Perspective Chapter: Modern Birth Control Methods

Abstract

This chapter focuses on various modern birth control methods, including combined oral contraceptives, progestogen-only pills, progestogen-only injectables, progestogen-only implants, intrauterine devices, barrier contraceptives, and emergency contraceptive pills. Each contraceptive method is covered in detail, including mechanism of action, effectiveness, health benefits, advantages, disadvantages, risks, and side-effects.

1. Introduction

In recent years, the desire for smaller families and healthy birth spacing has steadily increased in developed and developing countries alike [1, 2]. The United Nations Millennium Development Goals calls for universal access to contraceptive services so that women and couples are able to have the desired number of births at the desired time [3]. Measuring and documenting levels and trends in contraceptive use and the unmet need for family planning services is crucial to informing the decisions of healthcare providers, program planners, and those in charge of resource allocation, particularly in developing nations [4].

Available information regarding unmet needs for contraception in developing countries allows health promoters, professionals, policymakers, and funding bodies to identify the necessary level of investment required in family planning programs [5]. Women are considered to have an unmet need for contraception if they are sexually active and want to avoid becoming pregnant, but are not using any method of contraception to achieve this goal [6]. When women receive health guidance in preventing unintended pregnancies, this helps reduce unwanted births and unsafe abortions, ultimately improving both maternal and child health [7].

The ideal contraceptive method needs to be highly effective in preventing pregnancy with the minimum number of possible side-effects and risks; in addition, it should be affordable, reversible, widely available, and acceptable to people of various cultures and religions [8]. These characteristics are believed to enable better utilization of modern contraception methods by couples and, more specifically, by women, with research showing that women transform their knowledge into behavior—in other words, that knowledge of contraceptives reduces fertility [9].

Investing in family planning is one of the most crucial measures to improve human wellbeing, as population dynamics have a fundamental influence on the pillars of sustainable development. Most importantly, the utilization of modern contraceptives is believed to be highly cost-effective in enhancing the socioeconomic status of nations and thus reducing poverty [3, 9]. This chapter gives the reader an overview of the various methods of modern contraception available, as well as their mechanisms of action, health benefits, and potential side-effects and risks, thereby allowing health care practitioners to better support women in making informed decisions about their fertility.

2. Combined hormonal contraception

Combined hormonal contraception (CHC) is a combined formulation of progestin and synthetic estrogen [10]. This type of contraception has been utilized by women worldwide for almost 60 years, with significant changes in dosage and preparation over time [11, 12]. More than a third of women aged 16–44 years in the UK use oral contraception; in addition, oral contraceptive pills are used annually by approximately 10 million U.S. women [11]. Health care practitioners should support women to make informed decisions about choosing specific forms of CHC, ensuring that they are aware of their effectiveness—and how they compare to other contraceptive methods—as well as their potential risks and benefits.

2.1 Content

CHC contains estrogen paired with a progestogen in different formulations.

2.1.1 Estrogen

The majority of combined oral contraceptives (COCs)—as well as the combined transdermal patch and combined vaginal ring—contain between 20 and 35 μg of ethinylestradiol (EE), a synthetic form of estrogen. Current ‘low-dose’ COCs were developed to reduce the health risks associated with the high estrogen content of COCs used in the 1960s and 1970s [13]. Low-dose COCs (i.e., formulations containing <50 μg of EE) are a safe and reliable contraceptive option for the vast majority of women [14, 15].

2.1.2 Progestogens

Progestogens are synthetic steroids designed to have some of the properties of progesterone. The synthetic progestogen component of CHC allows for convenient dosing intervals, potent suppression of ovulation, and prevents overproliferation of the endometrium in response to estrogen. Newer progestogens were developed to have fewer androgenic and glucocorticoid effects; some are anti-androgenic and have potentially favorable anti-mineralocorticoid effects [16]. However, different progestogens can modify the effect of EE on hepatic clotting factors in different ways; for example, forms of CHC which contain certain newer progestogens in combination with EE appear to be associated with a greater risk of venous thromboembolism (VTE) compared to COCs containing other progestogens [17, 18, 19, 20, 21].

The different progestogens included in CHC are sometimes grouped by ‘generation’ as below, according to the time they were first marketed as constituents of COCs:

• First-generation: norethindrone (NET).

• Second-generation: levonorgestrel (LNG).

• Third-generation: desogestrel (DSG), gestodene, norgestimate.

• Other: drospirenone (DRSP), dienogest, nomegestrol acetate [16, 22].

2.2 Types

There are currently two types of CHC regimens offered: standard hormonal regimens or tailored/combined regimens.

2.2.1 Standard regimens

The majority of COCs are designed to be taken on a 28-day cycle, with 21 consecutive daily active pills followed by a 7-day hormone-free interval prior to starting the next packet of pills. The first 7 pills inhibit ovulation and the remaining 14 pills maintain anovulation.

For combined transdermal patches, 1 patch is applied to the skin and worn for 7 days to suppress ovulation. Thereafter the patch is replaced on a weekly basis for 2 further weeks. The fourth week is patch-free to allow a withdrawal bleed. A new patch is then applied after 7 patch-free days [23].

For combined vaginal rings, 1 ring is inserted into the vagina and left in place continuously for 21 days. After a ring-free interval of 7 days to induce a withdrawal bleed, a new ring is inserted [24].

The majority of COC products are monophasic; that is, all pills in the packet contain the same dose of estrogen and progestogen. Multiphasic (variable dose) COCs are also available in which the dose of either or both steroid hormones varies during the pill cycle. Evidence is inadequate to establish whether multiphasic COCs differ significantly from monophasic COCs in terms of bleeding patterns, side-effects, discontinuation rates, or effectiveness in preventing pregnancy [25, 26, 27]. As existing evidence suggests there is no particular advantage to multiphasic preparations, it is recommended that monophasic COCs should be used as a first-line intervention.

2.2.2 Tailored regimens

Tailored CHC regimens include:

• Continuous use of CHC with no free interval.

• Extended use of CHC with a less frequent hormone-free interval in which the timing of the hormone-free interval can be either fixed or flexible.

• CHC regimens in which the hormone-free interval is shortened.

In continuous or extended CHC regimens, the contraception is taken for more than 21 consecutive days without a hormone-free interval. Such regimens have the potential advantage of eliminating or reducing the frequency of withdrawal bleeding and associated symptoms; the bleeding pattern is, however, unpredictable. Less frequent hormone-free intervals could also reduce the risk of escape ovulation and, potentially, contraceptive failure [28, 29, 30, 31]. A shortened hormone-free interval, offering more continuous ovarian suppression, could also reduce the risk of escape ovulation, particularly if contraceptive use is imperfect around the hormone-free interval. A shortened hormone-free interval can be taken either after every 21 days of active CHC use or incorporated into an extended regimen.

