ABSTRACT

Although many contraceptive options exist, unintended pregnancy is still strikingly common. About half of pregnancies in the United States are mistimed or unwanted at the time of conception. Birth control is not one-size-fits-all. Most women prefer oral contraceptives, but daily adherence is often poor. Many are also unaware of longer-lasting or non-hormonal options that may fit their lifestyle better or be more effective. Contraceptive options are also growing. In recent years, 3 new choices have emerged: a yearly vaginal ring system, a hormone-free vaginal gel, and a fertility awareness-based phone app. Women may be unaware of these options and pharmacists can help identify patients for whom they are appropriate. Historically, birth control responsibility has mostly fallen to the woman, but researchers are also working on involving men. They are also developing new delivery methods, such as a monthly oral pill and transdermal contraceptive jewelry. A new barrier method is also in development to provide another hormone-free option. Among many things, pharmacists help patients assess and resolve adherence issues, combat adverse effects, and address missed doses and contraceptive failure. Pharmacists who understand newly-emerging birth control options can better assist patients in finding a contraceptive that fits into their lifestyle.

INTRODUCTION

In the United States (U.S.), the average desired nuclear family size is 2 children. To achieve a family of this size, a woman must use contraceptives for roughly 3 decades.¹ More than 67 million women of reproductive age live in the U.S., and about 43 million of them are at risk of unintended pregnancy.¹ This means they are sexually active and could experience unwanted pregnancy if they and their partners fail to use contraceptives consistently and correctly.

Here is a striking but under-reported fact: about 1 in 2 pregnancies in the U.S. is unintended (i.e., mistimed or unwanted at the time of conception).² Nationally, 1.5 million unplanned births occurred in 2010.³ Public insurance programs spend about $21 billion each year on unintended pregnancies, averaging to about $366 per woman of childbearing age in the U.S.³ Compared to intentional pregnancies, women experiencing unintended pregnancy experience more mental health problems, have less stable romantic relationships, and sometimes delay initiation of prenatal care.⁴ Also, women who are surprised by unplanned pregnancy should ideally be in good health and ready to care for a new child; sometimes that is not the case.

The Centers for Disease Control and Prevention (CDC) reports that hormonal methods requiring a prescription (pill, patch, ring, and injection) prevent pregnancy more effectively than

over-the-counter products, withdrawal, or fertility-awareness methods.⁵ Understanding all contraceptive options thoroughly is vital to help patients prevent unintended pregnancy. Often, contraception responsibilities fall to the woman; however, we will also discuss how to better assist males in pregnancy prevention efforts.

The Menstrual Cycle

Contrary to popular belief, a woman’s menstrual cycle is rarely a perfect 28 days. Only about 13% of women experience a 28-day cycle naturally.⁶ The first day of menstruation—or bleeding—is cycle day 1, and cycles range from 21 to 40 days in length. The menstrual cycle is hormone-regulated. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH), produced by the pituitary gland, promote ovulation and estrogen and progesterone release from the ovaries.⁷ This hormone fluctuation splits the menstrual cycle into 3 phases: follicular (before egg release), ovulatory (egg release), and luteal (after egg release), described in Table 1.

CLASSIC CONTRACEPTIVES

Contraception means the prevention of pregnancy following sexual intercourse by⁷

• inhibiting viable sperm from coming into contact with a mature ovum (i.e., methods that act as barriers or prevent ovulation)
• preventing a fertilized ovum from endometrial implantation (i.e., methods that create an unfavorable uterine environment)

Sexually active individuals have many options to prevent pregnancy.

Hormonal Pharmacologic Therapy

Hormonal contraceptives contain progestin with or without estrogen. Oral contraceptives first became available in the 1960s, but expanded delivery options have emerged since then, including a transdermal patch and vaginal ring. Longer-acting alternatives (e.g., depot injection, implantable, and intrauterine) for contraception are advantageous for patients with poor adherence to daily, weekly, or monthly formulations.

Estrogens’ role in birth control is to stabilize the endometrial lining and provide cycle control. However, they also suppress FSH release from the pituitary gland to help block the LH surge and prevent ovulation. Progestins provide most contraceptive effect. They block the LH surge, which inhibits ovulation. Progestins also thicken cervical mucus to⁷

• prevent sperm penetration
• slow tubal motility
• delay sperm transport
• induce endometrial atrophy (thinning)

Some hormonal contraceptives contain only a progestin, while others combine an estrogen and a progestin. Hormonal contraceptives do not protect patients from sexually transmitted infections, including human immunodeficiency virus. Combined hormonal contraceptives (CHCs)—any contraceptive containing both an estrogen and progestin—are not appropriate for women⁷

• older than 35 years who smoke
• with hypertension (greater than 160/100 mm Hg)
• with uncontrolled dyslipidemia (LDL greater than 160 mg/dL, HDL less than 35 mg/dL, triglycerides greater than 250 mg/dL) and additional risk factors (e.g., diabetes, hypertension, smoking)
• with migraines (especially with aura)

