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Contraception: Progestin-only pills (POPs)

Contraception: Progestin-only pills (POPs)
Literature review current through: Sep 2023.
This topic last updated: Jul 17, 2023.

INTRODUCTION — Progestin-only pills (POPs) are one option for individuals who cannot or prefer not to use estrogen-containing contraception. In addition to oral pills, progestin-only contraception is available as an implant, intrauterine device (IUD), and injection. This topic will review patient selection, counseling, and administration of POPs.

Unless otherwise noted, the information on POPs in this topic primarily applies to norethindrone POPs. Discussions of contraceptive selection and other types of progestin-only contraceptives include:

(See "Contraception: Counseling and selection".)

(See "Contraception: Postpartum counseling and methods".)

(See "Contraception: Etonogestrel implant".)

(See "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUD'.)

(See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. However, we encourage the reader to consider the specific counseling and treatment needs of transgender and gender diverse individuals.

FORMULATIONS — While multiple types of progestins are used in combined estrogen-progestin contraceptive pills, norethindrone and drospirenone are the main progestins available as POPs (table 1). The progestin dose of the norethindrone POP (0.35 mg) is substantially lower than the dose found in many estrogen-progestin pills (1 mg). The progestin dose of the drospirenone pill (4 mg) is higher than that found in combination oral contraceptives (3 mg). Norethindrone pills are dispensed in packs of 28 active pills. Accordingly, the norethindrone POP formulation is taken continuously (ie, no pill-free or nonhormonal pill week). Drospirenone pills are dispensed of 24 hormonally active tablets followed by four inert tablets.

Norethindrone – Norethindrone is commonly available as 0.35 mg tablets (commercial names include Camila and Errin). The dose is substantially lower than the dose in any combination oral contraceptive pills, and norethindrone POPs do not consistently suppress ovulation (table 2) (see 'Mechanism and duration of action' below). It is dispensed in packs of 28 active pills, which are taken continuously (ie, no pill-free or nonhormonal pill week) [1]. Unless otherwise noted, the information on POPs in this topic primarily applies to norethindrone POPs.

Drospirenone – Drospirenone is available in a package containing 24 tablets with 4 mg drospirenone and 4 inert tablets (commercial name Slynd) [2]. One tablet is taken daily until the pack is empty and then a new pack is started. The main mechanism of action is suppression of ovulation. Drospirenone has anti-mineralocorticoid activity comparable to a 25 mg dose of spironolactone. Patients at risk for hyperkalemia, either by medical condition or medication, should use drospirenone with caution. The manufacturer advises checking "serum potassium levels during the first treatment cycle in patients receiving daily, long-term treatment for chronic conditions of diseases with medications that may increase serum potassium concentrations." Negligible amounts of drospirenone are secreted in breast milk. An initial multicenter clinical trial reported pregnancy in 1.8 percent of users for a Pearl Index of 4.0 (95% CI 2.3-6.4). A multicenter phase III trial reported a perfect-use Pearl Index of 0.7 (95% CI 0.3-1.4) [3]. While the initial drospirenone data suggest the efficacy (ie, failure rate observed in clinical trials) of this new POP may approach that of traditional estrogen-progestin combined contraceptives, larger data sets are needed. Data on real-use effectiveness are not yet available. (See 'Efficacy' below.)

Desogestrel – In numerous countries (excluding the United States), desogestrel is available as a 75 mcg POP formulation [4]. This formulation has significant differences from norethindrone POPs discussed in this topic: The main mechanism of action is inhibition of ovulation, contraceptive efficacy is as high as that with estrogen-progestin contraceptive pills, and intake delay of up to 12 hours does not affect its contraceptive efficacy [5].

Norgestrel – Norgestrel-only pill packs contain 28 tablets of 0.075 mg of norgestrel (commercial name Opill) [6,7]. One pill is taken daily, at approximately the same time of day, with no pill-free interval between packs. A pregnancy rate of 2 percent was reported by clinical studies including over 21,000 28-day cycles [7]. Norgestrel-only pills suppress ovulation, thicken cervical mucous, lower mid-cycle peaks of follicle stimulating hormone (FSH) and luteinizing hormone (LH), slow passage of the ovum through the fallopian tube, and alter the endometrium. Contraindications and side effects are similar to those of norethindrone POPs. Prior removal of norgestrel-only POPs from US and Canadian markets was not related to patient safety issues [8]. (See 'Counseling points' below.)