2.3 Mechanism of action

The main mechanism of action of COCs is the suppression of ovulation through the inhibition of gonadotropin-releasing hormone from the hypothalamus, as well as inhibition of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and disruption of the mid-cycle LH surge. These effects are mediated by both the progestogen and estrogen components of the COC working synergistically; however, it is the estrogen’s ability to suppress FSH and thus prevent folliculogenesis that is likely the most important mechanism.

The additional estrogen exposure in continuous-use pills, pills with a shorter pill-free interval, and pills with an additional 10 μg of EE in the placebo week results in more complete suppression of FSH and less folliculogenesis. However, a substantial number of women can still develop follicles while taking low-dose COCs [32, 33]. Additionally, the estrogen component stabilizes sufficient endometrium production to maintain a regular withdrawal bleeding pattern, thereby permitting cycle control.

Additional progestogen-related mechanisms that contribute to the contraceptive effect of COCs include:

• Effects on the endometrium, rendering it less suitable for implantation. Long-term cyclic or daily progestogen exposure leads to endometrial decidualization and eventual atrophy.

• Thickening of the cervical mucus, which becomes less permeable to penetration by sperm.

• Impairment of normal tubal motility and peristalsis.

2.4 Effectiveness

The efficacy, or failure, of COCs can differ considerably based on the type of user. The perfect user never misses taking a pill, takes the pill at the same time each day, and never vomits or has diarrhea. The failure rate for perfect users is <1 pregnancy per 100 women (or 3 per 1000 women). In turn, the typical user’s behavior results in the failure rates reported for the general population, which is 5–8 pregnancies per 100 women in the first year [34, 35, 36, 37, 38].

It is important to note that the risk of pregnancy is greatest when a woman starts a new pack of pills 3 or more days late or misses 3 or more pills near the beginning or end of a pack.

2.5 Advantages

In addition to their high contraceptive efficacy, COCs have many advantages, including rapid reversibility, regulation of menstrual bleeding, decreased menstrual blood loss, and dysmenorrhea, as well as population-level reductions in the risk of ovarian and endometrial cancers. Furthermore, CHC use does not interfere with intercourse and can be easily discontinued at any time.

2.5.1 Non-contraceptive uses

COCs are also widely used to treat a variety of other disorders and conditions, including:

• Menstrual cycle disorders—COCs are often used in women with menstrual cycle disorders, such as oligomenorrhea due to polycystic ovary syndrome (PCOS), abnormal uterine bleeding (e.g., midcycle spotting or heavy menstrual bleeding), menstrual migraines, and premenstrual syndrome or premenstrual dysphoric disorder, although COCs are not considered a first-line therapy for the latter indications.

• Pelvic pain disorders—Women with pelvic pain (e.g., endometriosis-related or chronic pelvic pain) or dysmenorrhea often benefit from the hormonal and endometrial suppression associated with COC use to reduce their symptoms. Continuous or extended-cycle COCs are often more effective in this population compared with cyclic use.

• Ovarian cysts—COCs are often prescribed to women with a history of painful ovarian cysts to suppress ovulation and the subsequent formation of new cysts. However, COCs do not appear to aid the regression of existing functional ovarian cysts [39, 40].

• Hyperandrogenism—COCs can reduce the dermatologic manifestations of hyperandrogenism, such as acne and hirsutism, which are particularly common in women with PCOS or non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The relevant mechanisms of action for this effect include the inhibition of gonadotropin secretion, and thereby a decrease in ovarian androgen secretion, and an increase in serum sex hormone-binding globulin concentrations, which results in increased binding of androgens and a decrease in serum-free androgen concentrations [41].

• Cancer risk reduction—Women at increased risk of endometrial and ovarian cancer can benefit from COC use to reduce their cancer risk. There is a similar reduction in risk for women with BRCA1- or BRCA2-associated ovarian cancers. Although a history of COC use has been associated with a reduced risk of colorectal cancer in certain studies, the overall body of evidence is conflicting, and it is as yet unknown if the prophylactic use of COCs reduces colorectal cancer risk [42, 43].

• Bone health—Perimenopausal women who use COCs have improved bone mineral density (BMD) compared to nonusers [44]. COCs are also useful for the treatment of hot flashes and abnormal uterine bleeding in this population.

2.6 Disadvantages

There are certain disadvantages to CHC use. The efficacy of this form of hormonal contraception is highly user-dependent as it must be taken every day at the same time; forgetfulness and missing pills increases the likelihood of failure. Similarly, CHC effectiveness may also be lowered with the simultaneous use of certain medications. Moreover, this method requires periodic resupply and offers no protection against gastrointestinal tract infections or sexually-transmitted infections (STIs), like the hepatitis B virus and HIV/AIDS. Though very infrequent, CHC use may sometimes delay return of fertility for 2–3 months. Finally, CHC may cause minor side-effects and risks, as detailed below.

2.6.1 Side-effects

Patients may experience breast tenderness, nausea, and bloating when starting COCs. These symptoms typically resolve quickly. Other concerns can include unscheduled bleeding, which typically resolves within 3 months, and a possible impact on mood and sexual function. There is no evidence to show that COCs cause weight gain.

2.6.2 Risks

The risks associated with COC use are influenced by the type and dose of estrogen and progestogen contained in the formulation. These risks are as follows:

• VTE—COC use has been associated with an increased risk of VTE. The risk of VTE varies with estrogen dose and patient-specific factors, such as age, obesity, and smoking status. Nevertheless, while the VTE relative risk is increased, the absolute increase in VTE risk is still low for most women and does not outweigh the numerous benefits of this contraceptive method, particularly when compared with the VTE risk during pregnancy and the postpartum period [45].

• Cardiovascular health—COC use has been associated with increased risks of hypertension, myocardial infarction, and stroke in certain populations. However, the absolute risk of myocardial infarction and stroke attributable to COCs is low in women of reproductive age. Rarely, COCs can cause a mild elevation in blood pressure in the range of 3–5 mmHg; however, this is unlikely to be clinically significant in healthy women [46].

• Cancer—COC use does not appear to increase the overall risk of cancer. The impact of COC use on breast cancer risk is a subject of active debate, with conflicting data reported. At least 1 study has reported a differing risk of breast cancer with COC use based on hormone receptor subtype. Women who have taken COCs also appear to have a slightly increased risk of developing cervical cancer. By contrast, COC use is associated with a reduced risk of developing ovarian and endometrial cancers [47].

