Effect of erectile dysfunction medications on coexisting sexual dysfunctions in couples: Partners'...

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E!ect of erectile dysfunction medications on coexisting sexualdysfunctions in couples: Partners’ Preference Study

Helen M. Conaglena*, Amy R. Williamsonb and John V. Conaglenc

aDeakin University, Melbourne, Australia; bAccident Research Centre, Monash University,Melbourne, Australia; cWaikato Clinical School, Faculty of Medical & Health Sciences,

University of Auckland, Hamilton, New Zealand

(Received 6 January 2009; final version received 8 September 2009)

There is sparse information on how treatments for erectile dysfunction (ED)a!ects couples. This study investigated the e!ects of ED treatments on 100heterosexual couples’ sexual functioning and whether function achieved using ashort-acting versus a long-acting ED medication di!ered significantly. Coupleswere randomized to use tadalafil or sildenafil for each of two 12-week studyphases; they completed questionnaires (International Index of Sexual Functionand Female Sexual Function Index) and kept sexual event diaries. All participantsexperienced significant improvements over baseline sexual functioning, while themen used short- or long-acting ED medications with no significant di!erencesrelated to the duration of drug action recorded for either the men or women.Despite this lack of di!erence in e"cacy there was a strong preference by women(79%) and their partners (16%) for the longer-acting medication. The reasons forthis warrant further investigation. Understanding the e!ects on couples of the useof ED medications is a necessary aspect of ensuring ongoing sexual satisfaction incouples treated for ED.

Keywords: couples; sexual dysfunction; Female Sexual Function Index;International Index of Erectile Function; phosphodiesterase type 5 inhibitors;PDEV inhibitors; tadalafil; sildenafil

Introduction

Erectile dysfunction (ED) is common and distressing for the men involved (Feldman,Goldstein, Hatzichristou, Krane, &McKinlay, 1994). Numerous studies of the use oforal phosphodiesterase type 5 inhibitors (PDE5i) for the treatment of ED havedemonstrated their e"cacy with respect to erectile function (Brock et al., 2002;Goldstein et al., 1998), improvement in the quality of life of the men concerned (Deanet al., 2006; Sanchez-Cruz et al., 2003; Shabsigh & Stone, 2006), their self-esteem(Althof, O’Leary et al., 2006) and their satisfaction with treatment (Matic &McCabe,2007; Porst, Behre, Jungwirth, & Burkart, 2007; Tomlinson & Wright, 2004).However, the treatment of the man’s sexual problem has not always resulted in hispartner expressing the same satisfaction with the continued use of the medication(Althof, 2002; Chevret, Jaudinot, Sullivan, Marrel, & Solesse de Gendre, 2004;Colson, 2005; Edwards, Hackett, Collins, & Curram, 2006; Fisher, Rosen, Eardley,Sand, & Goldstein, 2005; Goldstein et al., 2005; McCabe, 2008). This disparity in

*Corresponding author. Email: [email protected]

Sexual and Relationship TherapyVol. 24, Nos. 3–4, August–November 2009, 316–332

ISSN 1468-1994 print/ISSN 1468-1749 online! British Association for Sexual and Relationship TherapyDOI: 10.1080/14681990903321775http://www.informaworld.com

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partner satisfaction with treatment has been variously attributed to: (1) requiredadjustment from the relative lack of intimacy experienced by the couple during the timethe man’s ED had been present (Althof, 2002; Kingsberg, 2002), (2) sexual di"cultiesnot necessarily being singularities in the age-group of couples typically experiencing ED,(Fugl-Meyer & Fugl-Meyer, 2002) and (3) women maybe being less than enthusiasticabout their partners renewed sexual capability because it highlighted their own sexualproblems (Cayan, Bozlu, Murat, Canpolat, & Akbay, 2004).

Some papers have reported the types of sexual problems partners of men with EDexperience (Shabsigh, Anastasiades, Cooper, & Rutman, 2006). Several such studieshave recruited participants from clinic populations and included female partnersonly when they accompanied the man with ED to clinic appointments (Cayan et al.,2004; Greenstein, Abramov, Matzkin, & Chen, 2006). Most studies in this area haveutilised the International Index of Erectile Function (IIEF) for men, with the SexualEncounter Profile questions for the women and, more recently, various treatmentsatisfaction measures (Althof et al., 1999; Kubin, Trudeau, Gondek, Seignobos, &Fugl-Meyer, 2004; Rosen, Cappelleri, & Gendrano, 2002). A few authors have usedthe Female Sexual Function Index (FSFI) to understand the sexual function of femalepartners, but these studies have often been small or retrospective (Cayan et al., 2004;Fisher, Rosen, Mollen, et al., 2005; Fisher, Rosen, Eardley, et al., 2005).

