrease dosage, or switch preparation if hematocrit is >0.54; if hematocrit remains high, consider stopping and reintroduce at lower dose.

Assess prostate health by PSA assessment and DRE before commencing testosterone therapy followed by PSA at 3-6 month, 12 month, and every 12 month thereafter.

Assess cardiovascular risk before testosterone replacement therapy is initiated and monitor cardiovascular risk factors throughout therapy.

Assess cardiovascular risk before testosterone therapy is initiated and monitor cardiovascular risk factors throughout therapy.

How long should testosterone therapy be given?

Hypogonadism is a chronic disease which requires long-term treatment, like diabetes. It is important to realise that testosterone therapy is considered lifelong therapy. In patients who have a positive response to testosterone therapy, treatment should continue in accordance with a standardised monitoring plan.

Compliance to testosterone therapy is crucial for achievements of health benefits. Discontinuation rates are higher among hypogonadal men treated with testosterone gels, and to a lesser degree, short-acting injections. Patient education about time to onset of symptom improvement is key for adherence to testosterone therapy. Patients need to be aware of the time-dependent and symptom-specific onset of effects of testosterone therapy:

Effects on sexual interest appear after 3 weeks plateauing at 6 weeks, with no further increments expected beyond. Changes in erections/ejaculations may require up to 6 months. Effects on quality of life manifest within 3–4 weeks, but maximum benefits take longer. Effects on depressive mood become detectable after 3–6 weeks with a maximum after 18–30 weeks. Effects on erythropoiesis are evident at 3 months, peaking at 9–12 months. Prostate-specific antigen and volume rise, marginally, plateauing at 12 months; further increase should be related to aging rather than therapy. Effects on lipids appear after 4 weeks, maximal after 6–12 months. Insulin sensitivity may improve within few days, but effects on glycemic control become evident only after 3–12 months. Changes in fat mass, lean body mass, and muscle strength occur within 12–16 weeks, stabilize at 6–12 months, but can continue to improve marginally over years. Effects on inflammation occur within 3–12 weeks. Effects on bone are detectable already after 6 months while continuing at least for 3 years.

In conclusion:

  • Doctors need to be made aware of medical societies catering to men’s health, and their guidelines.
  • Several patient populations are at high risk of hypogonadism, especially men with obesity, elevated waist circumference, metabolic syndrome, type 2 diabetes, and those taking opioid medications. In these men, screening for hypogonadism by checking their blood levels of testosterone should be mandatory.
  • Because of wide laboratory reference ranges, the diagnosis of hypogonadism should be based on action limits, such as 12 nmol/L rather than laboratory defined numeric values of what constitutes “low” testosterone.
  • Patients need to be made aware of the critical importance of compliance to testosterone therapy and requirement for long-term treatment in order to achieve maximal benefits, some of which (e.g. increased bone mineral density and improved body composition) take several years to manifest.

Physicians may only get one chance to positively impact the health of any given male patient – don’t waste that opportunity!

 


 

Speakers

Dr Janine David, MB BCh DRCOG DFFP MRCGP FECSM

Dr Janine David,
MB BCh DRCOG DFFP MRCGP FECSM
Portway Surgery, Porthcawl,
Wales