• STI acquisition—The impact of developing STIs in women using COCs appears to vary by type of infection. Two systematic reviews reported that COC use positively correlated with chlamydia infections, but not with gonorrhea, herpes simplex virus-2, trichomoniasis, syphilis, and human papillomavirus. While COCs may be associated with increased rates of chlamydia, rates of pelvic inflammatory disease (PID) do not appear to be increased. One study reported similarly increased rates of bacterial vaginosis, trichomoniasis, and vaginal candidiasis among women starting either COCs or an LNG-IUS device, which makes sexual exposure the likely risk factor for these infections and not the contraceptive method. Other studies have reported reduced rates of bacterial vaginosis in women using COCs. Data generally do not support any influence of COC use on the acquisition of HIV. There are currently no restrictions on COC use among women with STIs, PID, or HIV [48, 49, 50].

3. Progestogen-only pill

The progestogen-only pill (POP) is a form of hormonal contraception which contains a progestogen. It is often referred to colloquially as the “mini-pill”.

3.1 Content

The POP is formulated with a single synthetic hormone, progestin. Unlike CHC, POPs do not contain any estrogen. Moreover, the dose of progestin in POPs is substantially lower than that included in COCs (NET: 0.35–1 mg, DRSP: 3–4 mg).

3.2 Types

There are multiple types of progestins available:

• NET—Commonly available as individual 0.35-mg tablets, NET is dispensed in packs of 28 active pills, which are taken continuously (i.e., without a 7-day hormone-free interval) [51].

• DRSP—DRSP is dispensed in packs of 20 tablets containing 4 mg of DRSP and 4 inert tablets [52]. One tablet is taken daily until the pack is empty and then a new pack is started.

• DSG—In numerous countries, DSG POPs are available in a 75-μg formulation [53]. This formulation has significant differences from NET-POPs.

3.3 Mechanism of action

Depending on their formulation, POPs have several independent modes of action that contribute to their contraceptive effect [51, 52, 53]. POPs increase the volume and viscosity of the cervical mucus, preventing sperm penetration into the upper reproductive tract [54]. This change occurs soon after starting a POP, within 2 days of taking the pill. However, the contraceptive effect provided by these mucosal changes is short-lived; it has been estimated that full protection conferred via cervical mucosal changes may last less than 24 h unless maintained by regular pill-taking [53].

In addition, POPs can act to suppress ovulation [54]. However, the extent to which this occurs is variable; for example, up to 60% of cycles in women using LNG pills are anovulatory, whereas ovulation is suppressed in up to 97% of cycles in women using DSG pills [55, 56]. Other modes of action include endometrial changes that hinder implantation and reduction in cilia activity in the fallopian tube that slows the passage of the ovum [54]. The main mechanism of action of DRSP-POPs and DSG-POPs is the suppression of ovulation.

3.4 Effectiveness

The effectiveness of POPs in preventing pregnancy is as high as that of combined estrogen-progestin contraceptive pills; moreover, intake delay of up to 12 h does not affect contraceptive efficacy [57]. Nevertheless, the effectiveness of this method still depends on the user, as higher failure rates occur with poor compliance. For perfect users, the failure rate is <1 pregnancy per 100 women over the first year (3 per 1000 women). However, for typical users, the failure rate is 1 pregnancy per 100 women in the first year for breastfeeding women and 3–10 pregnancies per 100 women in the first year for non-breastfeeding women [58].

3.5 Advantages

The most important advantage of POPs is their rapid effectiveness (<24 h), if taken within the first 7 days of the menstrual cycle. Unlike COCs, intake delay of up to 12 h does not affect contraceptive efficacy [57]. Moreover, the lack of estrogen eliminates the possibility of estrogen-related side-effects and complications. POPs do not interfere with intercourse or affect breastfeeding. Women taking POPs can easily cease taking the pills with an immediate return of fertility. Anecdotally, some women mention that the POP tablets are easier to take compared to COCs because each tablet is the same color.

3.5.1 Non-contraceptive uses

Daily use of progestin protects against the development of endometrial cancer [59]. In addition, NET acetate has demonstrated efficacy in treating dysmenorrhea, abnormal uterine bleeding, and endometriosis-related pain, albeit at higher doses (2.5–15 mg per day) [60]. A single-arm trial of continued DRSP use over 13 cycles in adolescent females reported reduced rates of dysmenorrhea, as well as a corresponding decrease in the use of pain medication to treat the aforementioned dysmenorrhea [61].

Although POPs neither protect from nor increase the risk of acquiring STIs, progestin-induced thickening and increased viscosity of the cervical mucus has been hypothesized to inhibit the ascent of bacteria and thus potentially reduce the risk of PID development. Nevertheless, all women at risk of STI acquisition should be advised to use a condom.

3.6 Disadvantages

As with COCs, there are certain disadvantages to POPs. Although the window of time for contraceptive efficacy when taking POPs is more forgiving compared to COCs, the efficacy of POPs still relies on the user taking the pill every day. Similarly, this method also requires a periodic resupply of pills and offers no protection against STIs. Moreover, POP users may experience certain side-effects and risks, as detailed below.

3.6.1 Side-effects

• Bleeding—Altered bleeding patterns are a common reason given by women for stopping POPs [62, 63, 64]. Indeed, almost half of POP users experience prolonged bleeding and up to 70% report breakthrough bleeding or spotting in 1 or more cycles [64]. Bleeding patterns associated with POPs may depend upon the type of progestogen used, the dose at which it is given, circulating endogenous estradiol concentrations, and ovulation.

• Decreased libido—Decreased libido is a commonly reported adverse reaction (≥1 per 100 women) in clinical trials [64, 65]. However, establishing causation is difficult, given the subjective nature of sexual interest and the multitude of factors that may influence it. Studies looking specifically at the impact of POPs on libido are lacking.

• Weight changes—In women of reproductive age, minor weight fluctuation is common. However, a review of 16 randomized controlled trials (RCTs), one of which examined a POP, reported limited evidence of weight gain (<2 kg over 12 months) among users of progestogen-only contraceptives. Whilst there is a paucity of evidence relating to the POP specifically, the available evidence does not support a causal association between POP use and weight change [66].

• Headaches—Although there are limited data on the effects of progestogen on migraine development, the available evidence does not suggest an increased incidence of migraines associated with the use of POPs [67].

• Depression and mood changes—As with other forms of hormonal contraception, depression and mood changes are possible undesirable effects of POP use [68, 69, 70]. However, there is as yet no direct evidence from studies to suggest a causal association.

3.6.2 Risks

• Cardiovascular health—Few studies have been large enough to evaluate VTE risk associated with the use of progestogen-only contraceptives. However, the available evidence does not demonstrate an increased VTE risk with the POP [71, 72, 73]. Hypertension is a condition for which there is no restriction on the use of POPs, as there is no evidence that POPs increase blood pressure [54]. Even for women with vascular disease, the advantages of POPs generally outweigh the theoretical or proven risks [74]. POPs are generally appropriate for women with cardiac disease and are useful as a bridging method while specialist advice is being sought [75].