Combined Oral Contraceptives

Combined oral contraceptives (COCs)—those containing both an estrogen (e.g., ethinyl estradiol) and a progestin (e.g., norethindrone, levonorgestrel, norgestimate)—can be monophasic or multiphasic. Monophasic COCs contain the same amounts of estrogen and progestin for 21 days, followed by 7 days of placebo.⁷ Multiphasic COCs contain variable amounts of estrogen and progestin for 21 days, also followed by a 7-day placebo phase.⁷

Monophasic and multiphasic COCs have similar safety or efficacy profiles.⁷ Because all COCs prevent pregnancy with similar effectiveness, choosing between them relies on patient-preference, hormonal content, and coexisting conditions. Women without coexisting medical conditions should initiate a COC containing 35 mcg or less of ethinyl estradiol and less than 0.5 mg of norethindrone (or an equivalent).⁷ Monophasic COCs are preferred over multiphasic upon initiation, as adverse effects are easier to identify and manage. Manipulating menstrual cycle timing is also easier.⁷

Extended- and continuous-cycle COCs may be more convenient with fewer side effects. Their 84 days of active hormone tablets are followed by 7 days of inactive tablets.⁷ Patients therefore only have 4 menstrual cycles per year, which is helpful for women with severe premenstrual syndrome (PMS). While extended-cycle COCs are commercially available, patients can also use monophasic 28-day COCs to mimic extended-cycle products by skipping the 7-day placebo week.⁷ Continuous-cycle COCs shorten the pill-free interval (e.g., 2 to 4 days versus 7 days), thus reducing symptoms like dysmenorrhea (menstrual cramps), severe PMS, or menstrual migraines.⁷ Advise prescribers to clearly indicate when a patient is skipping the placebo week to bill insurance for the correct days-supply and prevent “refill too soon” rejections upon refill. Pharmacists and technicians can also empower women to have this discussion with their prescriber, so as to prevent lapses in therapy.

Progestin-Only Pills

Progestin-only pills (POPs)—“minipills”—contain 28 days of active hormone per cycle. They are less effective than COCs and associated with irregular, unpredictable menstrual bleeding.⁷ Patients must take POPs every day at approximately the same time (within 3 hours) to prevent pregnancy effectively. About 40% of women on POPs continue to ovulate regularly, so the risk of ectopic pregnancy—pregnancy outside the uterus—is higher than with COCs.⁷ Postpartum women can experience hypercoagulability, and should avoid CHCs for at least 30 to 42 days postpartum due to risk of venous thromboembolism. Those who take contraceptives commonly take POPs.⁷ Women who breastfeed should also avoid CHCs, as the estrogen component can affect lactation.⁷

Transdermal Patch

Some patients—especially those with poor adherence to oral tablets—may benefit from alternative delivery mechanisms administered less frequently. The only transdermal CHC patch available in the U.S. contains ethinyl estradiol and norelgestromin (norgestimate’s active metabolite). The transdermal patch has comparable efficacy to COCs. It may be less effective, however, for patients weighing more than 198 lbs (90 kg).^7,8 This formulation’s adverse effects are similar to those of COCs, but some patients experience application-site reactions. Rotating application sites reduces skin reactions. Dysmenorrhea and breast discomfort are also possible, as the patch causes higher estrogen exposure compared to COCs.⁸

Patients apply the patch to the abdomen, buttocks, upper torso, or upper arm at the beginning of the menstrual cycle. Counsel patients to avoid areas where the patch could be rubbed by tight clothing.⁸ Patients replace the patch once weekly for 3 weeks, followed by a patch-free week. The patch is formulated to release hormones for 9 days, allowing a 48-hour grace period for adherence.^7,8

Vaginal Ring

The first vaginal ring contraceptive—a 54 mm flexible ring, 4 mm in thickness—came to the market in 2001. The ring contains ethinyl estradiol and etonogestrel (desogestrel’s active metabolite).^7,9 Counsel patients on these points^7,9:

• compress between the thumb and index finger, then push the ring into the vagina
  • there is no danger of inserting too far; the cervix will prevent the ring from traveling up the genital tract
• leave the ring in place for 3 weeks
• remove the ring and discard (do not flush down the toilet); leave out for 1 week
• insert a new ring on the same day of the week as the previous cycle

Reassure patients that precise ring placement is not an issue; the hormones are absorbed anywhere in the vagina.⁷ Of note, patients can leave the ring inserted for up to 4 weeks (but should speak with their prescriber before doing so), reducing or eliminating the number of hormone-free days.⁹

Estrogen exposure is lower with the vaginal ring compared to COCs, so incidence of estrogen-related adverse effects is also decreased. Local reactions, like vaginal irritation and discharge, are more common.⁹ The U.S. Food and Drug Administration (FDA) also recently approved another vaginal ring—ethinyl estradiol/segesterone—that came to market in late 2019.¹⁰ This will be discussed later in detail.