PATIENT SELECTION

Candidates — Most patients can use POPs. We agree with the Centers for Disease Control and Prevention (CDC) guidelines regarding use of POPs in those with medical comorbidities. POPs appear to be appropriate contraceptive choices for many patients with contraindications to estrogen-containing contraceptives or those who prefer to avoid estrogen exposure [9].

Contraindications — Those who should not use POPs include those with [9,10]:

Known or suspected pregnancy. However, pregnancies conceived in individuals taking POPs have not been associated with adverse effects.

Known or suspected breast cancer.

Undiagnosed abnormal uterine bleeding.

Benign or malignant liver tumors, severe cirrhosis, or acute liver disease.

Additionally, those who have undergone malabsorptive bariatric surgeries and those taking certain anticonvulsants are advised not to use POPs [9]. Full lists of medical eligibility criteria for contraception use are available online at United States Medical Eligibility Criteria for Contraceptive Use and World Health Organization Medical Eligibility Criteria for Contraceptive Use.

Pill versus other progestin-only methods — Those who desire a progestin-only contraceptive must decide among the etonogestrel implant; levonorgestrel-releasing intrauterine devices (IUDs); depot medroxyprogesterone acetate (DMPA) injection; and the POPs norethindrone, drospirenone, and desogestrel (where available). Factors for consideration include:

Efficacy – For progestin-only methods, the long-acting contraceptives (etonogestrel implant and levonorgestrel-releasing IUDs) are the most efficacious (figure 1). The DMPA injection is also highly effective in persons who return on time for repeat injections. By contrast, the efficacy of POPs in highly fertile individuals may be lower than that with other hormonal contraceptive methods. National survey data used to estimate contraceptive failure rates with typical use have not generally distinguished between users of estrogen-progestin contraceptive pills (9 percent failure rate in first year of use) and POPs. (See 'Efficacy' below.)

Dosing frequency and convenience – POPs need to be taken daily and, ideally, at the same time of day. Daily dosing is less convenient than that of the injection (every 13 weeks), etonogestrel implant (three years), and levonorgestrel-releasing IUDs (three to six years). (See 'Need for back-up contraception' below.)

Resumption of fertility – POPs, the etonogestrel implant, and IUDs are associated with a rapid return of fertility after method discontinuation (typically within one cycle). (See 'Discontinuation and resumption of fertility' below.)

Conversely, the return of fertility with the DMPA injection is typically months and can be unpredictable. (See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration", section on 'Return to fertility after discontinuation'.)

Privacy – The need to store and take a daily pill reduces privacy. Although not typically externally visible, strings of an IUD and the etonogestrel implant can be palpated. The DMPA injection is completely private.

Need for procedure – Both the etonogestrel implant and levonorgestrel-releasing IUDs require insertion and removal by a trained clinician. DMPA requires injection, which can be done by a health care provider or, in some settings, by the patient. By contrast, POP use does not require any procedure and only minimal initial evaluation. (See 'Patient evaluation' below.)

Complications – While the overall complication rates are low for all progestin-only methods, serious complications are less common with POPs [11]. (See 'Risks' below.)

COUNSELING POINTS

Mechanism and duration of action — Norethindrone POPs work by thickening cervical mucus to inhibit sperm migration, suppressing ovulation, lowering the midcycle peaks of follicle-stimulating hormone and luteinizing hormone, slowing movement of an egg through the fallopian tubes, and thinning the endometrium [10]. In contrast with estrogen-progestin oral contraceptive pills and desogestrel POPs, ovulation is not consistently suppressed with norethindrone POPs, and approximately half of users still ovulate [10,12]. Therefore, the effects of norethindrone POPs on cervical mucus and endometrium represent the critical factors in prevention of conception [13]. By contrast, drospirenone and desogestrel POPs do suppress ovulation [2,14].