The IIEF and the FSFI have been used frequently in studies of couples’ sexualissues, providing a four-week snapshot of a person’s current sexual function (Rosenet al., 1997, 2000). Critique has been made of the scoring process because it mayresult in people being labelled dysfunctional when they report infrequent, butpossibly functional, sexual activity at greater than four-week intervals (Meyer-Bahlburg & Dolezal, 2007). In some studies (e.g. Goldstein et al., 2005) women wereexcluded if their FSFI score was less than the clinical cut-o! identified by WiegelMeston and Rosen (2005). Whether this criterion is used or not, the male and femalesexual function measures provide parallel assessment of their current status andpotential change in that status as couples undergo treatment.

It can be a challenge for clinicians to involve the partners of men with ED intreatment (Dean et al., 2007). Having reliable information about the women’sperspective in this context allows clinicians to better inform their patients andpartners of the benefits or di"culties they could potentially experience whilst usingsuch treatments. Additionally, understanding whether women prefer one type ofmedication to another, and the reasons for that preference, will assist partners andclinicians alike in decision-making at treatment initiation or continuation.

This study recruited couples from the community and monitored both partners’sexual function over a six-month period as the men underwent ED treatment usingtwo oral PDE5i. Of primary interest were the changes each partner experiencedduring the treatment phases and whether the use of a short- or long-actingmedication made a significant di!erence to sexual function in either partner.In addition we sought to understand whether women, in particular, preferred theshort- or longer-acting PDE5i for use by their partners.

Methods

Recruitment

Articles seeking participants for a study of couples experiencing ED were publishedin a local newspaper. Screening of the 430 respondents included the Erectile

Sexual and Relationship Therapy 317


Function (EF) subscale of the IIEF with the male volunteers. If the men were instable heterosexual relationships, scored EF ! 20 and reported no prior, or minimal(55 packets), use of either sildenafil or tadalafil the couple were sent studyinformation and consent forms (* 150 couples). Of these, 120 couples returnedsigned consent forms. The men then underwent a full medical examination andblood tests to determine the appropriateness of use of the study medications.Exclusion criteria are detailed elsewhere (Conaglen & Conaglen, 2008); 100participant couples were recruited to the study.

Study design

The study was a single-centre, prospective, repeated measures, open-label cross-overstudy of sildenafil and tadalafil for the treatment of erectile dysfunction with afocus on the sexual function of male and female partners before and during the 24weeks of medication. Study processes and disposition of participants are shown inFigure 1.

Materials and procedure

This single-centre study was community-based rather than derived from any specificspecialist practise. Approval for the study was obtained from the National EthicsCommittee and the participants provided individual written informed consent.Medical examinations were performed at the third author’s clinic and otherassessments were completed by the first author at The Psychology Centre, Hamilton,New Zealand. Thirty-six tablets of each drug were provided at no cost to theparticipants with instructions to use as required up to a maximum of one tablet perday. The participants kept sexual event diaries and completed questionnaire sets and

Figure 1. Study processes and participant retention.

318 H.M. Conaglen et al.


the women were interviewed at Baseline, 12- and 24-weeks during the study. In thispaper, reporting of the interview content is limited to the preference expressed by thewomen and their partners at the end of the study. Detail regarding the women’sexperience is published elsewhere (Conaglen & Conaglen, 2008).

The sexual function questionnaires were the IIEF (Rosen et al., 1997) and theFSFI (Rosen et al., 2000). From the sexual event diaries the number of tablets usedand the number of sexual events experienced were reported.

Analyses

The key outcome measures were the di!erences between the baseline sexual functionscores and those reported at mid-point and end-of-study by the couples. Thequantitative analyses were repeat measures t-tests, with calculation of thestandardized e!ect size statistic Cohen’s d1 for each significant change. Pearsonproduct-moment correlations between the sexual function sub-scales of the men andwomen were performed at each stage of the study and reviewed for significantassociations. Multiple regression analyses designed to understand how the IIEF sub-scales contributed to women’s pain and total FSFI scores were carried out at eachstudy stage. Analyses were conducted on data from all the couples that completedthe study (n ! 96). All statistical analyses were carried out using Statistica version6.1 (StatSoft Inc., USA).

In this paper we report on quantitative data detailing the sexual functioning ofeach partner as the couple was treated with sildenafil and tadalafil and the e!ect ofthe two medications on that function. We also document the preference expressed bythe women in the study and relate that preference to the other findings.

Results

Recruitment began in July 2005 and final data were obtained in July 2007. Themajority of the participants were New Zealand Caucasians (86%) for whom ED hadbeen a problem for a median time of two years. Examination of the reportedduration of ED showed that the men tended to report ED had been present for lesstime than did their partners, but these di!erences were not statistically significant.Severity of ED ranged from mild to severe. Most of the couples were in long-termrelationships (median 25.0 years, range 0.25–52.0 years). Details of the participant’scharacteristics are shown in Tables 1a and 1b.

During the course of the study four couples withdrew and yielded incompletedata due to ill health or termination of their relationship. Three further couplesfinished the second phase of the study early due to incompatibility with medications;however, each of these couples completed all questionnaire sets, so their data hasbeen pro-rated and included in the analysis. End-of-study questionnaire data wentmissing for two participants (#6, #82); in those cases the last observation carriedforward (LOCF) procedure was used to enable their inclusion in the analyses.Details of participant disposition during study procedures are shown in Figure 1.

