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Keywords:

  • sexual assessment monitor;
  • premature ejaculation;
  • PE diagnosis;
  • PE diagnostic device

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Associate Editor

Michael G. Wyllie

Editorial Board

Ian Eardley, UK

Jean Fourcroy, USA

Sidney Glina, Brazil

Julia Heiman, USA

Chris McMahon, Australia

Bob Millar, UK

Alvaro Morales, Canada

Michael Perelman, USA

Marcel Waldinger, Netherlands

OBJECTIVE

To validate the Sexual Assessment Monitor (SAM), a novel apparatus designed to collect electronic data on ejaculatory latency time (ELT) for diagnosing premature ejaculation (PE), and for accurately measuring treatment outcomes in clinical trials.

PATIENTS, SUBJECTS AND METHODS

Men with PE, and healthy volunteers aged 18–75 years, were enrolled in three open-label studies, conducted in the UK. The SAM, which consists of a control box with two front attachments, a vibrator and sensor, was attached to the penis. The vibrator, which provides stimulation, was positioned at the frenulum using a soft cuff; the vibrator intensity was set at 80 units for most subjects. The sensor is an indium-gallium elasticated loop, which was positioned around the base of the penis to detect ejaculatory pulses. These pulses were transmitted to a data recorder in the control box. The data, which are displayed graphically as traces, were automatically classified by a computer-generated algorithm to quantify ELT.

RESULTS

In all, 53 healthy volunteers and 58 men with PE provided 213 and 195 evaluable records, respectively. Most were complete records (99% and 96%). The pooled data showed that the ELT was much higher for healthy volunteers than for men with PE (geometric means: 687 vs 169 s, respectively), with a healthy volunteer to PE patient ratio of 2.87 (P < 0.001). Only 6.3% of subjects reported mild adverse events, which were unrelated to the SAM.

CONCLUSIONS

These open-label studies show that the SAM can consistently and safely measure times to erection (from the start of vibration) and ejaculation, and ELT in healthy volunteers and men with PE. These findings show that the SAM has the potential to become the ‘gold standard’ in the diagnosis of PE and in clinical trials design.


Abbreviations
PE

premature ejaculation

(I)ELT

(intravaginal) ejaculatory latency time

DSM-IV

Diagnostic and Statistical Manual of Mental Disorders, 4th edition

SAM

Sexual Assessment Monitor

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Premature ejaculation (PE) is the most common sexual problem in men, with estimates giving a prevalence of 25–40%[1–7]. However, PE is extremely difficult to define and diagnose. A search of the literature from 1996 to 2004 showed that PE has no universally agreed definition or diagnostic criteria, and that many definitions and diagnoses are partial, subjective or not specific [8].

Traditionally, the most commonly used diagnosis of PE is that provided by the ‘Diagnostic and Statistical Manual of Mental Disorders, 4th edition’ (DSM-IV) [9], which defines PE as ‘persistent or recurrent onset of orgasm and ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it’. The condition should also cause marked distress or interpersonal difficulty.

In clinical trials the primary measure of PE is the ejaculatory latency time (ELT) or intravaginal ELT (IELT), which is used as part of a PE diagnosis and to assess the clinical efficacy of treatments. The normal duration of IELT is 2–7 min, and men with PE have an IELT of <2 min [10]. However, there is no published guidance about the duration of ELT in normal, healthy controls. It was proposed that a more comprehensive definition of PE should be adopted, taking into account ELT, male and female satisfaction, psychological and pathological factors [8]. However, improvements in the accuracy and reproducibility of these assessments are needed.

Currently, the most common measure of IELT is a ‘stopwatch’, which can lead to poor consistency across trials. The need for an easy-to-use, validated diagnostic device that can accurately monitor both IELT and ELT has been paramount. This key reason led to the development of the PE diagnostic device known as the ‘Sexual Assessment Monitor’ (SAM). The original device was developed as a result of discussions with Dr Mike O’Leary and Harvard University, and forms the basis of a USA Patent, number 6814695.

The SAM is a portable device comprising a control box and two attachments to the patient, a vibrator and sensor, which are attached to the penis. The vibrator provides non-manual stimulation and the sensor measures the time to erection and ejaculation. The ELT is electronically quantified via a computer-generated algorithm. With the development of the SAM, future clinical trials can be designed to incorporate objective measurements of ELT. It is envisaged that the device will become the ‘gold standard’ for the diagnosis and treatment of PE.