Long-Lasting Contraceptives

Often, patients struggle with adherence. These patients may benefit from longer-lasting depot injections, subdermal implants, or intrauterine devices (IUD). A 2016 survey showed that women of reproductive age were most familiar with birth control pills and condoms, and only 31% knew that more effective, longer-lasting options existed.¹¹ Less than half of the women surveyed thought IUDs were very effective at preventing pregnancy, and even fewer (37%) viewed implants as very effective. More than 1 in 5 women questioned IUD’s or implant’s safety.¹¹ In the past, physicians only offered long-lasting contraception to women with contraindications to estrogen or those with poor adherence.⁷ Now, due to their high effectiveness, all women are considered candidates. Pharmacists and technicians can monitor for poor contraceptive adherence based on refill history and refer patients to their prescriber for a longer-lasting alternative when appropriate.

Depot Medroxyprogesterone Acetate

Depo-medroxyprogesterone acetate (DMPA) is a longer-lasting injectable contraceptive. A patient or healthcare provider injects DMPA every 3 months either intramuscularly into the gluteal or deltoid muscle or subcutaneously into the abdomen or thigh.¹² This eliminates daily adherence concerns. With perfect use (used correctly all the time), the DMPA’s efficacy exceeds 99%, but with typical use (what generally happens in real life) about 3% of women will still get pregnant.⁷

Injection timing is somewhat flexible. Early DMPA injection is safe if women cannot return at routine intervals, and providers can inject the patient up to 2 weeks late without requiring back-up contraception.⁷ Women who are more than 2 weeks late, however, should use back-up contraception for 7 days after receiving the injection.⁷ Return to fertility may be delayed 6 to 12 months after discontinuation.^7,12 Therefore, DMPA is not recommended for women desiring pregnancy in the near future.

DMPA’s most common adverse effects are weight gain, decreased bone mineral density, and bleeding irregularities (e.g., spotting, prolonged bleeding, amenorrhea).¹² Bleeding irregularities peak at 30% in the 1^st year, falling to 10% thereafter.⁷ A 2004 FDA-issued Boxed Warning indicates DMPA should not be used for more than 2 years due to bone mineral density loss, which may be irreversible.^7,12 Patients should only use DMPA for more than 2 years if all other contraceptive methods are inadequate. Patients often refill DMPA at the pharmacy to bring to their prescriber for injection. Pharmacists and pharmacy technicians can monitor for length of use, and encourage patients using DMPA for more than 2 years to speak with their provider about possible alternatives.

Subdermal Etonogestrel Implant

The matchstick-sized etonogestrel implant is a single flexible, plastic rod. A prescriber inserts the implant under the skin on the underside of the non-dominant upper arm, leaving it in place for up to 3 years. The implant releases 60 mcg of etonogestrel daily for the 1^st month, then an average of 30 mcg daily by the end of 3 years.^7,13 The implant’s primary mechanism of action is suppressing ovulation, but it also thickens cervical mucus and creates an atrophic endometrium.

Women of all ages can use the etonogestrel implant, and fertility returns rapidly after removal. As with other progestin-based therapies, bleeding irregularities are common. Digestive difficulties, headaches, breast pain, weight gain, and acne are also possible.¹³ Pharmacists should note patients who use the implant and recognize possible adverse effects upon consultation. Technicians who speak with patients about adverse effects at the check-out counter should refer them to the pharmacist for consultation.

Intrauterine Device

A physician inserts an IUD—a small, T-shaped device—into the uterus. An IUD works mainly by preventing fertilization of an egg by sperm. The copper-containing IUD, approved for up to 10 years of use, releases copper into the uterus to interfere with sperm’s ability to move.¹⁴ Three progestin-containing IUDs are also available in the U.S, and they are approved for 3 to 5 years of use depending on the brand. Progestin-based IUDs release levonorgestrel into the uterus to thicken cervical mucus.¹⁴ Both of these mechanisms make it harder for sperm to enter the uterus and reach an egg.

IUDs are more than 99% effective; typically, fewer than 1% of woman will become pregnant in the 1^st year.⁷ Women of all ages can use IUDs, including adolescents, as can nulliparous and parous women (before and after 1^st pregnancy).¹⁴ Pharmacists, as the most accessible health care providers, may find themselves fielding questions from patients using IUDs. Remember these important things about IUDs¹⁴:

• changes in menstrual bleeding and increased pain are normal and not harmful; they usually resolve over time
• for some women using levonorgestrel IUDs, bleeding stops completely
• IUD’s most common adverse effects are headaches, nausea, breast tenderness, and mood changes

Patients with current pelvic inflammatory disease, sexually transmitted infection, undiagnosed abnormal vaginal bleeding, or genital tract malignancy should not use IUDs.⁷ Pharmacists and technicians may also encounter prescriptions for misoprostol for IUD insertion. While older studies suggested pre-treatment with misoprostol eased insertion, more recent studies show no benefit with increased adverse effects. The American College of Obstetricians and Gynecologists (ACOG) makes no recommendation.^14,15