Within hours of administration, all POPs reduce the volume of cervical mucus and increase its viscosity, which prevents sperm from passing through the cervical canal and endometrial cavity. These changes persist for 20 hours [15,16]. Upon discontinuation, fertility returns rapidly [10].

Efficacy — United States package insert information for norethindrone states the typical user failure rate is estimated to be approximately 5 percent, which places these POPs in the middle efficacy zone (figure 1) [17]. Studies on norgestrel report pregnancy rates of approximately 2 to 3 percent [6,18]. An initial clinical trial of drospirenone POPs reported an overall pregnancy rate of 1.8 percent [2]. While the efficacy (ie, the failure rate observed in clinical trials) of the norgestrel and drospirenone products may approach, or possibly surpass, that of traditional estrogen-progestin combined contraceptives, larger data sets are needed.

Comparison of norethindrone and drospirenone POPs – Studies directly comparing the efficacy of norethindrone and drospirenone POPs are not yet available. However, it is reasonable to believe that drospirenone POPs may be more effective. Norethindrone POPs contain one-third the hormone dose used in common estrogen-progestin contraceptive pills (0.3 versus 1 mg of norethindrone or norethindrone acetate) (table 2). By contrast, the drospirenone POP contains a higher dose of hormone compared with that found in drospirenone-containing oral contraceptive pills (4 versus 3 mg). However, this hypothesis is purely speculative and requires confirmation through randomly assigned trials.

Comparison of POPs and estrogen-progestin pills – National survey data used to estimate contraceptive failure rates with typical use have not generally distinguished between users of estrogen-progestin contraceptive pills and users of POPs. Estrogen-progestin contraceptive failure rates for the first year of use have been estimated as 7 percent for typical-use failure and 0.3 percent in clinical trials [19]. As the great majority of oral contraceptives used in the United States are estrogen-progestin contraceptive pills and the typical-use failure rate with POPs is likely to be higher than with estrogen-progestin contraceptive pills, the typical user failure rate with POPs is likely to be greater than 7 percent [20]. In addition, individuals choosing POPs are often subfertile as a result of breastfeeding or older reproductive age; the failure rate in these populations is thought to be lower than in more fertile populations, which may result in artificially low typical-use failure rates reported for POPs.

Side effects — Unscheduled bleeding and changes in menses are the most common side effects associated with POPs; an increased prevalence of follicular ovarian cysts [21] and acne flare [13] have also been reported. POPs do not cause significant weight gain [22] and are not likely to increase headache frequency [23].

Unscheduled bleeding and menstrual changes As with all continuous progestin-only contraceptives, menstrual irregularities are common in POP users and represent the most frequent cause for contraceptive discontinuation. Unscheduled bleeding and spotting are the most common bleeding patterns during POP use, and prospective as well as current users should be counseled accordingly [10].

Norethindrone – Norethindrone users have more frequent, longer episodes and shorter, less predictable intervals than combined pill users [24], but up to one-half of users experience a mostly regular monthly bleeding pattern [25]. Amenorrhea and prolonged episodes of bleeding also occur, but less frequently than in depot-medroxyprogesterone acetate (DMPA) users [26].

Drospirenone – In the subject diaries from the initial four trials of drospirenone, unscheduled bleeding was common but improved with time; unscheduled bleeding dropped from 64 percent in cycle 1 to 40 percent by cycle 13 [2]. In a single-arm safety trial of 102 adolescents (12 to 17 years) using drospirenone, the median number of overall bleeding days dropped from 14 to 11 days (cycles 2 to 4 versus cycles 11 to 13), but the number of unscheduled bleeding days increased from five to six days to eight days during the same time period [27]. Irregular bleeding led 5 percent of participants to withdraw from the study.

One consequence of unscheduled bleeding and spotting is that interpreting signs and symptoms of pregnancy, whether intrauterine or extrauterine, can be challenging in POP users. Pregnancy testing is appropriate for POP users experiencing nausea, breast tenderness, a change in bleeding pattern, or lower abdominal pain.

Unscheduled bleeding and its management in POP users are discussed in more detail separately. (See "Evaluation and management of unscheduled bleeding in individuals using hormonal contraception", section on 'Progestin-only pills'.)

