The European Journal of Contraception and Reproductive Health Care, 2013; 18: 234–241

Vaginal health in contraceptive vaginal

ring users – A review
Iñaki Lete∗,†, Mar ía C. Cuesta∗, Juan M. Mar ín∗,† and Sandra Guerra∗
∗Department of Gynaecology, Hospital Universitario Araba-Santiago, Basque Health Service-Osakidetza,Vitoria, Spain,
and †School of Medicine, Basque Country University,Vitoria, Spain
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ABSTRACT Background To provide an overview of the available data from clinical studies of vaginal
conditions in women who use a vaginal ring as a contraceptive.
Methods A systematic review of the literature.
Results Millions of women have already used the ethylene vinyl acetate vaginal ring that
releases ethinylestradiol and etonogestrel for contraception. Because of its small size, more
than four out of five women using the ring report that they do not feel it, even during
sexual intercourse. No colposcopic or cytological changes have been observed in users,
although approximately 10% have increased vaginal discharge. While in vitro studies have
shown adhesion of Candida yeasts to the vaginal ring surface, clinical studies have not
demonstrated a greater incidence of Candida infections compared to users of equivalent
For personal use only.

oral contraceptives. Some clinical studies suggest a lower incidence of bacterial vaginosis.
No interaction exists between concomitant use of the vaginal ring and other drugs or
products for vaginal use.
Conclusion The use of a contraceptive vaginal ring does not alter the vaginal ecosystem
and therefore does not substantially affect vaginal health.

K E Y WO R D S Contraceptive vaginal ring; Vaginal health; Vaginal infections; Cytology; Colposcopy

I N T RO D U C T I O N
The first description of a vaginal ring releasing a
steroid dates back to the late 1960s1. That ring,
intended for contraception, was made of Silastic® and
was impregnated with medroxyprogesterone. Differ-
ent devices have subsequently been designed and
developed; of these, the most widely studied is a ring
designed to release ethinylestradiol (EE) and nore-
thisterone acetate, although this ring is no longer
available2.
The only combined contraceptive vaginal ring cur-
rently on the market is the NuvaRing®, manufactured
by N.V. Organon, Oss, the Netherlands; it was approved
by the European Medicines Agency in July 2001,
and by the US Food and Drug Administration, in
October of that same year. This ring belongs to the
group of reservoir devices, so named because drugs
– in this case steroids – are dispersed or dissolved in
a central core surrounded by an outer, non-medicated
polymer membrane. The ring is made of ethylene
vinyl acetate (EVA), a polymer which has the advan-
tages of increased flexibility, adhesion, and breaking
strength. This substrate has been widely used for other
medical and pharmacological applications3. Each ring,
with an outer diameter of 54 mm and a cross-sectional
diameter of 4 mm, releases 15 μg of EE and 120 μg

Correspondence: Iñaki Lete MD, PhD, Servicio de Ginecología, Hospital Universitario Araba, sede Santiago, Olaguibel 29, 01004 Vitoria, Spain.
Tel: ⫹ 34 945007600. Fax: ⫹ 34 945007901. E-mail: luisignacio.letelasa@osakidetza.net