Barrier Contraceptives and Spermicides

For some patients, hormonal contraceptives are inappropriate. Pharmacists can recommend barrier methods available by prescription (e.g., diaphragms) and over-the-counter (OTC) options (e.g., male and female condoms, chemical spermicides). Technicians can also recognize patients seeking and/or purchasing OTC contraceptives and refer them to the pharmacist for consultation when necessary. Most male condoms are latex, which is impermeable to viruses. A small proportion are made of lamb intestine, which are permeable to viruses.⁷ This means latex condoms protect from sexually-transmitted infections, but those made of lamb intestine do not. A female condom is a pre-lubricated, loose-fitting polyurethane sheath, closed at 1 end, with flexible rings on both ends. When properly positioned, the closed end fits over the cervix and the sheath lines the vaginal walls. The outer ring remains outside the vagina, covering the labia.⁷

 Male latex condoms are the most effective option, but only when used correctly.^7,16 They can break if stored improperly. Concomitant use with oil-based lubricants or vaginal medications can also cause condom failure. In fact, mineral-oil based vaginal drug formulations (e.g., clindamycin vaginal cream, conjugated estrogen vaginal cream, and OTC yeast infection treatments) can decrease latex’s barrier strength by 90% in just 60 seconds.^7,17 Male latex condoms protect individuals from sexually transmitted infections; female condoms do not. Male and female condoms also should not be used together, as slippage and device displacement may occur.⁷ Technicians may encounter patients at the check-out counter purchasing condoms and vaginal drug formulations or male and female condoms. Refer these patients to the pharmacist to ensure they understand the need to separate use of these products.

Diaphragms and cervical caps are also barrier contraceptives used with spermicide and placed intravaginally over the cervix. Women can place a diaphragm up to 6 hours before intercourse, and must not remove them until at least 6 hours after, reapplying spermicide before each act of intercourse. Wear time should not exceed 24 hours. Women should place cervical caps 15 to 40 minutes before intercourse and wait at least 6 hours before removing them. Cervical cap wear should not exceed 48 hours.¹⁶

Nonoxynol-9, the only chemical spermicide available in the U.S., is supplied as a foam, film, gel, cream, suppository, tablet, or sponge. Women should place nonoxynol-9 in the vagina no more than 1 hour before intercourse and repeat before each act. It can cause local irritation.¹⁶ To use the nonoxynol-9 sponge, patients should moisten it with water until sudsy and wet, then place it over the cervix (indented side up) before intercourse. Patients must leave it in for 6 hours following intercourse but remove it by 24 to 30 hours later due to risk of toxic shock syndrome.⁷

THE CHANGING FACE OF CONTRACEPTIVES

The evolving contraceptive landscape provides more choices for birth control that fits patients’ lifestyle and needs. Staying up-to-date on what’s new and what’s to come in contraception helps pharmacists and technicians support patients pursuing the new options.

Yearly Vaginal Ring

Vaginal rings offer excellent cycle control, as the patient can insert and remove them. Patients return to fertility rapidly after removal.¹⁹ FDA approved the segesterone acetate/ethinyl estradiol (SAEE) vaginal system in 2018, creating a new vaginal option for women. SAEE is a silicone ring slightly larger in diameter than the monthly ring (56 mm versus 54 mm) with 2 drug reservoirs. The ring delivers 0.15 mg and 13 mcg of segesterone and ethinyl estradiol respectively on average daily.^10,19 No trials have directly compared the 2 vaginal ring systems. Patients should not wear the SAEE ring continuously (skipping the ring-free week) as it has not been studied this way, and safety is not established.

Similar to the traditional vaginal ring, patients wear the SAEE ring vaginally for 3 weeks, followed by 1 ring-free week. The same SAEE ring can be used for up to 1 year, while patients must use a new ethinyl estradiol/etonogestrel vaginal ring monthly.¹⁹ The SAEE ring’s most common adverse effects are headache/migraine, nausea, vomiting, vaginal infections, abdominal pain, dysmenorrhea, vaginal discharge, urinary tract infection, breast discomfort, bleeding irregularities, diarrhea, and genital itching.¹⁰ Counsel patients using the SAEE ring about the following^10,19:

• wash your hands with mild soap and water before handling the ring
• wash the ring after removal and again before reinsertion; use mild soap and water, rinse, and pat dry with a clean cloth or paper towel
• during the ring-free week, store the ring only in the provided case away from children, pets, and extreme temperatures
• if the ring is removed, intentionally or otherwise, no backup contraception is needed if the ring is removed for less than 2 hours
• if the ring is removed, intentionally or otherwise, for more than 2 cumulative hours during the 21-day wear period, backup contraception is recommended for 7 days after ring reinsertion
• oil based lubricants are not recommended
• do not use the same ring for more than 13 menstrual cycles

Additionally, pharmacists and technicians who recognize patients switching from one ring formulation to the other should ensure they understand the key differences to prevent birth control failure.