Baseline measures

Baseline FSFI scores for women in this study are reported in Table 2. Comparison ofscores recorded by the women at baseline with those of the control group reported in



a study describing FSFI clinical cut-o!s (Wiegel et al., 2005) showed our participantsrecorded significantly lower mean scores in each sub-scale. Further, comparing thewomen’s full-scale scores with the clinical cut-o! of "26, we found that 46 of ourparticipant women at baseline would be considered as warranting furtherinvestigation for sexual dysfunction. Examination of the data for women reportingno sexual activity in the past four weeks, showed that nine women recorded ‘Did notattempt intercourse’ (resulting in a 0 score) on the pain sub-scales, while five of theparticipants also reported no sex across the other sub-scales that allow such aresponse. Consideration was given to excluding those couples who had had no sex inthe four weeks prior to baseline, but this runs counter to clinical endeavour, so thedata from these couples were left in the data set.

Because we randomized couples to receive either tadalafil (T-S) or sildenafil (S-T)first and then crossed over to the alternate drug, we wanted to ascertain whetherthere were any significant di!erences in characteristics or basic sexual functioningbetween the groups of women at randomization. The women’s groups wereremarkably similar on all characteristics tested with the only di!erence being theorgasm function (OF) sub-scale on the FSFI; the T-S group’s mean score was3.68 + 1.88 while the S-T group recorded a mean score of 4.40 + 1.59 (out of apossible 6) for this variable, suggesting more facility with orgasm in the latter groupat baseline, t(97) ! 2.04, p ! .05.

Baseline IIEF scores are reported in Table 3. Comparison of the men’s baselineIIEF scores with the clinical cut-o!s outlined in 1999 (Veterans A!airs, 1999)showed that, in addition to the erectile dysfunction that was a pre-requisite for thestudy, over 70% of the men had sexual function sub-scale scores indicative ofcoexisting problems. Seventy men had OF scores "8 varying between mild andsevere dysfunction. Sexual desire (SD) scores "8 ranging between mild and moderatedysfunction were recorded for 89 men. Intercourse satisfaction (IS) scores "12

Table 1a. Participant demographics and other baseline characteristics – women.

Tadalafil thensildenafil (n ! 50)

Sildenafil thentadalafil (n ! 50)

Total(n ! 100)

Age, (years, mean) [SD] 52.60 [9.13] 52.86 [8.72] 52.73 [8.89]Baseline menstrual status, n (%){

Still menstruating regularly 13 (27) 11 (22) 24 (24)Currently peri-menopausal(periods irregular)

10 (20) 6 (12) 16 (16)

Menopausal (no period in 1 year) 16 (33) 21 (42) 37 (37)Other (hysterectomy,post-menopausal, using IUD)

10 (20) 12 (24) 22 (22)

Baseline current medications, n (%)None 24 (48) 17 (34) 41 (41)Taking prescription or over thecounter medications*

26 (52) 33 (66) 59 (59)

Notes: {Data missing where numbers sum to less than column total; *Medications included: ACEinhibitors, anti-bacterials, antidepressants, anti-diarrhoeal, anti-diuretics, antihistamines, antihyperten-sives, anti-inflammatories, anti-malarials, anti-viral agent, aspirin, asthma medications, beta-blockers,birth control meds, blood pressure tablets, calcium, calcium channel blockers, corticosteroids, diabetesmeds, diuretics, folates, glucosamine, lipid lowering agents, magnesium, Metamucil, migraine meds, multi-vitamins, osteoarthritis meds, osteoporosis meds, phosphates, proton pump inhibitors, ranitidine, tegretol,thyroxine, topical estrogen cream.



indicating mild to severe levels of dysfunction were reported by 90 men. Overallsatisfaction (OS) scores "8 ranging between mild and severe dysfunction wererecorded for 93 men.

Table 1b. Participant demographics and other baseline characteristics – men.

Tadalafil thensildenafil (n ! 48)

Sildenafil thentadalafil (n ! 50)

Total(n ! 98)

Age, (years, mean) [SD] 57.6 [9.51] 57.31 [7.87] 57.46 [8.70]Erectile dysfunction duration, (months)Median (SD) 32.5 (27.01) 39.86 (39.21) 36.11 (33.57)Range (min–max) 3–120 3–192# 3–192#

Severity of ED (Baseline IIEF-EF score)Severe dysfunction " 10 19 (38) 19 (22) 38 (39)Moderate dysfunction 11–16 19 (38) 20 (40) 39 (39)Mild to moderatedysfunction* 17–21

12 (24) 11 (38) 23 (23)

*all men in this category in study EF " 20Mild dysfunction 22–25 0 0 0

Mean baseline IIEF-EF (SD) 11.56 (5.90) 12.46 (5.47) 12.01 (5.68)Baseline hormone dataTestosterone, Mean (SD) 15.06 (3.94) 15.92 (4.59) 15.48 (4.27)Range (Reference range:9–30 nmol/L)

