Ethinylestradiol/etonogestrel

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Ethinylestradiol/etonogestrel
Vaginal Ring Application (Step 1).png
Vaginal ring application (step 1)
Combination of
Ethinylestradiol Estrogen
Etonogestrel Progestogen
Clinical data
Trade names NuvaRing, others
AHFS/Drugs.com Monograph
MedlinePlus a604032
License data
Routes of
administration 		Vaginal (ring)
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
  • None
KEGG

Ethinylestradiol/etonogestrel, sold under the brand names NuvaRing among others, is a hormonal vaginal ring used for birth control and to improve menstrual symptoms. [1] It contains ethinylestradiol, an estrogen, and etonogestrel, a progestin. [2] It is used by insertion into the vagina. [1] Pregnancy occurs in about 0.3% of women with perfect use and 9% of women with typical use. [3]

Contents

Common side effects include irregular vaginal bleeding, nausea, sore breasts, vaginitis, mood changes, and headache. [4] Rare but serious side effects may include blood clots, toxic shock syndrome, anaphylaxis, gallstones, and liver problems. [4] Use is not recommended in those who both smoke and are over the age of 35. [4] While use in pregnancy is not recommended, such use has not been found to be harmful to the baby. [4] Use during breastfeeding is typically not recommended as it may decrease the milk supply. [4] It mainly works by decreasing gonadotropins thereby stopping ovulation. [4]

The combination was approved for medical use in the United States in 2001. [2] It is available as a generic medication in the United Kingdom. [1] In 2021, it was the 198th most commonly prescribed medication in the United States, with more than 2 million prescriptions. [5] [6]

Medical use

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 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. [7] [8] [9]

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 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. [10] [11]

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. [10] [11]

Benefits

The benefits of the ring include:

Contraindications

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. [18]

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. [19] [20] 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. [21] 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, but what effect this has on the risk of blood clots has not been established. [11]

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. [11]

NuvaRing should not be used while breastfeeding. The hormones may pass to the baby through the milk, and it may decrease milk production. [22]

Side effects

The NuvaRing, shown with a ruler for scale Nuvaringwithruler.jpg
The NuvaRing, shown with a ruler for scale

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. [13]

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%). [11] [23] [24] NuvaRing is weight neutral. [25] [26] Additional side effect information (including, but not limited to, severe blood clots) is provided in the NuvaRing full prescribing information. [11] [24] Breakthrough bleeding occurs in 2.0 to 6.4% of NuvaRing users. [27]

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. [19] This is similar to the risk of blood clots with combination birth control pills, which range between 3 times to 14 times the risk. [28] As such, birth control vaginal rings do not necessarily appear to pose a lower risk of thrombosis than do birth control pills. [19] [28] Additionally pregnancy and the period immediately following pregnancy is associated with a high risk of blood clots. [4]

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. [29] NuvaRing should not be used if a woman is pregnant.

NuvaRing delivers 120 μg of etonogestrel (a progestin) and 15 μg of ethinylestradiol (an estrogen) each day of use.

Society and culture

Restrictions on use

In July 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". [30]

Lawsuits

Lawsuits were filed in the US against Merck alleging it concealed health risks associated with the product. [18] These were settled for $100 million in 2014. [31]

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. [32] Subsequent plaintiffs alleged multiple problems with the advertising of NuvaRing and that they downplayed its risks of injury and death. [33] The company denied these allegations. [33]

The first bellwether trial, selected from a pool of federal lawsuits, was scheduled to begin in April 2014. [34] In February 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 [35] lawsuits and the settlement was initially estimated pay about $58,000 per complaint. [36] Approval of the settlement required 95% of the plaintiffs to agree to settle in March 2014, [35] otherwise Merck could retract their offer. [37] In June 2014, US District Judge Rodney W. Sippel approved the $100 million settlement. About 3,800 claimants would share the settlement. [38]

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 (FDA) in October 2001. [39] [40]

NuvaRing was first marketed in the United States in July 2002, [41] followed by a number European countries since then. [42]

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 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. [20]

See also

Related Research Articles

<span class="mw-page-title-main">Combined oral contraceptive pill</span> Birth control method which is taken orally

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. It is the oral form of combined hormonal contraception. The pill contains two important hormones: a progestin and estrogen. When taken correctly, it alters the menstrual cycle to eliminate ovulation and prevent pregnancy.

<span class="mw-page-title-main">Progestogen (medication)</span> Medication producing effects similar to progesterone

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. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.

<span class="mw-page-title-main">Levonorgestrel</span> Hormonal medication used for birth control

Levonorgestrel is a hormonal medication which is used in a number of birth control methods. It is combined with an estrogen to make combination birth control pills. As an emergency birth control, sold under the brand names Plan B One-Step and Julie, among others, it is useful within 72 hours of unprotected sex. The more time that has passed since sex, the less effective the medication becomes, and it does not work after pregnancy (implantation) has occurred. Levonorgestrel works by preventing ovulation or fertilization from occurring. It decreases the chances of pregnancy by 57–93%. In an intrauterine device (IUD), such as Mirena among others, it is effective for the long-term prevention of pregnancy. A levonorgestrel-releasing implant is also available in some countries.

