Which of the following actions will reduce risks associated with the use of oral contraceptives?

Implants

The US Food and Drug Administration (FDA) approved the contraceptive use of the first levonorgestrel implant (Norplant) in 1990. The Norplant was removed from the market in 2002 due to adverse side effects. In 2001, a desogestrel-based implant (Implanon) was approved and is associated with fewer side effects. The newest version of the implant (Nexplanon), radiopaque for easier diagnostic testing, was introduced in 2011. This method consists of a single rod of ethylene vinylacetate copolymer, measuring 40 mm long and 2 mm in diameter and containing 68 mg of etonogestrel. Etonogestrel is a biologically active metabolite of desogestrel. Desogestrel is significantly more potent than levonorgestrel; a serum concentration of 0.09 ng/mL can inhibit ovulation in most women. The implant releases approximately 70 mcg of etonogestrel per 24 hours during the first year of use, achieving peak serum concentrations of 0.7-0.8 ng/mL within the first few weeks. The rate of release decreases to an average of 30 mcg/d in the latter years of use. Contraceptive protection begins within 24 hours of insertion if inserted during the first week of the menstrual cycle. The rod is inserted subcutaneously, usually in the woman's upper arm over the area of the triceps muscle, where it is visible under the skin and can be easily palpated. [4]

The mechanism of action is a combination of suppression of the LH surge, suppression of ovulation, development of viscous and scant cervical mucus to deter sperm penetration, and prevention of endometrial growth and development.

Efficacy

The contraceptive efficacy of the method is more effective than surgical sterilization. Overall, pregnancy rates with proper insertion and use remain 0.05% for at least 3 years.

Advantages

The longevity of its effectiveness is an advantage. Exogenous estrogen is absent. Prompt return to the previous state of fertility occurs upon removal. No adverse effect on breast milk production occurs. Complications of implants are rare and differ little between adolescents and adults. [5]

Disadvantages

A minor surgical procedure is necessary for removal. Menstrual irregularities are common. Other adverse effects, including headache, breast tenderness, and moodiness, are less common. Irregular bleeding may be improved with nonsteroidal anti-inflammatory drugs (NSAIDs) or a short-term course of low-dose combined oral contraceptives or estrogen.

Other contraceptive implants include the 2-rod levonorgestrel system, termed Norplant II or Jadelle. Each rod is 4.4 cm long and contains a cured homogenous mixture of the drug and a polydimethylsiloxane elastomer covered by silicone tubing. Norplant II is approved for 5 years of use. Studies have shown Norplant II to have release rates, pregnancy rates, and adverse effect profiles similar to Norplant. At this time, Norplant II is not currently being marketed in the United States. Jadelle is currently available in both developed and developing nations around the world.

Injectable depomedroxyprogesterone acetate

Depomedroxyprogesterone acetate (DMPA) is a suspension of microcrystals of a synthetic progestin that is injected intramuscularly. Pharmacologically active levels are achieved within 24 hours after injection, and serum concentrations of 1 ng/mL are maintained for 3 months. During the fifth or sixth month after injection, the levels decrease to 0.2 ng/mL, and they become undetectable by 7-9 months after injection.

DMPA acts by the inhibition of ovulation with the suppression of FSH and LH levels and eliminates the LH surge. This results in a relative hypoestrogenic state. Single doses of 150 mg suppress ovulation in most women for as long as 15 weeks. The contraceptive regimen consists of 1 dose every 3 months.

Efficacy

DMPA is an extremely effective contraceptive option. Neither varying weight nor use of concurrent medications has been noted to alter efficacy. Within the first year of perfect use, the failure rate is 0.3%.

Advantages

DMPA does not produce the serious adverse effects of estrogen, such as thromboembolism. Diminished anemia occurs. Dysmenorrhea is decreased. The risks of endometrial and ovarian cancer are decreased. It contains no estrogen, thus making it suitable for women who cannot or will not take estrogen products. It also is safe for breastfeeding mothers.

