Contraception: Hormonal contraceptive vaginal rings

INTRODUCTION — Combined (estrogen-progestin) hormonal contraception is available as an oral pill (ie, oral contraceptive or OC), transdermal patch, or vaginal ring. All are user-controlled and are safe and highly effective when used consistently and correctly. They have approximately the same benefits and risks, but vaginal rings have the advantage of longer duration of action than other combined methods. Commonly available combined hormonal contraceptive rings include the one-month etonogestrel/ethinyl estradiol ring (ENG/EE, sample brand names NuvaRing, EluRyng) and the one-year segesterone acetate/ethinyl estradiol ring (SA/EE, sample name Annovera). The hormonal contraceptive vaginal rings have the advantage of avoiding difficulty with daily or weekly use. This topic will review the indications, contraindications, side effects, and use of hormonal contraceptive vaginal rings.

Related content on contraceptive counseling and method selection and estrogen-progestin combined contraceptives is presented separately:

●(See "Contraception: Counseling and selection".)

●(See "Combined estrogen-progestin contraception: Side effects and health concerns".)

In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. We encourage the reader to consider the specific counseling and treatment needs of transgender and gender diverse individuals.

DESCRIPTION AND STRUCTURE

Etonogestrel and ethinyl estradiol ring — The etonogestrel/ethinyl estradiol (ENG/EE, sample names NuvaRing, EluRyng, Haloette, EnilloRing) ring is a flexible device measuring 54 mm in diameter and 4 mm in cross-section that is worn vaginally for three weeks and then removed (and discarded) for one week (picture 1) [1-3]. The outer ring is composed of both ethinyl estradiol (EE) and an ethylene vinyl acetate copolymer that contains crystals of ENG, the 3-keto-metabolite of desogestrel. The device releases an average of 120 mcg/day of ENG and 15 mcg/day of EE over 21 days of use [1,4]. The device is latex-free.

There is an immediate increase in serum hormonal concentration after insertion with a slow decrease over the cycle [5]. The concentration of EE is lower with the ENG/EE vaginal ring compared with other combined hormonal contraceptives:

●In one study, the maximum serum concentration of EE was 30 percent lower than desogestrel-containing oral contraceptives (OCs; 34.7±17.5 ng/L versus 124.9±46.3 ng/L) and systemic exposure to EE was half that of desogestrel-containing OCs [4].

●In a randomized trial comparing a levonorgestrel-containing OC, transdermal patch, and ENG/EE vaginal ring, users of the ENG/EE vaginal ring experienced 3.4 times lower EE exposure than patch users and 2.1 times lower EE exposure than OC users [5]. Exposure to EE in the ENG ring, OC, and patch groups were 10.6±2.5 ng-h/mL, 21.9±2.9 ng-h/mL, and 35.8±5.5 ng-h/mL, respectively. These differences were not all proportional to differences in EE dose of the three contraceptives: 30 mcg/day for the OC, 20 mcg/day for the patch, and 15 mcg/day for the ENG ring.

Unlike OCs where the peak concentration of the progestin occurs daily, the ENG/EE vaginal ring reaches its peak ENG concentration once per cycle, within seven days of insertion. Systemic exposure to ENG (as determined by area-under-the-curve) is similar for the ENG vaginal ring and desogestrel-containing OCs [4].

Segesterone and ethinyl estradiol ring — The one-year reusable segesterone acetate/ethinyl estradiol (SA/EE, sample name Annovera) ring is 56 mm in overall diameter and 8.4 mm in cross-sectional diameter [6]. The ring is worn for three weeks and removed for one week, and that pattern is repeated for a total of 13 cycles. This pattern of use results in regular withdrawal bleeding and an overall pooled unintended pregnancy rate (Pearl index) of 2.98 per 100 woman-years. The ring contains two internal channels: one channel with both SA and EE and the other channel with SA only. The device releases approximately 150 mcg/day of SA and 13 mcg/day of EE over the 21-day use period. The inactive ingredients include silicone elastomers, titanium dioxide, dibutyltin dilaurate, and silicone medical adhesive. The device is latex-free. The median T_max of both hormones is approximately 2 hours after vaginal insertion; concentrations become more constant approximately 96 hours after insertion. Other product advantages include that it does not require refrigeration for storage and that it is not orally active, which may appeal to lactating people who want to avoid exposing their infants to progestin. This one-year ring is approved by the US Food and Drug Administration and available for use.

CANDIDATES AND SPECIAL POPULATIONS

Candidates — People who desire highly effective, reversible, noncoitally dependent contraception and who have no contraindications to taking estrogen or progestins are candidates for the vaginal ring. The United States Centers of Disease Control and Prevention (CDC) and the World Health Organization have published medical eligibility criteria for people with various medical conditions and personal characteristics who desire an estrogen-progestin contraceptive. The combined hormonal rings provide the same benefits of combined oral contraceptive (OC) pills, including contraception, regulation of bleeding, endometrial protection, and, in some, reduction of dysmenorrhea and endometriosis-related pain. In addition, the ring is a good option for people who want the benefits of combined OCs but prefer to avoid a method that requires daily user compliance [7,8].