Male Contraceptives

The responsibility of contraception most often falls to women, but science is evolving. A North Carolina-based organization, the Male Contraceptive Initiative (MCI), facilitates research and development of male contraceptives. MCI believes that global availability of male contraceptive options provides men with a safe, reversible option; increases access and contraceptive choices; and fosters shared responsibility between sexual partners.²⁰

MCI funds research in spermatogenesis (the creation and development of new sperm), sperm transport, sperm motility, and fertilization. A drug that stops spermatogenesis would have a potential onset time of 2 to 3 months because sperm development takes time.²¹ Even after stopping generation of new sperm, existing sperm in the pipeline would remain. Researchers worldwide are exploring diverse approaches to halting spermatogenesis.²¹

Preventing sperm from exiting the reproductive tract is the basis of one of the only existing forms of male contraception: vasectomy. In a vasectomy, a clinician cuts and ties the vas deferens to seal it. This simple, effective procedure is sometimes reversible. However, reversal is not always successful, so a vasectomy cannot be considered universally “non-permanent”.²² Researchers are developing “vas-occlusive” devices— polymers injected into the vas deferens to block sperm transport—as reversible forms of vasectomy. The polymers can remain in place for years. To remove them, scientists are working on another injection to dissolve the polymer or an ultrasound-like technique that breaks the polymer.²²

Sperm motility—the ability of sperm to swim through the female reproductive tract to reach an egg—is powered by the flagellum (sperm’s tail).²³ Sperm move in many directions (e.g., straight, zig-zag, vibrating) when exposed to different signals. Once the sperm nears the egg, calcium triggers “capacitation.” The sperm are hyper-activated, meaning the flagella move with high curvature and wavelength to propel toward the egg. Hyper-activation also destabilizes the acrosomal membrane, which is crucial for fertilization.²³ Drugs targeting sperm motility could be short-acting and taken a short time before coitus. Additionally, since sperm are mobile in the female reproductive tract, women may also be able to use this type of contraceptive.

Binding the sperm to an egg relies on the acrosome reaction. The acrosome, a structure at the sperm’s head, contains enzymes that break through the egg’s coating. Zona pellucida (ZP)—a mixture of sugars and proteins surrounding the outer membrane of the egg—is where the magic happens. When sperm binds to ZP, enzymatic reactions create a “lock and key” recognition and trigger enzyme release from the acrosome. Once a sperm has traversed the ZP, it expels new enzymes which harden the ZP, making it impermeable to other sperm.²⁴ All of these highly regulated processes create multiple failure points that can become drug development targets. Like sperm motility, targeting fertilization would be short-acting and allow for patients to take the drug shortly before intercourse.

Male contraceptives have the potential to equalize the burden of contraception. Pharmacists and patients interested in the future of male contraceptives should be directed to the MCI website or to their podcast, “Intended.”²⁰

Hormone-Free Vaginal Gel

In May 2020, FDA approved a first-of-its-kind prescription, hormone-free vaginal gel (HFVG) contraceptive. The HFVG’s active ingredients —lactic acid, citric acid, and potassium bitartrate—are common food additives.²⁵ Patients administer 1 pre-filled single-dose applicator vaginally up to 1 hour before each act of intercourse. Counsel patients on the proper use of HFVG²⁶:

1. wash hands with soap and water
2. remove pre-filled applicator and plunger rod from the foil pouch
3. insert the plunger rod into the applicator and push until they connect (use a new applicator if gel goes into the pink cap)
4. remove the pink cap
5. hold applicator by the grooved area and insert it into the vagina as far as it will comfortably go
6. use index finger to push the plunger rod until it stops
7. remove the used applicator from the vagina (a small amount of gel may remain in the applicator after it delivers the full dose)
8. throw away the used applicator and cap

A new dose of HFVG is necessary before every act of vaginal intercourse (similar to using a new condom).²⁶ Patients can use HFVG at any point in the menstrual cycle, but remind them that it is ineffective when administered after intercourse.²⁵

HFVG reduces sperm motility, as discussed previously.²⁵ Vaginal pH can range from 3.5 to 4.5. When sperm enters the vagina, it increases the pH to improve its mobility through the reproductive tract. HFVG maintains normal vaginal pH and reduces sperm motility, lowering the chance of sperm reaching the egg.²⁶

The most common adverse effects of the HFVG are²⁵

• vulvovaginal burning, itching, and/or discharge
• urinary tract infection
• vulvovaginal/genital discomfort or pain
• bacterial vaginosis
• dysuria (painful urination)

In clinical trials, 9.8% of patients’ male partners experienced local discomfort (burning, itching, pain, and “other”). Studies also showed that common vaginal preparations (e.g., miconazole, metronidazole, etc.) showed no significant effect on HFVG’s pH or buffering effects.²⁵ HFVG may be used concomitantly with hormonal contraceptives, condoms (latex, polyurethane, and polyisoprene), and vaginal diaphragms, but not with vaginal rings.²⁵