• Breast cancer—The annual risk of breast cancer increases with age, irrespective of hormone use. Due to the small numbers of women using progestogen-only methods in studies that have investigated the association between hormonal contraceptive use and breast cancer, data are limited with regards to determining breast cancer risk associated with POP use [76]. Any attributable risk is likely to be small and, as with COCs, likely to reduce with time after discontinuation of the contraceptive.

• Ectopic pregnancy—The risk of ectopic pregnancy associated with any particular contraceptive method is determined, in the first instance, by the ability of the method to prevent pregnancy and, subsequently, by the proportion of ectopic to intrauterine pregnancies that occur. Other factors may also influence this risk, including age, smoking status, and a previous history of ectopic pregnancy. The incidence of ectopic pregnancy associated with POPs is difficult to determine due to the small numbers of ectopic pregnancies that occur and the inability to adequately control for other risk factors. Up to 10% of pregnancies that occur in traditional POP users may be ectopic [54]. Methods that suppress ovulation are likely to be associated with a lower overall rate of ectopic pregnancy than those that do not. Women should be informed of possible signs of ectopic pregnancy (e.g., lower abdominal pain or shoulder tip pain). A previous history of ectopic pregnancy does not place any restrictions on the use of POPs [74].

4. Progestogen-only injectables

Progestogen-only injectables (POIs) are one of the most effective contraceptive methods and are reversible, safe, and easy to use [77]. These long-acting contraceptives consist of injections of progestogen which are steadily released into the bloodstream over several weeks. Injections are given every 8–13 weeks, depending on the type of injectable [78, 79].

4.1 Content

Much like POPs, POIs contain progestin, a synthetic hormone that mimics progesterone, the natural hormone present in a woman’s body.

4.2 Types

There are three types of POIs currently available:

• 150 mg of depot medroxyprogesterone acetate (DMPA) given intramuscularly every 3 months (DMPA-IM).

• 104 mg of DMPA given subcutaneously every 3 months (DMPA-SC).

• 200 mg of NET enanthate given intramuscularly every 2 months [78, 80].

In 1992, the U.S. Food and Drug Administration (FDA) approved the marketing of DMPA as a contraceptive agent [81]. Of the three options outlined above, DMPA-IM is the most commonly used and extensively researched injectable progestin [79]. It should be administered deep into the muscles, as the preparation is released slowly into the blood stream from the site of injection [82]. For DMPA-SC, the BD Uniject™ system (Becton, Dickinson & Co., Franklin Lakes, NJ) is a useful option for community-based programs or home delivery as it can be self-administered using the system’s prefilled, single-dose, disposable hypodermic syringes [83]. The efficacy of DMPA-SC is likely maintained when administered in the upper arm, abdomen, or thigh, which may be preferrable for some women [84].

4.3 Mechanism of action

There are three primary mechanisms of action that contribute to the efficacy of injectable DMPA in preventing pregnancy:

• Inhibition of ovulation through suppression of the hypothalamus, the main mechanism of action [85].

• Mucosal changes in which the cervical mucus becomes more viscous, thick, and scanty, thereby inhibiting sperm from reaching the oviduct (fallopian tubes) and preventing egg fertilization [81, 82].

• Thinning and atrophy of the endometrium through decreased estradiol concentrations [86].

4.4 Effectiveness

POIs containing DMPA are one of the most effective methods of contraception. Contraceptive efficacy is achieved rapidly (<24 h) and, because there is a grace period of 4 weeks, is non-user-dependent. Nevertheless, it is important that the injections are given consistently and correctly. Pregnancy protection rates reach 99% with perfect use and 96% with typical use, assuming occasional non-use and/or incorrect use for the latter [80, 87]. The risk of pregnancy is higher when a woman misses an injection. The failure rate is up to 6 pregnancies per 100 women in the first year of use [88]. Age, income, desire to prevent or delay pregnancy, and culture affect the consistent and correct usage of any method of contraception [80].

4.5 Advantages

In general, POIs are a good choice for women who want a reliable, long-lasting, reversible method of contraception without the need for daily action on their part, such as pill-taking. This type of contraceptive can be used by women of any age and parity status and is easily discontinued. Client satisfaction is high, as injections are often considered more convenient compared to other forms of contraception and follow-up injections can be easily given by a nurse. There is no need for a pelvic examination prior to the use of POIs. Furthermore, the injections do not affect breastfeeding or interfere with intercourse. Overall, POIs have a good safety profile and few specific health risks. They have minimal drug interactions.

4.5.1 Non-contraceptive uses

Since its introduction into the market in the 1960s, DMPA has been used for a variety of gynecological conditions, including endometriosis and abnormal menstrual bleeding [81]. Because it decreases menstrual blood loss by 50% at 1 year of use and by 70% after 2 years of use, DMPA improves iron deficiency anemia and amenorrhea [83]. The mechanism of action of progestin with regards to endometrial thinning and atrophy contributes to its use in the treatment of endometriosis, plus its direct effect on endometrial lesions [86]. DMPA can also be used in the treatment of abnormal uterine bleeding associated with uterine fibroids, adenomyosis, or coagulopathies [39]. In addition, it protects against endometrial cancer and symptomatic PID.

DMPA also improves cyclical menstrual symptoms, such as pain, mood changes, headaches, and breast tenderness, and decreases the incidence of benign breast disease, ovarian cysts, and ectopic pregnancy. Furthermore, women with sickle cell disease will have fewer sickle cell crises, while those with epilepsy will have fewer grand mal seizures [79, 81, 82].

4.6 Disadvantages

There are several limitations to the use of DMPA. The main disadvantage of this type of contraception is its ability to engender changes in the bleeding pattern of a woman’s menstrual cycle, potentially limiting its uptake. Indeed, discontinuation of DMPA is reported to be 25–50% in the first year of use [89, 90]. Moreover, POIs do not provide protection against STIs such as chlamydia, gonorrhea, and HIV. The client has to return to the clinic for follow-up injections and, once given, their contraceptive action cannot be stopped until the time of the next injection. Furthermore, there is some delay in return of fertility which takes approximately 7–10 months from the date of the last injection [79, 82].

Counseling is highly recommended to ensure that the possible side-effects and risks of POIs, described below, are explained to clients, particularly the reasons behind any menstrual changes.

4.6.1 Side-effects

• Bleeding—Unpredictable, irregular, frequent, or heavy bleeding usually occurs with the first 3 months of POI use; subsequently, by 1 year of use, the majority of women have achieved amenorrhea [82].

• Weight changes—There is some evidence to show that the use of progestogen-only contraceptives up to 12 months may cause weight gain (mean of <2 kg/4.4 lb). In addition, progestogen-only contraceptive users showed greater increases in body fat and decreases in lean mass compared to users of non-hormonal contraceptive methods [66]. Another prospective study with a longer follow-up over 36 months found that DMPA users gained an average of 5.1 kg/11.2 lb, whereas women who used COCs did not gain any weight [91, 92]. Weight gain with the first injection may be predictive of weight gain over time and women who are overweight and obese may be at higher risk [81].