The noncontraceptive benefits, risks, and side effects of combined estrogen-progestin contraceptives are reviewed in detail separately:

●(See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use".)

●(See "Combined estrogen-progestin contraception: Side effects and health concerns".)

Contraindications — People who should not use combined estrogen-progestin contraceptives, including vaginal contraceptive rings, include those with [1,6]:

●A high risk of arterial or venous thromboembolic disease, including those over age 35 who smoke

●Estrogen- or progestin-sensitive cancer, including breast cancer

●Liver tumors or disease, particularly with abnormal liver function tests

●Undiagnosed or abnormal uterine bleeding

●Likely or confirmed pregnancy

●Hepatitis C who are taking drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir

Use in special contexts — Information regarding estrogen-progestin contraceptive use in individuals with specific medical issues can be found through the United States Centers of Disease Control and Prevention (CDC) and the World Health Organization. Commonly encountered distinct populations include:

●Adolescence – Vaginal contraceptive rings are a good option for adolescents [9]. Use of a vaginal ring can be more private than OCs and the transdermal patch. Compared with the depot medroxyprogesterone acetate injection, another contraceptive method that is popular with adolescents, vaginal rings offer the benefits of a combined hormonal method: shorter, lighter, and less painful periods, no association with weight gain, and no adverse effect on bone mineral density. Contraception selection for adolescents is discussed in detail separately. (See "Contraception: Issues specific to adolescents".)

●Obesity – Theoretically, contraceptive efficacy of combined hormonal contraceptives may be lower in obese individuals. (See "Contraception: Counseling for females with obesity", section on 'Contraceptive ring'.)

Data on use of the hormonal contraceptive rings in people with body mass index (BMI) ≥30 are sparse as the initial etonogestrel/ethinyl estradiol (ENG/EE) clinical trials did not include such people and the segesterone acetate/ethinyl estradiol (SA/EE) trials excluded this subpopulation after two participants with BMI >29 developed venous thromboembolisms [1,6]. Thus, it is not known if the contraceptive efficacy of the hormonal rings is reduced in those with BMI ≥30. However, preliminary data do not indicate any increased risk or decreased efficacy.

There are limited data on efficacy or venous thromboembolism risk in obese individuals who use contraceptive rings. Most studies of obesity assess the impact of combined oral hormonal contraception [10,11]. The United States Centers of Disease Control and Prevention (CDC) lists all combined estrogen-progestin contraceptives as Group 2 (advantages generally outweigh theoretical or proven risks) for obese individuals but does not provide subgroup recommendations by type of combined contraceptive or obesity class.

More information on contraceptive selection for obese individuals can be found elsewhere. (See "Contraception: Counseling for females with obesity".)

●Postpartum and lactation – Nonlactating postpartum people with no other contraindications to combined estrogen-progestin contraceptives can use the contraceptive vaginal ring, although initiation is delayed until 21 days postpartum or more to reduce the risk of thromboembolic events [12,13]. Although there are conflicting data on the impact of combined hormonal contraception on lactation, lactating individuals are generally advised to delay contraceptive vaginal ring insertion until 30 days postpartum. (See "Contraception: Postpartum counseling and methods".)

●Postabortion – For those with no other contraindications, combined hormonal contraceptives, including the contraceptive vaginal ring, can be started after first- or second-trimester abortions [12,13]. While the ENG/EE and SA/EE manufacturers advise people who undergo second-trimester abortion to wait four weeks before initiating the contraceptive vaginal ring (because of increased risk of venous thromboembolism), the CDC supports initiating combined hormonal contraception within seven days of the procedure, including the same day [1,6,13]. (See "Contraception: Postabortion".)

●Perimenopause – Individuals over age 35 can use contraceptive vaginal rings if they do not have additional risk factors for cardiovascular or thromboembolic disease (eg, hypertension, diabetes, dyslipidemia, and obesity) [6].

COUNSELING POINTS — In addition to discussing the contraceptive benefits with patients, we discuss the efficacy, side effects, potential complications, and noncontraceptive benefits below.

Efficacy — Combined hormone vaginal contraceptive rings are highly effective at preventing pregnancy when used consistently and correctly (figure 1). For the etonogestrel/ethinyl estradiol (ENG/EE) ring, the failure rate, defined as the number of pregnancies per 100 woman-years of exposure in the first year of use, is equivalent to that of oral contraceptives (OCs) and the patch (0.3 percent for perfect use and 9 percent for typical use) (table 1) [14,15]. For the segesterone acetate/ethinyl estradiol (SA/EE) ring, the unintended pregnancy rate is nearly 3 per 100 person-years based on pooled data from over 2000 participants including over 17,400 cycles [6]. Ovulation also appears to be suppressed with off-label five- and six-week ring use [16-18]. Typical use effectiveness is lower than that for methods that are less user-dependent (eg, intrauterine contraception and implants).