9.2–24.1 10.3–27.9 9.2–27.9

Prolactin, Mean (SD) 191.48 (70.84) 211.29 (81.18) 201.18 (76.34)Range (Reference range:5450 mIU/L)

76–372 79–400 76–400

Baseline current medications, n (%)None 23 (46) 17 (34) 44 (44)Taking prescription orover-the-counter medications*

27 (54) 33 (66) 56 (56)

Notes: *Medications included: ACE inhibitors, anti-bacterials, anti-coagulants, antidepressants, anti-diarrhoeal, anti-diuretics, antihistamines, antihyperurecaemic, antihypertensives, anti-inflammatories,anti-malarials, anti-viral agent, aspirin, asthma medications, beta-blockers, blood pressure tablets,calcium, calcium channel blockers, corticosteroids, decongestants, diabetes meds, diuretics, folates,glucosamine, lipid lowering agents, magnesium, Metamucil, migraine meds, multi-vitamins, osteoarthritismeds, osteoporosis meds, phosphates, proton pump inhibitors, ranitidine, tegretol, thyroxine; ED !erectile dysfunction; SD ! standard deviation, IIEF-EF ! International Index of Erectile Function-erectile function domain.

Table 2. Female Sexual Function Index means at baseline, mid-point and end-of-study.

Baseline Mid-point{ End-of-study{

Mean (SD)(n ! 96)

RangeMin–max

Mean (SD)(n ! 96)

RangeMin–max

Mean (SD)(n ! 96)

RangeMin–max

Desire 3.75 (0.99) 1.2–6.0 3.86 (0.96) 1.2–6.0 3.79 (1.07) 1.2–6.0Arousal 4.09 (1.37) 0–6.0 4.78 (1.04)c 0–6.0 4.44 (1.35)a,ii 0–6.0Lubrication 4.51 (1.63) 0–6.0 5.07 (1.07)b 0–6.0 4.97 (1.40)b 0–6.0Orgasm 4.07 (1.74) 0–6.0 4.75 (1.24)c 0–6.0 4.47 (1.48)a 0–6.0Satisfaction 4.13 (1.74) 0.8–6.0 5.15 (0.94)c 2.8–6.0 4.88 (1.37)c,i 0.8–6.0Pain 4.98 (1.82) 0–6.0 5.54 (1.05)b 0–6.0 5.43 (1.32)a 0–6.0Full-scale 25.51 (6.90) 3.8–35.7 28.83 (5.4)c 4.4–36.0 27.96 (6.35)b,i 4.4–36.0

Notes: {Significantly di!erent to baseline: ap 5 .05; bp 5 .01; cp 5 .0001. {Significantly di!erent to mid-point: ip 5 .05; iip 5 .01; iiip 5 .0001.



Sexual intercourse frequency over the previous four weeks as determined by Q6of the baseline IIEF showed that 9 men reported no activity, 19 reported one or twoattempts; 28 recorded three or four attempts; 19 recorded five or six attempts; 13reported seven to eleven attempts, while 11 men reported eleven or more attempts atsexual intercourse in the past four weeks. Investigation of the influence of durationof ED on reported frequency of attempts revealed no significant patterns. Similarly,age groupings did not a!ect intercourse frequency in this sample.

Following randomization, t-tests of the men’s characteristics by medicationgroup showed that the only variable on which the two men’s groups di!ered was theSD sub-scale on the IIEF. The T-S group’s mean score was 6.14 + 1.55, while thosemen in the S-T group recorded a mean score of 6.96 + 1.35 (out of a possible 10) forthis variable, suggesting higher levels of sexual desire in the latter group at studybaseline, t(97) ! 2.80, p ! .01. Overall, men and women in the two medicationgroups were very similar in terms of personal characteristics and sexual function atbaseline.

A comparison of the sexual frequency data from participants showed similarnumbers of men and women reported no sexual activity via questionnaires. Toinvestigate the associations between partners’ sexual function characteristics,product-moment correlations between their baseline scores on the scales wereperformed. Using the Bonferroni approach to control for Type 1 error across thecorrelation of 13 separate variables, a p value of less than .0003 (0.05/132 ! .0003)was required for significance. After this correction there were 13/42 baseline scoresthat correlated positively and significantly; the strongest association was betweenFSFI-pain and IIEF-IS, r(96) ! .547, r2 ! .300, p 5 .0001, linking less pain inwomen and greater intercourse satisfaction in men.

A multiple regression analysis found that the linear combination of the sub-scalesof the IIEF was significantly related to the women’s FSFI total, F(5, 93) ! 11.26,p 5 .0001. The sample multiple correlation coe"cient was. 61, indicating that about38% (adj R2 ! .34) of the variability in the sample at baseline can be accounted forby the men’s sub-scale scores. The partial correlation of the FSFI total with the SDsub-scale, t(93) ! 2.23, p ! .03, and the IS sub-scale, t(93) ! 3.64, p ! .0005, werestatistically significant. This analysis links greater desire and intercourse satisfactionin the men with better overall sexual function of the women. (For details ofregression results see Table 4).

Table 3. International Index of Erectile Function means at baseline, mid-point and end-of-study.

