Quality of sexual life of women using the contraceptive vaginal ring in extended cycles: preliminary report.

The European Journal of Contraception and Reproductive Health Care, 2014; 19: 307–314

Eur J Contracept Reprod Health Care Downloaded from informahealthcare.com by Nyu Medical Center on 06/01/15 For personal use only.

Quality of sexual life of women using the contraceptive vaginal ring in extended cycles: Preliminary report Salvatore Caruso, Stefano Cianci, Chiara Malandrino, Carla Cicero, Lucia Lo Presti and Antonio Cianci Research Group for Sexology, Gynaecological Clinic, Department of Medical Surgical Specialties, University of Catania, Italy ............................................................................................................................................................................................................

ABSTRACT

Objective To evaluate the quality of the sexual life of healthy women who are using a contraceptive vaginal ring (CVR) in extended cycles. Methods Fifty-two women (18 to 32 years old) seeking hormonal contraception were enrolled in this prospective study. Women were to use a CVR releasing daily 15 μg of ethinylestradiol (EE) and 120 μg of etonogestrel (ENG) for 63 days, followed by a four-day hormone-free interval, for two such extended cycles. At baseline and at the first (day 63–73) and second (day 126–134) follow-ups the Female Sexual Function Index (FSFI) and the Short Form-36 (SF-36) questionnaires were administered to investigate, respectively, sexual behaviour and the quality of life (QoL). The Female Sexual Distress Scale (FSDS) was used to verify whether sexual dysfunction caused significant personal distress to the woman. Results The FSFI and FSDS scores obtained at the first and second follow-up appointments detected an improvement with respect to the baseline score (p ⬍ 0.05). QoL measures of body pain, general health and emotional role improved at the first follow-up visit (p ⬍ 0.05); at the second one, all variables showed improvement (p ⬍ 0.05). Conclusion According to these preliminary data the CVR in extended cycles could improve the sexual function and the QoL of women.

K E Y WO R D S

Combined hormonal contraceptive; Contraceptive vaginal ring; Extended cycles; Female Sexual Function Index (FSFI); NuvaRing®; Quality of life; Sexual behaviour

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I N T RO D U C T I O N

Combined hormonal contraceptives (CHCs) can be used flexibly so as to suit women’s needs and wishes with regard to withdrawal bleeding.Therefore, the first step in prescribing a CHC to a woman is to understand her needs and to help her choose the regimen and way of administration that are best for her1. The

objective of contraception should be not only to avoid unwanted pregnancies without interference with the woman’s sexuality and sexual pleasure, but also, if possible, to enhance the latter2,3. Extended cycles of CHC use reduce the frequency of withdrawal bleedings to four times a year or less. Extended and continuous regimens are new options

Correspondence: Salvatore Caruso, MD, Research Group for Sexology, Gynaecological Clinic, Department of Medical Surgical Specialties, University of Catania, Policlinico Via S.Sofia 78, 95124 Catania, Italy. Fax: ⫹ 39 (0)95 3781326. E-mail: [email protected] © 2014 The European Society of Contraception and Reproductive Health DOI: 10.3109/13625187.2014.914488


Use of NuvaRing® in extended cycles and sexuality

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for women desirous of avoiding symptoms of endometriosis, dysmenorrhoea, and other menstruationassociated discomforts4,5. The contraceptive vaginal ring (CVR; NuvaRing®, Merck, Italy) is used in extended cycles by certain women6. After placement in the vagina, the ring releases daily, on average, 15 μg ethinylestradiol (EE) and 120 μg etonogestrel (ENG) over its three-week period of use, which is followed by a one-week ringfree period, according to a traditional 28-day regimen. Withdrawal bleeding is to be expected within two to three days of ring removal. Subsequently, a new ring is inserted and the cycle is repeated. Usually, the CVR ensures good cycle control with a low incidence of irregular bleeding and altered withdrawal bleeding7. Moreover, the CVR does not modify insulin sensitivity and lipid metabolism8. Compared to an oral contraceptive, which must be taken daily, the CVR is associated with a lesser risk of woman-related errors in use9,10. Acceptability of the CVR would be high for both the user and her partner11. There are few studies on CVR extended-use regimens evaluating the bleeding patterns and tolerability12, the non-contraceptive benefits13, and the effects on carbohydrate and lipid metabolism14,15. Our objective was to design a preliminary study to evaluate the quality of life (QoL) and the sexual function of healthy women using a CVR uninterruptedly for 63 days followed by a four-day hormone-free interval, for two such extended cycles.