Disadvantages

Disruption of the menstrual cycle to eventual amenorrhea occurs in 50% of women within the first year. Persistent irregular bleeding can be treated by administering the subsequent dose earlier or by prescribing temporary low-dose estrogen therapy. Because DMPA persists in the body for several months in women who have used it on a long-term basis, it can delay the return to fertility. Approximately 70% of former users desiring pregnancy conceive within 12 months, and 90% of former users conceive within 24 months. Similar to the delay in fertility after discontinuation of DMPA, other adverse effects, such as weight gain, depression, and menstrual irregularities, may continue for as long as 1 year after the last injection.

A study by Bonny and colleagues found that adolescent girls who gained more than 5% of their baseline weight after 6 months of DMPA use are at increased risk for excessive future weight gain. They concluded that weight gain after 6 months can be used to identify those at risk for further weight gain. Counseling can then be instituted for these patients. [6]

The FDA issued a "black-box" warning in November 2004, stating that bone loss from using Depo-Provera "may not be completely reversible" even after stopping the drug. Studies have contradicted the FDA warning. Women who stopped using DMPA experienced an average bone gain of 1.34% at the hip versus a loss of 0.19% for women who never took the drug. Spine density increased 2.86% for women who stopped using the drug, compared with an increase of 1.32% for nonusers. Furthermore, teenagers regained their bone density faster than older women who used Depo-Provera. [7]

Most users of DMPA are teenagers at a crucial age for the building of bone density; about 10% of American females aged 15-19 years who use birth control use Depo-Provera, compared with 3% of women in the United States overall.

The main limitation, from the patient's point of view, has been the intramuscular (IM) route of injection, which requires an office visit every 12-14 weeks for administration. A subcutaneous version of the drug is now available (Depo-SubQ Provera 104) that delivers a lower dose of medroxyprogesterone acetate (MPA) than does the intramuscular formulation (104 mg vs 150 mg). The subcutaneous route opens the possibility for home self-injections, and the lower dose could decrease suppression of pituitary function and ovarian estradiol production. Further study is needed.

Subcutaneous DMPA, like its intramuscular counterpart, is associated with changes in bone mineral density and also carries a "black box" warning regarding this risk. Studies demonstrate lower decreases in bone mineral density as compared with the intramuscular route and the same reversible effect. [8]

Progestin-only oral contraceptives

Progestin-only oral contraceptives, also known as minipills, are not used widely in the United States. Less than 1% of users of oral contraceptives use them as their sole method of contraception. Candidates for use include women who are breastfeeding and women with contraindications to estrogen use. Several formulations are available. One formulation contains 75 mcg of norgestrel. Another has 350 mcg of norethindrone. Drospirenone 4 mg was approved as a progestin-only oral contraceptive in 2019.

Prevention of conception involves a combination of mechanisms similar to, but not as efficacious as, combination oral contraceptives. Mechanisms of action include (1) suppression of ovulation (not uniformly in all cycles); (2) a variable dampening effect on the midcycle peaks of LH and FSH; (3) an increase in cervical mucus viscosity by a reduction in its volume and an alteration of its structure; (4) a reduction in the number and size of endometrial glands, leading to an atrophic endometrium not suitable for ovum implantation; and (5) a reduction in cilia motility in the fallopian tube, thus slowing the rate of ovum transport.

Efficacy

Serum progestin levels peak approximately 2 hours after administration. Within 24 hours, rapid distribution and elimination returns the level to baseline. Greater efficacy is achieved with consistent administration. Failure rates with typical use are estimated to be 7% in the first year of use. However, any variation can increase the failure rate.

Advantages

Due to the lack of estrogen, evidence of serious complications to which estrogen can contribute (ie, thromboembolism) is minimal. Noncontraceptive benefits include decreased dysmenorrhea, decreased menstrual blood loss, and decreased premenstrual syndrome symptoms. Unlike DMPA, fertility is immediately reestablished after the cessation of progestin-only oral contraceptives.

Disadvantages

The most significant disadvantage is the continuous need for compliance with usage. Users need to be counseled on the need for a backup method of contraception if a pill is missed or taken late. A pill is considered late if ingestion occurs 3 hours after the established time of administration. If a pill is missed, it should be taken as soon as possible; the next pill should be taken at the scheduled time. Backup contraception should be used for the next 48 hours. Unscheduled bleeding and spotting are common even with correct use. Other adverse effects include nausea, breast tenderness, headache, and amenorrhea.