Baseline Mid-point{ End-of-study{

Mean (SD)(n ! 96)

RangeMin–max

Mean (SD)(n ! 96)

RangeMin–max

Mean (SD)(n ! 96)

RangeMin–max

Erectile function 13.49 (5.76) 1–23 23.97 (6.65)b 1–30 24.15 (6.50)b 1–30Orgasm function 7.22 (2.56) 0–10 8.34 (2.46)a 0–10 8.44 (2.44)b 0–10Sexual desire 6.55 (1.50) 3–10 7.25 (1.54)b 3–10 7.39 (1.65)b 2–10Intercoursesatisfaction

7.89 (3.40) 0–14 11.44 (3.29)b 0–15 11.54 (3.16)b 0–15

Overallsatisfaction

5.47 (2.06) 2–9 8.19 (1.89)b 2–10 7.97 (2.01)b 2–10

Full-scale 41.33 (12.46) 7–64 59.18 (14.04)b 8–75 59.03 (14.29)b 5–75

Note: {Significantly di!erent to baseline; ap 5 .01; bp 5 .0001.



Mid-point measures

By study mid-point, all mean scores on the FSFI had improved for the women(n ! 96) as shown in Table 2. The mean full-scale score (88.83 + 5.4) indicated theaverage participant was sexually functional again. At this stage there were still twowomen reporting low levels of sexual activity: one who subsequently withdrew fromthe study and another whose partner underwent an operation shortly after the mid-point measure was completed. In all, 78 women scored above the clinical cut-o!di!erentiating sexually functional from dysfunctional women. Most mean sub-scaleand the full-scale FSFI scores showed women to have significantly improved sexualfunction over baseline and the mean full-scale score was above the cut-o! for normalsexual function. The standardised e!ect sizes (‘‘d’’ statistic) for the significantchanges from baseline were: medium for arousal (d ! 0.57), lubrication (d ! 0.41),orgasm (d ! 0.45), satisfaction (d ! 0.71) and full-scale (d ! 0.63) and small forpain (d ! 0.38).

At the study mid-point the men’s IIEF scores had improved, as shown in Table 3.In comparison with baseline, twice as many men had no orgasm problems (n ! 62);almost twice as many reported no sexual desire problems (n ! 19); and there was afive- to six-fold improvement in intercourse and overall satisfaction for the men.E!ect sizes are typically described as small if the ‘d ’ statistic is *0.2, medium if ‘d’*0.5 and large if ‘d’ is 0.8 or greater. The standardised e!ect sizes for the changesfrom baseline were very large for EF sub-scale (d ! 1.69), for the OS sub-scale

Table 4. Summary of regressions using IIEF sub-scales as predictors of FSFI totals at eachstudy stage.

Beta Std Err of Beta B Std Err of B p

Baseline R ! .6140; R2 ! .3770; Adjusted R2 ! .3435; F(5,93) ! 11.256, p 5 .0001Intercept 11.464 2.875 50.0001EF 70.219 0.118 70.267 0.144 0.0667OF 70.005 0.090 70.014 0.247 0.9545SD 0.202 0.090 0.973 0.436 0.0279*IS 0.557 0.153 1.153 0.317 0.0005*OS 0.111 0.127 0.384 0.438 0.3829

Mid-point R ! .7483; R2 ! .5600; Adjusted R2 ! .5363; F(5,93) ! 23.672, p 5 .0001Intercept 13.580 1.959 50.0001EF 70.279 0.147 70.210 0.110 0.0605OF 0.106 0.103 0.222 0.217 0.3084SD 0.126 0.089 0.430 0.302 0.1581IS 0.640 0.171 0.971 0.259 0.0003*OS 0.204 0.132 0.537 0.347 0.1250

End-of-study R ! .7564; R2 ! .5722; Adjusted R2 ! .5492; F(5,93) ! 24.879, p 5 .0001Intercept 11.677 2.294 50.0001EF 70.016 0.123 70.016 0.119 0.8950OF 70.078 0.103 70.207 0.275 0.4528SD 70.096 0.096 70.389 0.390 0.3215IS 0.721 0.177 1.432 0.351 0.0001*OS 0.186 0.135 0.595 0.432 0.1716

Notes: EF ! Erectile function; OF ! Orgasm function; SD ! Sexual desire; IS ! Intercourse satisfac-tion; OS ! Overall satisfaction.



(d ! 1.38) and full-scale (d ! 1.35), large for IS (d ! 1.07) and medium for OF(d ! 0.45) and SD sub-scales (d ! 0.46).

At this stage of the study, 31/42 of the correlations between the couple’s sexualfunction scores were positively statistically significant. The FSFI orgasm, satisfactionand full-scale scores were most strongly correlated with the IIEF sub-scales at thispoint.

A multiple regression analysis found that the linear combination of the sub-scalesof the IIEF remained significantly related to the women’s FSFI total, F(5,93) ! 23.67, p 5 .0001. The sample multiple correlation coe"cient was .75,indicating that about 56% (adj R2 ! .54) of the variability in the women’s FSFItotals at mid-point of the study can be accounted for by the men’s sub-scale scores.The partial correlation of the FSFI total with the IS sub-scale, t(93) ! 3.74,p ! .0003 was statistically significant. In other words, the men’s intercoursesatsfaction was the best predictor of the women’s FSFI scores.

