NuvaRing was named one of the best healthcare inventions of the year by TIME Magazine in 2001. It was a new birth control option that allowed women to avoid taking daily pills, receiving injections, or inserting a hormonal implant. The first contraceptive vaginal ring (CVR) approved in the U.S., NuvaRing is a flexible, self-administered, transparent ring that contains progestin (etonogestrel) and estrogen (ethinyl estradiol). These hormones are released continuously (average 0.12 mg/day etonogestrel and 0.015 mg/day ethinyl estradiol) when inserted in the vagina. NuvaRing remains a popular method of hormonal contraception today.
After being on the market for almost 2 decades, vaginal ring use has increased and use can be tailored to fit patients’ needs, such as skipping the monthly withdrawal bleed. According to the manufacturer’s prescribing information, maximum effectiveness is achieved when the ring is inserted in the vagina continuously for 3 weeks and then removed for one week to allow for a monthly withdrawal bleed — mimicking the natural menstrual cycle. However, prescribers may write prescriptions with different instructions for use. Continuous use regimens may be prescribed to insert a new vaginal ring every 3 or 4 weeks without a ring-free week. Patients that use a continuous use regimen (omitting a ring-free week) will likely not experience a withdrawal bleed. However, breakthrough spotting or unscheduled bleeding may be experienced with continuous use regimens.
What is the evidence behind using the vaginal ring for four weeks instead of the usual three weeks?
The manufacturer states NuvaRing is still an effective hormonal contraception if inserted for 4 weeks (instead of the usual three weeks), but the manufacturer recommends removing it for a ring-free week before inserting a new ring for maximum contraceptive effectiveness. Ovulation inhibition to prevent pregnancy is maintained with insertion of the CVR for up to 4 weeks. However, the manufacturer recommends ruling out pregnancy for placements longer than 4 weeks before inserting a new ring.
Some systemic side effects of the CVR are comparable to oral contraceptives with similar incidence of headaches and weight gain. However, CVRs have an increased risk for local vaginal side effects like vaginitis (12.2% in CVR versus 6.8% in oral contraceptives) and vaginal discharge (4.8% in CVR versus 1.6% in oral contraceptives). Patients using CVR report less nausea and breast tenderness when compared with patients using oral contraceptives. Side effects may be related to the serum level differences between CVRs and oral contraceptives. Bioavailability of ethinyl estradiol are similar between CVR versus oral contraceptives at 55.6% versus 43% to 55%, respectively. However, the bioavailability of the progestin in CVRs are almost double at 100%, compared to 64% in oral contraceptives. The NuvaRing package insert includes precautions for carbohydrate and lipid metabolic effects, high blood pressure, headaches, uterine bleeding, vascular risks, liver disease, and Toxic Shock Syndrome.
While a potential risk, Toxic Shock Syndrome has rarely been reported with CVR use. The table below summarizes the evidence found in clinical studies of extended CVR use.
Table 1. Summary of clinical studies of extended regimens of the contraceptive vaginal ring (CVR).
(PubMed ID, Year)
|Purpose||Design (Study size)||Results||Conclusion|
|Extended regimens of the combined contraceptive vaginal ring containing etonogestrel and ethinyl estradiol: effects on lipid metabolism
|To evaluate lipid changes with continuous CVR use for one year||Prospective cohort (n=75) of continuous use for 3 months, followed by one ring-free week||Significant increase in total triglycerides||Extended CVR use may cause lipid changes, but this side effect is similar to oral or parenteral estrogen use|
|Extended regimens of the combined contraceptive vaginal ring: evaluation of clinical aspects
|To evaluate symptoms, body weight, and blood pressure changes with continuous CVR use for one year||Prospective cohort (n=75) of continuous use for 3 months, followed by one ring-free week||Less irritability, less dysmenorrhea, increased body weight (within an expected range), no changes in blood pressure||Extended CVR use is well-tolerated with some non-contraceptive benefits (mood, less painful menstruation)|
|Extended regimens of the combined contraceptive vaginal ring: cycle control
|To compare menstrual patterns of women using extended CVR or oral contraceptives||Prospective cohort (n=75 on CVR, 75 on oral) of continuous use for 3 months, followed by one contraceptive-free week||Significant decrease in total days of bleeding and spotting for both methods, slightly lower for oral route||Continuous oral use may result in less menstruation, but CVR offers more predictable menstrual cycle control with less unscheduled bleeding|
|Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial
|To evaluate bleeding patterns with continuous CVR||Prospective cohort (n=74) on CVR for continuous 6 months. Group 1 did not have ring-free days. Group 2 instructed to remove CVR for 4 days if bleeding occurs, and reinsert the same ring||Group 2 experienced less days of bleeding compared to Group 1||A 4-day ring-free period helped resolve breakthrough bleeding better compared to continuous ring use without ring-free periods|
- Agile Therapeutics. Women’s Health Specialty Pharmaceutical Company [Internet]. Jefferies; 2016. Available from: Link
- Barreiros FA, Guazzelli CAF, Barbosa R, Torloni MR, Barbieri M, Araujo FF. Extended regimens of the combined contraceptive vaginal ring containing etonogestrel and ethinyl estradiol: effects on lipid metabolism. Contraception. 2011;84(2):155–9.
- Barreiros FA, Guazzelli CAF, Barbosa R, Assis FD, Araújo FFD. Extended regimens of the contraceptive vaginal ring: evaluation of clinical aspects. Contraception. 2010;81(3):223–5.
- Best Inventions of 2001 [Internet]. Time. Time Inc.; 2001. Available from: Link.
- Guazzelli CAF, Barreiros FA, Barbosa R, Araújo FFD, Moron AF. Extended regimens of the vaginal contraceptive ring: cycle control. Contraception. 2009;80(5):430–5.
- Kerns J, Darney P. Contraceptive Vaginal Ring. In: Schreiber C, editor. UpToDate. [Internet].: UpToDate; 2017. Available from Link.
- Merck & Co. NuvaRing: Highlights of Prescribing Information. 2018. Available from: Link.
- NuvaRing. DrugDex Evaluations. In: Micromedex 2.0 [Internet]. Ann Arbor, MI: Truven Health Analytics. c2018. Available from Link
- Sulak PJ, Smith V, Coffee A, Witt I, Kuehl AL, Kuehl TJ. Frequency and Management of Breakthrough Bleeding With Continuous Use of the Transvaginal Contraceptive Ring. Obstetrics & Gynecology. 2008;112(3):563–71.
About the Author:
Christine Yu is a fourth-year pharmacy student at the University of California San Francisco School of Pharmacy in San Francisco, California.