© 2013 The European Society of Contraception and Reproductive Health

DOI: 10.3109/13625187.2013.801954
 Vaginal health in contraceptive vaginal ring users
of etonogestrel (ENG) daily; the latter is the active
metabolite of desogestrel. Its main mechanism of
action is inhibition of ovulation, and the contraceptive
efficacy rates are very high4. A recent review of the
efficacy of contraceptive methods estimated that the
Pearl Index in typical users of the vaginal ring is
0.25–1.235. Unlike oral contraceptives, which must be
taken daily, the vaginal ring is designed to be used for
three consecutive weeks, followed by a ring-free
interval of one week. In a cross-sectional study con-
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ducted in Spain in 2006 which surveyed nearly 10,000
women who started using a combined hormonal con-
traceptive method, the main reasons given by those
who refused to employ the vaginal ring were related
to the administration route. Thus, 50% of the respon-
dents who rejected this contraceptive method did so
because they thought that the presence of the ring in
the vagina would cause discomfort, and 37% were
uneasy about having a foreign body inside the vagina6.
In addition, in a review of clinical trials comparing
the vaginal ring with different contraceptive pills, a
For personal use only.
greater proportion of ring users reported having
experienced vaginitis and leucorrhoea7. Adolescents
may also express concerns about experiencing vaginal
discomfort and difficulty with inserting or removing
the ring, as reflected by a recent cross-sectional study8.
The adolescents surveyed also feared that the contra-
ceptive vaginal ring would interfere with their sexual
activities or cause urinary tract infections, leucor-
rhoea, or vaginitis.
Given these perceptions among the target popula-
tion, we considered it appropriate to review the effects
the use of the contraceptive vaginal ring may have on
the local conditions of the vagina.
Objective
The objective of this review was to provide an over-
view of available data from clinical studies on vaginal
conditions in women who resort to a vaginal ring for
contraception.The review focuses on vaginal infection,
vaginal lesions, vaginal discomfort, cytological changes,
and concomitant use of other vaginal products.
METHODS
Medline and Embase databases were searched using the
Ovid interface from January 1970 to September week
2, 2012. The search was limited to studies published
The European Journal of Contraception and Reproductive Health Care
Lete et al.
in English although a search of the Índice Médico Espa-
ñol (Spanish Medical Index, a database which brings
together almost all Spanish medical journals) was also
performed to identify articles published by Spanish
groups that are not included in Medline or Embase.
The preliminary search was carried out according
to the following strategy (translated terms were used
for the search of the Índice Médico Español): ‘contracep-
tive vaginal ring.mp’ (mp indicates a search of title,
original title, abstract, name of substance word, sub-
ject heading word) and ‘vagina.mp’ or ‘vaginosis bac-
terial.mp’ or ‘vaginitis.mp’ or ‘epithelial cells.mp’ or
‘Lactobacillus aicdophilus.mp’ or ‘pap smear.mp’ or
‘colposcopy.mp’.
Of the 303 articles retrieved, 17 were excluded
because they were not written in English or in Span-
ish. Of the 286 remaining articles, 68 duplicates were
excluded; the abstract of each of the remaining 218
papers were screened and read. At this stage, a further
157 articles were excluded because efficacy, safety,
acceptability and tolerability data on the use of the
vaginal ring were included with no specific informa-
tion on vaginal conditions. Thus only 61 articles were
considered for full-text reading and assessment. After
careful reading of these articles, it appeared that only
32 fulfilled the established criteria for inclusion in our
review. The other 29 articles were excluded due to
lack of information on vaginal complaints (17 articles)
or because they were review articles (12 review articles).
Information about the selection procedure is presented
in Figure 1, in accordance with the recommendations
of the Prisma Group9.
R E S U LT S
Vaginal infections and the contraceptive
vaginal ring
Preliminary comparative studies performed in the
early 1980s with a ring containing EE and levonorg-
estrel (LNG) and a combined oral contraceptive
(COC) with the same components10,11, in which
vaginal cultures were taken before and after use of the
ring or pill, showed no significant changes in the
number and types of bacteria. Schwan et al.11 found
a greater number of leucocytes suggesting a weak
inflammatory reaction which could explain the
increase in vaginal discharge in ring users. Dieben
et al.12 reported the findings of an observational study
235
 Vaginal health in contraceptive vaginal ring users Lete et al.

