Sexual function in first-time contraceptive ring and contraceptive patch users

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1 CONTRACEPTION Sexual function in first-time contraceptive ring and contraceptive patch users Clarisa R. Gracia, M.D., M.S.C.E., a Mary D. Sammel, Sc.D., b Sarah Charlesworth, B.Sc., C.C.R.C., a Hui Lin, M.S., c Kurt T. Barnhart, M.D., M.S.C.E., a and Mitchell D. Creinin, M.D. d a Department of Obstetrics and Gynecology; b Department of Biostatistics and Epidemiology; c Center for Research and Reproduction and Women s Health, University of Pennsylvania, Philadelphia, Pennsylvania; and d Department of Obstetrics and Gynecology, Magee-Women s Hospital, Pittsburgh, Pennsylvania Objective: To assess sexual function of first-time users of the contraceptive ring and contraceptive patch. Design: Open-label randomized trial. Setting: Multicenter study. Patient(s): A total of 500 healthy, premenopausal, nonpregnant women who had recently used combined oral contraceptives. Intervention(s): Contraceptive ring vs. contraceptive patch. Main Outcome Measure(s): Subjects completed the Female Sexual Function Index (FSFI) before randomization to the study product and after 3 months. Unadjusted and adjusted changes in total and domain FSFI scores from baseline to exit were compared between treatment groups using linear regression (intention-to-treat approach). Result(s): Final adjusted mean total FSFI scores increased by 0.32 points in the patch group and decreased by 0.74 points in the ring group. Subjects in the ring group had worsening scores in the areas of arousal (score change ring vs patch), lubrication (score change ring vs patch), and pain (score change ring vs patch). Conclusion(s): Among recent combined oral contraceptive users, slight decrements in sexual function scores were noted with contraceptive ring use overall and in several domains of sexual functioning, whereas slight increases were noted with patch use. However, for both products, these changes are not likely to be clinically significant. (Fertil Steril Ò 2010;93:21 8. Ó2010 by American Society for Reproductive Medicine.) Key Words: FSFI, sexuality, desire, arousal, contraception, OrthoEvra, NuvaRing Female sexual dysfunction is prevalent in the United States; it affects more than 40% of women aged years and seems to be influenced by a variety of emotional, psychological, and physiologic factors (1). The combined oral contraceptive (COC), daily orally administered estrogen and progestincontaining contraceptive, was introduced in the United States for birth control in 1960 and remains the most commonly used Received May 29, 2008; revised September 1, 2008; accepted September 18, 2008; published online October 31, M.D.C. receives research funding from Bayer and Organon and serves as a consultand for Organon and Conceptus. K.T.B. receives research funding from Organon, Wyeth-Ayerst, Johnson & Johnson, Duramed, Xanodyne, Boehringer Ingelheim, Third Wave, Pfeizer, and MGI Pharma; serves on the speakers bureau for Organon; and serves as a consultant for Novo Nordisk. C.R.G. has nothing to disclose. M.D.S. has nothing to disclose. S.C. has nothing to disclose. H.L. has nothing to disclose. Supported by an investigator-initiated grant from Organon to the Magee- Women s Health Corporation. M.D.C. received independent research funding from Organon as the principal investigator for the entire multicenter study (ClinicalTrials.gov identifier: NCT ). Funding to other study sites for this study was directly from the Magee-Women s Research Institute and Foundation using funds from Organon. Reprint requests: Clarisa R. Gracia, M.D., 3701 Market Street, Suite 800, Philadelphia, PA (FAX: ; cgracia@obgyn. upenn.edu). method in the United States (2). Despite its widespread use, the effect of combined contraception on female sexuality is not clear. It has been hypothesized that combined contraceptives could have a detrimental affect on sexual function because free T and E 2 concentrations are decreased, a result of suppressed ovarian steroid hormone production and increased sex hormone-binding globulin associated with use (3, 4).However, the link between COCs and decreased sexual functioning has not been substantiated (5). Some studies indicate that COC users can experience a decrease in libido (6, 7), whereas others report that overall sexual enjoyment and frequency increases (3, 7 9), and still other studies show no effect of COC on sexual function whatsoever (4). McCoy et al. (10) demonstrated that although COC use was associated with less vaginal lubrication compared with nonuse, subjects using COCs had increased sexual thoughts and fantasies. Androgen replacement in women complaining of COC-related sexual dysfunction does not seem to be beneficial (11). In actuality, decreased libido may be related to the variability in hormones rather than absolute level (12). In 2002, two combined hormonal products became available to U.S. consumers; these deliver the same types of hormones /10/$36.00 Fertility and Sterility â Vol. 93, No. 1, January doi: /j.fertnstert Copyright ª2010 American Society for Reproductive Medicine, Published by Elsevier Inc.