End-of-study measures

The end-of-study FSFI scores are reported in Table 2. While the mean scores at thisstage reflect significantly better functioning than at baseline, there is a slight settlingto a lower point than found at mid-point of the study. The inclusion of allparticipants’ data using the LOCF technique may have contributed to this result.Examination of whether these di!erences were significant showed that while sexualdesire, lubrication, orgasm and pain did not di!er, arousal, t(95) ! 2.55, p ! .01,satisfaction, t(95) ! 2.27, p ! .03 and the full-scale scores, t(95) ! 2.06, p ! .04,were significantly lower at end-of-study than at study mid-point. The e!ect sizesfor these latter changes were small. Despite the mid-point to end-of-studydecreases, the mean end-of-study full-scale score showed the women to havesignificantly improved sexual function since baseline, with scores above the cut-o!for sexual dysfunction.

The men’s IIEF scores at end-of-study are shown in Table 5. There were nosignificant di!erences between their mid-point and end-of-study scores.

End-of-study correlations between couple’s sexual function sub-scales showed31/42 significant positive associations. The areas that showed strongest correlationwere the women’s full-scale FSFI scores related to the men’s IS (r ! .703, r2 ! .494,p 5 .001), OS (r ! .656, r2 ! .430, p 5 .001) and full-scale IIEF scores (r ! .616,r2 ! .379, p 5 .001).

The end-of-study multiple regression analysis showed an ongoing significantrelationship between the IIEF sub-scales and the FSFI total, F(5,93) ! 24.88,p 5 .0001. The sample multiple correlation coe"cient was. 76, indicating that about57% (adj R2 ! .55) of the variability in the women’s FSFI at end-point of the studycould be accounted for by the men’s sub-scale scores. Again, the partial correlationof the FSFI total with the IS sub-scale, t(93) ! 4.08, p ! .00001 was statisticallysignificant.

Whilst both partners were issued with diaries to keep independently, manywomen reported they had copied their partner’s data. For this reason we chosethe record nominated by the couple as the most reliable for the number ofevents experienced and numbers of tablets used. There was a high level of agree-ment between tablets reported used and remainder returned. The mean numberof events recorded using tadalafil (mean ! 33.45 + 24.13) and sildenafil



(mean ! 30.92 +24.13) were not significantly di!erent. The average number ofevents per week was similar for each drug (tadalafil 2.54 + 1.83; sildenafil2.39 + 1.91). The mean number of days between events recorded using tadalafilwas 4.64 + 7.59 and 5.12 + 5.00 days for sildenafil, but this variation was notstatistically significant. The mean number of tablets used was the same in both armsof the study (tadalafil 22.46 + 9.91; sildenafil 22.46 + 10.44).

E!ect of medication randomization

For the women, the two medication groups FSFI scores were very similar atbaseline, as detailed above, and by mid-point between-groups t-testing showedthere were no significant di!erences between them for all aspects of the sexualfunction measures. At end of study the two groups of women were still statisticallyundi!erentiated. However, examination of changes by group as each progressedthrough the study showed that the standardized e!ect sizes for the T-S groupwomen from baseline to mid-point and from baseline to end-of-study varied withthose the S-T group experienced. The T-S group experienced medium e!ects forarousal (d ! 0.68), lubrication (d ! 0.54), orgasm (d ! 0.63) and pain (d ! 0.43),large e!ect on the full-scale score (d ! 0.77) and a very large increase insatisfaction (d ! 1.15). The significant S-T group e!ects were medium e!ects forarousal (d ! 0.45), satisfaction (d ! 0.61) and the full-scale score (d ! 0.49). Thiscan be seen graphically in Figure 2. When sexual function scales were tested fordi!erences according to the drug taken by the women’s partners, that is, alltadalafil responses versus all sildenafil responses, no significant di!erences werefound.

The men showed significant improvements in all IIEF sub-scales and examina-tion of the separated medication groups found no significant di!erences between thegroups at either mid-point or end of study. However the standardized e!ect statisticsshowed variation between the groups; the T-S group recorded medium increases inOF (d ! 0.53) and SD (d ! 0.6), very large e!ects on IS (d ! 1.19), on EF(d ! 1.86), OS (d ! 1.67) and full-scale scores (d ! 1.52). The S-T group e!ects weresmall for OF (d ! 0.37) and SD (d ! 0.32), large for IS (d ! 0.95), OS (d ! 1.12)full-scale (d ! 1.19) and EF (d ! 1.53). Figure 3 details the changes by group aseach progressed through the study.

Preference for short or long-acting PDE5i by participants

At the end of the study all women who completed the study (n ! 96) were asked ifthey preferred one of the drugs their partner had taken rather than the other. Ninety-one of the women expressed a preference, with a further four stating either drugworked for their partner so they had no particular preference and one woman sayingneither worked well so she preferred neither drug. Of the women who expressed apreference, 76 (83.5%) said they preferred tadalafil while 15 (16.5%) would choosesildenafil for their partner’s treatment of their ED.