Abstracts identified yeast infections in users of the contraceptive vaginal

through database ring. Camacho et al.14, in a study designed to assess in
searching N = 303
vitro adhesiveness of different yeasts (four isolates of
Abstracts excluded Candida sp. and one of Saccharomyces cerevisiae) to the
(not written in NuvaRing® observed adhesion of the microorganisms
English) N = 17 to the ring surface, which could possibly facilitate the
Duplicates
development of fungal vulvovaginitis. Scanning elec-
removed tron microscopy confirmed the presence of irregulari-
N = 68 ties on the ring surface that may play a role in the
adhesion process.
Chassot et al.15 showed that the use of probiotics
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Abstracts screened
N = 218 containing Lactobacillus acidophilus or the presence of
this bacterium in vaginal microbiota not only did not
prevent adhesion of Candida albicans to the ring but
Papers excluded
N = 157 may even promote it.Veres et al.16 reported the results
of a cross-over study in which 64 women were ran-
domised to use either NuvaRing® or a COC contain-
Full-length articles
assessed for ing 20 μg of EE and 100 μg of LNG, each during
eligibility N = 61 three cycles. The investigators did not find a higher
number of vaginal infections or a greater presence of
Full-length articles yeasts during use of the ring as compared to during
excluded
For personal use only.

N = 29 treatment with the COC. Interestingly, they also

Studies included in
the qualitative
synthesis N = 32
Figure 1 PRISMA flow diagram.
of 2322 women who used the NuvaRing® for 13
cycles. The most commonly reported adverse events
resulting in treatment discontinuation were device-
related events (2.5%). In that study, 0.7% of women
withdrew because of vaginitis, and 0.6% due to leu-
corrhoea. Miller et al.13 examined a vaginal ring that
had been used for 28 days and an unused ring under
an electron microscope. The used ring, after removal,
was immediately cut in two. One half was placed into
fixative without rinsing. The other half was rinsed
under sterile water, with no mechanical agitation, to
remove any visible mucus and debris before immer-
sion in the fixative. The unused ring was also cut and
placed in fixative. The surfaces of both rings showed
no significant differences when studied with electron
microscopy. No erosion, bacterial impregnation, or
structural changes were detected on the surface of the
used ring.
Despite these initially reassuring data, recent labora-
tory studies have suggested a greater risk of vaginal
observed that there were significantly larger numbers
of hydrogen-peroxide producing Lactobacillus during
ring use (p ⬍ 0.001). Oddsson et al.17 conducted a
clinical trial with a one-year follow-up period com-
paring the vaginal ring with a COC containing 30 μg
EE and 150 μg LNG. A total of 512 women were
enrolled into the vaginal ring group. Eleven percent
of them reported vaginitis or leucorrhoea during the
study, but only seven (1%) discontinued use of the ring
for this reason.
An observational, prospective, non-comparative
study conducted in Switzerland assessed 1503 new
vaginal ring users at baseline and after about four
cycles18. Two percent of the women reported they had
experienced vaginal discharge during use of the ring,
although the study did not determine whether leucor-
rhoea was due to a yeast infection. In another prospec-
tive, non-comparative, open-label study19, 81 women
who had undergone a surgical abortion began wearing
a vaginal ring one week after the procedure. After one
cycle of ring use, 2% of the patients had developed a
Candida infection, and 4% bacterial vaginosis (BV).
The possibility of an increased bacterial vaginosis rate
with vaginal ring usage has been assessed by other
authors. Archer et al.20 studied 47 women who
employed the contraceptive vaginal ring during 13
cycles; they reported an improved Nugent score