2 found in COCs but without requiring daily compliance. The contraceptive vaginal ring (NuvaRing; Organon, Roseland, New Jersey) and the contraceptive patch (OrthoEvra; Ortho Pharmaceuticals, Raritan, NJ) were developed as a means of potentially improving compliance to improve patient satisfaction and efficacy as compared with COCs. The contraceptive vaginal ring is a flexible 2-inch-diameter product containing etonogestrel and ethinyl E 2 and is placed in the vagina. The contraceptive patch is an adhesive patch containing norelgestromin and ethinyl E 2 that is applied to clean dry skin. Both methods are placed during the early follicular phase of the cycle for 3 weeks and removed for 1 week. Limited studies have been conducted to evaluate the sexual function of women using the new combination contraceptive delivery systems. These new delivery methods provide therapeutic hormone levels with low daily doses and less variability compared with traditional COCs (13 15). We hypothesized that women using both of these formulations would have improved sexual functioning because of the more stable circulating levels of exogenous hormones compared with recent COC use. In addition, we believed that the increased local concentration of ethinyl E 2 in the vagina associated with the contraceptive ring would result in less dyspareunia compared with the contraceptive patch. Support for this hypothesis comes from findings of a recent trial comparing contraceptive ring with COC, in which subjects reported more vaginal wetness during ring use (16).In addition, two small randomized studies comparing sexual function in vaginal ring users compared with COC users revealed improvements in sexual desire and sexual satisfaction in vaginal ring users (7, 9). The aims of this study were [1] to compare measures of sexual functioning in women at baseline (either with or without COC use) with measures of sexual functioning after 3 months of patch or ring use; and [2] to compare changes in sexual functioning in women randomized to contraceptive patch vs. contraceptive ring. This study was a planned substudy of a randomized controlled trial conducted primarily to compare continuation rates after 3 months of use of the contraceptive ring and the contraceptive patch (17). MATERIALS AND METHODS This study was conducted as part of an open-label, prospective, multicenter, randomized comparative continuation trial of contraceptive ring and contraceptive patch (17). The study was reviewed and approved by the institutional review boards of each of the 10 participating institutions. The University of Pittsburgh served as the sponsoring institution; all protocol changes were submitted and approved by the University of Pittsburgh Institutional Review Board before submission to other institutions. All participants were informed and provided written consent before participation in the study. Women were recruited in different ways at different centers but primarily by flyers in the community (clinics, around campus, at nearby merchants) advertising a study for women using an oral contraceptive and interested in switching to the ring or patch. Because sexual function (not sexual dissatisfaction) was a secondary outcome, there was no mention of that variable in the advertising or in the screening materials before consent was provided. We enrolled 500 healthy, premenopausal, nonpregnant women who had no past experience using the contraceptive ring or patch and were currently using COCs or had discontinued COC use within 3 months of the enrollment date. All subjects stated that they were content with their COCs and would otherwise continue their product; for the women who had recently discontinued, the reasons for discontinuation needed to be unrelated to satisfaction. Women must also have been willing to avoid intravaginal products unless prescribed by an investigator. Women who were heterosexually active needed to have been with a single partner for at least the past 3 months and not planning on having a new partner while participating in the study, be willing to use their assigned method as their primary contraceptive for the duration of the study, and willing to avoid anal intercourse during the study. Detailed exclusion criteria are described in the previously published report (17). After informed consent was obtained a screening visit was conducted. Once eligibility was confirmed, the patient was enrolled in the study and randomized to use either the contraceptive ring or patch for four continuous cycles beginning with the first day of menses after the enrollment visit. Subjects were given four cycles of their assigned study medication with detailed instructions. The final visit was scheduled during the first week of the fourth cycle or sooner if the patient requested or required early discontinuation. The Female Sexual Function Index (FSFI) was administered to participants at the enrollment visit and at the final visit. This questionnaire is a 19-item, multidimensional self-report instrument for assessing the key dimensions of sexual function in women as outlined in the recent International Consensus Development Conference of Female Sexual Dysfunction (18). Domains include desire, arousal, lubrication, orgasm, satisfaction, and pain. Each question is answered using a 5-point Likert