Combination oral contraceptives

Oral contraceptives have been marketed in the United States since 1962. The dose of sex steroids has declined significantly in the past 40 years. Prior to 1992, the estrogenic component of oral contraceptives consisted of either ethinyl estradiol or mestranol. Today, ethinyl estradiol is used in all preparations containing 35 mcg or less of estrogen in the United States. The progestin component consists of norethindrone, levonorgestrel, norgestrel, norethindrone acetate, ethynodiol diacetate, norgestimate, and desogestrel. The most recent addition to the progestin group is the addition of drospirenone, found in Yasmin birth control pills.

The other major development is the reduction in the dosage of ethinyl estradiol to 20 mcg. [9] The major impetus for this change is to improve the safety and reduce adverse effects. However, few data exist to indicate whether reduction of the estrogen dose is associated with a decreased risk of serious sequelae. These lower doses are associated with a decrease in the incidence of estrogen-related adverse effects, such as weight gain, breast tenderness, and nausea.

Another recent development is the release of a combined oral contraceptive pill to raise folate serum levels. Beyaz contains the same progestin and estrogen contents as Yaz (drospirenone 3 mg/ethinyl estradiol 20 mcg) plus 0.451 mg levomefolate calcium (folic acid metabolite).

In the United States today, more than 30 oral contraceptive formulations are available. Monophasic oral contraceptives have a constant dose of both estrogen and progestin in each of the hormonally active pills. Phasic combinations can alter either or both hormonal components. Use should be initiated either on the first day of the menses or the first Sunday after menses has begun. Most of the formulations have 21 hormonally active pills followed by 7 placebo pills. This facilitates consistent daily pill intake.

A French study found that among women taking combination oral contraceptive pills, those using a tailored regimen (pills taken daily until the occurrence of 3 consecutive days of bleeding, followed by 3 pill-free days) experienced significantly less bleeding than did women using a standard regimen (pills taken daily for 21 days, followed by 7 pill-free days). The pills used contained 30 mcg of ethinyl estradiol and 150 mcg of levonorgestrel. [10]

The randomized, controlled trial evaluated various outcomes from the standard and tailored regimens after 1 year in over 350 women (out of an initial 503) aged 18-45 years. The rate of satisfaction with the regimen and with the bleeding pattern was higher in patients on the standard regimen than in those on the tailored one (94% vs 86% and 87% vs 79%, respectively). Women on the tailored regimen, however, had a higher rate of continuation at 1 year than did those on the standard regimen (82% vs 80%, respectively), as well as a lower median number of bleeding days per month (2.4 days vs 4.9 days, respectively).

Analysis of data from the International Active Surveillance of Women Taking Oral Contraceptives showed higher contraceptive effectiveness for women taking the 24-day oral contraceptive pill regimen containing progestogen with a long half-life, under normal medical conditions. [11]

If a woman misses 1 pill, she should take her missed pill as soon as she remembers followed by her regularly scheduled pill. Women who have missed 2 or more consecutive pills should be advised to use a backup method of contraception and could require an emergency contraceptive method dependent upon cycle timing (especially during the first week of active pills).  If she is in the third week of active pills, she should continue the active pill through the placebo week.

Prevention of ovulation is considered the dominant mechanism of action. Either estrogen or progesterone alone is capable of inhibiting both FSH and LH sufficiently to prevent ovulation. The combination of the 2 steroids creates a synergistic effect that greatly increases their antigonadotropic and ovulation-inhibitory effects. They also alter the consistency of cervical mucus, affect the endometrial lining, and alter tubal transport.

Efficacy

Failure rates are correlated to individual compliance. Rates range from 0.1% with perfect use to 5% with typical use.

Advantages

Oral contraceptives are used as treatment for menstrual irregularity because menses is more regular and predictable. In the prevention of ovulation, oral contraceptives can reduce and sometimes eliminate mittelschmerz. Women with anemia secondary to menorrhagia increase their iron stores. Women can manipulate the cycle to avoid menses during certain events, such as vacations or weekends, by extending the number intake days of hormonally active pills or by skipping the placebo pill week. Oral contraceptives prevent benign conditions, such as benign breast disease and pelvic inflammatory disease (PID). Suppression of ovarian stimulation by FSH and LH reduces functional cysts. Cessation of ovulation prevents ectopic pregnancies.