Studies specific to each ring type include:

●For the ENG/EE ring:

•In a noncomparative study of 2322 participants from Europe and North America, the efficacy of the ENG/EE vaginal ring was 99.1 percent [8]. Over half of the pregnancies (11 in 21) were attributable to compliance problems. North American participants experienced more pregnancies than their European counterparts, perhaps because a greater percentage of North American participants were new contraceptive users instead of switchers from another method (59 versus 38 percent), and more reported that they removed the ring during intercourse.

•A randomized trial in college students found that those assigned to the ENG/EE vaginal ring reported more perfect use in the first two months compared with OC users, but differences were not statistically significant in the third month [19].

●For the SA/EE ring, in a multicenter study that included over 2200 participants, the unintended pregnancy rate was 2.98 (95% CI 2.13-4.06) per 100 person-years [20]. The ring was more than 97.5 percent effective in Kaplan-Meier analysis. More than one-half of the participants completed up to 13 cycles. Of the 290 participants followed after ring discontinuation, all had resumption of menses, or pregnancy as desired, within six months.

For both ring types, the principal mechanism of contraceptive action is inhibition of ovulation [6,16,17,21]. Other contributory mechanisms include thickening of cervical mucus, which prevents penetration of sperm into the upper genital tract, inhibition of sperm capacitation, and slowing of tubal motility [22]. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Mechanisms of action'.)

Side effects

●Systemic – Systemic side effects from the vaginal rings are generally similar to those of combined estrogen-progestin OCs [23-27]. Breast tenderness and nausea (estrogen-related side effects) are reported less often by vaginal ring users than OC users, a finding that is consistent across three trials comparing the varying ethinyl estradiol (EE) doses and different progestins [23-25]. No differences in headache [23-25] or weight gain [26,28,29] are seen across studies comparing ring users with OC users. Ring use is not associated with clinically significant metabolic effects (eg, changes in blood pressure, blood chemistries, lipid levels, carbohydrate metabolism, thyroid function, hematological indices) [22]. (See "Combined estrogen-progestin contraception: Side effects and health concerns".)

●Local – Ring users report more vaginitis, vaginal wetness, and leukorrhea compared with OC users [15,23,25-27]. In a meta-analysis of trials comparing the ENG/EE vaginal ring with various estrogen-progestin contraceptive pills, the odds of vaginitis were approximately 2.5 times greater (odds ratios [OR] 2.48 to 2.84) and the odds of leukorrhea were three to six times greater (OR 3.21 to 6.42) for those using the contraceptive ring [15]. These symptoms did not result in discontinuation of the ring nor did they require treatment.

Although the contraceptive ring appears to alter vaginal discharge, contraceptive ring users do not appear to have an increased risk of acquiring vaginal or cervical infections, including human immunodeficiency virus and human papilloma virus, although supporting data are partly derived from studies of OCs and other vaginal rings [30-35].

●Unscheduled bleeding – The vaginal ring provides cycle control equivalent or superior to OCs and the transdermal patch [26,36,37]. Compared with an extended cycle regimen of contraceptive pills, the traditional 28-day ENG/EE ring cycle has a lower number of unscheduled bleeding days but a higher total number of bleeding/spotting days. A study of people using a continuous or 364-day ring cycle reported a median of zero bleeding days and 10 spotting days during the first three months of extended use; by comparison, for those using a 28-day ring cycle, the median number of bleeding and spotting days was 7.5 and 8, respectively [38]. Acceptability of continuous use is high, even with unscheduled bleeding [38-40]. For people who are bothered by this bleeding but otherwise benefit from continuous use, instituting a four-day ring-free period can improve their symptoms [39]. (See "Evaluation and management of unscheduled bleeding in individuals using hormonal contraception", section on 'Estrogen-progestin contraceptives'.)

●Mood – Data on the impact of combined estrogen-progestin OCs, which are often used as a proxy for the estrogen-progestin vaginal rings, on mood disorders are conflicting [41-44]. Specific to the ENG/EE vaginal ring, a trial of 188 participants comparing depressive symptoms among those using the contraceptive ring or a levonorgestrel-containing OC pill reported no differences in depressive symptoms for ring users at cycles 6 (OR 0.31, 95% CI 0.08-1.19) and 12 (OR 0.23, 95% CI 0.05-1.03) [15]. A different trial of 201 participants initiating either the ENG/EE vaginal ring or a triphasic norgestimate-containing OC reported that ring users were more likely to report no change in mood while OC users were more likely to report worsening mood [24]. Given that the data do not support an association between mood and use of the contraceptive vaginal ring, universal counseling is not necessary. For patients who are concerned about mood changes, providers should use a patient-centered approach and counsel that mood could improve, decline, or stay the same after initiating use.

●Bone mineral density – There is no evidence that the rings have an adverse effect on bone mineral density, although data are limited. One randomized trial compared markers of bone formation and resorption as well as bone mineral density between ENG/EE ring users, patch users, and controls and reported no differences by method or compared with controls [45].

Serious complications — The combined hormonal vaginal rings carry the same risks as other combined hormonal methods. There are limited data specifically about the rings, and recommendations regarding safety come mostly from studies of OCs. The United States Centers for Disease Control and Prevention's Medical Eligibility Criteria for Contraceptive Use is a useful guide for evaluating the safety of contraceptive methods, including vaginal rings, for particular patients.