Mood Available data on the impact of POPs on mood are limited and conflicting [28]. Challenges to interpreting the data include varied study designs, duration of follow-up, sources of information (trial versus pharmacy or hospital database), and types of progestins. A trial including 150 women followed for three months reported lower Beck Depression Scores for women receiving levonorgestrel oral pills compared with those receiving either placebo or combined estrogen-progestin oral contraceptive pills [29]. However, a nationwide cohort study of Danish women reported an increased risk of first use of antidepressants (relative risk [RR] 1.3, 95% CI 1.27-1.40) and first hospital discharge diagnosis of depression (RR 1.2, 95% CI 1.04-1.31) for women using norethindrone, levonorgestrel, or desogestrel progestin-only oral contraception; or levonorgestrel-releasing intrauterine devices (IUDs) [30]. The inability to control for potentially confounding factors and the modest elevations in these relative risks make the clinical implications of this Danish database study uncertain [31,32].

Weight gain – Although available data are limited, POPs do not appear to be associated with significant weight gain [33]. A 12-month observational study including 102 perimenopausal women reported nonsignificant increases in weight for women using a desogestrel pill or levonorgestrel-releasing IUD compared with nonusers [34]. However, individuals in both progestin groups did have a statistically significant small increase in fat mass.

Follicular cysts – Sonographic studies have observed that follicular cysts are more common in POP users than in those not using hormones [21]. The follicular changes tend to increase and regress over time [35,36]. No intervention other than reassurance is required in asymptomatic individuals. POP users who have persistent concerns about ovarian follicular changes or symptoms from follicular cysts (eg, pain) should be offered another method of contraception. For individuals with follicular cyst symptoms who do not want to change their contraceptive method, an alternate off-label option is to prescribe two or three progestin-only tablets daily. The higher progestin dose may more fully suppress follicle-stimulating hormone release and cyst formation, but supporting data are lacking [13]. (See "Approach to the patient with an adnexal mass", section on 'Management according to mass type'.)

Effect on carbohydrate metabolism – Most studies have reported that POPs have little impact on carbohydrate metabolism [37-40]. A 1998 retrospective cohort study reported that lactating individuals with a history of gestational diabetes had an increased risk of subsequent type 2 diabetes mellitus when using POPs but not when using estrogen-progestin contraceptives [41]. We suggest clinicians monitor glucose tolerance in high-risk lactating individuals using POPs per current guidelines [42]. POPs are an appropriate contraceptive choice for those with diabetes, including those with vascular disease [9].

Effect on bone mineral density – The only study assessing skeletal health in POP users was conducted in lactating individuals. Although breastfeeding resulted in a reversible reduction in spinal bone mineral density in persons using barrier contraception, the small amounts of hormone in the POP protected against this loss [43].

Risks — POPs have not been associated with serious complications.

Cardiovascular risk – We and others [9,44] believe POPs represent a safe contraceptive choice for patients with high risk of (or known) coronary artery disease, cerebrovascular disease, venous thromboembolic disease, hypertension, or other conditions in which use of contraceptive doses of estrogen are contraindicated.

POP impact on markers of cardiovascular disease – POPs have little effect on coagulation factors [37], blood pressure [38,45], inflammatory markers [46], or lipid levels [37-40]. A large cross-sectional analysis reported that use of norethindrone POPs was associated with lower high-density lipoprotein levels but had little effect on low-density lipoprotein or triglyceride levels [39].

History of embolism – POP benefits are believed to outweigh the risks in individuals with deep venous thrombosis or pulmonary embolism (active or history of), regardless of anticoagulation therapy [9]. Large epidemiologic studies and a systematic review did not identify a statistically increased risk of stroke, myocardial infarction, or venous thromboembolism with use of POPs [47-52]. In a case-control study of women with venous thromboembolism, use of POPs, the levonorgestrel-releasing IUD, or the progestin-only contraceptive implant was not a significant risk factor for venous thromboembolism [51]. Use of DMPA injection was identified as a significant risk factor, but the association was less robust than for estrogen-progestin contraceptives (odds ratio [OR] 2.2 versus 5.3).