M AT E R I A L S A N D M E T H O D S

This prospective preliminary study took place at the Family Planning Centre of the Research Group for Sexology, University of Catania, Italy. The study protocol was approved by the Departmental Institutional Review Board and conformed to the ethical guidelines of the 1975 Helsinki Declaration. Informed, written consent was obtained from each woman before she entered the study. Participants did not receive payment of any kind. Subjects and setting During the recruitment period, January to July 2012, 126 women seeking a traditional CHC regimen at the Family Planning Centre were invited to participate in 308

the study. After having been informed about the aim of the study and having received counselling about the usage of extended cycles, such as the likely improvement of premenstrual syndrome and/or dysmenorrhoea, and the occurrence of amenorrhoea, as well as adverse events such as bleeding, nausea, and breast tenderness, 53 women decided not to participate and opted for a CHC traditional regimen. Consequently, 73 women, aged 18 to 40 years (mean age ⫾ standard deviation [SD] of 26.4 ⫾ 6.7) were enrolled. They were sexually active, had no sexual dysfunction, were living for more than six months with a partner also without sexual dysfunction, and were planning to use a CHC for fertility control for at least one year. Forty-five of them (87%) mentioned they wished to have (more) children in the future. We did not gather information about the socio-economic status and the educational level of their partner, or about their own income level or that of their partner. The women were not using any hormonal contraceptives at baseline, and had no contraindications to their use. Previously – for a period from six months to ten years before – 94% of them had used CHCs according to a 21/7 (44%) or a 24/4 (56%) regimen. The discontinuation of CHC usage had been due to a desire for pregnancy (38%), to not having a partner (42%), or to adverse events such as bleeding (12%) and/or premenstrual syndrome (8%), mainly among women on the 21/7 CHC regimen. Moreover, 27% of the participants had used a CHC for treatment of dermatologic symptoms suggestive of a polycystic ovary syndrome. At enrolment, the medical, surgical and medication history was assessed, and physical and gynaecological examinations were performed, to ensure study eligibility on the basis of inclusion and exclusion criteria16. Because ovarian steroids may cyclically influence the sexual behaviour of premenopausal women17, only subjects with ovulatory menstrual cycles were included. To verify this, sonography was performed on days 10, 13 and 16 of the menstrual cycle, and serum progesterone concentrations were measured on cycle day 20 or 21 by enzyme-linked immunoabsorbent assay (ELISA) using commercially available kits (Roche, Monza, Italy). The menstrual cycle was defined as being ‘ovulatory’ when the mean follicular diameter decreased by at least 3 mm (mean maximum follicle diameter was 20.1 ⫾ 3.5 mm), and the serum progesterone was ⬎ 11 ng/ml (normal range 11–27 ng/ml).

The European Journal of Contraception and Reproductive Health Care



Instruments Each woman was interviewed about her sexual history. The interview collected information on sexual activity, desire, number of sexual fantasies, physical arousal sensation, physical arousal lubrication, enjoyment, orgasmic and coital frequency, pain, and relationship with partner. The sexual interview aimed at excluding any woman with sexual dysfunction during the previous six months. To define female sexual dysfunction (FSD), the revised definition and classification of the international consensus development conference on FSD was used18: desire (absent or diminished feelings of sexual interest, absent sexual thoughts or fantasies and a lack of responsive desire); arousal disorder (absence of or markedly diminished feelings of sexual arousal from any type of sexual stimulation with impaired genital sexual arousal); orgasmic disorder (despite the self-report of high sexual arousal/excitement, there is either lack of orgasm, markedly diminished intensity of orgasmic sensations or marked delay of orgasm from any kind of stimulation); vaginismus (the persistent or recurrent difficulties of the woman to allow vaginal entry of a penis, a finger, and/or any object, despite the woman’s expressed wish to do so); dyspareunia (the persistent or recurrent pain with attempted or complete vaginal entry and/or penile-vaginal intercourse). Quality of Life (QoL) and sexual function of women were assessed with standardised, validated questionnaires. The Short Form-36 (SF-36) questionnaire was used to assess QoL19. It contains 36 questions grouped into eight categories: physical functioning (ten items), physical role functioning (four items), bodily pain (two items), general health (six items), vitality (four items), social functioning (two items), emotional role functioning (three items), and mental health (five items). Women were instructed to place a mark on a one to five or six-point visual analogue scale (Likert scale) or to answer yes or no, concerning specific items. Thereafter, the scores for all items of each category were added up and the mean values calculated. Consequently, eight scale scores were obtained, with higher scores indicating better functioning. Sexual function was assessed using the selfadministered Female Sexual Function Index (FSFI)20. The FSFI consists of six domains: desire (two items), arousal (four items), lubrication (four items), orgasm (three items), satisfaction (three items), and pain (three

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items). Women had to answer on a five or six-point Likert scale, ranging from 0 (no sexual activity) or 1 (never/very low) to 5 (always/very high) for the first five domains, and from 5 (almost never or never) to 1 (almost always or always) or 0 (no sexual activity) for pain. Individual domain scores were obtained by adding the scores of the individual items and multiplying the sum by the domain factor: 0.6 for desire; 0.3 for arousal and lubrication; and 0.4 for orgasm, satisfaction and pain. Finally, the total score – which ranges from 2 to 36 – was obtained by adding up the six domain scores. A cut-off of 26 is usually accepted for diagnosis of sexual dysfunction in women within a wide age range21. Moreover, for diagnosis of sexual dysfunction an essential element is the requirement that the condition causes significant personal distress for the woman. Therefore, the Female Sexual Distress Scale (FSDS) was used22. The FSDS consists of 12 items. The maximum score is 48. An FSDS score of ⱖ 15 corresponds to clinically significant distress. We considered women with a FSFI score of less than 26 to be affected by sexual dysfunction if they also had a FSDS score of 15 or greater. The SF-36, FSFI and FSDS questionnaires were administered before starting CVR usage, and again at the first (day 63–73) and the second (day 126–134) follow-up appointments. Furthermore, each subject received a diary to record daily sexual events as well as adverse events, before and during the CVR usage. Statistical analysis On the basis of our previous studies1,3, assuming a standard deviation (SD) of 1.7 and a mean difference of 0.5 in the total FSFI score at p ⬍ 0.05, the sample size calculation indicated that 45 subjects would be the minimum number required for the study to achieve 95% power. The primary endpoint was to evaluate changes, if any, of the total FSFI score. Intention-to-treat analyses were performed for all efficacy variables with the last observation carried forward for patients who prematurely discontinued treatment. All women who had a baseline evaluation and at least one efficacy assessment after the baseline examination/ interview were included in the analysis. Paired Student’s t test was used to compare the values obtained at baseline with those of both followups from the SF-36 domains. For comparisons of the values obtained from the FSFI and the FSDS


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items between baseline and the first and second follow-ups, the nonparametric Wilcoxon rank-sum test with z values was used. Scores are presented as means ⫾ SD. The result was considered statistically significant when p was ⬍ 0.05. For statistical analysis we employed the Primer of Biostatistics statistical computer package23.


R E S U LT S

Of the 73 women, 16 (21%) refused to use the CVR in extended cycles after the baseline evaluation; they chose to have their monthly withdrawal bleeding using the ring in accordance with the original regimen of 28-day cycles. Five (7%) women having both sonographic aspects of anovulatory cycles and serum progesterone levels ⬍ 11 ng/ml were also excluded from the study. Consequently, 52 (71%) women aged 18–32 years, with a mean age ⫾ SD of 23.8 ⫾ 3.8 years constituted the sample undergoing clinical and statistical evaluation. Although this was not an inclusion criterion, all women and their partners were native Italians. Table 1 shows their demographic characteristics. Women reported mild adverse events that did not cause discontinuation, arising during the first extended cycle, namely, bleeding (n ⫽ 6, 12%), nausea (n ⫽ 5, 10%) and breast tenderness (n ⫽ 7, 13%); and during the second cycle, namely, bleeding (n ⫽ 4, 8%), and nausea (n ⫽ 3, 6%). No absence of withdrawal bleeding was observed during the four-day hormone-free interval between the two cycles. Compared to the duration of the menstrual period before starting CVR usage (4.8 ⫾ 2.8 days), those of the withdrawal bleedings at the end of the first and second extended cycles were 3.4 ⫾ 2.1 days (p ⬍ 0.005) and 3.1 ⫾ 2.8 days (p ⫽ 0.003) days, respectively; the intensity of bleeding was reported to be moderate or heavy. In Table 2 the statistical comparisons of Wilcoxon’s rank-sum of the FSFI scores for each sexual aspect observed and of the FSDS scores obtained at baseline and at the first and the second follow-up visits are shown. The total FSFI score at baseline was 26.8 and the FSDS score was 12.4; at the first and second follow-up appointments the total FSFI score had risen to 28.1 (p ⫽ 0.01) and 31 (p ⫽ 0.001), respectively, and the FSDS score had dropped to 11.6 (p ⫽ 0.01) and 9.2 (p ⫽ 0.001), respectively. Interestingly, women reported an increase in desire, arousal, lubrication, orgasm and 310

Table 1 Socio-demographic characteristics of the participants (N ⫽ 52). Age range, years Mean age, years Body mass index, kg/m2 Age at menarche, years Menstrual cycle length, days Duration of menses, days Premenstrual syndrome, n (%) Dysmenorrhoea, n (%) Educational level, n (%) Secondary school Advanced, non university University Number of partners, n (%) One Two ⬎Two Parity, n (%) Nulliparous One child Miscarriages, n (%) One Two Induced abortions, n (%) One Two Three Professional situation, n (%) Student Working Unemployed Housewife Systolic blood pressure, mmHg Diastolic blood pressure, mmHg Heart rate, beats per minute

18 to 32 23.8 ⫾ 3.8 23.4 ⫾ 3.6 12.4 ⫾ 1.7 26 to 32 4.8 ⫾ 2.8 10 (19) 14 (27) 5 (10) 37 (71) 10 (19) 15 (29) 24 (47) 13 (24) 38 14 14 9 5 21 15 4 2

(73) (27) (27) (64) (36) (40) (71) (19) (10)

10 (19) 23 (44) 9 (18) 10 (19) 107.4 ⫾ 10.1 71.2 ⫾ 6.4 68.3 ⫾ 9.3

satisfaction, and an improvement of dyspareunia during the second extended cycle of CVR usage. According to the diary cards they kept on daily sexual events, women experienced changes in the frequency of sexual activity during neither of the two extended cycles of CVR usage in comparison to baseline values (p ⫽ NS). The changes in SF-36 scores between baseline and the first and second follow-up assessments are depicted in Figure 1. Women reported changes in their QoL at the first follow-up consisting of reduced bodily pain, and improved general health and emotional role (p ⬍ 0.05). At the second follow-up, in addition to the three aforementioned improvements, they mentioned



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Table 2 Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) scores at baseline and during the first and second extended cycles of use of the contraceptive vaginal ring NuvaRing® (N ⫽ 52).


FSFI items Desire Arousal Lubrication Orgasm Satisfaction Pain FSFI Total Score FSDS Score

Baseline

First cycle

Second cycle

p-value∗ 1st cycle vs baseline

3.9 ⫾ 1.3 4.6 ⫾ 1.2 4.8 ⫾ 1.1 4.2 ⫾ 1.1 4.6 ⫾ 1.1 4.7 ⫾ 1.0 26.8 ⫾ 1.4 12.4 ⫾ 1.3

4.0 ⫾ 1.1 4.8 ⫾ 1.5 5.1 ⫾ 1.3 4.4 ⫾ 1.3 4.8 ⫾ 1.2 5.1 ⫾ 1.4 28.1 ⫾ 3.3 11.6 ⫾ 1.8

4.6 ⫾ 1.4 5.1 ⫾ 1.3 5.6 ⫾ 1.3 5.2 ⫾ 1.3 5.1 ⫾ 1.1 5.4 ⫾ 1.4 31 ⫾ 1.5 9.2 ⫾ 1.4

NS NS NS NS NS NS 0.01 0.01

p-value∗ 2nd cycle vs baseline

p-value∗ 2nd cycle vs 1st cycle

0.01 0.03 0.001 0.001 0.02 0.004 0.001 0.001

0.1 NS 0.5 0.002 NS 0.05 0.001 0.001

Values are means ⫾ SD. ∗p values determined by non parametric Wilcoxon’s rank sum test. NS, not significant

better physical function, vitality, and social function (p ⬍ 0.001). DISCUSSION

Findings and interpretation We investigated the QoL and the sexual function of a small sample of selected women using NuvaRing®

during two extended cycles of 63 days of intake followed each by a four-day hormone-free interval. The first event observed was that participants experienced an improvement in their sexual life from the first extended cycle of CVR usage, as shown by the higher total FSFI score. They also reported mild adverse events that did not cause discontinuation. The reduction of adverse events, namely, bleeding, nausea and breast tenderness reported by women during the

Figure 1 SF-36 quality of life (QoL) scores at baseline and during the first and second extended cycles of use of the contraceptive vaginal ring NuvaRing® (N ⫽ 52). ∗Vs baseline, p ⬍ 0.05; ∗∗Vs baseline, p ⬍ 0.001.


