Burden of Hypogonadism & Cost Savings with Testosterone Therapy
Men with hypogonadism (also known as testosterone deficiency and low testosterone) have increased risk of type 2 diabetes, obesity, heart disease and osteoporosis, and men with these conditions have the highest prevalence of hypogonadism. Once established, obesity, type 2 diabetes and heart disease create a metabolic and inflammatory state that further reduces testosterone levels and worsens the severity of hypogonadism and its comorbidities, creating a self-perpetuating vicious cycle.1,2 Accordingly, men with hypogonadism have a greater comorbidity burden than men without hypogonadism.3,4
Evidence shows that testosterone therapy significantly reduces suffering caused by hypogonadism symptoms, as well as the severity of its comorbidities, especially obesity, type 2 diabetes and osteoporosis.5,6 However, until recently, there was little evidence about the economic impact and potential cost savings of reducing the direct and indirect hypogonadism disease burden with testosterone therapy. Here we summarise the health burden caused by hypogonadism, its related comorbidities, and the patient benefits and cost savings of testosterone therapy.7
- A bidirectional link exists between hypogonadism, obesity, type 2 diabetes and heart disease, with each condition worsening the others, creating a vicious cycle.
- Hypogonadism and its related comorbidities obesity, type 2 diabetes and heart disease are associated with reduced quality of life and premature mortality.
- Testosterone therapy can help reduce waist size and body fat mass, and increase muscle mass, which in turn may prevent development of type 2 diabetes.
- Real-world evidence studies show that men with hypogonadism who receive continuous long-term treatment with testosterone undecanoate injections for 8-12 years without interruptions can reduce the incidence of heart attack, stroke and mortality, compared to men with hypogonadism who do not receive treatment with testosterone undecanoate injections.
- Significant and sustained improvement in patient-reported erectile function, urinary function, and aging male symptoms have been documented in patients with low testosterone who have received uninterrupted treatment with testosterone undecanoate injections.
- Medical care for men with untreated hypogonadism and its related diseases - particularly obesity, type 2 diabetes, heart disease and osteoporosis - imposes a significant economic burden on the healthcare system.
- Hypogonadism can be effectively treated with testosterone therapy, which by restoring testosterone levels reduces both hypogonadism symptoms and severity of comorbidities.
- Treating hypogonadism with testosterone undecanoate injection is a cost-effective way to reduce medical expenses related to obesity, type 2 diabetes, heart disease and/or osteoporosis.
Disease Burden of Hypogonadism
Hypogonadism is a common medical condition that negatively impacts men’s health in many ways. Men with hypogonadism suffer from bothersome symptoms and/or signs, including erectile dysfunction, lack of energy, depressed mood, reduced muscle mass and strength, weight gain (due to excess body fat) and increased waist size.8-10 Furthermore, hypogonadism significantly increases risk for development and progression of obesity, type 2 diabetes, heart disease, osteoporosis, as well as premature mortality.8,10-14
Hypogonadism and burdensome patient-reported symptoms
Men with low testosterone report significantly worse self-rated health, regardless of age, obesity, smoking or comorbidities, compared to men with higher testosterone levels.15 Low testosterone and erectile dysfunction are independently correlated with worse physical function, reduced vitality and impaired general health.16 For more information, see “What are the symptoms of hypogonadism?”