Risks associated with pregnancy – Pregnancy can increase the risk of adverse cardiovascular outcomes for individuals with contraindications to contraceptive doses of estrogen. While POPs are a contraceptive option for these patients, such individuals may benefit from alternate progestin-only contraceptives that have higher contraceptive efficacy (eg, IUDs, the etonogestrel implant, or DMPA).

Ectopic pregnancy risk – POPs lower the overall risk of ectopic pregnancy, as well as intrauterine pregnancy, by preventing ovulation or conception. Since persons taking POPs do not appear to have a higher absolute risk of ectopic pregnancy than those using no contraception, a history of ectopic pregnancy does not contraindicate POP use [1]. However, if pregnancy occurs, the likelihood that the pregnancy is ectopic is higher in POP users than in those not using contraception (5 versus 2 percent) [53]. Clinicians caring for patients who conceive during use of POPs can perform an early vaginal sonogram to establish the location of the pregnancy.

Breast cancer – After considering the available data (which conflict and are limited to observational studies), we suggest clinicians advise their patients that use of POPs does not have any clear impact on risk of breast cancer. Additional challenges to answering this question include limited duration of follow-up, lack of ability to control for other risk factors (eg, family history, genetic status), and use of multiple types of progestin-only contraceptives and doses.

Reports of no effect:

-A United States population-based case-control study comparing 4575 patients with breast cancer with 4682 control individuals reported no evidence that POP use was associated with an elevated risk of breast cancer [54].

-Likewise, a large Nordic multi-country prospective cohort study reported that ever-use of POP was not associated with an elevated risk of breast cancer [55]. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Breast cancer' and "Dysmenorrhea in adult females: Treatment".)

Associated increased risk – A 2023 nested case-control study from a UK primary care database comparing nearly 9500 patients with breast cancer with over 18,000 control patients reported that use of progestin-only oral pills increased the relative risk of breast cancer by roughly 25 percent in adjusted analysis (adjusted odds ratio [aOR] 0.26, 95% CI 1.16-1.37) [56]. The adjusted risk was similar for progestin injections (aOR 1.25, 95% CI 1.07-1.45) and IUD (aOR 1.32, 95% CI 1.17-1.49), but not for the progestin implant (aOR 1.22, 95% CI 0.93-1.59) [56]. As the authors point out, the lack of a dose response in their findings is hard to explain. Although progestin IUD use is associated with lower serum progestin levels than POPs, the odds ratio for progestin IUDs was higher than that for POPs, raising concern that unidentified confounding may explain the authors' findings. Another concern with this study is that reported ORs are only modestly higher than 1.0. Some epidemiologists indicate that modest elevations in risk reported by observational studies should be viewed with skepticism and not impact clinical practice [31].

Noncontraceptive benefits — Daily use of a progestin protects against development of endometrial cancer [57]. Use of POPs for management of heavy menstrual bleeding or pelvic pain has not been well studied. Norethindrone acetate has demonstrated efficacy in treating dysmenorrhea, abnormal uterine bleeding, and endometriosis-related pain, but at higher doses (2.5 to 15 mg per day) [58]. A single-arm trial of drospirenone in adolescent females reported reduced rates of dysmenorrhea, as well as reduced rates of pain medication used to treat dysmenorrhea, with continued drospirenone use over 13 cycles [27]. (See "Endometriosis: Treatment of pelvic pain", section on 'Progestins' and "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management".)

Impact on sexually transmitted infection acquisition — POP use neither protects from nor increases the risk of acquiring STIs. However, progestin-induced thickening and increased viscosity of cervical mucus has been hypothesized to inhibit ascent of bacteria and thus potentially reduce the risk of development of pelvic inflammatory disease.

We counsel all people at risk for STI acquisition regarding concomitant condom use. (See "External (formerly male) condoms", section on 'Protection from STIs'.)

ADMINISTRATION

Patient evaluation — Physical examination and laboratory tests are not indicated before beginning POPs [59]. Clinicians are advised to measure baseline weight and body mass index (BMI), as having these baseline measurements may be helpful in monitoring POP users over time, but this is not required.