236 The European Journal of Contraception and Reproductive Health Care

 Vaginal health in contraceptive vaginal ring users
(a Gram stain scoring system of vaginal smears to
diagnose BV) in 40% of them.
Vaginal lesions in users of contraceptive
vaginal rings
The most superficial layer of the vaginal epithelium is
in contact with the vaginal ring in situ, and this close
contact may potentially cause lesions or erosions.
Roumen et al.21 studied 76 healthy female volun-
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teers who agreed to use a combined contraceptive
vaginal ring made of Silastic® that released 15 μg of
EE and 120 μg of etonogestrel for 20 cycles; inflam-
matory lesions of the vaginal epithelium were seen
at colposcopy in only one of the 24 women who
completed the study. The bacterial flora was physio-
logical in almost half of the women before the start
of the study, and in at least half of them at the end.
In four women, the flora remained physiological for
almost the whole study period. In all other women
the bacterial flora showed considerable variation. The
For personal use only.
percentage of non-physiological vaginal flora in this
group of sexually active women was high. None of
the women with a non-physiological bacterial flora
complained of inconvenient vaginal discharge that
required therapy. These data confirm earlier findings
according to which the combined contraceptive vag-
inal ring has no significant influence on the bacterial
flora of the vagina21.
Bounds et al.22 reported that erythematous lesions
or ulcerations of the vaginal epithelium had been
identified in 48 of 139 (35%) women using a silicone
vaginal ring releasing LNG. Subsequently, Fraser et al.23
evaluated 169 users of four different contraceptive
vaginal rings. The rings studied, which were used for
four to 12 months, released different dosages of Nesto-
rone® alone, EE plus Nestorone®, EE plus norethin-
drone acetate, and EE plus norethindrone acetate. The
rings also had different elastomers in their composi-
tion: Silastic®, Silastic® 382, and MDX 4-4210. The
authors concluded that the presence of a ring in the
vagina contributed little or nothing to the appearance
of vaginal lesions.
Vaginal discomfort in users of contraceptive
vaginal rings
Fear of feeling the vaginal ring during sexual inter-
course – and even during normal daily life – is one of
The European Journal of Contraception and Reproductive Health Care
Lete et al.
the concerns of women who contemplate resorting to
this method6.
Three studies involving between 805 and 1492 users
of the NuvaRing® for either six or 13 cycles have been
published. On completion of the study periods, 87%,
89%, and 85% of the participants, respectively, reported
that they had not felt the ring during coitus24–26.
Recently the acceptability of NuvaRing® was evalu-
ated in a sample of nurses; only four of the 34 users
(12%) discontinued the use of the ring due to vaginal
discomfort27.
Cytological changes in users of contraceptive
vaginal rings
Use of combined hormonal contraception has been
linked to a greater risk of developing cervical cancer28.
If the steroids are released close to the cervix, the effect
could possibly be magnified. Archer et al.19 enrolled 47
women who used the NuvaRing® for 13 cycles and
evaluated their cervix by colposcopy. In 80% of the
cases no changes in the appearance of the cervix were
detected at one year when compared to baseline,
whereas in 10% the aspect had worsened, and in 10%
it had improved. In that same study, no significant cyto-
logical changes had taken place after one year of use of
the ring. Roumen et al.24 evaluated cervical cytology
in 1145 women before and after 12 cycles of use of the
NuvaRing®. At baseline women were excluded from
enrolment if they had cytological anomalies. A
change from a normal to a pathological cytology
report occurred in 21 women (2%).The most common
change seen was transformation from a normal cytology
to one suggestive of a low grade squamous intraepithe-
lial lesion (LG-SIL; 18 cases). No cytological changes of
the squamous or the columnar epithelium were noted
in any of the smears during the whole study period.
Atypical metaplastic cells were not detected in any of
the samples. HPV was found in 13% of the tested
women, which is in the range to be expected among
sexually active women. At least two of the three HPV-
positive women reverted to an HPV-negative status dur-
ing the study period and remained HPV negative24.
Contraceptive vaginal ring and concomitant
use of other vaginal products
Different drugs and products, particularly for the treat-
ment of vaginal infection, are administered via the
237
 Vaginal health in contraceptive vaginal ring users
vagina29. An important question is whether vaginal
administration of other products with the contracep-
tive vaginal ring in situ might alter the absorption of