Hypogonadism increases incidence of type 2 diabetes, heart attack, stroke and mortality
It is well established that men with low testosterone have a significantly increased risk of type 2 diabetes, heart attack, atrial fibrillation, stroke and premature mortality. For more information about the health consequences of hypogonadism, see:
Hypogonadism markedly increases risk of type 2 diabetes and death
Low testosterone is associated with elevated cardiovascular disease biomarkers
Normalization of testosterone level is associated with reduced incidence of heart attack, stroke and mortality in men
Effective testosterone treatment reduces incidence of atrial fibrillation
Adverse health effects of testosterone deficiency in men
Testosterone, mortality and longevity
Testosterone and cardiovascular risk in men
Low testosterone is common in men with coronary heart disease and negatively impacts survival
The serious long-term health consequences of untreated hypogonadism have been demonstrated in several real-world evidence studies. In patient registries of men with hypogonadism who are followed for 8-12 years in clinical practice, men who do not receive testosterone therapy commonly experience significant weight gain and increased waist size, hyperglycemia, dyslipidemia, and markedly higher incidence of type 2 diabetes, heart attack, stroke and death.17-20
A growing number of large population studies show that men with low testosterone levels have significantly increased mortality rates compared to men with higher testosterone levels.21-29 For instance, one study found that during a 5-year follow-up period, men with low testosterone (n=4771) had a 2.6-fold increased incidence of all-cause mortality (17.8% vs 6.8%) than men with normal testosterone levels (n=13467).28 Importantly, the link between low testosterone and all-cause mortality persisted even after adjustment for age and co-morbidities.28 A recent report from one of the largest studies of endogenous testosterone and mortality, the UK Biobank prospective cohort study of 149 436 community-dwelling men aged 40-69 years old, showed that after a follow-up of 11 years, lower serum testosterone was independently associated with higher all-cause and cancer-related mortality in middle- aged and older men.29
Economic Burden of Hypogonadism on the Healthcare System
The disease burden of hypogonadism imposes a significant burden on healthcare system, as men with hypogonadism have significantly more physician visits, medical claims, and higher drug costs.3,30,31 A 2010 report from the population-based prospective German Study of Health in Pomerania (SHIP) examined the association of serum testosterone with health care utilization/costs among 2023 men aged 20-79 years at baseline. After a follow-up of 5 years, a significant association was found between low testosterone and increased outpatient visits and costs, independent of socioeconomic and lifestyle factors (p<0.05). Even after controlling for age, men with low testosterone levels had 29% more outpatient visits and 38% higher outpatient costs.30 Costs for comorbidities that are caused by or worsened by hypogonadism appear to be a major contributor to this overall burden.
In an analysis of a US insurance database (n=4269), men with hypogonadism, compared with controls, had higher baseline comorbidity rates, including hyperlipidemia (50.2% vs. 25.3%), hypertension (37.7% vs. 21.1%), back/neck pain (32.0% vs. 15.7%), and HIV/AIDS (7.1% vs. 0.3%) (all P<0.0001).3 Men with hypogonadism had higher direct ($10,914 vs. $3,823) and indirect costs ($3,204 vs. $1,450) for management of comorbidities. Hypogonadism-related direct costs were $832 (all P<0.0001). In this analysis, total comorbidity-related costs (comprising medical claim costs and prescription drug costs) were greater than hypogonadism-related costs, underscoring the importance of early identification, diagnosis and treatment of hypogonadism in order to prevent development, or worsening, of hypogonadism-related comorbidities.
Hypogonadism may also be associated with greater odds of postoperative medical complications, revisions, increased hospital length of stay, and cost of care following surgery.31 In a large US registry study of men undergoing total knee arthroplasty (n=8393), men with hypogonadism had significantly increased incidence and odds (9.45% vs 4.67%; OR 2.12) of developing 90-day medical complications (P<0.0001), greater incidence and odds (3.99% vs 2.80%; OR 1.89) of 2-year revisions (P < 0.0001), 6.11% longer in-hospital stay (3.47 vs 3.27 days, P = 0.02), and greater 90-day costs ($15,564.31 vs $14,856.69, P = 0.018) compared to controls.31
In the US alone, among men aged 45-74, over a 20-year period, hypogonadism has been projected to be involved in the development of approximately 1.3 million new cases of cardiovascular disease, 1.1 million new cases of type 2 diabetes, and over 600,000 osteoporosis-related fractures.32 Consequently, hypogonadism has been estimated to be directly responsible for approximately $190-$525 billion in inflation-adjusted U.S. health care expenditures.32 This suggests that timely diagnosis and treatment of hypogonadism represents an opportunity for a widespread public health initiative aimed at preventive care and medical cost savings.