• Hormonal side-effects—Like other hormonal contraceptives, DMPA has other related side-effects, including breast tenderness, headaches, nausea, acne, abdominal bloating and discomfort, and hypo-estrogenic effects such as hot flashes, reduced libido, and vaginal dryness. While DMPA may cause mood changes, depression is not a contraindication to its use [93].

• Bone health—In suppressing gonadotropin production and ovulation, DMPA also suppresses ovarian production of estradiol and hypoestrogenemia causes a decline in BMD in current DMPA users [94]. The rate of loss is greatest during the first 1–2 years of use (by 0.5–3.5% at first and 5.7–7.5% subsequently) [95]. This reduction in BMD normalizes after discontinuation of DMPA use for up to 5 years [96, 97, 98]. There is no reported increase in fracture risk among DMPA users [99].

• Allergic reactions—Allergic reactions are a serious side-effect of DMPA [81].

4.6.2 Risks

• Cardiovascular health—DMPA use is not associated with an increased risk of cardiovascular events in healthy women, including VTE, myocardial infarction, or stroke. Although circulating lipids are affected by DMPA use, it does not increase production of coagulation factors and has no adverse effect on blood pressure. No adverse clinical effects on cardiovascular disease have been observed [83].

• Depression—prospective studies do not support a causal relationship between DMPA use and depression.

5. Implantable contraception

Implants are small, flexible, impermeable plastic rods about the size of a matchstick that are placed just under the skin of the upper arm [100, 101]. Over the past 35 years, various types of contraceptive implants have been approved in more than 60 countries; today, this method of contraception is used by millions of women worldwide [102]. Implants are a good choice for women of reproductive age who are sexually active and desire continuous, long-term contraception.

5.1 Content

Contraceptive implants include a progestin which is released in a low, steady dose into the bloodstream. The most common forms of progestin used in implants are LNG and etonogestrel.

5.2 Types

There are several types of contraceptive implants on the market:

• Jadelle® (Bayer, Leverkusen, Germany), which consists of 2 rods each containing 75 mg of LNG, labeled for up to 5 years of use [103].

• Implanon NXT®/Nexplanon® (Organon, Jersey City, NJ), which consists of 1 rod containing 68 mg of etonogestrel, labeled for up to 3 years of use. The Nexplanon® has replaced the Implanon NXT® which is now discontinued [104].

• Levoplant®/Sino-Implant (II) (Shanghai Dahua Pharmaceutical Co. Ltd., China), which consists of 2 rods each containing 75 mg of LNG, labeled for up to 4 years of use. Levoplant® is also sometimes referred to as Sino-Implant (II) [105].

• Norplant® (Wyeth Pharmaceuticals, Madison, NJ), which consisted of 6 capsules each containing 36 mg of LNG and was effective for 5–7 years. This device was discontinued in 2008 and is no longer available for insertion.

Of the various types of contraceptive implants available, the Implanon NXT®/Nexplanon® is the most commonly used and is registered in approximately 80 countries worldwide [106]. It is radio-opaque (visible on X-ray) and has an improved insertion device.

5.3 Mechanism of action

Contraceptive implants have two primary mechanisms of action: inhibition of ovulation and restriction of sperm penetration [107]. The anti-estrogenic effect of the progestin causes the cervical mucus to become more viscous and scanty, thereby stopping sperm penetration and egg fertilization [108]. Furthermore, high doses of progestin diminishes gonadotropin secretion, inhibiting follicular maturation and ovulation. While progestin also suppresses endometrial activity by causing the endometrial thinning and atrophy, thereby impeding implantation, these two actions remain the major mechanisms of action in preventing fertilization [109]. There is no evidence of embryonic development among implant users, indicating that progestin implants have no abortifacient properties [81].

5.4 Effectiveness

The etonogestrel implant (Implanon NXT®/Nexplanon®) is among the most effective and long-lasting contraceptives available and is as good as or better than sterilization procedures, with pregnancy protection rates of >99% for both typical and perfect users [88, 110]. If inserted within the first 5 days of the menstrual cycle, the implant is effective immediately after insertion, with peak serum levels occurring within 4 days [111]. The failure rate is negligible at <1 pregnancy per 100 women in the first year (or 1 per 1000 women). Beyond the first year of use, a small risk of pregnancy remains and continues as long as the client is relying on the implant as the only form of contraception.

The efficacy of implants is based on correct sub-dermal insertion and removal of the device. All healthcare providers should receive instructions and training prior to the insertion or removal of the implant. Women taking efavirenz for HIV should be advised to use condoms along with implants, as this medication may reduce the effectiveness of contraceptive implants.

5.5 Advantages

Contraceptive implants are a highly effective, long-acting form of user-independent, non-coitus-related contraception that provides protection against pregnancy without the need for repeated adherence. Moreover, they have few side-effects and are rapidly reversible [100, 101]. Implants are a good option for adolescents, as they do not require the user to do anything after insertion and there is no need for routine follow-up visits, as well as for adult women who desire highly efficient, easy-to-use, long-term protection. Implants can be inserted without the need for a pelvic examination, breast examination, blood tests, or any other laboratory tests, barring another indication for doing so. Moreover, implants do not interfere with intercourse and clients are ensured of a complete return of fertility after removal.

5.5.1 Non-contraceptive uses

Implants do not disturb lactation and reduce the risk of ectopic pregnancy and symptomatic PID, probably as a result of the effects of progestin on the cervical mucus; moreover, they may protect against iron-deficiency anemia. Furthermore, implants do not increase the risk of STIs [78, 81]. Implants have been shown to be beneficial in women with dysmenorrhea as they decrease abdominal cramps by up to 80% [112]. Unlike DMPA, etonogestrel implants have not been found to induce bone loss [78, 110].

5.6 Disadvantages

A woman cannot start or stop using implants on her own as insertion and removal of the device constitutes a minor surgical procedure which must be performed by a well-trained provider. Furthermore, implants are a relatively expensive method of contraception and do not protect against STIs.

5.6.1 Side-effects

Contraceptive implants may cause changes in menstrual bleeding in the first several months to 1 year of use, including lighter bleeding, fewer days of bleeding, prolonged bleeding, irregular bleeding, and even no bleeding. After about 1 year of use, the pattern of bleeding becomes more regular. Changes in bleeding patterns as a result of implants are not harmful but are a common drawback of this contraceptive method. Amenorrhea occurs in approximately 20% of women in the first year of use, although this rates declines with duration of use to 13% by year 3 [113].

