Researchers have removed different numbers of pills at different places in the pill pack in an effort to identify how many days without hormonal pills it takes for women to ovulate. Some packets had two, three, or four hormonal pills removed from the third week. Others had hormonal pills removed at the start of the packet: days 1–4, 3–6, or 6–9.

These studies involved various low-dose formulations, both multiphasic and monophasic, including those with one of the lowest available doses of ethinyl estradiol, 20 mg. While results varied—from no ovulation to ovulation in 10% of women in one study—in every study women developed ovarian follicles (48, 112, 121, 122, 127, 140, 203, 219).

A review of the findings from these studies, coupled with observations about pill-taking and pill failure, suggest several conclusions:

• Some women are biologically more likely to become pregnant than others. These women quickly achieve normal hormonal levels during the hormone-free interval, making missing only a very few pills on either side of the hormone-free interval extremely risky (118). In fact, variation in follicular development is so great among women that some researchers feel that individual body chemistry can be a greater risk factor for pregnancy than missing a specific number of pills (112, 118, 219).
• While women do resume normal pre-ovulatory hormonal function during the seven-day hormone-free interval, this does not compromise the effectiveness of the pill. Hormonal levels have not been shown to rise to those needed for ovulation, cervical mucus remains thickened, and the lining of the uterus remains thin throughout these seven hormone-free days (112, 118, 140, 203).
• For most women, taking seven hormonal pills in a row is enough to provide maximum contraceptive effectiveness, even immediately after the seven-day hormone-free period (118). Studies looking at follicular development among women missing pills found that the follicles regressed in the majority of women after seven days of taking hormonal pills (112, 118, 140, 203). Some women, however, may need more than seven pills to make the follicles on the ovary regress and thus establish full contraceptive effectiveness (118).

Shortening the Hormone-Free Interval

When compared with a 21-day hormonal pill formulation with 20 µg of ethinyl estradiol and 150 µg of desogestrel, the 24-day hormonal pill pack was just as effective in preventing pregnancy (252). Women using the 24-day hormonal pack had shorter and lighter withdrawal bleeds and more breakthrough bleeding than women using the 21-day hormonal packets. Fewer women discontinued due to breast tenderness or nausea with the 24-day formulation (252).

This guidance is based on observations that usually up to seven straight days of taking pills are needed to suppress a woman's hormonal cycle at the beginning of a pill pack (112, 118, 140, 203). It also recognizes that women are not at risk of pregnancy for the seven days they are not taking hormonal pills at the end of the pack even though their bodies are producing the hormones that start the process of ovulation (112, 118, 140, 219).

Over the years a variety of rules have been proposed to help women make up missed pills, but no consensus developed. In October 2001, the World Health Organization gathered a scientific working group to make selected practice recommendations for contraceptive use. Based on a review of scientific evidence, the group developed guidance for making up missed pills.

The following principals underlie the guidance:

• It is important to take an active pill as soon as possible when active pills are missed;
• If pills are missed, the risk of pregnancy depends on how many pills were missed and when the pills were missed;
• If pills are missed in the first week of the pill pack (including starting a pack late) or if five or more pills are missed, a woman should abstain from intercourse or use a back-up method for the next seven days (260).

Missing One Active Pill

In the special cases below, a woman begins correcting the error by resuming pill-taking as she would after missing just one pill (see diagram, A). She ALSO follows one of these special rules:

Starting a New Pill Pack Two or More Days Late

Missing Two to Four Consecutive Active Pills

Days 8–14. She should take a pill as soon as she remembers and than one each day as needed. Back-up methods or abstinence is not needed.

Days 15–21. She should take one pill as soon as she remembers. She should continue to take one pill each day, as usual, until she finishes all of the hormonal pills in the pack. She then should start a new pack the very next day, without the usual seven-day wait. A women using 28-day pill packs should skip the last seven pills because these pills contain no hormones. She should start a new pack the next day after taking the last hormonal pill (see diagram, B).

Missing Five or More Active Pills

Missing Inactive Pills(28-day pill packs only)

Providers Play a Key Role

In order for pill users to understand the principle behind the missed pill rules, providers must explain to women how pills work, and that for seven days every month they are not taking active pills. This is especially important for 28-day users to remember. Good counseling can help. Telling women that the pill puts their ovaries to sleep and that missing pills can wake their ovaries up is a good way of explaining it in understandable terms.

The other 80% of pregnancies in 12 months after starting OC use will occur among the one-third of women who discontinue pill use. In particular, 68% of unintended pregnancies will occur among the 12% who discontinue pill use and do not switch to another method. (Another 11% of pill users will not need another method once they stop using the pill; they are no longer fecund, want to become pregnant, are not having intercourse, or have already become pregnant. About 5% will adopt a less effective family planning method after discontinuing the pill, and about 7% will switch to a more effective method.)

Among women who discontinue OCs and do not adopt another method within 12 months despite continuing need, over half—nearly 7 million women—will become pregnant. This estimate is based on a study of Ghanaian pill users, which found that 53% of pill discontinuers became pregnant within several months (227).

Thus most pill users who become pregnant actually become pregnant when they stop OCs without switching to another method. Family planning programs should focus on helping women continue their methods or switch to new methods without a gap in contraceptive protection. In particular, providers can advise OCs users about common side effects and their management and emphasize that clients are welcome back to seek help or another method at any time.

Similarly, in rural Bangladesh women whose husbands participated in selecting OCs used them longer than women whose husbands were not involved in selecting a family planning method. These women also reported lower rates of discontinuation due to common side effects. Researchers report that husbands helped by urging their wives to obtain more information or counseling from a provider about how to manage side effects. Discussing her side effects with her partner can relieve anxiety. Such discussion also promotes switching to a different method when appropriate (170).

When men help in selecting a contraceptive method, they are more likely to be involved in its correct use. A Chinese study looked at the effect of partner involvement on contraceptive use-effectiveness. The pregnancy rate for users of temporary methods was lower among women who attended contraceptive counseling with their husbands than among women who obtained a method on their own (232).

Of course, men also can influence their spouses to stop using family planning. Some 37% of women in Bangladesh who had stopped using the pill in less than three months reported that their husbands influenced them to stop (3).

Family planning programs can reach men in a variety of ways, especially at places where men gather—for example, at sporting events and community meetings—as well as through mass-media messages (46). