help button home button ClinMed NetPrints
HOME HELP FEEDBACK BROWSE ARTICLES BROWSE BY AUTHOR
Warning: This article has not yet been accepted for publication by a peer reviewed journal. It is presented here mainly for the benefit of fellow researchers. Casual readers should not act on its findings, and journalists should be wary of reporting them.

This Article
Right arrow Abstract Freely available
Services
Right arrow Similar articles in this netprints
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harvey, I.
Right arrow Articles by Donovan, J. L
Right arrow Search for Related Content
PubMed
Right arrow Articles by Harvey, I.
Right arrow Articles by Donovan, J. L
Related Collections
Right arrow Infectious Diseases:
Sexually Transmitted Infections

Right arrow Sexual Medicine:
Other sexual medicine

Right arrow Obstetrics and Gynaecology:
Other Obstetrics and Gynaecology

Right arrow Statistics and Research Methods:
Randomised Controlled Trials: descriptions

Right arrow Systematic reviews (incl meta-analyses): examples

clinmed/2001090001v1 (September 4, 2001)
Contact author(s) for copyright information

Title: Reporting on sexual function in randomised controlled trials

Running head: Reporting on sexual function

Authors: Gavin Daker-White, BA, PhD1, Jenny L. Donovan, BA, PhD,2 and Ian Harvey, MB, PhD.3

1 Faculty of Health and Social Care, University of the West of England, Bristol, UK.

2 Department of Social Medicine, University of Bristol, UK.

3 School of Health Policy and Practice, University of East Anglia, Norwich, UK.

Correspondence and requests for reprints to: Gavin Daker-White, Senior Research Fellow, Faculty of Health and Social Care, University of the West of England, Glenside Campus, Blackberry Hill, Stapleton, Bristol BS16 1DD, UK

Telephone: 0117 344 8497

Fax: 0117 975 8848

Email: Gavin.Daker-White@uwe.ac.uk

Grant support: Gavin Daker-White was funded by NHS Research and Development (South West).

 

 

 

 

 

Title: Reporting on sexual function in randomised controlled trials

Abstract

Objectives - To evaluate the means by which sexual function has been reported on and measured in randomised controlled trials (RCTs).

Methods – Design: Search of the Cochrane Controlled Trials Register (1977 to 1998) to identify all trials reporting on sexual function or dysfunction outcomes. Assessment of abstracts of all articles. Full assessment of a random sample of articles for methods of measuring and reporting on sexual function, and overall trial quality. Main outcome measures: methods of measuring and reporting on sexual function, overall trial quality.

Results - Of 38 trials obtained for full assessment, 13 (34%) measured sexual function using questionnaires, 5 (13%) used objective measures, 4 (11%) used both and 16 (42%) did not use any measures (12 used adverse event recording). Seven trials (18%) did not provide response rates for sexual function measures and nearly half (18, 47.4%) only measured sexual function at follow-up (not reported in 2 trials). In six (16%) articles it was not clear who was reporting function or how the information was collected. The mean Jadad score (overall reporting quality) in these articles was 60.00% of the maximum possible score.

Conclusions - There are specific deficits in the reporting and measurement of the different components of sexual function in randomised controlled trials. These deficits could lead to misinterpretation of findings and need to be addressed in future studies.

Key Words: Sexual function, randomised controlled trials, measurement scales, reporting quality, patient outcomes

 

 

 

 

Title: Reporting on sexual function in randomised controlled trials

INTRODUCTION

Sexual dysfunction is an increasingly important outcome measure for health care interventions, including studies measuring it as a primary outcome and as a side effect (for example, of anti-hypertensive drug therapy). Although a wide range of disease states and treatments can affect sexual function in women and men [1], recent interest in its measurement is particularly associated with the development and testing of drugs for the treatment of erectile dysfunction [2,3]. Sexual function is itself considered to form a component of quality of life [4], which is now an accepted trial end-point in its own right [5].

The measurement of sexual function presents particular problems as human sexuality is both a psychosomatic and psychosocial process where biological, psychological, social and cultural factors interact. Thus, the potential for disease or treatment effects [6] varies widely between different individuals or couples. Furthermore, the term sexual dysfunction, although often employed as a condition in its own right, rather encompasses many particular disorders broadly distinguished as being related to desire, drive and interest, arousal and excitement, orgasm or pain [7].

To our knowledge, the methods of reporting sexual function in clinical trials have not been assessed, so this study was aimed at examining the means by which sexual function has been measured in randomised trials. We also set out to measure the quality of these trials and the completeness of reporting on sexual function measurement.

METHODS

Identification of studies

We searched the Cochrane Controlled Trials Register (CCTR) on The Cochrane Library (issue 4, 1998 [8]) for studies reporting on ‘sexual function’ or ‘sexual dysfunction’ (searched as key words), published 1977-1998.

Assessment of abstracts

All abstracts obtained were assessed by the first author and then checked by the second, to identify English language reports of randomised trials, published in peer-reviewed journals, that included the evaluation of sexual function in adult humans. Correspondence, reports of meetings, preliminary reports of other included trials, duplicate entries in the register and studies where patients were not evaluated, were all excluded from further assessment. Data on the condition studied, the type/s of intervention assessed, and the year of publication were recorded for included studies.

Assessment of full papers

A one-in-three random sample of papers was obtained for full assessment, random sampling being performed by a statistician not otherwise involved in the study. The first author examined all papers, and the others independently examined 50% each, the allocation of which was also determined in random manner by the statistician. Each assessor examined every paper allocated to them by use of a data extraction sheet, based largely on one used in a similar study [9]. Discrepancies were resolved in discussion and by revisiting the papers.

RESULTS

Identified studies

The preliminary search of the CCTR identified 174 articles, of which 59 (33.9%) were excluded for not being a randomised controlled trial (RCT) (n=20), not published in English (n=15), correspondence or a meeting report (n=13), duplicate entry in register (n=6), patient function not evaluated (n=2), preliminary report of other included trial (n=1), concerned with children (n=1) and focused on physiological assessment of fertility (n=1). Included articles were published between 1977 and 1998, although just over half were published since 1994 (n=59). Table 1 lists the most common condition groups studied. The most common interventions were drugs (n=98, 86.0%) and the only psychotherapeutic interventions (10/114, 8.8%) were in trials of interventions for sexual dysfunction.

Assessment of full papers

Thirty-eight articles were obtained for complete assessment (see appendix for references - appendix could be excluded for paper publication). Inter-assessor agreement for each article assessed was high (range 55.6-92.6% mean agreement for all items in each included article, median 81.5%). Following discussion and further checks, it appeared that the first author was originally correct in 39.1% of disagreements, as compared with 58.3% for the second assessors. In the remaining 2.6% of disagreements, both assessors were judged to have been incorrect in their original assessments.

The distribution of conditions reflected those represented in the full sample (table 1). The distribution of interventions (drugs or chemical compounds 32/38, 84.2%; psychotherapeutic 4/38, 10.5%; others n=2) was also similar. In 16 (42%) trials, no measures were reported as being used to collect information on sexual function (12 of these used adverse event recording). In the remainder, 5 used objective or clinical measurements alone (such as recording of nocturnal penile tumescence), 12 used one or more questionnaires, 4 used both objective measurements and a questionnaire, and in 1 trial sexual function questions formed part of a quality of life questionnaire. Table 2 details the different measures used. Of the 16 trials that used a questionnaire measure, only 7 (43.8%) provided a statement to the effect that the selected instrument was known to be a valid measure, only 9 gave details of the type of measurement scale used (most (8/9, 88.9%) used Likert response scales) and only 4 provided "full" details of the measure used (10 gave some details). "Full" details were defined as identification of measurement domains, provision of examples of questions used and explanation of methods of scoring items.

Twenty-three (60.5%) trials had sexual function as the primary outcome, although the specific components of function varied (table 3). Other primary end points included blood pressure (n=4), safety and / or efficacy (n=4), with the remainder relating to specific trials (n=7).

Half of the trials (n=19) measured sexual function alone, 8 measured function and satisfaction, 5 measured function, satisfaction and behaviour, 1 measured function, satisfaction and quality of life, and 1 measured function and quality of life. Interestingly, 4 (10.5%) did not appear to measure anything sexual at all, although sexual dysfunctions were reported as adverse events. Twelve (31.6%) trials measured sexual function by self-report, 7 (18.4%) relied on verbal reports where it was unclear whether all trial participants were asked systematically or not, 5 (13.2%) used administered interviews, 5 combined administered interviews with verbal report, 3 made exclusive use of objective measures and in 6 (15.8%) trials it was unclear who was reporting function.

Seven trials did not provide response rates for sexual function measurements. In the remainder response rates ranged from 52% to 100%. Approximately half (18, 47.4%) measured sexual function at baseline and follow-up, and the remainder at follow-up only. In two trials, it was unclear when function was measured. The majority of trials (23, 60.5%) measured sexual function in men only, with 12 (31.6%) measuring both sexes and 3 measuring women only. Ten (26.3%) trials showed more favourable sexual outcomes for an experimental arm, in 4 (10.5%) results were more favourable for a control group, in 12 (31.6%) there were no significant differences, whilst in the remaining 12, sexual comparisons between arms were either not clear (n=6) or not reported (n=6). Fifteen (39.5%) provided probability values for sexual function measures, two reported means and S.E.M.s, but none provided confidence intervals.

The mean Jadad score - a measure of trial quality [10] - was 60.00% of the maximum quality score. Unsurprisingly, the quality of reporting on sexual function measurement was higher in the sub-set of trials that had sexual function as a primary end-point (results not shown).

DISCUSSION

The measurement of sexual function in randomised controlled trials has been primarily associated with the positive and negative effects of drug treatments. "Positive" evaluation has more often focused on the treatment of erectile dysfunction in men, whilst "negative" evaluation has focused on the sexual side effects of compounds used in the treatment of other conditions, notably hypertension and depression. The results of this study have shown that researchers have measured a wide variety of components of sexual function using a plethora of questionnaires and other measurement techniques. There is both scope and need for standardisation of the questionnaire instruments used in these studies. The diversity of measures used is so great that the meaningful pooling of data would be impossible.

This article has highlighted the wide variation in the quality of reporting on sexual function measurement in randomised controlled trials. It is not always clear what is being measured sexually, when it is being measured, who is reporting function, nor who is making the measurement. There seems to be a particular problem in relation to the reporting of sexual dysfunction as an "adverse event" of treatment, when it was not always clear what the response rates for these measures were nor how such data were elicited from trial participants. In extreme cases, it was not even clear whether sexual effects were systematically evaluated in every trial participant or rather volunteered by respondents themselves. The fact that approximately half of the articles evaluated in this study did not seemingly undertake any baseline assessments of sexual function is also of concern. These findings indicate that extreme caution should be taken when interpreting the results of trials using assessments of sexual function. However, the mean quality of trial reporting (Jadad score) was slightly raised when compared with other studies [9, 10, 11]. This suggests that the reporting and measurement of sexual function requires special attention in future studies.

 

REFERENCES

1. Finger WW, Slagle MA. Changes in sexual function secondary to medication effects. Drugs of Today 1998; 34 (4): 307-320.

2. Rosen RC, Riley A, Wagner G, et al. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49 (6): 822-830.

3. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999; 281 (6): 537-544.

4. Fallowfield L. The quality of life: the missing measurement in health care. London: Souvenir Press; 1990

5. Patrick DL, Bergner M. Measurement of health status in the 1990s. Ann Rev Public Health 1990; 11: 165-183.

6. Bancroft J. Clinical trials and human sexuality: basic concepts and problems. Int J Impo Res 1998; 10 (Suppl. 2): S4-S6.

7. Potts S, Bhugra D. Classification of sexual disorders. Int Rev Psychiatry 1995; 7: 167-174.

8. Cochrane Controlled Trials Register (CCTR/CENTRAL). The Cochrane Library. Cochrane Collaboration. Oxford: Update Software; 1998.

9. Sanders C, Egger M, Donovan J, et al. Reporting on quality of life in randomised controlled trials: bibliographic study. BMJ 1998; 317: 1191-1194.

10. Jadad AR, Moore RA, Carrol D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1-12.

11. Egger M, Zellweger-Zahner T, Schneider M, et al. Language bias in randomised controlled trials published in English and German. Lancet 1997; 350 (9074): 326-329.

.

 

 

 

Appendix - Papers obtained for full assessment (could be omitted for paper publication)

Aydin S, Ercan M., Çaskurlu T, et al. Acupuncture and hypnotic suggestions in the treatment of non-organic male sexual dysfunction. Scand J Urol Nephrol 1997; 31(3): 271-274.

Bancroft J, Dickerson M, Fairburn CG, et al. Sex therapy outcome research: a reappraisal of methodology. 1. A treatment study of male sexual dysfunction. Psychol Med 1986; 16 (4): 851-854.

Berges RR, Windeler J, Trampisch HJ, et al. Randomised, placebo-controlled, double-blind clinical trial of b-sitosterol in patients with benign prostatic hyperplasia. Lancet 1995; 345 (8964): 1529-1532.

Brennemann W, Stitz B, van Ahlen H, et al.. Treatment of idiopathic erectile dysfunction in men with the opiate antagonist naltrexone - a double-blind study. J Androl 1993; 14 (6): 407-410.

Brook AC, Johnston DG, Ward MK, et al. Absence of a therapeutic effect of zinc in the sexual dysfunction of haemodialysed patients. Lancet 1980; 2 (1895 part 1): 618-620.

Buvat J, Costa P, Morlier D, et al. Double-blind multicenter study comparing alprostadil a-cyclodextrin with moxisylyte chlohydrate in patients with chronic erectile dysfunction. J Urol 1998; 159 (1): 116-119.

Chang SW, Fine R, Siegel D, et al. The impact of diuretic therapy on reported sexual function. Arch Intern Med 1991; 151 (12): 2402-2408.

Crenshaw TL, Goldberg JP, Stern WC. Pharmacologic modification of psychosexual dysfunction. J Sex Marital Ther 1987; 13 (4): 239-252.

Duch S, Duch C, Pastó L, et al. Changes in depressive status associated with topical beta-blockers. Int Opthalmol 1992; 16 (4-5): 331-335.

Ehrensing RH, Kastin AJ, Schally AV. Behavioral and hormonal effects of prolonged high doses of LHRH in male impotency. Peptides 1981; 2 (Suppl. 1): 115-121.

Goldiner WH, Hamilton BP, Hyman PD, et al. Effect of the administration of zinc sulfate on hypogonadism and impotence in patients with chronic stable hepatic cirrhosis. J Am Coll Nutr 1983; 2 (2): 157-162.

Gore R, Musselman D, Micalizzi E, et al. Losulazine, a new antihypertensive. Clin Pharmacol Ther 1985; 38 (2): 195-198.

Greminger P, Vetter H, Boerlin HJ, et al. A comparative study between 100mg atenolol and 200mg pindolol slow-release in essential hypertension. Drugs 1983; 25 (Suppl. 2): 37-41.

Haensel SM, Rowland DL, Kallan KTHK, et al. Clomipramine and sexual function in men with premature ejaculation and controls. J Urol 1996; 156 (4): 1310-1315.

Hellstrom WJG, Bennett AH, Gesundheit N., et al. A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil. Urology 1996; 48 (6): 851-856.

Kaisary AV, Tyrell CJ, Beacock C, et al. A randomized comparison of monotherapy with casodex 50 mg daily and castration in the treatment of metastatic prostate carcinoma. Eur Urol 1995; 28 (3): 215-222.

van Kammen DP, McEvoy JP, Targum SD, et al. A randomized, controlled, dose-ranging trial of sertindole in patients with schizophrenia. Psychopharmacology 1996; 124 (1-2): 168-175.

Knoll LD, Benson RC, Bilhartz DL, et al. A randomized crossover study using yohimbine and isoxsuprine versus pentoxifylline in the management of vasculogenic impotence. J Urol 1996; 155 (1): 144-146.

Kowalski A, Stanley RO, Dennerstein L, et al. The sexual side-effects of antidepressant medication: a double-blind comparison of two antidepressants in a non-psychiatric population. Br J Psychiatry 1985; 147: 413-418.

Lamberts SWJ, Quik RFP. A comparison of the efficacy and safety of pergolide and bromocriptine in the treatment of hyperprolactinemia. J Clin Endocrinol Metab 1991; 72 (3): 635-641.

Lynch MG, Whitson JT, Brown RH, et al. Topical b-blocker therapy and central nervous system side effects. Arch Opthalmol 1988; 106 (7): 908-911.

Mann K, Klingler T, Noe S, et al. Effects of yohimbine on sexual experiences and nocturnal penile tumescence and rigidity in erectile dysfunction. Arch Sex Behav 1996; 25 (1): 1-16.

Montorsi F, Guazzoni G, Barbieri L, et al. Genital plus audiovisual sexual stimulation following intracavernous vasoactive injection versus re-dosing for erectile dysfunction-results of a prospective study. J Urol 1998; 159 (1): 113-115.

Morokoff PJ, LoPiccolo J. A comparative evaluation of minimal therapist contact and 15-session treatment for female orgasmic dysfunction. J Consult Clin Psychol 1986; 54 (3): 294-300.

Özeren S, Çorakçi A, Yücesoy I, et al. Fluoxetine in the treatment of premenstrual syndrome. Eur J Obstet & Gynecol 1997; 73 (2): 167-170.

Piazza LA, Markowitz JC, Kocsis JH, et al. Sexual functioning in chronically depressed patients treated with SSRI antidepressants: a pilot study. Am J Psychiatry 1997; 154 (12): 1757-1759.

Ravindran AV, Judge R, Hunter BN, et al. A double-blind, multicenter study in primary care comparing paroxetine and clomipramine in patients with depression and associated anxiety. J Clin Psychiatry 1997; 58 (3): 112-118.

Reynaert C, Parent M, Mirel J, et al. Moclobemide versus fluoxetine for a major depressive episode. Psychopharmacol Berl 1995; 118 (2): 183-187.

Rowland DL, Kallan K, Slob AK. Yohimbine, erectile capacity, and sexual response in men. Arch Sex Behav 1997; 26 (1): 49-61.

Rutledge JC, Paumer L, Laslett L, et al. Efficacy of antihypertensive therapy at rest and during exercise. J Cardiopulmonary Rehabil 1988; 8 (3): 116-122.

Susset JG, Tessier CD, Winze J, et al. Effect of yohimbine hydrochloride on erectile impotence: a double-blind study. J Urol 1989; 141 (6): 1360-1363.

Takefman J, Brender W. An analysis of the effectiveness of two components in the treatment of erectile dysfunction. Arch Sex Behav 1984; 13 (4): 321-340.

Tran PV, Hamilton SH, Kuntz AJ, et al. Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacol 1997; 17 (5): 407-418.

Veterans Administration Cooperative Study Group on Antihypertensive Agents. Comparison of prazosin with hydralazine in patients receiving hydrochlothiazide. Circulation 1981; 64 (4): 772-779.

Villamil A, Weber C, Desche P, et al. Antihypertensive effect and acceptability of perindopril: a 3-month double-blind trial vs. atenolol in 40 patients with mild to moderate hypertension. Drug Invest 1991; 3 (5): 308-314.

Vogt H-J, Brandl P, Kockott G, et al. Double-blind, placebo-controlled safety and efficacy trial with yohimbine hydrochloride in the treatment of nonorganic erectile dysfunction. Int J Impot Res 1997; 9 (3): 155-161.

Wiklund I, Karlberg J, Mattson L-Å. Quality of life of postmenopausal women on a regimen of transdermal estradiol therapy: a double-blind placebo-controlled study. Am J Obstet Gynecol 1993; 3(1): 824-830.

Williams GH, Croog SH, Levine S, et al. Impact of antihypertensive therapy on quality of life: effect of hydrochlothiazide. J Hypertens Suppl 1987; 5 (1): S29-S35.

Table 1: Most common conditions studied in RCTs reporting on sexual function

Condition Studied

In all identified trials (n=114)

In trials assessed in full (n=38)

Sexual dysfunction

50 (43.9%)

17 (44.7%)

Hypertension

20 (17.5%)

7 (18.4%)

Depression

12 (10.5%)

4 (10.5%)

Schizophrenia

4 (3.5%)

2 (5.3%)

Hyperprolactinemia

2 (1.8%)

1 (2.6%)

Panic disorder

2 (1.8%)

-

Prostate cancer

2 (1.8%)

1 (2.6%)

Other

22 (19.3%)

6 (15.8%)

 

Table 2: Sexual function measures used in 22 RCTs reporting on sexual function

Objective / clinical measures

"Buckling test": a measure of axial penile rigidity

1

Laboratory evaluation of latency to ejaculation

1

Nocturnal penile tumescence recording

5

Penile duplex ultrasonography

1

Real time evaluation of erections

2

Questionnaire / interview measures

Arizona Sexual Experience Scale

1

Brief Sexual Function Questionnaire (BSFQ)

1

Derogatis Sexual Functioning Inventory (DSFI) – selected items

1

Erectile Difficulty Questionnaire

1

Erection Assessment Scale - adapted

1

Locke-Wallace Marital Adjustment Test

1

Locke-Wallace Marriage Inventory

1

Marital Adjustment Scale, short form

1

Maudsley Marital Questionnaire

1

McCoy Sex Scale – 9 items only

1

Own measures / unnamed questionnaires

9

Sexual Behaviour Questionnaire

1

Sexual History Form (SHF)

2

Sexual Interaction Inventory (SII)

2

Sexual Symptoms Distress Index (SSDI)

2

 

Table 3: Sexual function measures in 23 RCTs with sexual function as a primary end point

Ability to have intercourse

1

CNS effects (including libido)

1

Degree of impotence

1

Erectile function

6

Erectile function, sexual function, marital function and sexual communication

1

Libido, erections and frequency of intercourse

1

Libido, erections and sexual pleasure

1

Libido, frequency, intensity and pleasure of sexual desires

1

Nocturnal erections

1

Orgasmic functioning

1

Quality of life (including sexual function)

2

Satisfaction with current sexual activity

1

Sexual desire, satisfaction and erectile function

1

Sexual function

2

Sexual response

1

Time to reach ejaculation

1

 

 

 

ACKNOWLEDGEMENTS

The random sampling was performed by Sara Brookes. The data extraction form used was based largely on one supplied by Caroline Sanders and used in a previous study [9].





This Article
Right arrow Abstract Freely available
Services
Right arrow Similar articles in this netprints
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harvey, I.
Right arrow Articles by Donovan, J. L
Right arrow Search for Related Content
PubMed
Right arrow Articles by Harvey, I.
Right arrow Articles by Donovan, J. L
Related Collections
Right arrow Infectious Diseases:
Sexually Transmitted Infections

Right arrow Sexual Medicine:
Other sexual medicine

Right arrow Obstetrics and Gynaecology:
Other Obstetrics and Gynaecology

Right arrow Statistics and Research Methods:
Randomised Controlled Trials: descriptions

Right arrow Systematic reviews (incl meta-analyses): examples


HOME HELP FEEDBACK BROWSE ARTICLES BROWSE BY AUTHOR