Vaginal ring application (step 1)
|Trade names||NuvaRing, others|
|AHFS/Drugs.com||Micromedex Detailed Consumer Information|
Ethinylestradiol/etonogestrel (brand names NuvaRing) is a contraceptive vaginal ring containing the estrogen ethinylestradiol and the progestin etonogestrel which is marketed in the United States and Europe.
A study found that users of vaginal rings with ethinylestradiol and etonogestrel have a 6.5 times increased risk of venous thrombosis compared to non-users. This is commensurate with the risk of thrombosis due to the use of combination birth control pills, which in studies ranged between 2.9 times to 13.7 times the risk. As such, contraceptive vaginal rings do not necessarily appear to pose a lower risk of thrombosis than do birth control pills.
The ring is placed into the vagina for a three-week period, then removal of the ring for one week, during which the user will experience a menstrual period. The break week is comparable to the placebo week for combined oral contraceptive pills ("the Pill"), and the contraceptive effect is maintained during this period. Extended use regimens (seven-week, quarterly, or annual) involving back-to-back use of (2, 4, or 17) rings have been studied in clinical trials, but are not currently approved.
Insertion of the ring is comparable to insertion of other vaginal rings. The muscles of the vagina keep NuvaRing securely in place, even during exercise or sex. Women can check the contraceptive ring periodically with their finger. In rare instances, NuvaRing may fall out during sexual intercourse, while straining before or during a bowel movement, or while removing a tampon.
In the case of accidental expulsion, the manufacturer recommends rinsing the ring with lukewarm water before reinserting. If not done correctly, the risk of pregnancy is increased. Contraceptive efficacy is reduced if the ring is removed, accidentally expelled, or left outside of the vagina for more than three hours. If left outside of the vagina for more than three hours, the device is to be rinsed and reinserted immediately. If this occurs, the manufacturer recommends that a backup method of contraception be used until the ring has been used continuously for a subsequent seven days.
The benefits of the ring include:
- once-a-month self-administered use offering convenience, ease of use and privacy (most users and most partners do not feel the ring, and of those who do, most do not object to it)
- lower estrogen exposure than with combined oral contraceptive pills or the contraceptive patch Ortho Evra.
- a low incidence of estrogenic side effects such as nausea and breast tenderness
- a low incidence of irregular bleeding despite its lower estrogen dose
The contraceptive vaginal ring is contraindicated for a risk of blood clots. This is because it contains the hormone etonogestrel, the active metabolite of the prodrug desogestrel. It is a third-generation contraceptive.
A study in the BMJ, with over 1.6 million women, found that users of vaginal rings with ethinylestradiol and etonogestrel have a 6.5 times increased risk of venous thrombosis compared to non-users. Epidemiological studies have shown that oral contraceptives that contain desogestrel can increase the risk of blood clots (venous thrombosis) by 1.5 to 2.4 times the risk of second-generation oral contraceptives. Second-generation oral contraceptives do not contain desogestrel. Hormones are released continuously from NuvaRing, thus peak and total estrogen and progestin doses are significantly lower than with combined oral contraceptives, but what effect this has on the risk of blood clots has not been established.
NuvaRing also has the cardiovascular contraindications associated with combined oral contraceptives, such as stroke and heart attack. These risks have been shown to be much greater if combined with other risk factors such as smoking, recent surgery, a history of cardiovascular disease, or women over 40 years old.
In two large studies, over a one-year period, 15.1% of users discontinued NuvaRing because of adverse events. Device-related adverse events (foreign object sensation, sexual problems, or expulsion) were the most frequently reported adverse events that resulted in discontinuation (by 2.5% of users). Device-related adverse events were reported at least once during the one-year study period by 4.4% of NuvaRing users.
The most common adverse events reported by 5 to 14% of the 2501 women who used NuvaRing in five clinical trials were: vaginitis (14.1%), headache (9.8%), upper respiratory tract infection (8.0%), leukorrhea (5.8%), sinusitis (5.7%), nausea (5.2%), and weight gain (4.9%). NuvaRing is weight neutral. Additional side effect information (including, but not limited to, severe blood clots) is provided in the NuvaRing full prescribing information. Breakthrough bleeding occurs in 2.0 to 6.4% of NuvaRing users.
Mechanism of action
Like all combined hormonal contraceptives, NuvaRing works primarily by preventing ovulation. A secondary mechanism of action is inhibition of sperm penetration by changes in the cervical mucus. Hormonal contraceptives also have effects on the endometrium that theoretically could affect implantation, however no scientific evidence indicates that prevention of implantation actually results from their use. NuvaRing should not be used if a woman is pregnant.
Society and culture
Restrictions on use
On July 31, 2014, CTV News reported that Merck Canada Inc. stated that women who are over 35 and smoke should not use the Nuvaring. In addition to this group of women, women who have any of the following conditions also should not use the Nuvaring: abnormal blood-fat levels, clotting disorders, diabetes, heart disease, high blood pressure, migraine headaches with vision problems or "constant stomach pain caused by pancreatic dysfunction along with high levels of fats in the blood".
In March 2008, the first lawsuit was filed against the manufacturers, distributors, and marketers of NuvaRing. The plaintiff alleged that these companies concealed the health risks associated with using the device, which is claimed to have caused the death of the plaintiff's wife. Subsequent plaintiffs alleged multiple problems with the advertising of NuvaRing and that they downplayed its risks of injury and death. The company denied these allegations.
The first bellwether trial, selected from a pool of federal lawsuits, was scheduled to begin on April 7, 2014. On February 6, 2014, however, Merck & Co announced that it was ready to settle the NuvaRing lawsuits for $100 million. At that time, there were more than 1,850 lawsuits and the settlement was initially estimated pay about $58,000 per complaint. Approval of the settlement required 95% of the plaintiffs to agree to settle by the end of the day, March 10, 2014, otherwise Merck could retract their offer. On June 5, 2014 US District Judge Rodney W. Sippel approved the $100 million settlement. About 3,800 claimants would share the settlement.
NuvaRing was first approved in The Netherlands on February 14, 2001, then by all 14 other countries then in the European Union on June 12, 2001, and in the United States by the U.S. Food and Drug Administration (FDA) on October 3, 2001. NuvaRing was first marketed in the United States in July 2002, followed by a number European countries since then. In March 2007, Organon announced the market launch of NuvaRing in Australia, bringing the total number of countries where NuvaRing is available to 32. A study by Danish researcher Dr. Øjvind Lidegaard in 2012 with 1.6 million women found a 6.5 times increase in the likelihood of venous thromboembolism when compared to users of non-hormonal based birth control. In Canada, Lidegaard's study led to a change in labeling warning of increased risk of blood clots, but not in the United States.
- "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 22 December 2016.
- Lidegaard, Øjvin; Øjvind Lidegaard; Lars Hougaard Nielsen; Charlotte Wessel Skovlund; Ellen Løkkegaard (May 2012). "Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10" (PDF). BMJ. 344: 1–9. PMID 22577198. doi:10.1136/bmj.e2990. Retrieved 30 June 2013.
- Vlieg, A van Hylckama; F M Helmerhorst; J P Vandenbroucke; C J M Doggen; F R Rosendaal (August 2009). "The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study". BMJ. 339. doi:10.1136/bmj.b2921. Retrieved 23 Dec 2013.
- Mencimer, Stephanie (2009). "Is NuvaRing Dangerous?". Mother Jones. Retrieved 30 June 2013.
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