The men who completed the study (n ! 96) expressed preferences showing a highlevel of agreement between partners; 71 (85.5%) of the men preferred tadalafil and17 (19%) would choose to use sildenafil for treatment of their ED. As with thewomen, five expressed no strong preference and data was not collected for theremaining three men.



Discussion

This study shows the extent of the significant and positive impact on women oftreatment of their partner’s ED with tadalafil and sildenafil. In addition the menrecorded significant and positive changes in their sexual function as a result ofthe PDE5i treatment of their ED. Taken alone these are not totally novel findings,but this was a larger and prospective study than had previously investigated theseissues in couples during ED treatment. In addition this study showed that, whilethe improvements in sexual function experienced by the couples did not vary agreat deal between the short- or long-acting drug, both women and their partnersexpressed a strong preference for the longer-acting drug. Reasons for this arevarious and detailed elsewhere (Conaglen & Conaglen, 2008) but this study addsunderstanding of how questionnaire responses capture the changes that cameabout for the couples in association with treatment for the men’s ED.

At the beginning of the study a number of women scored below the clinical cut-o! for normal sexual function. This may imply that the woman involved has a sexualdysfunction herself, although alternatively, her partner’s erectile di"culties mayaccount for most of the minimal scores recorded by these women. A feature of theFSFI measure is that if a couple has not had any sexual activity during the prior fourweeks most domains will yield a zero score. Most of the women in this study wereexperiencing some sexual activity, so the lower scores recorded by the majority of thewomen probably relate to them experiencing lesser quality sexual activity prior totheir partner receiving treatment for his ED.

Figure 2. Significant changes in FSFI by medication randomization group. Notes: T-S:Tadalafil then sildenafil; S-T: Sildenafil then tadalafil.



Similarly many men recorded low ‘dysfunctional’ scores on various scales withinthe IIEF; this measure, too, defines male sexual problems in a way that gives pre-eminence to the erectile function aspect of sexual activity over the prior four weeksonly; this results in men who have been avoiding sexual activity, whether capable ofit or not, being recorded as dysfunctional.

Previous studies of women’s sexual function changes in response to PDE5itreatment of their partners have found some similar sub-scale comparisons; like thisstudy, Cayan and colleagues (2004) showed no significant changes in women’s sexualdesire when their partners were treated. Whether the reason for this relates to thefemale participants having a steady sexual desire level prior to and throughout bothstudies or a relative lack of sensitivity of the FSFI for changes in sexual desire inwomen is a consideration for further research.

The FEMALE Study (Fisher, Rosen, Eardley et al., 2005) asked women,retrospectively, whether their partner’s oral treatment for ED had improved theirpersonal sexual function; this study reported results from 36% of the partners andconcluded that treatment of a man’s ED also had a significant positive impact on thefemale partner’s sexual function. In our study, much of the putative sexual dysfunctionexperienced by the women was reversed by the men being treated with oral EDmedications, indicating more reliably the wider e!ect of ED treatments for couples;previous studies have been limited to retrospective or single point in time assessment.

The women’s reporting of sexual pain during this study is another area wherefindings di!er from previous reports. The FEMALES study (Fisher, Rosen,

Figure 3. Significant changes in IIEF by medication randomization group. Notes: T-S:Tadalafil then sildenafil; S-T: Sildenafil then tadalafil.



Eardley, et al., 2005), retrospective questioning of women about whether theyexperienced sexual pain prior to their partner’s ED and once he had developed ED,stated that the women reported no change in their pain levels with the developmentof their partner’s ED. This same group reported a significantly greater proportion ofwomen experiencing pain once their partners were treated with vardenafil, comparedto those whose partners received placebo. However, a further paper describing FSFIchanges in women in the same study reported a slight but not significant rise(indicating improvement) in pain scores (Goldstein et al., 2005). In the present studywomen reported significantly less pain once their partners were treated. Our datawere collected prospectively unlike that of both papers cited above. Another possibleexplanation includes the psychological aspects to the women’s sexual experience.During their interviews (papers in preparation) many women reported feelinganxious about sexual activity prior to treatment because of the probability of failureand the consequences of this failure for the couple. They reported much less anxietyonce their partners were using one or other of the medications. This decrease inanxiety would have potential benefits for their arousal and enjoyment of the activity,along with their partner’s more reliable erection and greater enjoyment, resulting in aconcomitant reduction in pain for the women. In addition, these women had chosento participate in the study from the outset, being prepared for increased sexualactivity once their partner began PDE5i treatment.

Another finding that di!ers from previous studies relates to the men’s sexualdesire levels as recorded by the IIEF. In this study men’s sexual desire levels didimprove significantly from baseline to mid-point and end-of-study. Previous studieshave been equivocal about this with early sildenafil studies showing no change tosexual desire (Goldstein et al., 1998), while tadalafil studies showed some change(Padma-Nathan et al., 2001). As the majority of couples in this study were in long-term relationships, we postulate that the men in our study may have attributed theirlack of interest in sex to their ED and recorded significant changes because in theirtreated state they were once more interested in sexual activity. This fits with clinicalexperience where men can describe themselves as lacking interest in sex becausethey have less ability to perform when experiencing erectile problems. Why suchfindings have not occurred more consistently in previous studies warrants furtherinvestigation.