Initiation and dosing

Drug and dose

Standard formulations – For each of the options below, the pill should be taken at approximately the same time of day, every day, even if the patient has vaginal bleeding. Detailed discussions of each formulation are available above (See 'Formulations' above.).

-Norethindrone 0.35 mg tablet orally once daily.

-Drospirenone pack – Pack contains 24 tablets with 4 mg drospirenone and four inert tablets. Take one table orally once daily.

-Desogestrel 75 microgram tablet orally once daily (available outside of the United States).

-Norgestrel 0.075 mg tablet orally once daily (available without a prescription in many countries, including the United States [7]).

Two-pill daily norethindrone regimen – Some clinicians have theorized that taking a daily dose of two norethindrone POP tablets (two tablets as a single dose) might increase the contraceptive efficacy of POPs in young, nonlactating persons who presumably have high fecundity [1,60]. For those with normal fertility (ie, not postpartum, lactating, or perimenopausal) who desire to use POPs, the author prescribes the two-pill regimen (ie, 0.35 mg norethindrone, two tablets taken daily). The additional cost is a disadvantage of this approach. The author and other experts counsel patients that there are no published data regarding this off-label contraceptive strategy [61].

Start options

First-day start – We suggest that POPs be initiated on the first day of menses; back-up contraceptive is not necessary if POPs are started within the first five days of start of menses (including for individuals switching from non-intrauterine device [IUD] contraception) [59].

Any-day start – Some clinicians initiate POPs at any time in the cycle, as long as they are reasonably certain that the patient is not pregnant (table 3). Back-up contraception is needed for two additional days if the patient is >5 days from onset of menses. Although the US Selected Practice Recommendations for Contraceptive Use recommends two rather than seven days of back-up contraception with POP initiation, presumably because of the rapid effect of the POP on cervical mucus; clinically, it is simpler to advise all people initiating contraception more than five days from onset of menses to use back-up contraception (or abstinence) for seven days [59].

Providing or prescribing a one-year supply of POPs enhances continuation rates [59,62].

Daily use – Because of the short duration of action and the short half-life of POPs, it is essential that the norethindrone POP be taken at the same time each day to maximize contraceptive efficacy [63-65]. Individuals initiating norethindrone POPs are counseled that POPs are taken continuously with no hormone-free days. Those who miss taking a norethindrone POP dose by more than three hours are advised to use additional contraception (eg, condoms) for 48 hours after the late dose [10]. (See 'Need for back-up contraception' below.)

Need for back-up contraception — Back-up contraception (eg, condoms) should be used or the individual should abstain from sex for at least two days if the norethindrone POP is taken more than three hours late or missed on any given day, or if the patient starts POPs more than five days from the onset of menses [10]. Those with delayed or missed pill intake should also resume taking daily POPs as soon as possible, even if this means that two pills are taken on one day (the missed pill and the usual time pill) [59]. Emergency contraception (EC), not including ulipristal acetate, can be offered to persons who have unprotected intercourse during the 48-hour window that back-up contraception or abstinence is advised. Back-up contraception/abstinence can be discontinued after POPs have been taken correctly, on time, for two consecutive days.

Vomiting or severe diarrhea within three hours of taking a POP may decrease contraceptive effectiveness. These clinical scenarios are managed in a similar way to a late or missed pill. The patient should continue taking POPs daily at the same time each day and use back-up contraception (eg, condoms) or avoid sex until two days after vomiting or diarrhea has resolved [59].

Individuals who have been using an IUD and are switching to POPs may have residual sperm in their reproductive tracts, which could result in fertilization and implantation if the IUD is removed. Options discussed with the patient include [59]:

Retain the IUD for at least two days after POPs are started and then return for IUD removal.

Abstain from sexual intercourse or use barrier contraception for seven days before removing the IUD and starting POPs.

For those who cannot return for interval IUD removal and have had unprotected vaginal intercourse within seven days, we offer EC use at the time of IUD removal. For EC methods other than ulipristal acetate, POPs can be started immediately after EC use. Individuals using ulipristal acetate should initiate POPs no sooner than five days after ulipristal use. (See "Emergency contraception".)