Cardiovascular and thromboembolic events — Use of combined hormonal (estrogen-progestin) contraceptives (CHCs), including pills, patch, and rings, increases the risk of thromboembolic events over that of nonusers [1,6]. For comparison, the risk of having a venous thrombotic event (VTE), per 10,000 individuals, is 1 to 5 for non-CHC users and 3 to 12 for CHC users. However, the VTE risk does not appear to be higher for ring users compared with users of other combined estrogen-progestin OCs. Similar to combined OCs, cases of stroke, both arterial and venous, thrombotic and hemorrhagic, as well as myocardial infarction have been reported in contraceptive ring users [46-49].

Examples of representative studies for the ENG/EE ring include:

●A 15-year Danish historical cohort study evaluated data from national registries to determine the risk of arterial events, thrombotic stroke, and myocardial infarction in users and nonusers of hormonal contraception [46]. The cohort included the entire population of Danish individuals identifying as women aged 15 to 49 years for the period 1995 through 2009. During over 38,000 person-years of ENG/EE contraceptive vaginal ring use, thrombotic strokes occurred more often in users than nonusers (31.4 versus 24.2 per 100,000 person years) for an adjusted relative risk of 2.5 (95% CI 1.41-4.41) near the lower range of the increased risk for combined oral contraceptives. The number of myocardial infarctions in ENG/EE ring users was too low to provide reliable estimates of relative risk.

●A 2013 multicenter analysis from the United States and several European sites compared venous and arterial thromboembolism risk among new users of the ENG/EE ring and new users of combined OCs [50]. In this study, which included over 66,000 woman-years of contraceptive use, ring users were not at greater risk of VTE or arterial thromboembolism than users of combined OCs containing a variety of progestins and low dose EE (VTE incidence for ring and OC users: 8.3 and 9.2 per 10,000 person-years, respectively; arterial thromboembolism 2.2 and 2.8 per 10,000 person-years, respectively).

●A 2013 cohort study of over 570,000 individuals from the United States identifying as women initiating combined hormonal contraception reported no increase in venous or arterial thrombotic events among those initiating the ENG/EE contraceptive ring compared with those initiating one of four low-dose comparator combined OCs (relative hazard total mortality for ATE and VTE 0.96, 95% CI 0.29-3.14) [51].

●A 2017 systematic review of three studies comparing ENG/EE ring users with users of combined OCs containing levonorgestrel noted mixed outcomes; one cohort study reported an elevated rate ratio for VTE, while a case-control and different cohort study reported no difference in VTE risk [52].

The relative and absolute cardiovascular and thromboembolic risks of combined estrogen-progestin OC, including the impact of differing estrogen doses and progestin types, is reviewed in detail separately.

●(See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Cardiovascular effects'.)

Toxic shock — Rare cases of toxic shock syndrome have been reported in ENG/EE contraceptive ring users [22]. No cases of toxic shock syndrome occurred during the clinical trials for the SA/EE ring [6]. Causation has not been proven and may have been related to concurrent tampon use. (See "Staphylococcal toxic shock syndrome" and "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".)

Noncontraceptive benefits — Estrogen-progestin contraceptives, including vaginal rings, have several noncontraceptive benefits (table 2). Details specific to the vaginal ring include:

●Cycle control and bleeding reduction – While cycle control is a benefit of all combined hormonal contraceptive methods, vaginal rings provide cycle control that is at least equivalent, and possibly superior, to OCs and the transdermal patch based on studies of the ENG/EE ring [26,36,37]. Several studies have reported that ENG/EE ring users are less likely than users of monophasic or triphasic OCs to experience breakthrough bleeding, especially in the first few months of use [25-27,37,53,54]. Prolonged or frequent bleeding [37] and early or late withdrawal bleeding [25] are also less likely among ring users. There were no differences in bleeding patterns between those just starting hormonal contraception or those switching to the ENG/EE ring [55]. An improvement in cycle control has been demonstrated among individuals who switch from OC or transdermal patch to the ENG/EE vaginal ring [56].

In addition, contraceptive ring users have reductions in bleeding volume and duration similar to that of OC users. A trial comparing the ENG/EE contraceptive ring with oral norethisterone in 95 participants with idiopathic heavy menstrual bleeding reported a 2/3 reduction in bleeding volume and three day reduction in bleeding duration after three cycles of use [57].

●Reduction of endometriosis pain – The contraceptive ring appears to reduce endometriosis-related pain. A cohort study comparing the ENG/EE vaginal ring with the transdermal patch for treatment of persistent endometriosis pain reported that both treatments reduced dysmenorrhea [36]. Ring users were more satisfied with their treatment than patch users (72 versus 48 percent). (See "Endometriosis: Treatment of pelvic pain", section on 'Estrogen-progestin contraceptives'.)

●Less impact on insulin resistance – Woman at risk for, or diagnosed with, insulin resistance may benefit from the contraceptive ring compared with OCs. One prospective observational study comparing the contraceptive ring users with estrogen-progestin OC users reported the ring had no impact on insulin resistance while OC use increased insulin levels [58].