the steroids released by the ring.Verhoeven et al.30 con-
ducted two pharmacokinetic studies designed to assess
the impact of a treatment with miconazole in 26
women using a NuvaRing®. The authors reported a
slight increase in systemic release of both EE and
etonogestrel that was unlikely to affect the efficacy and
the tolerability of the vaginal contraceptive ring. A
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similar study designed to assess the effect of use of the
spermicidal nonoxynol-9 on the pharmacokinetics of
the steroids released by the vaginal ring showed no
interaction between these products31. Similarly, use of
vaginal tampons does not modify steroid absorption
through the vaginal epithelium32.
DISCUSSION
Findings and their interpretation
For personal use only.
Vaginal symptoms reported by ring users include vagi-
nitis, vaginal wetness, and leucorrhoea33–35. Although
EVA has proven to be suitable and safe for use in
medical applications, in particular for delivery of sex
steroids36, some studies have suggested that vaginitis is
more common among users of the contraceptive vagi-
nal ring made of this polymer37.
The studies we assessed suggest that Candida albicans
adheres to a certain extent to the surface of the con-
traceptive vaginal ring, but it may not be concluded
that this leads to an increased incidence of candidal
vulvovaginitis.
In women of reproductive age, oestrogens are the
main contributor to the maintenance of the normal
vaginal ecosystem. The stratified luminal epithelium
thickens, and a saprophytic flora, consisting mainly of
lactobacilli, converts the glycogen present in the
desquamated epithelial cells into lactic acid. The latter
in turn contributes to maintaining an acidic pH (⬍ 4.5)
and to inhibiting growth of potentially pathogenic
bacteria38. Despite these favourable conditions, most
women will experience one or more vaginal infections
during their lifetime39. In the US, according to data
from a clinical trial comparing users of the vaginal ring
and a contraceptive pill, up to 42% of women recruited
reported prior candidal vulvovaginitis16.Vaginal infec-
tions, particularly those caused by Candida albicans and
related fungi, and bacterial vaginosis, are common in
238 The European Journal of Contraception and Reproductive Health Care
Lete et al.
the sexually active general population regardless of the
contraceptive method used. The high prevalence of
vaginal infections in the general population may be a
confounding factor when assessing the relationship
between use of the vaginal ring and the incidence of
vaginitis caused by Candida albicans.
Bacterial vaginosis (BV) is the most common cause
of symptomatic vaginal discharge in women of repro-
ductive age. It is characterised by a reduction or elimi-
nation of normal lactobacilli and overgrowth of other
endogenous microorganisms. The prevalence of BV
varies widely, ranging from 4% in asymptomatic col-
lege students to 60% among women attending a sexu-
ally transmitted diseases clinic40.
It is speculated that increased oestrogen may aug-
ment levels of available glycogen in epithelial cells and
thus facilitate bacterial lactic acid production, thereby
inhibiting the growth of BV-associated organisms41.
Different studies have shown that combined hormonal
contraceptives may protect against BV42–44 and the
findings of our review show this same effect in users
of NuvaRing®.
With regard to vaginal lesions caused by the vaginal
ring, one must keep in mind that colposcopic findings
of vaginal lesions are common among young women.
A review of 13 studies that assessed the vaginal epi-
thelium, using colposcopy, in healthy women of repro-
ductive age revealed that 317 of the 569 participants
(56%) presented lesions, mainly petechiae and ery-
thema45. Since other investigators, also using colpos-
copy, had found vaginal erythematous lesions and
ulcerations in fewer women (35%) using vaginal
rings22, there seems to be no increased risk of this
condition among users of contraceptive vaginal rings.
According to the literature, most women cannot feel
the contraceptive vaginal ring during coitus. This can be
explained by the innervation of the vagina, which depends
on two different systems.The supra-diaphragmatic upper
two-thirds of this organ are supplied by the autonomic
nervous system while the lower third is innervated by
the central nervous system through the pudendal
nerve, which originates in the sacral plexus46. These
differences in nerve supply explain why the lower
third of the vagina is highly sensitive to temperature
and pressure changes, while the upper two-thirds lack
this sensitivity. Thus, objects, such as tampons, may be
present with full comfort and no sensation of foreign
bodies for users47. A study using magnetic resonance
imaging showed that the contraceptive vaginal ring