Oral contraceptives are noted to prevent epithelial ovarian and endometrial carcinoma. Studies have noted an approximate 40% reduced risk of malignant and borderline ovarian epithelial cancer. This protection appears to last for at least 15 years following discontinuation of use and increases with duration of use. This protection has not been studied with low-dose oral contraceptives or in women with genetic ovarian cancer syndromes. Use of oral contraceptives is associated with a 50% reduction of risk of endometrial adenocarcinoma. Protection appears to persist for at least 15 years following discontinuation of use.

Disadvantages

Adverse effects include nausea, breast tenderness, breakthrough bleeding, amenorrhea, and headaches. Oral contraceptives do not provide protection from STDs. Daily administration is necessary, and inconsistent use may increase the failure rate. A few months of delay of normal ovulatory cycles may occur after discontinuation of oral contraceptives. Women who continue to have amenorrhea after a discontinuation period of 6 months require a full evaluation.  Women with certain conditions such as seizure disorder may be taking cytochrome-p450 inducers that could decrease the effectiveness of a combined oral contraceptive method.

Metabolic effects and safety

See the list below:

• Venous thrombosis: The estrogen component of oral contraceptives has the capability of activating the blood clotting mechanism. Use of low-estrogen oral contraceptives is associated with a lower risk of thromboembolism than use of oral contraceptives with higher levels of estrogen. Although use of oral contraceptives is not associated with a detectable hypercoagulable state for most women, users at a greater risk for thromboembolism include women who smoke heavily, women with high or abnormal blood lipids, women with severe diabetes with damage to the arteries, women with consistently elevated blood pressures, and women who are obese.

• Hypertension: Oral contraceptives have a dose-related effect on blood pressure. With the older, high-dose pills, as many as 5% of patients could expect to have blood pressure elevations of 140/90 mm Hg or higher. This elevation is believed to be secondary to an estrogen-induced increase in renin substrate in susceptible individuals. Although today's low-dose pills have minimal blood pressure effects, maintaining a surveillance of blood pressure is advisable.  For women with high blood pressure, an alternative progesterone-only method should be recommended.

• Atherogenesis and stroke: Although androgens and a few of the progestins actually may increase low-density lipoproteins and decrease high-density lipoproteins, past use of oral contraceptives does not increase the risk of cardiovascular disease. Limited preliminary data have demonstrated that oral contraceptive use does not lead to coronary atherosclerosis. In rare cases in which myocardial infarcts have been found, the cause has been noted to be of thrombotic rather than of atherosclerotic etiology. In general, a woman's habits are more significant than the use of oral contraceptives in determining her risk of cardiovascular disease. The patient who is sedentary, is overweight, smokes heavily, is hypertensive, is diabetic, or has hypercholesterolemia is clearly at risk.

• Hepatocellular adenoma: These benign liver tumors have been associated with the use of oral contraceptives. Although these tumors are histologically benign, their danger lies in the risk of rupture of the capsule of the liver, leading to extensive bleeding and, possibly, death. With the current low-dose oral contraceptive combination, the risk of liver tumors is much lower.

• Cancer

  • The association of oral contraceptive use and breast cancer in young women is controversial. The Collaborative Group on Hormonal Factors in Breast Cancer performed the most comprehensive analysis of breast cancer and oral contraceptive use and reported findings in 1996. This group evaluated original published epidemiological data from more than 20 countries. The results demonstrated that current oral contraceptive users, and those who had used oral contraceptives within the past 1-4 years, had a slightly increased risk of breast cancer. Although these observations support the possibility of a marginally elevated risk, the group noted that the oral contraceptive users had more breast examinations and breast imaging than the nonusers. Thus, although the consensus states that oral contraceptives can lead to breast cancer, the risk is small and the resulting tumors spread less aggressively than usual.

  • A second study involved over 8000 women, half of which had the diagnosis of breast cancer (118). Ever users and current users of oral contraceptives were found not to have an increased risk of breast cancer compared to women who had never used oral contraceptives (OR 0.9, 95%CI 0.8-1.0 and 1.0, 95% CI, 0.8-1.0, respectively). [12]

  • The relationship between oral contraceptive use and cervical cancer is also quite controversial. A weak association may exist between oral contraceptive use and squamous cell cancer of the cervix. Important risk factors include early sexual intercourse and exposure to the human papillomavirus. The overall consensus is that if indeed oral contraceptive use increases the risk of cervical neoplasia, it is a minimal risk. Thus, women who use oral contraceptives should have annual Pap tests.