Unscheduled bleeding was reported as the reason for discontinuation of this method among 14.8% of users in the U.S. and Europe and 3.7% in Southeast Asia, Chile, and Russia [114]. About 90% of women who discontinued the implant experienced frequent or prolonged bleeding/spotting versus 22% of those who continued using the device [115].

Like other progestogen-only forms of contraception, other possible-side effects of contraceptive implants include headaches, abdominal pain, mood changes, nausea, breast tenderness, dizziness, acne (either improvement or exacerbation), weight change, and possibly enlarged ovarian follicles [78, 110].

5.6.2 Risks

Complications are reported in 0.3–1% of implant insertions and 0.2–1.7% of removals [116]. Uncommon insertion/removal complications include infection, hematoma formation, and local irritation and rashes at the insertion site; these occur mostly within the first 2 months of insertion. Clinician training and experience, and the use of a stringent, aseptic technique reduces the incidence of such complications.

In addition, rare complications can occur, including expulsion of the implant (occurring within the first 4 months of insertion) and migration of the implants over time a short distance (<2 cm) from the site of insertion [78, 117]. Nerve injuries have also been reported with implants, including injury to the branches of the medial antebrachial cutaneous nerve during placement and the medial antebrachial cutaneous nerve [118, 119].

6. Intrauterine contraception devices

Intrauterine contraception devices (IUCDs) are small, flexible devices inserted in the uterine cavity to provide effective, long-acting, reversible contraception. The IUCD is a safe, easy-to-use, and highly cost-effective means of contraception, with significantly low failure rates [120, 121]. It provides a nonsurgical option for pregnancy prevention that is as effective as surgical sterilization. The IUCD is one of the most commonly used methods of long-acting, reversible contraception worldwide, with an average utilization rate of approximately 23% among female contraceptive users, although there is wide variation between countries, ranging from <2% to >40% [122, 123].

6.1 Content

There are different types and shapes of IUCD available globally. Most IUCDs have a plastic frame and release either copper or a progestin to prevent pregnancy.

6.2 Types

Generally, most frequently used IUCDs are divided into two main categories: hormonal and non-hormonal. Various terms are used to describe IUCDs, including intrauterine device and intrauterine contraception; hormonal IUCDs or progestin-containing devices are also referred to as an IUS.

Copper IUCDs (Cu-IUCDs) are non-hormonal and vary in size and shape. They consist of a piece of plastic and copper, with some types containing silver or other metals. Theoretically, this may increase the longevity of the device; however, no evidence has been identified to confirm any clinical benefit of mixed-metal IUCDs over IUCDs that only contain copper. In addition to their use as long-acting, reversible forms of contraception, Cu-IUCDs can also be used as a method of emergency contraception [124, 125].

In turn, the LNG-IUS is a T-shaped device with an elastomer core containing LNG. There are different LNG-IUSs available which release a varying amount of LNG. In addition to its use for contraception, the LNG-IUS can be used in the management of heavy menstrual bleeding and as endometrial protection during estrogen replacement therapy [126].

6.3 Mechanism of action

The IUCD has multiple mechanisms of action that contributes to its contraceptive properties. The device causes chemical changes that damage the sperm and ova before they can meet, thus preventing fertilization [127]. Moreover, copper ions released by Cu-IUCDs reduce sperm motility and viability and inhibit sperm penetration and migration by affecting the uterotubal fluid, thus decreasing the number of sperm reaching the oviduct and their capacity to fertilize the ova. Copper also induces changes in the endometrium, causing a cytotoxic inflammatory response increasing levels of white blood cells, enzymes, and prostaglandins in the uterine fluid, thereby impairing sperm function and preventing implantation. Additionally, Cu-IUCDs inhibit ova development [114, 128, 129].

The LNG-IUS inhibits fertilization by thickening the cervical mucus which acts as a barrier to the upper genital tract, as well as causing changes in the uterotubal fluid that impair sperm migration. Inhibition of implantation via endometrial changes is the secondary mechanism of action of the LNG-IUS. A foreign body effect may also be a contributing factor, as has been observed with other intrauterine methods [128, 130, 131]. While the LNG-IUS also has a minor effect on the hypothalamic pituitary ovarian axis, serum estradiol concentrations are not reduced, and the majority of women (>75%) continue to ovulate [132, 133, 134, 135].

Progestogenic effects of the LNG-IUS on cervical mucus have been demonstrated, but it is not fully understood how quickly such changes are established [136, 137, 138]. Prevention of implantation occurs via a progestogenic effect on the endometrium [139, 140, 141]. Within 1 month of insertion, high intrauterine concentrations of LNG induce endometrial atrophy [130, 131, 142, 143, 144]. The LNG-IUS also causes changes in the endometrium that may also contribute to its contraceptive effect, particularly by altering the intercellular junctions between the epithelial and stromal cells and increasing the number of phagocytic cells [140, 143, 145].

All of the anti-fertility actions of IUCDs occur prior to implantation [114, 128, 129, 146]. The common belief that the mechanism of action of IUCDs is the destruction of an implanted embryo is not supported by evidence. Studies of IUCD users were unable to find embryos or detect human chorionic gonadotropin, indicating that transient, or chemical, pregnancies had not occurred [128, 147, 148]. In summary, there is no evidence to suggest that IUCDs disrupt an implanted pregnancy [149].

6.4 Effectiveness

Failure rates within the first year of IUCD insertion are 0.6–0.8% for women with a Cu-IUCD and 0.2–0.9% for women with an LNG-IUS. The cumulative failure rate over 10 years of use of the Cu-IUCD is 2.1–2.8%, while that of the LNG-IUS over 5–7 years of use is 0.7–1.1% [150]. Unlike most other forms of reversible contraception, the IUCD does not rely on patient participation or adherence for correct usage; thus, failure rates for typical and perfect users are similar.

6.5 Advantages

The IUCD is one of the most cost-effective methods of long-acting, reversible contraception available; even though the cost of the device and insertion can be high initially, the overall cost with long-term use decreases with time because no additional expenditure is required [151]. Moreover, this method is highly effective, acts immediately, and is not dependent on user compliance as it does not require regular adherence to maintain its effectiveness. It requires only a monthly self-checking for strings, and yearly follow-up visits. In addition, the IUCD does not interfere with intercourse or breastfeeding and can be inserted 6 weeks after giving birth. Clients are assured of a rapid return of fertility upon removal. Depending on the type of IUCD inserted, women can avoid the use of either exogenous estrogen (both IUCD types) or hormones in general (Cu-IUCDs only).

6.5.1 Non-contraceptive uses

The IUCD offers a reduced risk of cervical, endometrial, and ovarian cancers [152, 153, 154, 155]. Moreover, the LNG-IUS can be used in the treatment of menorrhagia, endometriosis, and pelvic pain [155, 156, 157].