 Vaginal health in contraceptive vaginal ring users
tends to position itself in the upper third of the
vagina48, and this explains the generally good tolerance
to the device.
The second factor influencing non-perception of
the ring is its size. Some vaginal rings, such as the one
delivering Nestorone®, with an outer diameter of
55 mm and a cross-sectional diameter of 9 mm, may
be large enough for their presence in the vagina to be
perceived23. During the clinical development of
NuvaRing®, rings of different sizes were evaluated in
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order to determine the most adequate configuration:
a ring with an outer diameter of 54 mm and a cross-
sectional diameter of 4 mm was the one best accepted
by women49.
In the studies reviewed, the proportion of women
with cytological changes during use of a vaginal ring
varied from 2% in a study involving 1145 women24
to 15% in another one including only 47 women20.
These figures should be interpreted and compared to
the prevalence of pre-invasive cervical lesions in the
general population. The risk of cervical neoplasia is
For personal use only.
increased in current users of oral contraceptives and
declines after use ceases. Ten years of use of oral
contraceptives from around age 20 to 30 years is
estimated to increase the cumulative incidence of
invasive cervical cancer by age 50 from 7.3 to 8.3
per 1000 in less developed countries and from 3.8 to
4.5 per 1000 in more developed countries28. In dif-
ferent European countries the proportion of women
with abnormal cytology ranges from 1 to 12%50.
Some studies found no link between the use of
combined hormonal contraception and an increased
risk of a cervical intraepithelial lesion, even in women
infected by oncogenic genotypes of human papilloma-
virus (HPV)51. In a case-control study of 650 women
using COCs with lesions caused by HPV and 670
women with the same type of lesions but not taking
COCs, no differences were found between the groups
with regard to the recurrence rate of lesions caused by
HPV52. Based on the reported data, there appears to
be no increased risk of cervical intraepithelial lesions
in users of the contraceptive vaginal ring. In our review,
we did not find any study that related use of the vagi-
nal ring to an increased risk of cervical intraepithelial
neoplasia.
Studies included in this review that examined the
pharmacokinetics of the EE and etonogestrel released
by the ring showed that the presence of other prod-
ucts in the vagina did not affect plasma levels of these
The European Journal of Contraception and Reproductive Health Care
Lete et al.
steroids. Concomitant use of the ring and either
miconazole or vaginal tampons is not contraindi-
cated. Studies of vaginal conditions developing in
women who use the contraceptive vaginal ring in
extended or continuous regimens were not found.
Strengths and weaknesses of the study
There are some limitations in our review. The most
important are related to the funding of the studies.The
majority of these were industry-sponsored, and the
data could have been influenced by this feature. Nev-
ertheless, the results of the different studies are consis-
tent, and the conclusions clear.
The strength of our review lies in the fact that we
collected all studies concerning vaginal conditions in
NuvaRing® users, published in English and Spanish.
Relevance of the findings: Implications for
clinicians
Given that the most important reason for not using
the vaginal ring is fear of possible adverse effects in
the vagina6, this review could help guide recommen-
dations made by healthcare providers to women dur-
ing counselling.
CONCLUSIONS
The vaginal ring causes no substantial changes in the
vaginal ecosystem and its use is not associated with an
increased risk of vaginal lesions and cytological anom-
alies. Although some women may feel the ring in the
vagina, particularly during sexual intercourse, most do
not notice its presence. One out of every ten users of
the vaginal ring reports an increased vaginal discharge,
which is the reason for discontinuation of the method
in some cases. Candidal vaginitis appears not to be
more frequent, but in vitro studies suggest that Candida
yeasts adhere to the ring surface. Further clinical stud-
ies are needed to investigate whether use of the con-
traceptive vaginal ring augments the risk of developing
candidal vaginitis.
AC K N OW L E D G E M E N T S
The original manuscript was initially written in
Spanish. The funding to cover the cost of English
239
 Vaginal health in contraceptive vaginal ring users
translation and copy editing was provided by Merck,
Sharp & Dohme de España, S.A.
Declaration of interest: I. Lete has been a consultant
for Bayer Healthcare, Merck (formerly Schering Plough,
Organon), and Teva Laboratories, and has received
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