Natural Cycles App

Some patients prefer fertility awareness-based methods (FABMs)—also known as “natural family planning”—for pregnancy prevention. The “fertile window” is a limited period of time within a given menstrual cycle during which a woman can conceive. Ovulation occurs in a single day, and the ovum remains viable for fertilization for about 12 to 24 hours.²⁷ Sperm released into the vaginal canal before ovulation can survive in the reproductive tract for up to 5 days. This results in an estimated 6-day window to become pregnant. Probability of pregnancy is highest (~30%) in the 2 days before ovulation, then falls to 8% to 10% on the day of ovulation, and zero chance of conception on the subsequent days.²⁷

Women use FABMs by tracking various signs and symptoms to identify the “fertile window” when unprotected intercourse is most likely to lead to pregnancy.²⁷ FDA permitted marketing of the first mobile medical application (app) as a method of contraception in 2018.²⁸ The app is 93% effective at preventing pregnancy with typical use, meaning 7 women out of 100 get pregnant during 1 year of use. If a woman never has unprotected sex on “red days,” efficacy increases to 98%.²⁹ Women for whom pregnancy would be associated with significant risk to the mother or fetus due to a medical condition should not use Natural Cycles. Women using birth control or hormonal treatments that inhibit ovulation should also not use this app.²⁸ Patients must be 18 years or older to use Natural Cycles.²⁹

To use the app as contraception, women track their temperature every morning upon waking and record it in Natural Cycles. The app’s algorithm uses the temperature recorded to calculate a woman’s fertility status for that day.²⁹ If the app indicates a “red day,” the patient should use protection or abstain from intercourse. As a woman accumulates data in the app, it starts to predict future cycles and indicates “green days” when ovulation has been predicted. Advise women using the app that these predictions can change. The apps creators suggest tracking body temperature at least 5 days a week for the most accurate results.²⁹

While the app is free to download, it does require a subscription to use. As of September 2020, women can pay $89.99 annually and receive a free oral basal thermometer or pay $9.99 monthly and pay $14.50 for a thermometer.²⁹ Pharmacy teams and patients can visit www.naturalcycles.com for up-to-date pricing. Natural Cycles app isn’t only for birth control. It has 3 modes: (1) prevent a pregnancy, (2) plan a pregnancy, and (3) follow a pregnancy. Additionally, with FDA clearance, patients can purchase the app with a flexible spending account or health savings account.²⁹

Ovaprene

Women who don’t use hormonal birth control methods are limited to current barrier methods, copper IUDs, sterilization, natural family planning, abstinence, and most-recently HFVG. However, a hormone-free, self-administered, non-invasive option may become available in the near future. Considered a “redesigned female condom,” Ovaprene is a small, hormone-free, intravaginal ring inserted into the vagina monthly.³⁰ It is a unique knitted polymer that creates a barrier to physically block sperm from entering the cervical canal and releases a locally-acting, non-hormonal agent to impede sperm motility.^30,31 This novel approach could potentially be as effective as existing short-acting hormonal birth control pills, patches, and vaginal rings without hormones.³¹

Initial testing in late 2019 found that Ovaprene successfully blocked sperm. The manufacturer tested it in 23 women, comparing the number of sperm present in their cervical mucus—a surrogate marker for contraceptive effectiveness—2 to 3 hours after intercourse with and without Ovaprene use. The study concluded that Ovaprene blocked “essentially all sperm.”³² Additional trials are ongoing, and if results are positive and Ovaprene is approved, it is expected on the market in 2023. It would be the first new barrier contraceptive method in nearly 15 years. It would also be the 1^st barrier method capable of working for an entire month.³²

Levonorgestrel Monthly Pill

Although oral contraceptives are the most commonly utilized, their effectiveness relies on daily adherence. Adherence is poor; over a 3-month interval, 40% to 50% of women miss at least 1 dose of their oral contraceptive. A similar percentage take the medication at the wrong time.³² Reducing dose frequency improves patient adherence, and adherence to monthly therapies is greater than that of daily or weekly therapies.

Researchers at Harvard University and the Massachusetts Institute of Technology are exploring new technology for an oral, monthly birth control pill.³² They have developed a gastric resident dosage form that can be placed in a gelatin capsule. Once orally ingested, the dosage form expands and remains in the stomach for an extended period. It consists of 6 polymeric arms joined by an elastomeric core, which folds into a capsule. After the outer capsule dissolves, the dosage form recoils and assumes a size larger than the pylorus (opening between the stomach and the small intestine). The device releases the drug for 3 weeks, followed by a hormone-free period, which would be associated with typical breakthrough bleeding.³²

Researchers have successfully used this dosage form to achieve 1- to 2-week long delivery of anti-infectious disease agents but not yet month-long delivery of contraceptives.³² While this contraceptive is still in initial research, it presents a promising potential alternative for patients with adherence difficulties.