Benefits of Testosterone Therapy
Testosterone therapy is an effective treatment for hypogonadism with a good safety profile, providing a wide range of health benefits. The aim of testosterone therapy is to increase testosterone levels to the point where symptomatic improvement or symptom resolution is achieved. This in turn is accompanied by improvement in risk factors for obesity, type 2 diabetes, heart disease and osteoporosis, such as reduced waist size and body fat, increased muscle mass and bone mineral density, reduced blood glucose levels and improved lipid profile.17-20,33-38 Emerging evidence suggests that testosterone therapy also improves markers of endothelial function39-41 and atherosclerosis (CIMT).41
Importantly, long-term real-world evidence studies show that treatment with testosterone undecanoate injection for 8-12 years significantly reduces risk for development of heart attack, stroke, prostate cancer and premature death, compared to men with hypogonadism who do not receive treatment with testosterone undecanoate injections.17-20
Medical cost savings with testosterone therapy
Cost-effectiveness analyses of testosterone therapy in men with hypogonadism have demonstrated that testosterone therapy, by reducing risk and severity of comorbidities, is a cost-effective and cost-saving intervention.42,43
One study evaluated health outcomes and costs associated with life-long testosterone therapy in men with hypogonadism.42 A Markov model was developed to assess cost-effectiveness of testosterone undecanoate injection treatment compared with no treatment, taking into consideration effect on risk of cardiovascular and cerebrovascular events, type 2 diabetes, bone fractures and depression. It was found that the healthcare cost savings of testosterone therapy, by reducing long-term complications of hypogonadism-related comorbidities, significantly outweigh its treatment costs and hence is a cost-effective treatment of hypogonadism.42
In another study, using a 10-year time horizon, a cost model was developed to estimate the economic benefits of treatment with testosterone undecanoate injections in men with hypogonadism and the major hypogonadism-related comorbidities type 2 diabetes, obesity, cardiovascular disease and osteoporosis, compared to no treatment.43 It was found that testosterone treatment resulted in cost savings of £3,045 per treated individual per year, versus no treatment (figure). For men treated with testosterone therapy, individual yearly costs of £324, £134, and £229 for testosterone treatment, administration and monitoring were outweighed by a £3,732 reduction in inpatient cost of managing comorbidities (type 2 diabetes, obesity, cardiovascular disease and osteoporosis). Of this, £823 (22%) was attributed to treating obesity, £967 (26%) to osteoporosis, £216 (6%) to type 2 diabetes and £1,727 (46%) to heart disease. This can be considered to be an underestimation of savings, as drug costs for treatment of comorbidities were not included in the analysis. This cost model demonstrates that reduction of comorbidity rates in patients treated with testosterone therapy versus no treatment results in significant cost savings.
Figure: Yearly cost of inpatient management of hypogonadism-related comorbidities in men treated or untreated with testosterone therapy.43
TTh = testosterone therapy
Cost of treating comorbidities = cost for provision of medical care for men with type 2 diabetes, obesity, cardiovascular disease and osteoporosis.
Figure adapted from Yeo S, Holl K, Peñaherrera N, Wissinger U, Anstee K, Wyn R. c. ClinicoEconomics and outcomes research: CEOR. 2021; 13:31-38.
Many men with hypogonadism suffer from low testosterone symptoms, but remain undiagnosed and untreated.44-47 Hypogonadism increases risk for development of obesity, type 2 diabetes and heart disease, and in men with these conditions, low testosterone causes further deterioration in health and increased mortality.17-20
According to forecasts, in upcoming decades every country in the world will experience a pronounced and historically unprecedented population aging. Over the past six decades, countries of the world had experienced only a slight increase in the number of people aged 60 years and older, from 8% to 10%. But in the next four decades, this age group is expected to rise to 22% of the total population, which is a jump from 800 million to 2 billion people.48 Since older people have greater healthcare needs than younger people, this trend alone will lead to increased medical costs and put burden on healthcare systems throughout the world.
Another global trend, that may become a greater threat for the healthcare system than the aging demography, is the rising prevalence of obesity and type 2 diabetes in all age groups.49-56 In the context of men’s health, this is particularly concerning, because obesity and abdominal obesity are stronger risk factors for hypogonadism than age per se.57-68 Among men, in 2018 the prevalence of obesity was 40.3% among those aged 20–39, 46.4% among those aged 40–59, and 42.2% among those aged≥60, which is a significant increase from previous years.52 As a consequence, the prevalence of hypogonadism is increasing in all age groups, in parallel with the growing obesity epidemic.69 For instance, the Coronary Artery Risk Development in Young Adults (CARDIA) study showed that increasing degree of obesity, particularly abdominal obesity, is associated with decreasing testosterone levels in young men aged 18-30 years.70,71
The global prevalence of type 2 diabetes is around 10%, affecting 1 in 10 adults.51 Nearly half a billion people are living with type 2 diabetes worldwide and the number is projected to increase by 25% in 2030 and 51% in 2045,51 in large part due to obesity.49 Obesity is also a key driver of the reversal of heart disease mortality decline, and the increase in heart disease mortality in younger age groups,56 which can be expected to negatively impact future disease burden and life expectancy trends.
In summary, untreated hypogonadism imposes a substantial public health and economic burden. The disease burden of untreated hypogonadism causes personal suffering and worsens the severity of comorbidities, in particular obesity, type 2 diabetes, heart disease and osteoporosis. Treatment for these conditions consumes a large portion of healthcare resources. Health economics and outcomes research has documented that testosterone undecanoate injection is a cost-effective treatment of hypogonadism. Besides treating hypogonadism and its burdensome symptoms, which provides intangible benefits for suffering men, treatment with testosterone undecanoate injection significantly reduces severity/complications and costs caused by highly prevalent comorbidities, resulting in a win-win for the individual patient and the healthcare system.