Ethinylestradiol/etonogestrel, sold under the brand names NuvaRing among others, is a

hormonal vaginal ring A contraceptive vaginal ring is a type of hormonal insert that is placed in the vagina for the purpose of birth control. The rings themselves utilize a plastic polymer matrix that is inlaid or embedded with contraceptive drug. This drug, often o ...

used for

birth control Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...

and to improve menstrual symptoms. It contains ethinylestradiol, 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 acti ...

, and etonogestrel, a

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

. 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 ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

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 A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...

, toxic shock syndrome,

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 follow ...

, gallstones, and liver problems. Use is not recommended in those who both smoke and are over the age of 35. While use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

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 Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/chorio ...

thereby stopping ovulation. The combination was approved for medical use in the United States in 2001. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

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 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 (medicine), saline), sham surgery, and other procedures. In general ...

week for combined oral birth control pills ("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 A contraceptive patch, also known as "the patch", is a transdermal patch applied to the skin that releases synthetic oestrogen and progestogen hormones to prevent pregnancy. They have been shown to be as effective as the combined oral contrac ...

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

Contraindications

The contraceptive vaginal ring is contraindicated 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 environme ...

. This is because it contains the hormone etonogestrel, the active

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of the

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

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. 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 contraindications associated with combined oral contraceptives, such as

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

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 may tr ...

. These risks have been shown to be much greater if combined with other risk factors such as

smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...

, recent surgery, a history of

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...

, or women over 40 years old. NuvaRing should not be used while

. The

hormones A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and beh ...

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 Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

(9.8%), upper respiratory tract infection (8.0%),

leukorrhea Leukorrhea or (leucorrhoea American and British English spelling differences, 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 ...

(5.8%), sinusitis (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 Intermenstrual bleeding, previously known as metrorrhagia, is uterine bleeding at irregular intervals, particularly between the expected menstrual periods. It is a cause of vaginal bleeding. In some women, menstrual spotting between periods occ ...

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 etonogestrel (a

) and 15 µg of ethinylestradiol (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

Lawsuit - A lawsuit is a proceeding by a party or parties against another in the civil court of law. The archaic term "suit in law" is found in only a small number of laws still in effect today. The term "lawsuit" is used in reference to a civil actio ...

s were filed in the US against

Merck Merck refers primarily to the German Merck family and three companies founded by the family, including: * the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668 ** Merck Serono (known as EMD Serono in the Unite ...

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 In the law of torts, a bellwether trial is a test case intended to try a widely contested issue. Bellwether trials are an increasingly common phenomenon in U.S. legal practice. Bellwether trials are especially common in multidistrict litigation (MD ...

, selected from a pool of federal lawsuits, was scheduled to begin on April 7, 2014. On February 6, 2014, however,

Merck & Co Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, New Jersey, and is named for Merck Group, founded in Germany in 1668, of whom it was once the American arm. The company does business as Merck Sharp ...

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 s ...

(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