Contraindications

Contraindications to use include cerebrovascular disease or coronary artery disease; a history of deep vein thrombosis, pulmonary embolism, or congestive heart failure; untreated hypertension; diabetes with vascular complications; estrogen-dependent neoplasia; breast cancer; undiagnosed abnormal vaginal bleeding; known or suspected pregnancy; active liver disease; and age older than 35 years and cigarette smoking.

Lastly, drospirenone has antimineralocorticoid properties. It is contraindicated in patients with kidney or adrenal gland insufficiency or liver problems. Potassium levels should be checked during the first month of use, especially if drospirenone is taken daily with drugs that can increase potassium levels (eg, NSAIDs, angiotensin-converting enzyme inhibitors).

91-Day combination oral contraceptives

The 91-day combination oral contraceptives have touted a reduction in menstrual cycles per year. Seasonale is a 91-day oral contraceptive regimen in which tablets containing the active hormones are taken for 12 weeks (84 days), followed by 1 week (7 days) of placebo tablets. Conventional oral contraceptive use is based on a 28-day regimen (21 days of active tablets followed by 7 days of placebo tablets). Seasonale contains a progestin (levonorgestrel) and an estrogen (ethinyl estradiol), which are active ingredients in already approved oral contraceptives. With the Seasonale dosing regimen, the expected menstrual periods that a woman usually experiences are reduced from once a month to approximately once every 3 months. As with the conventional 28-day regimen, women experience menses while taking placebo tablets.

Although Seasonale users have fewer scheduled menstrual cycles, the data from clinical trials show that many women, especially in the first few cycles of use, had more unplanned bleeding and spotting between the expected menstrual periods than women taking a conventional 28-day cycle of oral contraceptive.

To counteract the unplanned bleeding, a newer version of Seasonale (Seasonique) was developed. This new brand completely eliminates the hormone-free interval. Seasonique also has 84 active pills (30 mcg of ethinyl estradiol and 150 mcg of levonorgestrel) but is followed by 7 more active pills (10 mcg of ethinyl estradiol) instead of the traditional placebo. Therefore, no hormone-free weeks occur.

The 2 main advantages to replacing the placebo week with a week of low-dose estrogen are a diminished amount of unplanned bleeding and spotting and fewer or no symptoms (eg, cramping, bloating, headaches) for women who are sensitive to the placebo-week hormone fluctuations (in particular, low estrogen). A study of 1000 sexually active adult women (aged 18-40 years) who used Seasonique for one year found that, for cycles 2-4, the median number of bleeding days on a per-patient month was minimal (< 1 day). [13]

The risks of using Seasonale are similar to the risks of other conventional combination oral contraceptives and include an increased risk of blood clots, heart attack, and stroke. The labeling also carries the warning that cigarette smoking increases the risk of serious adverse cardiovascular effects from the use of combination estrogen-containing and progestin-containing contraceptives. The study cited for Seasonique does not report any unexpected adverse events or thromboembolic events; the risk profile is the same as Seasonale.

In 2009, the makers of Seasonique came out with LoSeasonique. LoSeasonique consists of 84 orange tablets containing 0.1 mg levonorgestrel and 0.02 mg ethinyl estradiol and 7 yellow tablets containing 0.01 mg ethinyl estradiol. The risk profile is similar to its sister products Seasonale and Seasonique; however, the risk of unplanned breakthrough bleeding is increased.

In a clinical trial, over a 12-month period, 209 of the 2185 participants (9.6%) discontinued LoSeasonique, at least in part, due to bleeding and/or spotting. This breakthrough bleeding remained consistent over time, averaging 2-3 days of bleeding and/or spotting per each 91-day cycle. The breakthrough bleeding eventually decreased over successive 91-day cycles.