Follow-up — Routine follow-up is unnecessary [59]. The woman should return if she has concerns about the method, side effects, change in health status that might affect use of hormonal contraception, or if she wants to switch methods.

Discontinuation and resumption of fertility — POPs can be discontinued at any time the patient desires. Upon discontinuation, fertility returns rapidly and those who desire pregnancy can attempt conception any time they are ready [10]. Patients who are changing their contraceptive method from POPs to a levonorgestrel-releasing IUD, the etonogestrel implant, or depot medroxyprogesterone acetate (DMPA) injections may need back-up contraception or abstinence for seven days if the switch occurs more than five to seven days from the onset of menses (timing varies with contraceptive method) [59]. Those changing to all other contraceptive methods do not require a period of abstinence or back-up contraception.

(See "Intrauterine contraception: Insertion and removal", section on 'Patients switching from another method'.)

(See "Contraception: Etonogestrel implant", section on 'Back-up contraception'.)

(See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration", section on 'Switching from DMPA to another method'.)

DRUG INTERACTIONS — Hepatic enzyme-inducing anti-epileptic medications, including phenytoin, carbamazepine, topiramate, and barbiturates; and the antimicrobial drugs rifampicin and rifabutin appear to reduce the efficacy of POPs [9,10]. We advise patients requiring treatment with these medications to select a different contraceptive method or consistently use a back-up method of contraception (eg, condoms) with every act of vaginal intercourse. The anticonvulsant lamotrigine is compatible with POP use [9]. The advantages of POPs for patients who are also taking the antiretroviral fosamprenavir appear to be greater than the risks (established or theoretical); all other antiretroviral medications are compatible with POP use [9,66].

UNIQUE POPULATIONS

Adolescent and young adults – POPs can be used any time after menarche. However, the need for consistent timing of ingestion and possibly lower efficacy may make this option less ideal for adolescent and young adults. Contraceptive needs and counseling of adolescents are discussed in detail separately. (See "Contraception: Issues specific to adolescents".)

HIV infection – Although the body of evidence is limited, POP use does not appear to increase the risk of HIV acquisition or disease progression [67]. POP use is compatible with nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors. A discussion on the issues surrounding contraceptive selection in individuals with HIV infection is presented elsewhere. (See "HIV and women", section on 'Choice of contraception'.)

Obesity – POPs are not contraindicated for individuals with obesity [9]. However, data on efficacy of POPs specific to individuals with obesity are lacking. Given the availability of alternate contraceptive options (eg, intrauterine devices [IUDs], etonogestrel implant, depot medroxyprogesterone acetate [DMPA] injections, and combined estrogen-progestin methods), we prefer to avoid POPs in persons with obesity because of concerns for potentially decreased efficacy. Individuals with obesity who have additional comorbidities which increase cardiovascular risks associated with estrogen use, or those who want to avoid estrogen use, but who do not wish to use the etonogestrel implant, IUDs, or DMPA, an alternate option is to take two POPs daily, although supporting data for this approach are lacking. (See "Contraception: Counseling for females with obesity", section on 'Contraceptive implant'.)

Perimenopause – There are no age limits to POP use in medically eligible individuals [9]. The reduced fecundity of persons over age 35 to 40 years means they can expect higher contraceptive efficacy with use of POPs [68].

Postabortion, postpartum, and lactating individuals – POPs may be initiated immediately postabortion or postdelivery, and should be initiated by three weeks after delivery to assure effectiveness [9,44,66]. Breastfeeding is not a contraindication to use of POPs.

(See "Contraception: Postabortion", section on 'Progestin-only pills'.)

(See "Contraception: Postpartum counseling and methods".)

Medical comorbidities – Most individuals with medical comorbidities are candidates for POP contraception. However, as noted earlier, in persons with high risk of (or known) contraindications to contraceptive doses of estrogen, pregnancy is associated with an elevated risk of adverse cardiovascular outcomes. Accordingly, progestin-only contraceptives are more effective than POPs (eg, IUDs, the etonogestrel implant, or DMPA) and may be more appropriate than POPs for such patients. Full lists of medical eligibility criteria for contraception use are available online at United States Medical Eligibility Criteria for Contraceptive Use and World Health Organization Medical Eligibility Criteria for Contraceptive Use.