scale, and scores are transformed by multiplying domain scores by a factor of to equally weigh each domain depending on the number of questions per domain (two questions assess desire and have weights of 0.6 each, three questions assess orgasm, satisfaction, and pain and have weights of 0.4 each, and four questions assess arousal and lubrication and have weights of 0.3 each). The transformed maximum score for each domain is 6, and the maximum transformed total score is 36. Changing the response of 1 question by 1 interval on the Likert scale would change the total score by The questionnaire was specifically designed to be used in epidemiologic studies to assess these disorders as classified by the consensus conference. Of all instruments demonstrating acceptable reliability, the FSFI is the only published instrument validated and normed on a sample of women with clinically diagnosed female sexual dysfunction. Specifically, the questionnaire has been found to be valid and reliable in women with sexual arousal disorder, orgasmic disorder, and hypoactive sexual desire disorder (19, 20). A FSFI total score of has been found to be the optimal cutoff score for differentiating women with and without 22 Gracia et al. Sexual function in ring and patch users Vol. 93, No. 1, January 2010

3 sexual dysfunction (21). Although there is no literature defining a clinically important difference in scores, a change of at least 1 point in the total score might be considered clinically important in our view. Assessment of Partner Status At enrollment subjects were asked Are you in a sexual relationship with a man? At study exit, subjects were asked Did you have sex with a man during the study? Subjects who responded affirmatively to both questions were considered to have had a male partner during the study. Subjects who responded negatively to the first but affirmatively to the second were considered to have acquired a partner during the study. Subjects who responded affirmatively to the first but negatively to the second were considered to have lost a partner during the study. Those who responded negatively to both questions were considered to never have had a partner during the study. Because partner status is known to be associated with sexual function, this variable was explored as an independent predictor and a confounder in this analysis. At study endpoint subjects were also asked several questions regarding whether they or their partners could feel the ring during intercourse and whether their partner minded that they were using the product. Responses to these questions were dichotomized so that an answer other than never was considered an affirmative response. These questions were explored as factors associated with sexual function. Statistical Analyses All subjects randomized were considered the intent-to-treat population. For these analyses, participants without data at endpoint were assumed to have experienced no change over the 3 months of study. That is, the missing data were imputed by carrying the last observation forward. Additional analyses examined the change for the participants who returned at endpoint (completer analysis). Baseline demographic data and mean total and domain scores of the FSFI were compared according to treatment group using Student s t-test, Fisher s exact test, or the c 2 test, where appropriate. Change in sexual function was measured as the differences from endpoint to baseline in total and domain FSFI scores, which were compared between treatment groups. The proportion of subjects with sexual dysfunction, as defined by an FSFI total score <26.55, were compared between groups at baseline and endpoint. Among those with sexual dysfunction, mean score change was compared between treatment groups. Multivariable linear regression models were used to compare changes in overall and domain scores between groups, adjusting for baseline overall score, study site, age, and partner status. A subgroup analysis was conducted in those with a partner at baseline. Finally, the association between several other variables and sexual function change were explored to help explain the differences in sexual function change between groups. Baseline characteristics were compared between subjects who continued and subjects who discontinued the study. A two-tailed P value <.05 was considered statistically significant. RESULTS Between June 2005 and September 2006, 500 subjects were enrolled. One subject was excluded from analysis (randomized to the contraceptive ring group) because she was enrolled against protocol requirements. There were 477 subjects with complete baseline and endpoint FSFI data (240 in the contraceptive ring group, 237 in the contraceptive patch group). Twenty-one subjects (4%) did not complete the study: 12 women were lost to follow-up, 6 women withdrew consent after randomization, and 3 women never started their assigned treatment. In addition, 1 subject had insufficient data at endpoint for evaluation. Baseline characteristics were similar for subjects who did and did not complete the study, except that subjects who did not complete the study were more likely to be unemployed (P¼.041). Among subjects in the treatment groups, demographic characteristics were similar except that contraceptive ring users were older than patch users (26.2 vs years, P¼.014). Most subjects considered themselves Caucasian, had graduated from high school, reported being single, and were in a relationship with a man at baseline (Table 1). The mean overall FSFI score at baseline was 27.7, and there was no significant difference in overall or domain scores between the treatment groups. Using a cutoff of <26.55 for the overall FSFI score for sexual dysfunction, there was no difference in the proportion of subjects with sexual dysfunction at baseline (26.8% in the contraceptive ring group vs. 29.7% in the contraceptive patch group; P¼.47). However, at endpoint there were a greater proportion of subjects with sexual dysfunction in the contraceptive ring group compared with the contraceptive patch group (37.9% vs. 28.7%, respectively; P¼.03). Unadjusted Analyses Table 2 presents the unadjusted associations between treatment group and change in overall and domain FSFI scores from endpoint comparing all randomized participants (intention-to-treat analysis). Overall and domain sexual function scores declined in the contraceptive ring group and increased in the contraceptive patch group. However, the difference in change scores between groups only reached statistical significance for the change in pain scores. In the subset of subjects with sexual dysfunction (n ¼ 155), the change in overall sexual function scores was similar between the two groups (patch 3.87 vs. ring 2.39; P¼.315). Multivariable Model Results of the multivariable linear regression model comparing the change scores in the contraceptive ring group compared with the contraceptive patch group adjusting for Fertility and Sterility â 23

4 TABLE 1 Baseline characteristics of study population. Variable Contraceptive patch (n [ 250) Contraceptive ring (n [ 249) P value Age (y) Body mass index (kg/m 2 ) Oral contraceptive use.604 Current (active) 210 (84) 208 (84) Recently discontinued (within 40 (16) 40 (16) 3 mo) Race.944 White 179 (72) 179 (72) Black 27 (11) 29 (12) Asian 16 (6) 13 (5) Other 28 (11) 28 (11) Smoker 228 (91) 229 (92).757 Gravidity (77) 193 (78) 1 23 (9) 27 (11) R2 34 (14) 29 (12) Parity (86) 218 (28) 1 19 (8) 15 (6) R2 16 (6) 16 (6) Marital status.177 Single 204 (82) 187 (75) Married 39 (16) 55 (22) Divorced/separated (3) 7 (3) Education.068 %12 y 16 (6) 16 (6) Some college 98 (39) 76 (31) College graduate 101 (40) 105 (42) Graduate school 34 (14) 53 (21) Work status.456 Full time 96 (38) 108 (43) Part time 30 (12) 33 (13) Student 107 (43) 89 (36) Other 17 (7) 19 (8) Income (US$).524 <20, (39) 97 (39) 20,000 40, (32) 68 (27) 40,001 60, (21) 56 (22) >60, (8) 28 (11) In a relationship with a man 221 (88) 226 (91).396 FSFI overall score (baseline) a Desire Arousal Lubrication Orgasm Satisfaction Pain Note: Values are mean SD or number (percentage). a Female Sexual Function Index (maximum overall score is 36, maximum score for each domain is 6). Gracia. Sexual function in ring and patch users. Fertil Steril Gracia et al. Sexual function in ring and patch users Vol. 93, No. 1, January 2010

5 TABLE 2 Unadjusted associations of overall change in FSFI score and domains with treatment group for all participants. Difference in score from endpoint to baseline (95% CI) Domain Contraceptive patch (n [ 250) Contraceptive ring (n [ 249) P value Full score ( 0.504, 1.143) ( 1.686, 0.199).095 Desire ( 0.965, 0.154) ( 0.165, 0.108).540 Arousal ( 0.164, 0.183) ( 0.356, 0.018).170 Lubrication ( 0.134, 0.196) ( 0.395, 0.010).070 Orgasm ( 0.062, 0.309) ( 0.273, 0.132).165 Satisfaction ( 0.254, 0.142) ( 0.328, 0.106).713 Pain ( 0.002, 0.366) ( 0.400, 0.076).024 Gracia. Sexual function in ring and patch users. Fertil Steril baseline overall score, age, study site, and partner status throughout study are presented in Table 3. Overall sexual function scores decreased in the contraceptive ring group compared with the contraceptive patch group (P¼.012). Analysis of domain scores revealed statistically significant worsening of arousal, lubrication, and sexual pain scores in the contraceptive ring group (arousal P¼.047, lubrication P¼.013, pain P¼.005). Partner status was highly associated with overall and domain sexual function scores. Results were similar with analysis using only baseline partner status as a covariate rather than partner status throughout the study. Male Partner Status The presence of a male partner was explored as an independent predictor as well as a potential confounder of the observed associations. The majority, 419 subjects, reported having a male partner during the duration of the study; 26 subjects acquired a male partner during the study, whereas 10 subjects lost a male partner during the study. There were 22 subjects who were considered to not have had a male sexual partner at all during the study. The FSFI scores were compared among these categories of male partner status. Overall sexual function scores were significantly associated with partner status. Scores improved significantly with acquisition of a partner and decreased with loss of a partner. Subjects without a partner at both visits had consistently lower scores on the FSFI. Analysis of mean overall FSFI scores in subjects with a male partner at baseline revealed no significant difference in scores by treatment group (mean overall FSFI score 29 with contraceptive ring vs with contraceptive patch; P¼.52). However, mean scores at endpoint in subjects with a male partner were significantly lower in the contraceptive ring group (mean overall FSFI score 27.4 with contraceptive ring vs with contraceptive patch; P¼.002). Similarly when the analysis was restricted to subjects with a male sexual partner throughout the study, the proportion of subjects with sexual dysfunction as defined by an overall FSFI score TABLE 3 Adjusted FSFI change scores in contraceptive patch users compared with contraceptive ring users. Change score (95% CI) Domain Contraceptive patch (n [ 250) Contraceptive ring (n [ 249) P value Full score ( 0.394, 1.033) ( 1.459, 0.028).012 Desire ( 0.098, 0.155) ( 0.156, 0.098).307 Arousal ( 0.145, 0.164) ( 0.323, 0.014).047 Lubrication ( 0.122, 0.184) ( 0.355, 0.049).013 Orgasm ( 0.046, 0.293) ( 0.241, 0.099).085 Satisfaction ( 0.234, 0.122) ( 0.289, 0.067).347 Pain ( 0.000, 0.365) ( 0.345, 0.020).005 Note: Multivariable intention-to-treat linear regression model adjusted for full FSFI score at baseline, age, study site, and partner status throughout study. Gracia. Sexual function in ring and patch users. Fertil Steril Fertility and Sterility â 25

6 <26.55 was greater in subjects randomized to contraceptive ring compared with contraceptive patch at endpoint (35.6% with contraceptive ring vs. 24.2% with contraceptive patch; P¼.01), even though the difference was not statistically different at baseline (24.8% with contraceptive ring vs. 18.6% with contraceptive patch; P¼.11). Subgroup Analysis Table 4 presents results of a subgroup analysis of change in sexual function between groups in subjects with a partner both at baseline and at study endpoint. Amongst the 447 subjects who had a partner at baseline (contraceptive patch, n ¼ 221; contraceptive ring, n ¼ 226), scores declined in the contraceptive ring group compared with the contraceptive patch group in both unadjusted and adjusted analyses. Changes in scores were significantly different in the overall score and in the domains of arousal, lubrication, orgasm, and pain. Exploring Reasons for Decreased Sexual Function To assess possible explanations for decreased sexual function scores in the vaginal ring group, we explored whether the difference in sexual function scores was associated with an affirmative response to feeling the ring during intercourse. Overall, 25% of contraceptive patch users and 37% of contraceptive ring users reported feeling the product during intercourse. In the contraceptive ring group, feeling the ring was associated with a decrease in scores over the study (score change 1.80; 95% confidence interval [CI] 3.30, 0.30; P¼.043), and reporting that the partner minded her using the ring was associated with a decrease in scores over the study (score change 2.58; 95% CI 4.31, 0.85; P¼.005). However, reporting that the male partner felt the ring during intercourse was not associated with a decrease in scores over the study. DISCUSSION Advancements within hormonal contraceptive delivery systems have led to the development of nondaily methods that provide the potential for increased compliance. Although limited studies have been conducted to evaluate the sexual function of women using the new combination contraceptive delivery systems, reports indicate improvements in sexual function with the contraceptive ring compared with the COC. In this study, we used a validated questionnaire to compare the change in sexual functioning over 3 months in women recently satisfied with the COC who were subsequently randomized to the contraceptive patch or the contraceptive ring. We found that sexual function did not improve as hypothesized in the contraceptive ring group. Overall scores declined in the contraceptive ring group compared with the contraceptive patch group. Particular areas of decline included arousal, lubrication, and pain. The decline in total and specific domain scores in the contraceptive ring group was somewhat surprising given the existing data. A recent randomized study of 190 women comparing sexual function with the vaginal ring and two COCs revealed progressive improvements in sexual desire and sexual satisfaction over 12 months in the vaginal ring group compared with the COC groups (7). Another small randomized study revealed greater improvements in sexual complicity and satisfaction in ring users compared with COC users over six cycles (9). Unlike these studies, our study did not show such an improvement in sexual function with the vaginal ring. Several differences exist between these studies that should be pointed out. First, prior studies have been conducted in subjects not necessarily taking hormonal contraceptives and who were started on either the COC or the contraceptive ring. Inclusion to this particular study required subjects to have been satisfied with recent COC use. Therefore, the findings should not be generalized to all subjects considering combined contraception. In addition, different questionnaires were administered to assess sexual TABLE 4 Adjusted FSFI change scores in contraceptive patch users compared to Contraceptive Ring users restricted to participants with a sexual partner both at baseline and endpoint (change, 95% CI). Change score (95% CI) Domain Contraceptive patch (n [ 221) Contraceptive ring (n [ 226) P value Full score ( 0.644, 0.713) ( 1.789, 0.435).007 Desire ( 0.127, 0.143) ( 0.178, 0.093).480 Arousal ( 0.159, 0.139) ( 0.411, 0.114).011 Lubrication ( 0.106, 0.173) ( 0.403, 0.124).002 Orgasm ( 0.078, 0.254) ( 0.310, 0.021).029 Satisfaction ( 0.351, 0.012) ( 0.408, 0.070).365 Pain ( 0.071, 0.263) ( 0.327, 0.007).019 Note: Multivariable intention-to-treat linear regression model adjusted for full FSFI score at baseline, age, and study site. Gracia. Sexual function in ring and patch users. Fertil Steril Gracia et al. Sexual function in ring and patch users Vol. 93, No. 1, January 2010