6.6 Disadvantages

There are several disadvantages to the utilization of IUCDs. This type of contraceptive device requires the client to undergo a minor procedure for insertion and removal; as such, the client cannot discontinue use of this method on her own. Moreover, the client will need to check strings after each menstrual period. Pelvic examination and genital tract infection screening is mandatory before initiation of use, as per the Centers for Disease Control and Prevention guidelines. In addition, because she may experience heavier monthly bleeding, the device may contribute to anemia if the women has low iron stores prior to insertion [158, 159]. Finally, IUCDs do not protect against STIs.

6.6.1 Side-effects

• Pain and menstrual bleeding changes—The IUCD can result in abdominal cramps, pain, and changes in monthly bleeding patterns, especially in the first 3–6 months of use, including prolonged and heavy monthly bleeding, irregular bleeding, and no bleeding [158, 159, 160]. Users of the LNG-IUS are more likely to terminate use due to amenorrhea, while Cu-IUCD users are more likely to terminate the method because of pain and other menstrual events [160].

• Hormonal side-effects—Discontinuation because of hormonal side-effects is also more common among LNG-IUS users [158]. These side-effects include acne and weight changes, both of which are rare.

6.6.2 Risks

• Expulsion of the device—The incidence of expulsion is 3–10% for the Cu-IUCD and 3–6% for the LNG-IUS in the first year of use [146, 147, 161]. A trial reports that the expulsion of the Cu-IUCD occurs less frequently than with the LNG-IUS (8.4 versus 11.7 cases per 100 users). Another study reveals that the expulsion rate is equal between Cu-IUCD and LNG-IUS as well as reported pain.

• PID—The IUCD may increase the risk of PID in women who have chlamydia or gonorrhea at the time of insertion, although this is rare [162]. Rates of PID among users of IUCDs are fairly similar regardless of type of device (3.6 cases per 100 women).

7. Barrier methods

Barrier contraception is a safe, effective, and reversible form of contraception acceptable to many couples. These methods can be used either alone as the primary method of contraception, or in combination with other contraceptive methods. In terms of the latter, barrier methods may be used as a short-term combination therapy, for example when CHC is initiated, or in the long term to provide additional protection against pregnancy. Barrier methods are also the only method of contraception which can be used to prevent the transmission of STIs.

7.1 Content

Depending on the type of method utilized, barrier devices may be made of rubber, plastic, or organic components such as lambskin [12, 163].

7.2 Types

There are several types of barrier methods available, including:

• Male condoms (including latex, non-latex, and deproteinized latex varieties).

• Female condoms (latex, polyurethane, or nitrile).

• Diaphragms (latex or silicone).

• Cervical caps (silicone).

• Spermicides (foams, gels, and films with sperm-killing or blocking properties) [12, 163].

Male condoms are sheaths or coverings that fit on an erect penis. Female condoms are sheaths, or linings, that fit loosely inside a woman’s vagina, made of a thin, transparent, soft film. Female condoms have flexible rings at both ends; one ring at the closed end helps to insert the condom, while the ring at the open end holds part of the condom outside the vagina [78].

Diaphragms and cervical caps consist of plastic or silicone domes which are inserted inside the vagina to cover the cervix, primarily used in conjunction with a spermicidal agent. A recent survey found that <1% of women reported using diaphragms and caps [12].

7.3 Mechanism of action

Barrier methods provide a physical barrier to prevent the migration of sperm from the vagina to the upper reproductive tract where fertilization occurs, thereby preventing pregnancy. Male and female condoms work by keeping sperm out of the vagina and forming a barrier to ejaculate, pre-ejaculate, and vaginocervical secretions [78]. In turn, diaphragms and caps keep sperm from reaching the cervix. However, as only the cervix is covered by the latter two methods, they do not prevent exposure of the vaginal mucosa to semen or exposure of the penis to vaginocervical secretions.

7.4 Effectiveness

Data from the U.S. suggest that there is a 5% failure rate with the female condom and a 2% failure rate with the male condom with perfect use (i.e., correct and consistent use). With typical use (which includes incorrect and inconsistent use), failure rates are 21% and 18%, respectively [88]. Nevertheless, many factors other than user error may influence the efficacy of condoms in the prevention of pregnancy, including background fertility, coital frequency, or the use of emergency contraception. A study assessing semen exposure following condom failure suggested that even when condoms break or slip, the risk of pregnancy may be reduced in comparison to when using no method of contraception at all [164]. Although condom studies often report clinical breakage and slippage rates, these are not considered valid surrogate endpoints of pregnancy [165].

Data have suggested that, with perfect use, 4.3–8.4% of women using a diaphragm with a spermicidal cream or jelly experience an unintended pregnancy within the first year of use. With typical use, the percentage increases to 12% [88]. In a comparative study, the only contraceptive cap available in the UK was found to be less effective at preventing pregnancy than the diaphragm to which it was compared. The unadjusted typical-use probability of pregnancy at 6 months of use was 13.5% for contraceptive cap users and 7.9% for diaphragms users, with the adjusted risk of pregnancy being 1.96 times higher in the former group [166, 167].

7.5 Advantages

The advantages of male and female condoms include their rapid effectiveness, low cost, and the fact they are simple to use with no required medical supervision. As a non-hormonal method of contraception, they are free from the side-effects and risks associated with exposure to exogenous estrogen or hormones in general.

7.5.1 Non-contraceptive uses

Condoms are the only contraceptive method that provides protection against STIs and, by extension, help in the protection against conditions caused by STIs (e.g., PID and cervical cancer). Laboratory studies have shown that both male latex condoms and male and female non-latex condoms protect against many STIs, including hepatitis B and HIV/AIDS [168, 169, 170, 171, 172, 173]. Data from other studies suggest that female condoms may be as effective as male condoms in the prevention of STIs arising due to vaginal intercourse, including Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and genital ulcer disease [173, 174].

7.6 Disadvantages

The disadvantages of condoms are that they are entirely user-dependent, requiring continuous user motivation. Moreover, risk of failure is always present due to the possibility of condom slippage or breakage; as such, barrier methods are not suitable for high-risk pregnancy clients. In addition, they should be used at every act of sex, for which re-supply must be readily available. Condoms may interfere with sexual pleasure in some clients. They require appropriate storage and proper disposal. Allergic reactions to latex is the only known side-effect of barrier methods made of latex [78].

8. Emergency contraception

Emergency contraception, sometimes referred to as the “morning after” pill or postcoital contraceptives, is designed to prevent or delay ovulation after an act of unprotected sexual intercourse (UPSI).

8.1 Content

Current methods of emergency contraception include either the insertion of a Cu-IUCD or the administration of contraceptive pills with hormonal components, including either estrogen and progestin in combination, progestin only, or selective progesterone receptor modulators [175].