Another 91-day oral contraceptive, Quartette, was approved by the FDA in 2013. A phase 3 clinical trial found this product, a combination of levonorgestrel and ethinyl estradiol, to be 97% effective for the prevention of pregnancy. [14]

Lybrel is the first FDA-approved oral contraceptive with 365-day combination dosing. [15] It contains a low combined daily dose of the hormones levonorgestrel and ethinyl estradiol (90 mcg and 20 mcg, respectively). It provides women with more hormonal exposure on a yearly basis (13 additional weeks of hormone intake per year) than conventional cyclic oral contraceptives that contain the same strength of synthetic estrogens and similar strength of progestins.

The incidence of pill failure that results in pregnancy is approximately 1-2% per year (1-2 pregnancies per 100 women per year of use) if taken every day as directed. The average failure rate is approximately 5% per year (5 pregnancies per 100 women per year of use), including women who do not always take the pill exactly as directed without missing any pills.

Combination patch contraceptives

Ethinyl estradiol and levonorgestrel transdermal

The most recently approved transdermal contraceptive patch contains ethinyl estradiol and levonorgestrel (Twirla) and releases 30 mcg of ethinyl estradiol and 120 mcg of levonorgestrel per day. It is indicated for contraception in females of reproductive potential with a body mass index (BMI) of less than 30 kg/m2. Before prescribing, consider the drug’s reduced effectiveness in women with a BMI of 25 to < 30 kg/m2. The patch is not effective in women with a higher BMI and is contraindicated in females with a BMI of 30 kg/m2 or greater.

The patch is applied and worn for 7 days for 3 consecutive weeks (weeks 1, 2, and 3). The patch is then removed on day 22 for 7 days when withdrawal bleeding is expected. On the day after week 4 ends, a new 28-day cycle is started by applying a new patch.

Norelgestromin and ethinyl estradiol transdermal

First approved in the United States in 2001, norelgestromin and ethinyl estradiol (Xulane, Ortho Evra [discontinued from market]) is a transdermal hormonal contraceptive that releases 150 mcg of norelgestromin and 35 mcg of ethinyl estradiol per day. In August 2002, the FDA listed a failure rate for the patch of 1 pregnancy per 100 women per year, similar to that of other combination methods. Advantages include greater compliance and decreased adverse effects, such as nausea and vomiting, due to the avoidance of the first-pass effect. However, the patch may cause skin irritation, and, if it is removed unnoticed, such as from showering, this may compromise efficacy. Disadvantages and contraindications are similar to those of combination oral contraceptives. It may be less effective for women who weigh more than 198 pounds.

Ortho Women's Health, a unit of Ortho-McNeil Pharmaceutical Inc, updated the warnings section of the prescribing information for the Ortho Evra patch after new studies revealed that its pharmacokinetic profile differs from the pharmacokinetic profile for combination oral contraceptives. Findings noted a higher steady state concentration and lower peak concentrations in the patch as compared with combination oral contraceptives. Average concentrations at steady state for ethinyl estradiol are approximately 60% higher in women using Ortho Evra and peak concentrations are approximately 25% lower in women using Ortho Evra.

This led to a "black box" warning from the FDA in November 2005. This announcement warned about higher exposure to estrogen for women using the weekly patch compared with those taking a daily combination oral contraceptive containing 35 mcg of estrogen. The new bolded warning specifically states that women who use Ortho Evra are exposed to about 60% more total estrogen in the blood than if they were taking a typical combination oral contraceptive containing 35 mcg of estrogen. Again, peak blood levels of estrogen are about 25% lower with Ortho Evra than with combination oral contraceptive. While the estrogen level with the patch remains constant for 1 week until the patch is removed, the peak blood levels with a daily combination oral contraceptive rapidly decline to levels that are lower than the Ortho Evra levels. The increased estrogen exposure may increase the risk of side effects, such as a thromboembolic event.

These data contrast with those of another study, conducted by the Boston Collaborative Drug Surveillance Program, which looked at the risk of heart attack, stroke, and venous thromboembolic events in first-time users of the patch. In this study, published online in the journal Contraception, the authors found that "the risk of nonfatal venous thromboembolic events for the contraceptive patch is similar to the risk for oral contraceptives containing 35 mcg of ethinyl estradiol and norgestimate." [16]

Contraceptive vaginal ring

The actual design of vaginal rings as a mode of contraception was first developed in the 1970s. [17] The first rings studied were homogenous devices with the steroid mixed uniformly through a polysiloxane matrix. The design was abandoned because of a high initial release of drug with a rapid decrease of drug release thereafter. The vaginal rings can deliver progesterone or progesterone-estrogen combinations. Today, the combination contraceptive vaginal ring is a new form of contraception that was approved by the FDA in October 2001.