7 functioning, and all subjects were in sexual relationships with partners. These differences could have influenced the results. Despite the decline in sexual function over the study in vaginal ring users, it must be emphasized that the changes in sexual function scores in both groups, although statistically significant, may not indicate a clinically relevant change in sexual functioning. The total change in scores was less than 1 point out of a total score of 36 in each group. This represents a change in the response of one question by one or two intervals on the 5-point Likert scale. This small difference in scores should be kept in mind when interpreting these data. Nonetheless, we believe that the population chosen is a very relevant population in which to investigate this question because clinicians may change patients from COC use to the contraceptive ring to enhance sexual functioning. This study does not support such an approach. Even in subjects with sexual dysfunction at baseline, there was no difference in sexual function change scores over 3 months between the two groups. Despite the decrease in sexual function observed with the contraceptive ring compared with the contraceptive patch, previous analysis of data from this study indicates that women were much more satisfied with a contraceptive vaginal ring than a contraceptive patch (76% vs. 39%) and were more likely to recommend the ring to their friends. Most (71.0%) women who used the ring planned to continue the ring after the study, whereas most (73.5%) women who used the patch did not plan to continue that method. In our population, 21.6% and 41.6% of ring and patch users, respectively, opted to return to their oral contraceptive after trying their assigned nondaily method. In addition, menses were shorter and less painful with the contraceptive vaginal ring compared with the patch (17). Thus, sexual function is only one small component of product use; according to the overall acceptability results, it is relatively unimportant as compared with side effects or ease of use. It is not entirely clear why sexual function scores declined in the ring group compared with the patch group. We found that sexual change scores were significantly associated with the subjective report of feeling the ring during intercourse and with the subject s partner minding that the subject was using the ring. The physical presence of the ring could not be studied independently of the hormonal effects in this study because treatment allocation was not blinded. This weakness could be overcome in future studies designed specifically to answer questions about sexual functioning with use of a placebo patch and ring in conjunction with randomization to the active product. Interestingly, lubrication scores decreased even though studies have demonstrated increased vaginal discharge. Therefore, it is important to recognize that vaginal wetness does not translate into improved sexual lubrication. We identified other factors that were significantly associated with changes in sexual functioning over the study. Specifically, as found in previous studies, partner status was highly associated with FSFI scores. We also found that women with low baseline FSFI scores were more likely to report improved sexual function over time compared with those who had higher scores at baseline. A major strength of our study was that subjects were randomized to treatment allocation, thus any unidentified confounders of sexual function were evenly distributed. In addition, outcome misclassification should be limited given that a validated sexual function questionnaire was administered in this trial. This questionnaire has been used in a wide variety of populations including young reproductive-aged women such as this one (22, 23). A weakness of our study was that the study was not blinded. Treatment allocation was known to both the investigators and the study participants. It is possible that knowing the treatment may have biased the results if subjects had a preconceived notion about the potential effect of the product on sexual functioning. Another potential weakness is the relatively short duration of the study. It is possible, though not likely, that these methods of contraception result in a delay in changes in sexual functioning. According to the available data, changes in sexual functioning have been reported as early as 3 months in other studies (7). Finally, the generalizability of this study is limited because it was restricted to only those subjects satisfied with recent COC use, and the majority of subjects were Caucasian and had at least a high school education. 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