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second extended cycle of CVR usage could have contributed to improve further the quality of their sexual life. This would be mainly due to a better arousal, lubrication and satisfaction regarding sexual activity. Furthermore, an improvement of dyspareunia and an increased orgasmic experience was reported by the women. Interestingly, even if their sexual life improved, the frequency of sexual activity did not change, underlining the fact that women relying on a CHC for birth control could experience a qualitative improvement in their sexual life that is not necessarily associated with more sexual activity1. This may be due to the recruitment in studies of this type of healthy women, without sexual dysfunction. Assessment of QoL is a crucial parameter to take into account before concluding on the efficacy of a treatment. Our study showed an improvement in some categories of the SF-36 during the first extended cycle of CRV usage, mainly those related to bodily pain, general health and emotional role. However, during the second cycle, all categories improved. We considered the first cycle of CVR usage the time during which a series of adjustments could be initiated1. On the basis of our findings, women who contemplate using a CVR in extended cycles should not expect a change in the frequency of their sexual activity as a result. Probably the fact that we enrolled women who previously had used a CHC facilitated the compliance to the CVR extended regimen. This could be a weakness of our study. In fact, to confirm our results, we are considering applying the same regimen to women resorting to a CHC for the first time. Differences in results and conclusions in relation to other studies One of the reasons for discontinuation of CHC use is bleeding. Earlier studies showed that employing the CVR is usually associated with better cycle control than the intake of combined oral contraceptives (COCs)24. The authors of a recent review report that a small proportion of COC users experience some change affecting their sexuality, whereas most are unaffected25. Unlike women on COCs, those using a CVR in extended cycles experience at an early stage an improvement in the quality of their sexual life, possibly due to the facilitated arousal and better 312

lubrication, that women on COCs usually do not report. Some authors showed that both the CVR and the COC containing 20 μg EE and 150 μg desogestrel had a positive effect on some aspects of the female sexual function. However, the CVR would exert a further positive effect on sexual interest and fantasy, and on the psyche of the woman and her partner, evidenced by their greater complicity and satisfaction26. The quantity of oestrogen and the route of administration of the CHC are important variables. Plasma oestrogen levels of women on COCs usually are lowered. We showed that COCs containing 15 μg EE negatively influenced female sexual behaviour, mainly due to increased dyspareunia3. On the contrary dyspareunia improved in women on COCs containing 20 or 30 μg EE27,28 but also when these pills were taken according to an extended cycle regimen27. Even if the CVR releases, on average, only 15 μg/day of EE, the improved lubrication could be due to the direct local activity of the oestrogen. Moreover, the CVR increases the number of lactobacilli in the vaginal flora with respect to COCs, and the increased leucorrhoea in CVR users could be protective in preventing vaginal infection29. Other investigators recently assessed sexual function and behaviours of women in relation to the use of hormonal vs. non-hormonal methods of contraception; they emphasised that negative sexual side effects were experienced by many women using hormonal contraception, such as less frequent sexual activity, and reduced arousal, lubrication, pleasure, and orgasm. Surprisingly, the authors did not correlate the type and the way of administration of the CHC with the sexual function30. The design of conventional COCs, based on 21-day intake of the tablet containing the sex steroids and a seven-day hormone-free interval, was intended to cause a withdrawal bleeding every four weeks resembling the spontaneous menstruation. Currently, a new concept of low-dose hormonal contraception is being adopted based on the shortening of the hormone-free intervals; this kind of regimen contributes to a reduction of symptoms of endometriosis, dysmenorrhoea, and withdrawal bleeding-related symptoms that can adversely affect well-being and social life31,32, or the quality of sexual life1. Thus, when prescribing contraception one must be aware of the needs of the woman1.



Weaknesses of the study Our study had limitations, mainly its small sample. Another limitation was the lack of a control group constituted by women using the CVR according to the conventional regimen or another CHC in extended regimens.


Unanswered questions and future research Studies investigating the effects of long-term CVR usage on a larger number of women are needed, to analyse and understand the mechanisms whereby a woman’s QoL could change. To gain an insight into the clinical relevance of our results, we are starting to compare groups of women treated with a CHC according to different modalities: extended cycles of

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CVR use versus conventional cycles of that same contraceptive and extended cycles of other CHCs. CONCLUSION

Extended or continuous CHC regimens allow women to modify the length of their cycles and to reduce symptoms of coexisting medical conditions. This preliminary study seems to show, in a very small sample of selected women using CVR in extended cycles, that the QoL and sexual function could improve. Prospective randomised controlled trials are needed to confirm our findings. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and the writing of the paper.

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