8.2 Types

There are various types of emergency contraceptive pills (ECPs), including:

• Pills containing LNG or ulipristal acetate (UPA) alone.

• POPs containing LNG or norgestrel (LNG-ECPs).

• COCs containing both estrogen and a progestin (i.e., LNG, norgestrel, or NET).

In Europe, UPA-ECPs have been available since 2009; subsequently, they received approval in the U.S. from the FDA in 2010 for use as an emergency contraceptive. They are now available in more than 50 countries [78].

8.3 Mechanism of action

The risk of pregnancy after an episode of UPSI is difficult to estimate because it depends on a number of factors, including the fertility of both partners, the timing and number of acts of UPSI, cycle length and variability, and whether contraception has been used incorrectly or not at all. Pregnancy is extremely unlikely to occur as a result of UPSI in the first 3 days of a woman’s natural menstrual cycle [141]. However, pregnancy is theoretically possible after UPSI on most days of the cycle. A woman’s fertile period is considered to be the 6 consecutive days ending with, and including, the day of ovulation.

Sperm are viable in the female genital tract for about 5 days after UPSI [141]. If ovulation occurs within those 5 days, fertilization could take place and the woman is at risk of pregnancy. A judicial review concluded that pregnancy begins at implantation [176]. It is therefore currently accepted that any emergency contraception intervention must act either to prevent fertilization or to prevent implantation, rather than to disrupt established implantation. According to available data, the shortest time from ovulation to implantation is 6 days, although over 80% of pregnancies implant 8–10 days after ovulation [177].

LNG-ECPs inhibit ovulation, delaying or preventing follicular rupture and causing luteal dysfunction. If taken prior to the start of the LH surge, LNG inhibits ovulation for the next 5 days, until sperm from the UPSI for which it was taken are no longer viable [178]. In the late follicular phase, however, LNG-ECPs become ineffective [179]. Although post-ovulation effects of LNG-ECP have been suggested, subsequent studies have not shown a significant effect when administered after ovulation [180]. In vitro, LNG-ECPs have not been found to impair endometrial receptivity or the attachment of human embryos [181].

UPA is a selective progesterone receptor modulator that acts by delaying ovulation for at least 5 days, until sperm from the UPSI are no longer viable. Unlike LNG-ECPs, UPA-ECPs delay ovulation even after the start of the LH surge [179]. However, UPA-ECPs cannot inhibit ovulation at or after the LH peak. Moreover, UPA-ECPs have not been demonstrated to be as effective as other ECPs when administered after ovulation. Li et al. found a significant difference between observed and expected pregnancy rates for women who received UPA-ECPs prior to ovulation, but not for women who received UPA-ECPs after ovulation [182].

Despite this, various theoretical mechanisms of action have been suggested for a post-ovulation effect of UPA, including delayed endometrial maturation; however, the clinical relevance of this in terms of its contribution to preventing pregnancy is unclear [183]. In vitro, UPA-ECPs have not been found to inhibit endometrial receptivity, prevent human embryo attachment to the endometrium, or affect sperm function [184, 185].

8.4 Effectiveness

The overall effectiveness of ECPs is difficult to ascertain. Most studies report the pregnancy rate after use of various types of ECPs as a percentage of the number of women who used ECPs; however, a significant number of these women would not have become pregnant in any case. Studies assessing the effectiveness of ECPs in preventing pregnancy depend, therefore, on an estimation of the number of pregnancies that would have occurred without the emergency contraception intervention.

UPA-ECPs have been demonstrated to be effective when taken up to 120 h after an episode of UPSI, with no significant reduction in effectiveness observed with increasing time until this point [186, 187]. The overall pregnancy rate after taking UPA-ECPs has been reported to be 1–2% [186, 187].

Studies have reported the overall pregnancy rate among women taking LNG-ECPs within 72 h of an episode of UPSI to be 0.6–2.6% [186, 188]. However, in several of these studies, the LNG-ECPs were taken at any time of the cycle; thus, UPSI may or may not have occurred when the women were at risk of pregnancy. Two large RCTs comparing LNG-ECPs to other ECP regimens estimated the number of pregnancies that would have occurred without the intervention and compared this with the actual number of pregnancies observed [188]. The percentage of pregnancies prevented by LNG-ECPs, when taken within 72 h of a single episode of UPSI, was estimated to be about 85%.

8.5 Advantages

Overall, ECPs can be used by women of any age, including adolescents and women with HIV. They do not cause abortion and do not prevent or affect implantation. In addition, they do not cause birth defects if pregnancy occurs. ECPs are considered safe for women’s health and do not cause infertility. Oral ECPs can be used more than once in a women’s cycle and a woman can take ECPs when needed without first seeing a health care provider. No procedures or tests are needed before taking ECPs, apart from a pregnancy test if indicated [78].

8.6 Disadvantages

Women may have cultural or religious reasons for avoiding a method of emergency contraception that could have its effect after fertilization [189]. It is therefore important that a client who raises concerns about the mechanism of action of any emergency contraception intervention is given sufficient information about what is known and what is uncertain.

8.6.1 Side-effects

Nausea, abdominal pain, fatigue, headaches, breast tenderness, dizziness, and vomiting are commonly reported side-effects of ECPs. Some users also report changes in bleeding patterns after ECP administration, including slight irregular bleeding for 1–2 days or monthly bleeding that starts earlier or later than expected in the first several days after taking ECPs. However, irregular bleeding due to ECPs will typically stop without additional treatment [78].

8.6.2 Risks

A Cochrane review identified only 5 cases of ectopic pregnancy among over 55,000 oral ECP users [190]. Frequent repeated use of ECPs may be harmful for women with cardiovascular diseases, migraine, or severe liver disease [78].

Conflict of interest

The authors declare no conflicts of interest.

Abbreviations

CHC	combined hormonal contraception
COC	combined oral contraceptive
EE	ethinylestradiol
VTE	venous thromboembolism
NET	norethindrone
LNG	levonorgestrel
DSG	desogestrel
DRSP	drospirenone
LH	luteinizing hormone
FSH	follicle-stimulating hormone
IUS	intrauterine system
WHO	World Health Organization
PCOS	polycystic ovary syndrome
BMD	bone mineral density
STI	sexually-transmitted infection
PID	pelvic inflammatory disease
POP	progestogen-only pill
RCT	randomized controlled trial
POI	progestogen-only injectable
DMPA	depot medroxyprogesterone acetate
DMPA-IM	intramuscular DMPA
DMPA-SC	subcutaneous DMPA
FDA	Food and Drug Administration
IUCD	intrauterine contraception device
Cu-IUCD	copper-IUCD
UPSI	unprotected sexual intercourse
ECP	emergency contraceptive pill
UPA	ulipristal acetate