●Improved psychosexual function – Although there are conflicting data on the impact of the contraceptive ring on sexual function, the overall body of evidence suggests improved sexual functioning [25,59-61].

Acceptability

●Satisfaction – Most individuals find the vaginal ring a highly acceptable form of contraception because it is easy to use, remains effective if removal or reinsertion are not performed precisely on time, results in low systemic hormone levels, and is rapidly effective and reversible.

Studies of the ENG/EE ring have reported high satisfaction rates (84 to 96 percent) and high likelihood of recommending the method to a friend (87 to 98 percent) [8,55,56]. People like the method's ease of use, once-a-month administration, and low dose of hormones (vaginal hormone delivery increases bioavailability) [23,62]. Less than 3 percent of individuals report ring expulsion, feeling the ring, or coital problems [55]. Vaginal ring users are as satisfied, or more satisfied, than OC users [23,24]. Satisfaction with the SA/EE ring is similar to that of the ENG/EE ring.

●Continuation – Discontinuation of combined hormonal contraceptive methods is common. Studies of the ENG/EE ring reported that 28 to 35 percent of people discontinued the vaginal ring before one year, and most discontinuations occurred in the first three to four cycles. Although side effects are the most commonly reported reason for discontinuing a contraceptive method, they only accounted for 11 to 30 percent of the ENG/EE ring users discontinuations [8,23,54-56,63].

While one trial reported that ring users overall were less likely to discontinue the method than OC users (12 versus 22 percent) [25], another trial reported no difference in discontinuation rate by method [19]. A trial including 201 participants comparing the vaginal ring with a norgestimate-containing OC reported that among those using the "quick start" method, ring users were less likely to discontinue than OC users (11 versus 16 percent) [24].

As with all hormonal contraceptives, providing or prescribing up to a one-year supply of contraception enhances convenience and continuation of the method.

●Correct use – Correct and consistent use of the vaginal ring is similar to that with OCs. Individuals in ENG/EE clinical trials report following recommended use of the vaginal ring (three weeks in, one week out) in approximately 80 to 90 percent of cycles [23,54]. Many report altering use of the vaginal ring by prolonging the ring-free period (more than seven days) [8,53,55] and extending use up to five weeks to regulate their cycles [62]. For both the ENG/EE and SA/EE rings, cultural factors may play a role, as one study showed that North American participants were less likely (80 versus 91 percent) than their European counterparts to use the ring correctly (eg, failing to replace it within three hours after removal) [8].

ADMINISTRATION AND USE

Health screening and pregnancy exclusion — Ideally, blood pressure should be measured before initiation of combined hormonal contraceptives; physical examination and laboratory tests are not necessary [13]. However, in settings where access to health care is limited, it is reasonable to initiate use of the ring without blood pressure documentation. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Screening requirements'.)

Similar to oral contraceptives, contraceptive rings can be started anytime during the cycle once pregnancy has been reasonably excluded (table 3). The patient can insert the ring on the same-day they are seen or delay start to the onset of the next menstrual period (algorithm 1). If the date of last menses was more than 7 days prior (etonogestrel/ethinyl estradiol [ENG/EE] ring), more than 5 days prior (segesterone acetate/ethinyl estradiol [SA/EE] ring) or is uncertain, we advise the patient to use a back-up method of contraception (eg, male or female condom) for the first seven days of ring use. Of note, the ENG/EE manufacturer advises using a back-up method if the ring is inserted any time other than the first day of menses [64], while the United States Centers for Disease Control and Prevention (CDC) recommends back-up if it is inserted >5 days from the beginning of menstrual bleeding [13]. However, there is evidence that ring insertion initiated as many as 10 days after the beginning of the last menstrual period does not compromise ovulation inhibition [17].

Insertion and use — The vaginal ring requires a prescription, but does not need to be fitted. Both the ENG/EE and SA/EE rings are available in one size and are self-administered (picture 1). For people using a different contraceptive method, the approach to starting to the contraceptive ring is presented in the table (table 4).

●Insertion – To insert, the individual should choose a comfortable position (figure 2). The sides of the ring are pressed together, and then it is inserted into the vagina as high as possible for comfort and to prevent it from falling out (figure 3). The position of the ring does not affect contraceptive efficacy.

●Duration of use and removal – Both the ENG/EE and SA/EE rings are left in place for three weeks and then removed for a single ring-free week to allow withdrawal bleeding [1]. People using the ENG/EE ring discard the ring whereas those using the SA/EE ring remove it, wash it with mild soap and water, dry it with a clean cloth, and store the ring in its case [1,2,6]. As the SA/EE ring is used repeatedly for thirteen total cycles, the manufacturer advises writing the initiation and anticipated discard dates on the case so the product is not used longer than intended.

During the three weeks of use, people should periodically check to ensure the ring is in place, although the optimal timing or frequency is not known [65]. To begin a new cycle for either ring type, a new ring should be inserted on the same day of the week that the old ring was removed the previous week (ie, if the ring was removed on a Monday, a new ring should be inserted on the following Monday). The ring should not be removed during intercourse.