The aim of the present studies was to determine ELT in healthy volunteers and in men with PE, using the SAM. Data are taken from two open pilot studies and one multicentre, open-label, parallel-group study [11].

PATIENTS, SUBJECTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Three clinical studies were conducted: Study 302 was an open pilot study using healthy volunteers; Study 303 was an open pilot study which recruited men with PE; and Study 001 was a phase I, multicentre, open-label, parallel-group study in healthy volunteers and men with PE. The objective of these studies was to determine mean and individual times to erection and ejaculation, and ELT, using the SAM; data from these studies were pooled.

The three studies recruited healthy volunteers and men with PE from centres across the UK. For inclusion in the studies, men were aged 18–75 years inclusive, weighing ≥ 60 kg and with a body mass index of 18–28 kg/m2. There were no exclusion criteria for penile length or girth, as the device will fit all penises that do not show clinical abnormality. All subjects had to abstain from alcohol and participation in sexual activity leading to ejaculation for 24 h before each study day. Men with PE had a reported history of primary PE for ≥ 6 months and, for inclusion in Study 001, men with PE also fulfilled the DSM-IV criteria for PE. All subjects provided written, informed consent to participate.

Subjects were excluded if they had a history of clinically significant allergies, especially contact dermatitis, and if any significant abnormality was found at physical examination. Men were also excluded if they had received or were receiving treatment in the last 6 months for depression, psychiatric disorders, mood disorders, schizophrenia, substance abuse or anxiety disorders, or if they had received any investigational drug within 3 months before the first study day. Men with a history of erectile dysfunction or alcohol or drug abuse were also excluded. Men with PE with a previous history of surgery on their reproductive organs, other than vasectomy or circumcision, and those who were continuing to receive any PE treatment in the 4 weeks before study start were excluded.

The SAM is a diagnostic apparatus that electronically monitors and quantifies ELT (Fig. 1) in a clinical or ‘at home’ setting; it consists of a control box attached to a laptop computer, and two front attachments; a vibrator and sensor. The vibrator is 4 cm long and consists of an encapsulated low-powered electric motor that provides a constant or variable frequency of vibration, and is positioned at the frenulum using a cuff made of soft and extendible material. The optimum positioning of the vibrator and cuff were determined in previous pilot experiments. The sensor is an indium-gallium elasticated loop, which is positioned around the base of the penis to detect ejaculatory pulses as they travel through the penis (Fig. 2). These pulses are transmitted to a data recorder in the control box. The data, which are displayed graphically (as a trace), are automatically classified by a computer-generated algorithm to identify the times to erection and ejaculation, and hence ELT. The data can be downloaded to the computer for review and storage.

image

Figure 1. Illustration of the SAM.

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image

Figure 2. Positioning of the SAM on the penis.

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Subjects attended the study centre for screening, during which baseline characteristics and physical examinations were recorded. Subjects then attended at least two test procedures, on separate study days. The first study day was conducted within 10 days of screening. Each study day was separated by at least 24 h (Study 302) or 48 h (Studies 303 and 001), and each study day was to consist of ≈ 2 h in the clinic. A follow-up visit or interview was conducted at 5–7 days after the last study day. The maximum study duration was 6 weeks (Study 001).

On each study day, the SAM was attached to the penis (as described above). Subjects remained supine for the duration of the test. The position of the vibrator and sensor were checked. The control box was switched to record, and the vibration frequency set. The vibrator intensity was set at 80 units (equivalent to 60 Hz) for all subjects, except one in Study 302 where it was set at 60 units. The vibrator intensity was chosen from pilot experiments and is considered to be a supra-maximal stimulus. Visual sexual stimulation, in the form of a video, and vibratory stimulation were started at the same time. The subject was instructed not to do anything to enhance erection before being left until they called the staff once ejaculation was completed. The assessment of times to erection (from vibration start) and ejaculation, and ELT are shown in Fig. 3.

image

Figure 3. The overall design of the studies.

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The safety of the device was assessed by recording adverse events up to 7 days after the last study visit, by measurement of vital signs, and by physical examination.