Contraceptive Jewelry

The most unique new approach to birth control might be contraceptive jewelry.³³ A report published in the Journal of Controlled Release describes a transdermal levonorgestrel patch incorporated into jewelry worn on skin. Investigators incorporated small transdermal patches into earring backings. A woman could use her own earrings in combination with the delivery device. A patch was also incorporated into a clip-on earring for women without pierced ears. They also developed longer, thin patches that could be adhered to the underside of a ring, choker necklace, or wristwatch.³³

Researchers tested this method by applying the transdermal patches to pigs and hairless rats. Levonorgestrel levels were maintained well above human contraceptive threshold levels.³³ They also applied the patches cyclically (16 hours on, 8 hours off) to simulate jewelry removal at night. Levonorgestrel levels dipped during the off-period but still remained above human contraceptive thresholds.³³ Contraceptive jewelry was well-tolerated and effective. It may be a novel drug delivery method of the future.

PHARMACY TEAM’S ROLE

Pharmacists and pharmacy technicians are a vital source of information about contraceptive options. They can educate patients about available choices and offer insights into the following areas:

Generic Alternatives: Generic alternatives are available for many contraceptives (Table 2), but patients are often hesitant to use generic contraceptive products.³⁴ Reassure patients that generic contraceptives are bioequivalent and shown to produce the same effects and similar adverse effect profiles as innovator products. Breakthrough bleeding is a common cause of oral contraceptive discontinuation. Counsel patients that outside factors (e.g., missed pills, smoking, infection, drug interactions) are more likely to affect their experience with a generic alternative than possible subtle variations in pharmacokinetics. Pharmacy technicians should refer patients to the pharmacist to discuss these possible outside factors. Pharmacy teams should encourage generic alternatives whenever possible to decrease patients’ out-of-pocket costs.

Adverse Effect Management: Technicians who can recognize adverse effects can refer patients to the pharmacist for prompt attention. Pharmacists who know how to combat adverse effects by changing doses or products can prevent premature discontinuation. Too much estrogen causes nausea, breast tenderness, weight gain, headaches, and menstruation changes. Estrogen deficiency can lead to vasomotor symptoms (e.g., night sweats, hot flashes), early cycle (days 1 to 9) breakthrough bleeding or spotting, or amenorrhea (absence of withdrawal bleeding).⁷ If patients accept amenorrhea, no dose adjustment is necessary; however, if the patient desires menses, estrogen dose can be increased. Excess progestins cause breast tenderness, headache, fatigue, and mood changes (e.g., depression, irritability). Progestin deficiency can lead to dysmenorrhea, menorrhagia (heavy menstrual bleeding), or late-cycle (days 10 to 21) breakthrough bleeding or spotting.⁷ Counsel women that many symptoms occurring in the 1^st cycle improve by the 2^nd or 3^rd cycle, so adherence is important. Additionally, extended-cycle or continuous regimen contraceptives can help women experiencing bothersome dysmenorrhea or menorrhagia, as they would have fewer or no menses.⁷

Drug-Drug Interactions: Pharmacists and technicians can recognize potential interactions that could compromise birth control. CYP3A4-inducing drugs are the most common offenders, including anticonvulsants (e.g., barbiturates, carbamazepine, phenytoin, topiramate), protease inhibitors (e.g., amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir), and rifampin.⁷ St. John’s wort, available OTC, also induces CYP3A4, so technicians should be vigilant to query women buying this product about contraceptive use. Pharmacists should recommend oral contraceptives containing 50 mcg or more of ethinyl estradiol in conjunction with a 2^nd method of contraception for patients taking CYP3A4 inducers. IUDs are also appropriate.⁷ Tetracyclines and penicillin derivatives may also decrease ethinyl estradiol levels, which suggests a small risk of decreased contraceptive effectiveness.⁷ Counsel women to use alternative methods of contraception while taking these antibiotics.

Missed Doses and Birth Control Failure: Few methods of birth control are 100% effective, and mistakes happen. Inconsistent or incorrect use of hormonal contraceptive is a major cause of contraceptive failure.³⁵ Table 2 lists counseling points in the event of missed doses and birth control failure. Patient preference is important; patients are most likely to adhere to a contraceptive method if it fits into their lifestyle and is well-tolerated. If a woman misses a dose or her birth control fails, use motivational interviewing to explore why and explore more convenient options.

CONCLUSION & RESOURCES

Contraceptives are not one-size-fits-all, and a plethora of options exist. Some comorbidities preclude the use of certain birth control methods. CDC provides guidance and considerations for special populations (Table 3). Pharmacists should discuss new birth control options and understand ideal candidates.