●In event of delayed removal – If the ENG/EE ring has been in place more than 3 but ≤5 weeks, it is removed, and a new one is inserted after a one-week ring-free interval. Alternately, patients can immediately insert a new ENG/EE ring without using a one-week ring-free interval, although they may have breakthrough bleeding (see the menstrual suppression bullet below). If the ring has been in place for >5 weeks, the old ring is removed, a new ENG/EE ring is inserted, and back-up contraception (eg, male or female condom) is advised until the new ring has been in place for seven days. The ENG/EE ring contains sufficient steroids to maintain stable blood hormone concentrations for a five-week period of time [17]. Thus, inhibition of ovulation is sufficiently maintained if a user forgets to remove the ring after the usual three-week use period.

●In event of delayed insertion – The US Selected Practice Recommendations for Contraceptive Use provides an algorithm for counseling patients who delay insertion or reinsertion of the ring (algorithm 2) [13]. For people who have delayed insertion of a new ring or reinsertion of a current ring for less than 48 hours, they should reinsert the ring immediately and remove it at the regularly scheduled time. No additional contraception is required. People who have delayed ring insertion or reinsertion for 48 hours or more should also immediately insert the ring as soon as possible and use a second method of contraception, such as condoms.

●Continuous use for menstrual suppression – Data supporting continuous ring use for menstrual suppression come from studies of the ENG/EE ring. People who desire fewer days of withdrawal bleeding and are willing to tolerate some spotting can safely use an extended ring regimen whereby the prior ENG/EE ring is removed and a new ring is immediately inserted every three weeks, which omits the hormone-free week and resultant withdrawal bleeding for up to one year [38,40,66-68]. Extended use is effective and does not worsen bothersome side effects, except for unscheduled bleeding [38,40].

Data supporting continuous use of the SA/EE ring are not yet available, but continuous use (ie, no time break between yearly ring removal and replacement) is clinically reasonable. As with the ENG/EE ring, patients are counseled about possible increase in unscheduled bleeding. (See 'Side effects' above.)

●Broken ring – Rarely, the contraceptive ring may break at the weld joint [1]. Although the break does not impact the contraceptive effectiveness, it may make the ring more likely to slip out, which will reduce efficacy. In the event of a broken ring, the broken ring should be removed and new ring inserted.

Reinsertion after unintended removal or expulsion — Unplanned removal (eg, with removing a tampon) or expulsion (eg, during a bowel movement) of the contraceptive ring can occur. If it accidentally falls out, it may be rinsed with cool or warm (not hot) water and reinserted into the vagina. Instructions for reinsertion timing and need for back-up contraception vary by ring type.

●For the ENG/EE ring – If the ENG/EE ring is out of the vagina for less than three hours, no additional steps are needed [1]. If the ring remains out for more than three consecutive hours, subsequent steps depend on the week of the cycle that the ring is out [69]:

•During the first two weeks of the cycle, the ring is reinserted as soon as possible [1]. Pregnancy may not be prevented if the ring is out for more than three hours during this time, so an additional form of contraception, such as condoms with spermicide, is used until the reinserted ring has been in place for seven continuous days. The ring should subsequently be removed according to the original schedule, after which the individual can expect to have their normal period.

•During week 3 of the cycle, discard the ring, then choose one of two different restart options [1]:

-Option one – Insert a new ring and begin a new three-week cycle. Back-up contraception or abstinence is recommended until the new ring has been used continuously for seven days. The individual may not have a regular period until they reach their next ring-free week or they may have vaginal spotting or bleeding prior to then.

-Option two – This option is only used if the prior ring was in place for seven consecutive days. Leave the ring out for up to seven days. During this ring-free time the individual may have their period. By day seven, insert a new ring and begin a new cycle. Back-up contraception or abstinence is recommended until the new ring has been used continuously for seven days.

In contrast to the above approach, the CDC takes the more liberal stance that back-up contraception is not needed if reinsertion of the current ring occurs in less than 48 hours (algorithm 2) [13]. There is evidence that ovulation is inhibited when the ring has been in place for only three days [16]; however, there are no data about actual failure rates after only three days of use, so a back-up method is recommended for one week.

If the ring has been out of the vagina for an unknown amount of time, then pregnancy should be excluded prior to reinsertion of the ring (table 3) [65].

●For the SA/EE ring – If the SA/EE ring is expelled or removed for up to two hours, the ring is reinserted after washing it with mild soap and water and drying it [6]. No additional contraception is needed. If the SA/EE ring is out of the vagina for two continuous hours or more, or more than two cumulative hours (multiple episodes that add up to two hours), then the ring is cleaned and reinserted, and back-up contraception (eg, male condoms) is used for an additional seven consecutive days.

Follow-up — A routine follow-up examination is unnecessary, but blood pressure should be checked yearly, if possible. The individual should contact their provider if they have concerns about the method, want to discontinue contraception or switch to another method, or have changes in health status that might affect the appropriateness of use of an estrogen-progestin contraceptive [13].