NuvaRing (etonogestrel/ethinyl estradiol), a vaginal contraceptive ring, is a nonbiodegradable, flexible, colorless ring made up of a polymer of ethylene vinyl acetate and magnesium stearate. The outer diameter of the ring is 54 mm and the cross-sectional diameter is 4 mm. The ring contains 11.7 mg of etonogestrel and 2.7 mg of ethinyl estradiol. It releases 120 mcg of etonogestrel and 15 mcg of ethinyl estradiol each day. The hormones are released slowly and are absorbed directly by the reproductive organs.

The ring is used in the same schedule as oral contraceptives, with 3 weeks of ring usage (ring is left in place for 3 weeks) and 1 week without to produce a withdrawal bleed. The ring can be inserted any time during the first 5 days of the menstrual cycle. The ring should be placed in the vagina even if the woman has not finished bleeding, and she should use a backup contraceptive method for 7 days. A new ring should be inserted each month. If the ring comes out during the first 3 weeks of use, it should be washed with lukewarm water and replaced. If the ring-free interval is more than 3 hours, a backup contraceptive method should be used for 7 days. The ring should never be left in the vagina for more than 4 weeks. If left in for more than 4 weeks, pregnancy should be excluded before inserting a new ring and a backup contraceptive method should be used for 7 days after inserting a new ring.

Gilliam et al compared satisfaction and adherence to the contraceptive vaginal ring (n=136) with daily low-dose oral contraceptive pill (OCP) use (n=137) among college and graduate students. Participants completed daily Internet-based, online diaries during 3 cycles and a final online survey at 3 and 6 months.

The authors found that vaginal ring users were more likely to report perfect use during the 3-month trial period than were OCP users. Participants were equally satisfied with their assigned hormonal contraceptive method. At 6 months, less than 30% of participants were still using their assigned method. [18]

A reusable vaginal ring, Annovera (segesterone/ethinyl estradiol), was approved by the FDA in 2018. It is unique since it is reusable, nonbiodegradable, flexible vaginal ring that is placed in the vagina for 3 weeks and then removed for 1 week during which women experience a menstrual period. The schedule is repeated every 4 weeks for 1 year, covering 13 menstrual cycles of 28 days each. According to the FDA, efficacy and safety were studied in 3 open-label clinical trials with healthy women aged 18-40 years. Results showed about 2-4 pregnancies out of 100 women per year. [19]

Advantages

Vaginal rings are highly effective because they result in complete suppression of ovulation. The steady release of hormone provides exceptional cycle control. The rings are a very effective reversible method of birth control. With typical use, although no studies have been published, the ring is presumed to be more effective than combination oral contraceptives. For example, with typical usage, 8 of 100 pill users become pregnant; with perfect use of the NuvaRing, less than 1 of 100 women annually become pregnant. For Annovera, the range between 3 clinical trials was 2-4 of 100 women per year. [19]

Because daily intake is not a component of vaginal ring contraceptives, since they are easily inserted and removed by the woman herself, and because return of fertility is rapid upon discontinuation, vaginal rings are a highly acceptable method for women and their partners. During the clinical trials for NuvaRing, women and their partners reported an acceptability rate of 85%. Because the hormones are absorbed directly into the blood through the vaginal mucosa, the hepatic first-pass metabolism of progestin is prevented. The ring delivers the lowest dose of ethinyl estradiol compared with other combined hormonal contraceptives. In contrast to combined oral contraceptives, the adverse effects of nausea and vomiting are avoided with ring use.

Disadvantages

Adverse effects include headaches and vaginal irritation or discharge. The ring may accidentally slip out during intercourse and either the user or the partner may feel the ring during sexual intercourse. Contraindications are similar to those of combined oral contraceptives.

How can I reduce the side effects of oral contraceptives?

Which of the following are known to reduce the effectiveness of oral contraceptives?

What are the risk factors associated with oral contraceptives?

What contraceptive methods can help you reduce the risk of pregnancy?