The ELT was confirmed by independent assessors, and complete records (i.e. those with erection and ejaculation profiles present), and those with either erection or ejaculation profile were included in the analyses. As erection occurs over time rather than at a defined moment, a subject-recorded time of erection that lay within 60 s of the time recorded by the device was used for the analysis. All times are presented in seconds, and data are presented as descriptive statistics (geometric means are calculated, as the measurements of ELT were highly skewed), which are presented for each study and as a pooled overall mean. Adjusted geometric means for each group and ratios of geometric means (and 95% CI) between each group are also calculated from a linear model of the logarithm of ELT accounting for the effects of individual studies.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

The baseline characteristics are summarized in Table 1. Overall, there were 53 healthy volunteers (six in Study 302, and 47 in Study 001) and 58 men with PE (22 in Study 303 and 36 in Study 001). The demographics were similar for all three studies, although men with PE had a higher incidence of genitourinary abnormalities (5.2%, three of 57) than the healthy volunteers (1.9%, one of 53), which included varicoceles and hernia, testicular atrophy, and an epididymal cyst.

Table 1.  Baseline characteristics
CharacteristicHealthy volunteersMen with PE
  1. bpm, beats per minute

N 53 58
Mean (sd):
Age, years 28.5 (7.98) 34.7 (11)
Height, m  1.78 (0.07)  1.76 (0.08)
Weight, kg 76.9 (9.42) 77.4 (10.68)
BMI, kg/m2 24.2 (2.58) 24.8 (2.91)
Diastolic BP, mmHg 76.9 (6.79) 78.1 (7.18)
Systolic BP, mmHg 117.6 (14.28)126.6 (11.64)
Heart rate, bpm 71.9 (9.44) 73.6 (7.69)
%:
Race
 White 96.2 87.9
 Black  1.9  3.4
 Asian  1.9  5.2
 Other  0  3.4

In all, 91.9% (102/111) of subjects completed the studies. The main reasons for study withdrawal were insufficient clinical response (subjects were unable to gain an erection in response to the vibrator, or unwilling to undergo the procedure after delays, 3.6%), investigator decision (0.9%), study termination (1.8%) and subject decision (5.4%).

In all, 213 evaluable records were obtained for healthy volunteers and 195 for men with PE (Fig. 4). Most were complete records, with erection and/or ejaculation profiles present (99%, 208/210 and 95.8%, 185/193, respectively). Most subjects (68.5%, 76/111) provided at least four complete records.

image

Figure 4. Flow chart showing the origins of the SAM recordings.

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Times to erection and ejaculation and ELT values were obtained from 53 healthy volunteers and 55 men with PE (Fig. 5). The geometric means for ELT show that healthy volunteers had a much longer ELT than men with PE (687 vs 169 s). When the data were adjusted for differences between individual studies this reduced the ELT for healthy volunteers more than for men with PE (375 vs 131 s; Table 2); however, the ELT ratio for healthy volunteers to men with PE was still significant (2.87; P < 0.001).

image

Figure 5. Geometric mean times to (a) erection and (b) ejaculation, and (c) ejaculation latency time (ELT) for all studies (individual and pooled data shown).

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Table 2.  Adjusted* geometric means times to erection, ejaculation and ELT for all studies
Variable (95% CI), sHealthy volunteers (HV)Men with PEHV/PE ratio
  • *

    Adjusted for differences between individual studies;

  • **

    P < 0.001

Time to erection143 (104–195)104 (76–144)1.37 (0.95–1.97)
Time to ejaculation612 (588–836)294 (213–406)2.08 (1.45–2.99)**
ELT375 (245–574)131 (84–202)2.87 (1.75–4.72)**

Overall, the geometric mean time to erection was similar between the groups (166 vs 136 s; Fig. 5a) However, as expected, the geometric mean time to ejaculation was longer in the healthy volunteers than in men with PE (917 vs 394 s, Fig. 5b), which was supported by a statistically significant ratio of healthy volunteers to men with PE (2.08; P < 0.001).