The slight decrease in FSFI scores from mid-point to end-of-study warrants someexplanation. These seem to reflect the slight drop in excitement/satisfaction/noveltyvalue that the mid-point scores represented. Couples were very pleased to recoverfunction during phase 1 of the study and their habituation to the renewed ability toenjoy sexual experiences is reflected in the slightly lower end of study scores ascompared to mid-point. Those sub-scales of the FSFI that had significant drops werethe arousal or excitement phase of activity and satisfaction, both of which areexemplars. Despite this, the overall end of study scores showed decided benefits forthe women after six months treatment for their partners. The magnitude of thechanges in satisfaction for both partners was noteworthy. However, why one groupof women recorded a very large e!ect (T-S), whereas the other reported onlya medium e!ect (baseline to mid-point) cannot be clear from questionnaire responsesonly. Nor is the rationale for the preference percentages clear, although the clearlylarger increase in satisfaction for the women whose partners used tadalafil first, maywell relate to the preference for that drug being higher overall. These variationsare best clarified by interviews and other aspects of this study sought clearer



understanding from the women as to what their own sexual function was like beforeand during their partner’s treatment for ED and what factors prompted them toprefer one medication over another (papers in preparation). A further considerationin this regard is that including a placebo group in the study may have assisted indetermining changes that were due to non-medication e!ects. While such a groupwould have been desirable, the expense involved was not sustainable, so our findingsshould be viewed with this possible limitation in mind.

Previous studies recording partner satisfaction with ED medications foundno di!erences between the satisfaction increases from patients and partners(Althof et al., 2006). However, that study used a specific treatment satisfactionquestionnaire for both partners that would therefore be more likely to yield similarchange levels in both respondents, whereas we have relied on the satisfaction sub-scales from two parallel but di!erent measures. We found that the women recordeda 25% increase in satisfaction by mid-point of the study compared with a 49.7%increase for the men. Additionally, the mid- to end-point comparison was a 5.24%drop for the women while the men recorded a 2.69% decrease on overallsatisfaction levels. We did note, though, that satisfaction measure correlationsbecame stronger during the study and percentage changes in satisfaction on each ofthe measures used significantly increased for men (145.7%) and women (118%)from baseline to end-of-study.

Another previous study assessed female partners of men with ED using the BriefIndex of Sexual Function in Women (BISF-W: Taylor, Rosen, & Leiblum, 1994)questionnaire and made the point that a significant proportion of men with EDhave partners with sexual di"culties (Greenstein et al., 2006). We found a similarproportion of the partners in this study scored below the ‘‘clinical cut-o!’’ on thescale we used at baseline, but were no longer ‘‘dysfunctional’’ once their partner hadbeen treated. However, in the Greenstein study there was no reported correlationbetween the male and female sexual function and no treatment within the study,although the authors did suggest engaging the couple in the therapeutic process sothat di"culties experienced by both partners can be addressed when treating sexualdysfunctions in men, a recommendation we endorse.

In conclusion we have shown how the sexual problems in a sample of coupleswith ED can be related to the man’s problem and alter with treatment of the ED.However, a number of questions are raised by the variation in size of e!ect for thecouples in the medication randomization groups. For example, do the women havesexual problems unrelated to their partner’s ED? Do the di!erent medications havevariable impact on the women for reasons other than their e!ectiveness on erections?To clarify these issues requires more than standard psychometric measures. Theclinical implications of this study are that: (1) questionnaires only tell part of thestory, (2) the man’s level of ED is only part of the problem and (3) the partners ofmen with ED might well be more willing for their men to be treated if theyunderstood the potential positive impact of a man’s ED treatment on their ownsexual problems. There is still much to be understood about how couples in a sexualrelationship experiencing di"culties impact each other’s function and satisfaction.

Notes on contributors

Helen M. Conaglen is a Clinical Psychologist, currently a Lecturer at Deakin University inMelbourne, Australia. At the time the study was conducted she was working in Hamilton,New Zealand carrying out research and a clinical practice specializing in sexual dysfunction.



Her research focus is the impact on couples of various medical conditions contributing tosexual dysfunction.

Amy R. Williamson is currently a research fellow at Monash University, Melbourne, Australiacarrying out research in the Monash University Accident Research Centre.

John V. Conaglen is Director of Endocrinology at Waikato Hospital and Associate Professorin Medicine at Waikato Clinical School, in Hamilton New Zealand. He is the foundingDirector of the Sexual Research Charitable Trust and has 30 years clinical experience workingin the field of sexual dysfunction. Current research interests include studies into the impact ofsexual dysfunction on the couple, as well as basic research into genetic and molecularmechanisms of pituitary tumours as well as the impact of growth factors in heart failure.

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