<span class="mw-page-title-main">Contraceptive patch</span> Transdermal patch applied to prevent pregnancy

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 contraceptive pill with perfect use, and the patch may be more effective in typical use.

<span class="mw-page-title-main">Ethinylestradiol</span> Estrogen medication

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 disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring.

Extended or continuous cycle combined oral contraceptive pills are a packaging of combined oral contraceptive pills (COCPs) that reduce or eliminate the withdrawal bleeding that would occur once every 28 days in traditionally packaged COCPs. It works by reducing the frequency of the pill-free or placebo days. Extended cycle use of COCPs may also be called menstrual suppression, although other hormonal medications or medication delivery systems may also be used to suppress menses. Any brand of combined oral contraceptive pills can be used in an extended or continuous manner by simply discarding the placebo pills; this is most commonly done with monophasic pills in which all of the pills in a package contain the same fixed dosing of a synthetic estrogen and a progestin in each active pill.

<span class="mw-page-title-main">Desogestrel</span> Medication

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.

<span class="mw-page-title-main">Drospirenone</span> Medication drug

Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination with an estrogen under the brand name Yasmin among others. The medication is an analog of the drug spironolactone. Drospirenone is taken by mouth.

<span class="mw-page-title-main">Estrogen patch</span> Transdermal delivery system for estrogens

An estrogen patch, or oestrogen patch, is a transdermal delivery system for estrogens such as estradiol and ethinylestradiol which can be used in menopausal hormone therapy, feminizing hormone therapy for transgender women, hormonal birth control, and other uses. Transdermal preparations of estrogen are metabolized differently than oral preparations. Transdermal estrogens avoid the first pass through the liver and thus potentially reduce the risk of blood clotting and stroke.

<span class="mw-page-title-main">Vaginal ring</span>

Vaginal 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 and provides contraception protection. Vaginal rings come in one size that fits most people.

<span class="mw-page-title-main">Contraceptive vaginal ring</span>

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 one or two hormones, is absorbed directly through the bloodstream through the cells that line the vaginal wall. Some vaginal rings contain both an estrogen and a progestin, which are available in Europe and the United States. Other vaginal rings contain just progesterone. The progesterone-only ring is only available in Latin America, exclusively for postpartum breastfeeding parents.

<span class="mw-page-title-main">Hormonal contraception</span> Birth control methods that act on the endocrine system

Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive pill—was first marketed as a contraceptive in 1960. In the ensuing decades, many other delivery methods have been developed, although the oral and injectable methods are by far the most popular. Hormonal contraception is highly effective: when taken on the prescribed schedule, users of steroid hormone methods experience pregnancy rates of less than 1% per year. Perfect-use pregnancy rates for most hormonal contraceptives are usually around the 0.3% rate or less. Currently available methods can only be used by women; the development of a male hormonal contraceptive is an active research area.

<span class="mw-page-title-main">Etonogestrel</span> Chemical compound

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 combination with ethinylestradiol, an estrogen, as a vaginal ring under the brand names NuvaRing and Circlet. Etonogestrel is effective as a means of birth control and lasts at least three or four years with some data showing effectiveness for five years. Following removal, fertility quickly returns.

<span class="mw-page-title-main">Segesterone acetate</span> Progestin medication

Segesterone acetate (SGA), sold under the brand names Nestorone, Elcometrine, and Annovera, is a progestin medication which is used in birth control and in the treatment of endometriosis in the United States, Brazil, and other South American countries. It is available both alone and in combination with an estrogen. It is not effective by mouth and must be given by other routes, most typically as a vaginal ring or implant that is placed into fat.

<span class="mw-page-title-main">Ethinylestradiol sulfonate</span> Estrogenic drug

Ethinylestradiol sulfonate (EES), sold under the brand names Deposiston and Turisteron among others, is an estrogen medication which has been used in birth control pills for women and in the treatment of prostate cancer in men. It has also been investigated in the treatment of breast cancer in women. The medication was combined with norethisterone acetate in birth control pills. EES is taken by mouth once per week.

Combined birth control pills that contain natural estradiol or an estradiol ester include:

<span class="mw-page-title-main">Estrogen (medication)</span> Type of medication

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

<span class="mw-page-title-main">Combined hormonal contraception</span> Form of hormonal contraception combining both an estrogen and a progestogen

Combined hormonal contraception (CHC), or combined birth control, is a form of hormonal contraception which combines both an estrogen and a progestogen in varying formulations.

<span class="mw-page-title-main">Segesterone acetate/ethinylestradiol</span> Combination hormonal birth control

Segesterone acetate/ethinylestradiol (EE/SGA), sold under the brand name Annovera, is a contraceptive vaginal ring and combined form of hormonal birth control which contains segesterone acetate, a progestin and ethinylestradiol, an estrogen. It contains 17.4 mg ethinylestradiol and 103 mg segesterone acetate, releases an average of 13 μg ethinylestradiol and 0.15 mg segesterone acetate per day.

<span class="mw-page-title-main">Estradiol valerate/dienogest</span> Combination drug

Estradiol valerate/dienogest (EV/DNG), sold under the brand names Lafamme, Natazia and Qlaira among others, is a combination product of estradiol valerate, an estrogen, and dienogest, a progestogen, which is used in menopausal hormone therapy in and as a birth control pill to prevent pregnancy in women. It is taken by mouth.

References

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