ORIGINAL RESEARCHTadalafil Is Efficacious and Well Tolerated in the Treatment of Erectile Dysfunction (ED) in Men over 65 Years of Age: Results from Multiple Observations in Men with ED in National Tadalafil Study in the United States
Introduction
Erectile dysfunction (ED), the persistent inability to achieve and/or maintain an erection adequate for satisfactory sexual activity, is increasingly frequent with advancing age. Age is the clinical variable most strongly correlated with ED. In the Massachusetts Male Aging Study, the probability of complete ED tripled (to 15%) and the probability of moderate ED doubled (to 34%) in men age 70 compared to men age 40 [1]. Only about one in three men aged 70 years reported no erectile difficulties [1].
An increasing likelihood of ED with aging has been observed in the Americas, Europe, the Middle East, Asia, and Australia [2, 3, 4]. Largely because of population aging in industrialized societies, the number of men with ED worldwide has been projected in one study to more than double (to 322 million) from 1995 to 2025 [5]. Approximately 800,000 people across the world reach the age of 65 each month [6].
In addition to advancing age, coronary heart disease, hypertension [7], diabetes mellitus [8], dyslipidemia [9], lower urinary tract symptoms [10], and depression [11] are increasingly common with advancing age and are associated with ED. Treatments for many chronic disorders can also contribute to ED [12], and iatrogenic ED may be particularly relevant in the assessment of elderly patients who are taking multiple medications.
The pathogenesis of ED with aging is multifactorial. However, based on experiments in aged organisms, an important hypothesis that has emerged to explain the development of ED in elderly men and other individuals is decreased nitric oxide (NO)—cyclic nucleotide signaling in the corpus cavernosum [13, 14, 15].
Oral inhibitors of phosphodiesterase type 5 (PDE5), which increase cyclic guanosine monophosphate levels and promote NO-mediated cavernous vascular smooth-muscle-cell relaxation in response to sexual stimulation, are considered first-line therapies for ED. In the integrated analysis of 11 randomized, placebo-controlled trials involving ED patients of varying ages, the selective PDE5 inhibitor tadalafil was effective, safe, and well tolerated [16, 17]. Tadalafil has demonstrated significant improvement in erectile function (EF) for up to 36 hours after dosing [18].
Sexual activity and intimacy remain important to many elderly men well beyond typical reproductive years [19, 20, 21]. Although some men and their partners accept a decline in sexual interest and activity with age [22, 23], large proportions of elderly men remain sexually active and are bothered by ED or report diminished sexual satisfaction, quality of partner relationships, or overall quality of life because of ED [2, 10, 20, 24, 25, 26, 27]. By one estimate [19], 33% of men aged >60 years have sexual activity once weekly.
Data on the efficacy and safety of oral PDE5 inhibitors in the treatment of ED in men aged ≥65 years are limited. In prior pooled subgroup analyses of randomized controlled trials, treatment with either sildenafil citrate 25–100 mg or vardenafil hydrochloride 5–20 mg taken as needed up to once daily for ≥12 weeks improved EF across a number of outcome measures compared with placebo [27, 28]. A total of 17% of men aged ≥65 who received sildenafil (pooled doses) reported headache (vs. 4% with placebo) and 13% flushing (vs. 0% with placebo), while 20% of patients aged ≥65 who received vardenafil 20 mg reported headache (vs. 3% with placebo) and 19% flushing (vs. 0% with placebo) [27, 28].
Section snippets
Aims
The objective of the Multiple Observations in Men with ED in National Tadalafil Study in the United States (MOMENTUS) was to assess the efficacy and tolerability of tadalafil 20 mg, taken as needed for 12 weeks, by various prospectively identified groups of men with comorbid conditions or risk factors for ED, such as diabetes mellitus, depression, spinal cord injury, and older age [29]. Secondary aims included determining changes from baseline in psychosocial outcomes of ED treatment, such as
Study Design and Subjects
This multicenter, open-label study evaluated the efficacy and tolerability of tadalafil 20 mg in various populations of patients with ED, as reported recently by Morgentaler et al. [29]. The following analyses focused on the efficacy and tolerability of tadalafil 20 mg, taken as needed, in men over the age of 65. Other prespecified groups in the MOMENTUS trial included patients of different ethnicities (Caucasian, Black American, Hispanic) or with comorbid conditions (diabetes mellitus,
Efficacy and Psychosocial Measures
The efficacy of tadalafil 20 mg in elderly men was evaluated using the International Index of Erectile Function (IIEF [30]), Sexual Encounter Profile (SEP) diary, and Global Assessment Questionnaire (GAQ). The IIEF was administered after the run-in phase (baseline) and at end point (12 weeks or early discontinuation). The patients completed SEP diaries after each attempt at sexual intercourse. The primary efficacy outcome variable was the mean change from baseline to end point in the EF domain
Statistical Analyses
The analyses of efficacy and psychosocial outcomes were conducted on an intent-to-treat basis; all patients with both baseline and at least one post-baseline observation were included. Responses to the IIEF, SEP, and PAIRS were treated as continuous variables, with summary statistics including the mean. For comparisons of continuous data, two-sided Student's t-tests were conducted to assess the significance of mean changes from baseline at α = 0.05. Responses to the GAQ among patients answering
Patient Characteristics
Patients ranged in age from 66 to 89 (mean = 71.6) years, and the vast majority (97%) had ED for >1 year at baseline (Table 1). Most patients (71%) had moderate or severe ED, and 93 (50%) had two or more comorbidities.
Patient Disposition
Of 188 patients aged >65 years, 166 (88.3%) completed the study. Reasons for discontinuation among these patients included adverse events in nine patients (4.8%), lack of efficacy in five (2.7%), personal conflict in five (2.7%), sponsor decision in two (1.1%), and loss to follow-up
Discussion
Treatment with tadalafil 20 mg demonstrated statistically significant and clinically relevant improvement in EF across a broad range of efficacy outcome measures and was well tolerated in elderly men with ED in the MOMENTUS trial. Following 12 weeks of tadalafil therapy, patients experienced significant improvements from baseline in (i) mean scores on the EF domain and all other IIEF domains and (ii) mean per-patient percentage of “yes” responses to all SEP questions. Significant improvements
Conclusion
Tadalafil 20 mg was an effective and well-tolerated treatment of ED in patients >65 years of age.
Acknowledgments
Assistance in manuscript preparation was provided by Stephen W. Gutkin, Rete Biomedical Communications Corp. (Ridgewood, NJ). The authors thank Adeline Ai Lin Yeo, MS, Lilly Research Laboratories, Eli Lilly and Company, for assistance with statistical analyses and Jeffrey R. Means, PhD, Lilly Research Laboratories, Eli Lilly and Company, for reviewing and commenting on the manuscript. Funding: This study and its report were funded by Lilly ICOS LLC (Indianapolis, IN, and Bothell, WA). The
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