REFERENCES

1. Guttmacher Institute. Contraceptive use in the United States. April 2020. Accessed at https://www.guttmacher.org/fact-sheet/contraceptive-use-united-states, September 10, 2020.
2. U.S. Department of Health & Human Services Office on Women’s Health. Unplanned pregnancy. January 30, 2019. Accessed at https://www.womenshealth.gov/pregnancy/you-get-pregnant/unplanned-pregnancy, September 10, 2020.
3. The Washington Post. Unplanned pregnancies cost taxpayers $21 billion each year. March 3, 2015. Accessed at https://www.washingtonpost.com/news/wonk/wp/2015/03/03/unplanned-pregnancies-cost-taxpayers-21-billion-each-year/, September 10, 2020.
4. The Brookings Institution. The high cost of unintended pregnancy. July 12, 2011. Accessed at https://www.brookings.edu/research/the-high-cost-of-unintended-pregnancy/, September 10, 2020.
5. Centers for Disease Control and Prevention. Contraception. August 13, 2020. Accessed at https://www.cdc.gov/reproductivehealth/contraception/index.htm, September 10, 2020.
6. Bull JR, Rowland SP, Scherwitzl EB, et al. Real-world menstrual cycle characteristics of more than 600,000 menstrual cycles. NPJ Digit Med. 2019;2:83.
7. Shrader SP, Ragucci KR. Contraception. In: DiPiro JT, Talbert RL, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017:1247-1262.
8. Ortho Evra [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.;2014.
9. Nuva Ring [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.;2020.
10. Annovera [package insert]. New York, NY: Population Council;2018.
11. Urban Institute. Knowledge gaps and misinformation about birth control methods persist in 2016. September 14, 2016. Accessed at https://www.urban.org/research/publication/knowledge-gaps-and-misinformation-about-birth-control-methods-persist-2016, September 10, 2020.
12. Depo-Provera CI [package insert]. New York, NY: Pharmacia & Upjohn Company;2010.
13. Nexplanon [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.;2017.
14. American College of Obstetricians and Gynecologists. Long-acting reversible contraception (LARC): Intrauterine device (IUD) and implant. May 2020. Accessed at https://www.acog.org/patient-resources/faqs/contraception/long-acting-reversible-contraception-intrauterine-device-and-implant, September 10, 2020.
15. Hardeman J, Weiss BD. Intrauterine devices: an update. Am Fam Physician. 2014;89(6):445-450.
16. Choice of contraceptives. Med Lett Drugs Ther. 2018;60(1557):161-168.
17. Voeller B, Coulson AH, Bernstein GS, Nakamura RM. Mineral oil lubricants cause rapid deterioration of latex condoms. Contraception. 1989;39(1):95-102.
18. Cleveland Clinic. Toxic Shock Syndrome. July 11, 2018. Accessed at https://my.clevelandclinic.org/health/diseases/15437-toxic-shock-syndrome, September 10, 2020.
19. Annovera - a new contraceptive vaginal ring. Med Lett Drugs Ther. 2019;61(1587):197-198.
20. Male Contraceptive Initiative. Accessed at https://www.malecontraceptive.org/, September 10, 2020.
21. Male Contraceptive Initiative. Spermatogenesis. Accessed at https://www.malecontraceptive.org/spermatogenesis.html, September 10, 2020.
22. Male Contraceptive Initiative. Sperm Transport. Accessed at https://www.malecontraceptive.org/sperm-transport.html, September 10, 2020.
23. Male Contraceptive Initiative. Sperm Motility. Accessed at https://www.malecontraceptive.org/sperm-motility.html, September 10, 2020.
24. Male Contraceptive Initiative. Fertilization. Accessed at https://www.malecontraceptive.org/fertilization.html, September 10, 2020.
25. Phexxi [package insert]. San Diego, CA: Evofem Biosciences;2020.
26. Evofem Biosciences. Phexxi. September 2020. Accessed at www.phexxi.com/how-phexxi-works, September 10, 2020.
27. Simmons RG, Jennings V. Fertility awareness-based methods of family planning. Best Pract Res Clin Obstet Gynaecol. 2020;66:68-82.
28. U.S. Food and Drug Administration. FDA allows marketing of first direct-to-consumer app for contraceptive use to prevent pregnancy. August 10, 2018. Accessed at https://www.fda.gov/news-events/press-announcements/fda-allows-marketing-first-direct-consumer-app-contraceptive-use-prevent-pregnancy, September 10, 2020.
29. Natural Cycles. How does the birth control app work? Accessed at https://www.naturalcycles.com/, September 10, 2020.
30. Rewire News Group. Finally, a new barrier method contraception is on the horizon. February 11, 2020. Accessed at https://rewire.news/article/2020/02/11/finally-a-new-barrier-method-contraception-is-on-the-horizon/, September 10, 2020.
31. Daré Bioscience. Our pipeline: Ovaprene. 2020. Accessed at https://darebioscience.com/pipeline/ovaprene/, September 10, 2020.
32. Kirtane AR, Hua T, Hayward A, et al. A once-a-month oral contraceptive. Sci Transl Med. 2019;11(521):eaay2602.
33. Mofidfar M, O'Farrell L, Prausnitz MR. Pharmaceutical jewelry: Earring patch for transdermal delivery of contraceptive hormone. J Control Release. 2019;301:140-145.
34. American College of Obstetricians and Gynecologists. Brand versus generic oral contraceptives. August 2007. Accessed at https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2007/08/brand-versus-generic-oral-contraceptives, September 10, 2020.
35. Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(4):1-66.

Back to Top