Ethinylestradiol/etonogestrel, sold under the brand names NuvaRing among others, is a hormonal vaginal ring used for birth control and to improve

menstrual symptoms Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of horm ...

. It contains

ethinylestradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disord ...

, an

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

, and

etonogestrel Etonogestrel is a medication which is used as a means of birth control for women. It is available as an implant placed under the skin of the upper arm under the brand names Nexplanon and Implanon, and in combination with ethinylestradiol, an e ...

, a progestin. It is used by insertion into the

vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...

Pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

occurs in about 0.3% of women with perfect use and 9% of women with typical use. Table 26–1 = Table 3–2 Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception, and the percentage continuing use at the end of the first year. United States.
Common side effects include irregular vaginal bleeding, nausea, sore breasts,

vaginitis Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy. The three main ...

, mood changes, and headache. Rare but serious side effects may include blood clots,

toxic shock syndrome Toxic shock syndrome (TSS) is a condition caused by bacterial toxins. Symptoms may include fever, rash, skin peeling, and low blood pressure. There may also be symptoms related to the specific underlying infection such as mastitis, osteomyeli ...

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the foll ...

gallstones A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of mi ...

, and

liver problems Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the s ...

. Use is not recommended in those who both

smoke Smoke is a suspension of airborne particulates and gases emitted when a material undergoes combustion or pyrolysis, together with the quantity of air that is entrained or otherwise mixed into the mass. It is commonly an unwanted by-produc ...

and are over the age of 35. While use in

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

is not recommended, such use has not been found to be harmful to the baby. Use during

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

is typically not recommended as it may decrease the milk supply. It mainly works by decreasing gonadotropins thereby stopping

ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...

. The combination was approved for medical use in the United States in 2001. It is available as a generic medication in the United Kingdom. In 2020, it was the 194th most commonly prescribed medication in the United States, with more than 2million prescriptions.

Medical use

The ring is placed into the

for a three-week period, then removal of the ring for one week, during which the user will experience a

menstrual period The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs ...

. The break week is comparable to the

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

week for

combined oral birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progesti ...

s ("the Pill"), and the birth control 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 ring Vaginal rings (also known as intravaginal rings, or V-Rings) are polymeric drug delivery devices designed to provide controlled release of drugs for intravaginal administration over extended periods of time. The ring is inserted into the vagina a ...

s. The muscles of the vagina keep NuvaRing securely in place, even during exercise or sex. Women can check the birth control 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. Birth control 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 birth control be used until the ring has been used continuously for a subsequent seven days.

Benefits

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 Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

and

breast tenderness Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a br ...

* a low incidence of irregular bleeding despite its lower estrogen dose

Contraindications

The contraceptive vaginal ring is

contraindicated In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...

for a

risk In simple terms, risk is the possibility of something bad happening. Risk involves uncertainty about the effects/implications of an activity with respect to something that humans value (such as health, well-being, wealth, property or the environm ...

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 ''The BMJ'' is a weekly peer-reviewed medical trade journal, published by the trade union the British Medical Association (BMA). ''The BMJ'' has editorial freedom from the BMA. It is one of the world's oldest general medical journals. Origi ...

'', 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 Desogestrel is a progestin medication which is used in birth control pills for women. It is also used in the treatment of menopausal symptoms in women. The medication is available and used alone or in combination with an estrogen. It is taken b ...

. Hormones are released continuously from NuvaRing, thus peak and total estrogen and progestin doses are lower than with

combined oral contraceptives The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: proges ...

, but what effect this has on the risk of blood clots has not been established. NuvaRing also has the

cardiovascular The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

contraindications associated with combined oral contraceptives, such as stroke and

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...

. 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. NuvaRing should not be used while

. The hormones may pass to the baby through the milk, and it may decrease milk production.

Side effects

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:

(14.1%), headache (9.8%),

upper respiratory tract infection An upper respiratory tract infection (URTI) is an illness caused by an acute infection, which involves the upper respiratory tract, including the nose, sinuses, pharynx, larynx or trachea. This commonly includes nasal obstruction, sore thro ...

(8.0%),

leukorrhea Leukorrhea or (leucorrhoea British English), also known as fluor albus, is a thick, whitish, yellowish or greenish vaginal discharge. It has also been referred to as "the whites". There are many causes of leukorrhea, the usual one being estrogen ...

(5.8%),

sinusitis Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, head ...

(5.7%), nausea (5.2%), weight gain (4.9%) and hair loss . 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.

Blood clots

The vaginal ring with ethinylestradiol and etonogestrel increases the risk of venous blood clots 6.5 times compared to non-users of hormonal birth control. This is similar to the risk of blood clots with combination birth control pills, which range between 3 times to 14 times the risk. As such, birth control vaginal rings do not necessarily appear to pose a lower risk of thrombosis than do birth control pills. Additionally

and the period immediately following pregnancy is associated with a high risk of blood clots.

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. NuvaRing delivers 120 µg of

(a progestin) and 15 µg of

(an

) each day of use.

Society and culture

Restrictions on use

On July 31, 2014,

CTV News CTV News is the news division of the CTV Television Network in Canada. The name ''CTV News'' is also applied as the title of local and regional newscasts on the network's owned-and-operated stations (O&Os), which are closely tied to the national ...

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".

Lawsuits

Lawsuits were filed in the US against Merck alleging it concealed health risks associated with the product. These were settled for $100 million in 2014. 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''"NuvaRing's $100 Million Settlement Deadling is Monday"'', The Detroit Free Press, March 9, 2014, page 9A 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.

History

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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(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 Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs to ...

when compared to users of non-hormonal based birth control. In

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...

, Lidegaard's study led to a change in labeling warning of increased risk of blood clots, but not in the United States.

References

External links

FDA safety information on NuvaRing

DrugLib.com - NuvaRing prescribing information, published studies, current trials
{{DEFAULTSORT:Ethinylestradiol etonogestrel Wikipedia medicine articles ready to translate Combined hormonal contraceptives Schering-Plough brands Merck & Co. brands