Overall, 6.3% (seven of 111) of subjects had one mild adverse event during the study, all of which were unrelated to the SAM. Most of these (six of seven) occurred in Study 001, and involved two healthy volunteers and four men with PE. The adverse events included upper respiratory tract infections (four men with PE), a minor injury (one volunteer) and lacerations (one volunteer) both to the head acquired during other activities. One adverse event was reported by a healthy volunteer from Study 303, which was an injury of a similar nature.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

Existing techniques used to monitor and compare the efficacy of PE treatments include the use of a stopwatch to measure IELT and questionnaires to address quality-of-life issues; however, these measures have substantial drawbacks, and there is no validated measure of ELT. The requirement for an objective measure of ELT, which would enable a more controlled comparison of treatments, led to the development of the SAM. The system was designed to give a consistent indication of the ejaculatory reflex rather than the IELT. It is recognized that IELT and ELT (as determined by the SAM) might differ for the same individual, and that the measurement of IELT requires a stopwatch. Thus, depending on the mechanism of drug action or the nature of the PE, measurements using both the SAM and the stopwatch might be of value.

The aim of the present studies was to evaluate the use of the SAM in healthy volunteers and in men with PE in a clinical setting. Overall, 98.6% of SAM records for healthy volunteers and 99% of records from men with PE were evaluable, and most were complete records (99% and 96%, respectively), with erection and/or ejaculation profiles present, and validated by two independent assessors. A computer-generated algorithm to automatically detect erection and ejaculation times was developed, and these were found to correspond very well to times recorded by the patients, and times measured by independent assessors. A total of 45 (85%) healthy volunteers and 36 (65%) men with PE provided four or more complete records. Only five invalid records were recorded of 408, which were due to transcription errors (non-technical fault) in three subjects (one was recorded twice by the same subject) and a technical fault (problem with the device leads) in one subject. These findings show that the SAM provides consistent and reproducible results for both healthy volunteers and men with PE.

As expected, healthy volunteers had a much longer ELT than men with PE (geometric means of 687 and 169 s; pooled data). These values were higher than the IELT range for normal volunteers, which is usually 120–420 s, and that for men with PE, which is <120 s. These data indicate that ELT and IELT are not the same measures (ELT would be expected to be longer than IELT). However, as ELT is likely to depend on the stimulation parameters, the relationship between ELT and IELT remains to be established. The data also reinforce the need for more comprehensive and objective measures of PE, as even the DSM-IV criteria, which was used to recruit patients in Study 001, was criticised for being too subjective, as there is no objective measure for ‘before, on, or shortly after penetration’[8].

Although these pooled data confirm the clinical benefits of SAM, when used as part of a PE diagnosis, there are still several limitations with the studies. There were relatively few patients, and men with PE were recruited in Study 303 based on a self-reported history of PE, which might lead to greater variation in the outcomes; however, in the two pilot studies, patients also made manual records which were checked against the SAM records. Independent assessors also checked the SAM records. Despite these limitations, the SAM shows potential for greater clinical accuracy and less variation than another diagnostic device, known as RigiScan® (Timm Medical Technologies, Eden Prairie, MN, USA). RigiScan measures penile tumescence, and was used in several clinical studies [12–14]. In one study, the ability of alprostadil to induce erection was assessed using RigiScan [15]; RigiScan agreed with clinical observation for ≈ 80% of the time. Our pilot studies show a much higher response rate with the SAM, which is extremely encouraging.

In summary, the ability to objectively and accurately measure ELT will be of considerable benefit for both the diagnosis of PE and the comparison of treatments. The present open-label studies show that the SAM can consistently and safely measure times to erection and ejaculation, and ELT in healthy volunteers and men with PE. The SAM has the potential to become the ‘gold standard’ in the diagnosis of PE. Work is continuing to assess the use of the SAM to measure ejaculatory threshold, the relationship between ELT (as measured by the SAM) and IELT (using the stopwatch), and the effect of selective serotonin re-uptake inhibitors on ELT. Additionally, using the SAM in men with conditions such as anejaculation and delayed ejaculation might provide valuable information about the mechanism(s) of underlying pathologies.

CONFLICT OF INTEREST

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES

W. W. Dinsmore, D. J. Ralph, P. Kell, K. R. Wylie, and J. P. Dean are study investigators of sponsor; C. Novak and J. S. Wyllie are employees of sponsor; M. G. Wyllie is a board member of sponsor. Source of funding: Plethora Solutions PLC.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS, SUBJECTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. CONFLICT OF INTEREST
  8. REFERENCES
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    Stark S, Sachse R, Liedl T et al. Vardenafil increases penile rigidity and tumescence in men with erection dysfunction after a single oral dose. Eur Urol 2001; 40: 18190
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    Ogrinc FG, Linet OI. Evaluation of real-time RigiScan monitoring in pharmacological erection. J Urol 1995; 154: 13569