Ethinylestradiol/etonogestrel, sold under the brand name Nuvaring among others, is a hormonal vaginal ring used for

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

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. Ethinylestradiol was widely used for various indications such as the treatment of menopausal symptoms, gynecological ...

, an

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

, 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. It is a progestin that is also used in combinat ...

, 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 female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...

. It is used by insertion into the

vagina In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular sex organ, reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The #Vag ...

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

occurs in about 0.3% of women with perfect use and 9% of women with typical use. 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 mai ...

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

blood clots A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulati ...

toxic shock syndrome Toxic shock syndrome (TSS) is a condition caused by Exotoxin, 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, ...

anaphylaxis Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

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 ...

, 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. Liver diseases File:Ground gla ...

. Use is not recommended in those who both

smoke Smoke is an aerosol (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 unwante ...

and are over the age of 35. While use in

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

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

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

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. They are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. The h ...

thereby stopping

ovulation Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...

. 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 2022, 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 makes pregnancy possible. The ovarian cycle controls the production and release of eg ...

. The break week is comparable to the

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

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 Oral administration, taken orally by women. It is the oral form of combi ...

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 ...

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 contra ...

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. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

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 ...

* 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 (a situation or factor) 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 rea ...

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 environ ...

. 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 pharmacologically inactive 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 ...

desogestrel. It is a third-generation contraceptive. A study of more than 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 with 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. 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 by mouth. ...

. 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 Oral administration, taken orally by women. It is the oral form of combi ...

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

cardiovascular In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...

contraindications associated with combined oral contraceptives, such as

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

and

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

. 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 combusted, and the resulting smoke is typically inhaled to be tasted and absorbed into the bloodstream of a person. Most commonly, the substance used is the dried leaves of the tobacco plant, whi ...

, recent surgery, a history of

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

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

. The

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

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 A headache, also known as cephalalgia, 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 (mood), depression in those with severe ...

(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 throat ...

(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 an inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include production of thick nasal mucus, nasal congestion, facial congestion, facial pain, facial pressure ...

(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 Intermenstrual bleeding (IMB), or metrorrhagia, is vaginal bleeding at irregular intervals between expected menstrual periods. It may be associated with bleeding with sexual intercourse. The term metrorrhagia, in which metro means measure and ...

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

) and 15 μg of

(an

) each day of use.

Society and culture

Restrictions on use

In July 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 nationa ...

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 one or more parties (the plaintiff or claimant) against one or more parties (the defendant) in a civil court of law. The archaic term "suit in law" is found in only a small number of laws still in effect today ...

s 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 in April 2014. In February 2014, however,

Merck & Co Merck & Co., Inc. is an American Multinational corporation, multinational pharmaceutical company headquartered in Rahway, New Jersey. The company does business as Merck Sharp & Dohme or MSD outside the United States and Canada. It is one of the ...

announced that it was ready to settle the Nuvaring lawsuits for $100 million. At that time, there were more than 1,850Nuvaring'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 in March 2014, otherwise Merck could retract their offer. In June 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 in February 2001, then by the European Union in June 2001, and in the United States by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) in October 2001. Nuvaring was first marketed in the United States in July 2002, followed by a number European countries since then.

Research

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 the 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 lun ...

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.

References

External links

FDA safety information on Nuvaring
{{DEFAULTSORT:Ethinylestradiol etonogestrel Wikipedia medicine articles ready to translate Combined hormonal contraceptives Drugs developed by Schering-Plough Drugs developed by Merck & Co.