Effects of Testosterone Treatment, With and Without Exercise Training, on Ambulatory Blood Pressure in Middle-Aged and Older Men

Lauren C. Chasland; Daniel J. Green; Markus P. Schlaich; Andrew J. Maiorana; Brian R. Cooke; Kay L. Cox; Louise H. Naylor; Bu B. Yeap

Disclosures

Clin Endocrinol. 2021;95(1):176-186. 

In This Article

Abstract and Introduction

Abstract

Context: With age, testosterone (T) and physical activity levels often decline in parallel. The effect of combining T treatment and exercise training on ambulatory blood pressure (ABP) is unclear.

Objective: To assess T and exercise effects, alone and in combination, on ABP in men aged 50–70 years, waist circumference ≥ 95 cm and low-normal serum T (6–14 nmol/L), without organic hypogonadism.

Design: A 2 × 2 factorial randomised, placebo-controlled study.

Intervention: Randomization to daily transdermal AndroForte5® (Testosterone 5.0%w/v, 100 mg in 2 ml) cream (T), or matching placebo (P) (double-blind), and to supervised exercise (Ex) or no additional exercise (NEx), for 12 weeks.

Results: Average 24-h systolic blood pressure (SBP) increased with T treatment (testosterone*time, p = .035). Average 24-h SBP increased in T+Ex (T+Ex:+3.0 vs. P+NEx: −3.0 mmHg, p = .026) driven by day-time changes (T+Ex:+3.5 vs. P+NEx: −3.0 mmHg, p = .026). There was an effect of T for 24-h average diastolic blood pressure (DBP, testosterone*time, p = .044) driven by the decrease in P+Ex (P+Ex: −3.9 vs. T+NEx: −0.5 mmHg, p = .015). Night-time DBP was lower with exercise (P+Ex: −4.0 vs. P+NEx: +0.7 mmHg, p = .032). The effect of exercise to lower night-time DBP was not apparent in the presence of T (T+Ex: −0.4 vs. P+NEx: +0.7 mmHg, p > .05). Ex increased average 24-h pulse pressure (PP, exercise*time, p = .022), largely during daytime hours (exercise*time, p = .013).

Conclusions: There was a main effect of T to increase 24-h SBP, primarily seen when T was combined with Ex. Exercise alone decreased 24-h and night-time DBP; an effect attenuated by T. BP should be carefully assessed and monitored, when prescribing T treatment to middle-aged and older men, especially when combined with exercise training.

Introduction

High blood pressure (BP) is an important and modifiable risk factor for cardiovascular mortality.[1] The prevalence of hypertension increases with age and is forecast to affect more than 1.5 billion people by 2025.[1,2] Physical activity levels decrease with age, predisposing individuals to frailty and loss of independence.[3] Regular exercise is therefore strongly endorsed by peak bodies to improve fitness and BP while reducing all-cause mortality.[4–6]

In older men, the combination of low physical activity and low testosterone (T) levels has been associated with a higher risk of cardiovascular death.[7] Prescriptions of T have increased substantially in the past two decades,[8] driven by the notion that age-related decline in T concentration should be ameliorated. This has occurred despite ongoing controversy regarding the safety of T treatment in men without disorders of the hypothalamic-pituitary-testicular axis.[9] To date, no study has been adequately powered to assess the effect of T treatment on incident cardiovascular (CV) events. It is therefore relevant to assess the effect of T treatment on major preventable risk factors for CV disease, including BP.

The effect of exercise to lower BP is well-established,[10,11] whether using single occasion assessment of BP ('office BP') or 24-hour ambulatory blood pressure (ABP), a measure with higher prognostic accuracy.[12] However, the association of circulating T with BP is less clear. Cross-sectional and observational studies have reported inverse associations between T concentrations and office BP,[13,14] while others have reported no association.[15,16] Results from interventional studies of T treatment are also heterogeneous, demonstrating both improvements in systolic BP (SBP), diastolic BP (DBP) and resting heart rate (HR),[17,18] as well as no change in these parameters.[19] However, these studies have often been limited by use of office BP readings and variability in the characteristics of men studied and doses of T employed.

No study, to our knowledge, has assessed the effect of combining T treatment and exercise training on ABP in middle- to older-aged men. Therefore, we tested the hypothesis that the combination of T treatment and supervised exercise training would confer additive benefits to improve BP, assessed using 24-h ABP, in middle-to-older aged men with low-normal baseline T concentrations. This was not a study of T replacement in hypogonadal men, but a study of T as a pharmacological intervention in conjunction with exercise training. We used a 2 × 2 factorial analysis to examine additive versus attenuation effects between our interventions. We also compared the results obtained using ABP with office BP.

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