Return of fertility — Most people resume ovulation and regular menstrual cycles within a month after stopping contraceptive rings [1]. A study of 45 participants using the ENG/EE contraceptive ring reported that, after removal of the vaginal ring, the median time to ovulation was 19 days and earliest ovulation occurred after 13 days [70]. In the initial trials of the SA/EE ring, all 290 participants who desired pregnancy or switched to a nonhormonal method resumed menses within six months of discontinuation [6]. Those who desire pregnancy can attempt to conceive whenever they are ready.

Use with other vaginal devices and products — The contraceptive ring can interfere with other female barrier contraceptives [65,71]. For example, the diaphragm, cervical cap, or female condom should be not be used as back-up contraception with the contraceptive rings [1]. Tampons may be used during menses as they do not impact hormone absorption from the rings, which are typically not in place during the time frame of vaginal bleeding [1]. Water-based vaginal lubricants and spermicides are compatible with the combined contraceptive rings, but oil-based products (including silicone-based lubricants) are not [1,6].

DRUG INTERACTIONS

Systemic medications — Combined hormonal vaginal rings can interact with other systemic medications to both increase and decrease each other's levels. Much of the available information is based upon combined oral contraceptive (OC) pills. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Drug interactions'.)

●Reduced estrogen/progestin levels – Information on medication interactions that may reduce contraceptive ring estrogen and progestin levels is mostly based on studies of OC pills. Drugs that increase liver microsomal enzyme activity may decrease systemic exposure to the estrogen and progestins in contraceptive vaginal rings, and thus potentially decrease contraceptive efficacy. Such medications include aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, rifabutin, rufinamide, topiramate, and products containing St. John's wort [1,6]. In addition, reduced systemic estrogen and progestin levels have been noted with the HIV protease inhibitors nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir as well as the Hepatitis C protease inhibitors boceprevir and telaprevir. The non-nucleoside reverse transcriptase inhibitor nevirapine may also reduce systemic hormone levels. We advise individuals who require these medications to use an additional form of contraception (ie, backup contraception such as male condoms) or consider an alternate contraceptive method. (See "Contraception: Counseling and selection".)

●Altered levels of other medications – Combined hormonal contraceptives (CHCs) can decrease plasma lamotrigine levels [12,13]. People who require both medications are advised to have their lamotrigine levels monitored. CHCs are also avoided in those using Hepatitis C medications ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [1].

●Use with emergency contraception – The additional use of combined estrogen-progestin emergency contraception is not advised during segesterone acetate/ethinyl estradiol (SA/EE) ring use (eg, in event of ring expulsion for >2 hours) [6] Guidance for the etonogestrel/ethinyl estradiol (ENG/EE) ring is not available. Both the SA/EE and ENG/EE rings can be started after emergency contraception is used. (See "Emergency contraception".)

Use with vaginal medications — Water-based vaginal drugs, such as for the treatment of vaginal candidiasis or bacterial vaginosis, are compatible with the vaginal contraceptive rings [1,6]. However, the oil-based miconazole suppositories have been associated with increased hormone levels [1,6]. Thus, particularly for individuals using the SA/EE ring, only water-based or oral therapies are advised.

NEW DEVELOPMENTS IN VAGINAL RINGS

●Nestorone and ethinyl estradiol combined hormonal vaginal ring – The Population Council is studying vaginal rings containing estrogen (ethinyl estradiol [EE] or 17-beta-estradiol [E2]) and Nestorone (NES), a potent 19-nor-testosterone derivative that is not orally active, but is an effective contraceptive when administered via implants, transdermal systems, and rings [72-75]. NES does not bind to androgen or estrogen receptors and thus can potentially minimize some hormone-related side effects, such as acne. Three studies of long-acting (13 cycles) rings containing NES/EE reported efficacy and acceptability similar to other short-acting contraceptives [73-75]. As EE induces production of hepatic proteins and clotting factors [76], an E2/NES ring was created with the goal of providing a novel contraceptive method that did not appear to increase thrombogenic risk (based on studies in a postmenopausal population) [75].

●Progesterone-releasing vaginal ring – The Progering is a progesterone-releasing vaginal ring for lactating individuals. It is available in parts of South America and Africa [77]. Each ring releases 10 mg of progesterone daily and lasts for four months [77,78], although it is approved for only three months of use. A ring that releases a synthetic progestin (Nesterone) is under development.

Progesterone-only rings function primarily by thickening cervical mucus to prevent sperm penetration but also inhibit ovulation and endometrial receptivity. Progesterone-only rings may be less effective over the long-term than rings containing both a progestin and an estrogen but are still highly effective among breastfeeding individuals since breastfeeding provides some protection from pregnancy [79]. Unscheduled bleeding, which is a common side effect of all progestin-only methods, is less likely to occur in breastfeeding individuals because of prolonged lactational amenorrhea [80].

The progesterone vaginal ring contains 22.5 percent progesterone dispersed in silicone. The system delivers 10 mg/day of the physiological hormone progesterone, but due to its homogeneous design, serum levels decline during its three-month duration of use [81]. A Phase 3 trial demonstrated that it has high contraceptive efficacy (98.5 percent) and safety [81]. Despite its effectiveness and application for lactating individuals, the progesterone vaginal ring has not yet become popular [82].