Physical or intellectual disability – There are no contraindications to POP use specific to individuals with intellectual or physical disabilities. However, persons who desire menstrual suppression to aid with menstrual hygiene are advised to avoid POPs, as unscheduled bleeding and spotting are the most common bleeding patterns. The 52 mg levonorgestrel-releasing IUDs, injectable DMPA, and combined hormonal contraceptives are preferred for this indication. (See "Hormonal contraception for suppression of menstruation".)

RESOURCES FOR PATIENTS AND CLINICIANS

Bedsider.org – A free website developed by the National Campaign to Prevent Teen and Unplanned Pregnancy, a private nonprofit group

CHOICE Project – A free website sponsored by the Washington University School of Medicine in St. Louis that provides resources on contraceptive options and training resources for clinicians

Center for Young Women's Health – A free website run by Boston Children's Hospital that addresses reproductive health needs of teens and young adults

Beyond the Pill – A free website run by the University of California San Francisco

SexandU.ca – An educational site run by the Society of Obstetricians and Gynecologists of Canada that includes descriptions of various methods and a tool to help with selection of birth control

Planned Parenthood – A nonprofit organization dedicated to reproductive health with resources for patients and clinicians

ACOG Contraceptive FAQs – American College of Obstetricians and Gynecologists addresses frequently asked questions (FAQs) about progestin-only contraception (pills and injection)

ACOG LARC Program – American College of Obstetricians and Gynecologists Long-Acting Reversible Contraception Program

United States Medical Eligibility Criteria for Contraceptive Use

United States Selected Practice Recommendations for Contraceptive Use

World Health Organization Medical Eligibility Criteria for Contraceptive Use

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Contraception".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topic (see "Patient education: Hormonal methods of birth control (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Candidates – Progestin-only contraception represents an option for individuals in whom an estrogen-containing contraceptive is either contraindicated or causes additional health concerns. Additionally, most individuals with medical comorbidities are candidates for POP contraception. Full lists of medical eligibility criteria for contraception use are available online at United States Medical Eligibility Criteria for Contraceptive Use and World Health Organization Medical Eligibility Criteria for Contraceptive Use. (See 'Patient selection' above and 'Unique populations' above.)

Drug interactions – Patients using hepatic enzyme-inducing anti-epileptic medications are educated that these medications may reduce the efficacy of POPs. Such medications include the anticonvulsants phenytoin, carbamazepine, topiramate, and barbiturates and the antituberculosis drug rifampin. (See 'Drug interactions' above.)

FormulationsNorethindrone (0.35 mg tablet), drospirenone (4 mg tablet), norgestrel (0.075 mg tablet), and desogestrel (75 mcg tablet) are available as POPs (table 1). For norethindrone POPs, the progestin dose is substantially lower than the dose in any combination oral contraceptive. The norethindrone and desogestrel pills are dispensed in packs of 28 active pills while drospirenone packs contain 24 active pills and 4 inert tablets. (See 'Formulations' above.)

Mechanisms of action – The effects of norethindrone and norgestrel POPs on cervical mucus and endometrium are the critical factors in prevention of conception; ovulation is not consistently suppressed. By contrast, suppression of ovulation is the main mechanism of drospirenone and desogestrel POPs. (See 'Mechanism and duration of action' above.)

Efficacy – The typical user failure rate with POPs is estimated to be over 7 percent (figure 1). Patients who choose POPs are often subfertile because of lactation or older reproductive age. The failure rate of POPs is thought to be higher in more fertile populations. (See 'Efficacy' above.)

Common side effects – Menstrual irregularities and unscheduled bleeding are common in POP users and represent the most frequent causes for contraceptive discontinuation. (See 'Side effects' above.)

Initiation and use – Physical examination and laboratory tests are not indicated before beginning POPs in individuals who are appropriate candidates for this method. It is essential that the norethindrone and norgestrel POPs be taken at the same time each day to maximize contraceptive efficacy. A back-up contraceptive (eg, condoms) should be used for at least two days if the POP is taken more than three hours late or forgotten on any given day. (See 'Administration' above.)

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References

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