RESOURCES FOR PATIENTS AND CLINICIANS

●bedsider.org – A free website developed by the National Campaign to Prevent Teen and Unplanned Pregnancy, a private nonprofit group.

●CHOICE Project – A free website sponsored by the Washington University School of Medicine in St. Louis that provides resources on contraceptive options and training resources for clinicians.

●Center for Young Women's Health – A free website run by Boston Children's Hospital that addresses reproductive health needs of teens and young adults.

●SexandU.ca – An educational site run by the Society of Obstetricians and Gynaecologists of Canada that includes descriptions of various methods and a tool to help with selection of birth control.

●Planned Parenthood – A nonprofit organization dedicated to reproductive health with resources for patients and clinicians.

●ACOG Contraceptive FAQs – American College of Obstetricians and Gynecologists addresses frequently asked questions (FAQs) about contraception.

●United States Medical Eligibility Criteria for Contraceptive Use

●United States Selected Practice Recommendations for Contraceptive Use

●World Health Organization Medical Eligibility Criteria for Contraceptive Use

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Contraception".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Hormonal birth control (The Basics)")

●Beyond the Basics topic (see "Patient education: Hormonal methods of birth control (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Ring types – There are two contraceptive vaginal rings. The first consists of an outer ring composed of ethinyl estradiol (EE) and an ethylene vinyl acetate copolymer that contains crystals of etonogestrel (ENG), a metabolite of desogestrel (sample names NuvaRing, EluRyng, Haloette, EnilloRing). The second vaginal ring contains segesterone acetate/ethinyl estradiol (SA/EE) and provides contraception for one year (sample name Annovera). (See 'Description and structure' above.)

●Efficacy – Vaginal rings are a highly effective method of contraception when used consistently and correctly (figure 1). The failure rate, defined as the number of pregnancies per 100 woman-years of exposure in the first year of use, is equivalent to that of oral contraceptives (OCs) and the patch (0.3 percent for perfect use and 9 percent for typical use). The unintended pregnancy rate for the SA/EE ring appears to be closer to 3 percent. (See 'Efficacy' above.)

●Candidates – Appropriate candidates for vaginal ring contraception are people desiring contraception with no contraindications to estrogen or progestin therapy. The Centers of Disease Control and Prevention and the World Health Organization have published medical eligibility criteria for people with various medical conditions and personal characteristics who desire an estrogen-progestin contraceptive. (See 'Candidates and special populations' above.)

●Side effects – Systemic side effects from the vaginal rings are generally similar to those of combined estrogen-progestin OCs. In contrast to OC users, ring users report more local (vaginal) symptoms, including vaginitis, wetness, and leukorrhea. However, these symptoms do not require treatment and generally do not result in ring discontinuation. (See 'Side effects' above.)

●Cardiovascular risk – While the risk of cardiovascular and thrombotic events is increased in ring users compared with nonusers of combined hormonal contraception, the risk does not appear to be higher compared with users of other combined hormonal contraceptives. (See 'Cardiovascular and thromboembolic events' above.)

●Prior to initiation – Prior to starting the contraceptive vaginal ring, blood pressure should be measured and pregnancy should be reasonably excluded. Physical examination and laboratory tests are not necessary. (See 'Health screening and pregnancy exclusion' above.)

●Ring prescription and use – The vaginal ring requires a prescription, but does not need to be fitted. Both rings are available in one size and is self-administered. (See 'Administration and use' above.)

•ENG/EE ring – For the ENG/EE ring, the ring is left in place for three weeks and then removed and discarded. No ring is in place for a single ring-free week. To begin a new cycle, a new ring is inserted on the same day of the week that the old ring was removed the previous week (ie, if the ring was removed on a Monday, a new ring should be inserted on the following Monday). The ring does not need to be removed during sexual intercourse, but may be removed for up to three hours without affecting contraceptive efficacy. (See 'Insertion and use' above.)

•SA/EE ring – For the SA/EE ring, the ring is also worn for three weeks and then removed for one ring-free week. However, the ring is not discarded but is washed and stored in its case for reinsertion for the next cycle [6]. As the SA/EE ring is used repeatedly for thirteen total cycles, the manufacturer advises writing the initiation and anticipated discard dates on the case so the product is not used longer than intended. (See 'Insertion and use' above.)

●Unplanned removal or expulsion – Unplanned removal or expulsion of the contraceptive ring can occur. If it accidentally falls out, it may be rinsed with cool or warm (not hot) water and reinserted into the vagina. Subsequent steps, including need for back-up contraception, depend on the number of hours without the ring and the week of the cycle (for the ENG/EE ring only). (See 'Reinsertion after unintended removal or expulsion' above.)

●Resumption of fertility – Fertility returns within approximately one month after discontinuing the ring. (See 'Return of fertility' above.)

●Co-use of other vaginal products – The contraceptive ring can interfere with other female barrier contraceptives (ie, diaphragm, cervical cap, and female condom) but not most vaginal medications. One exception is that the SA/EE ring should not be used with oil-based vaginal products or medications. Tampons may be used during menses as they do not impact absorption of hormones from the ring. (See 'Use with other vaginal devices and products' above.)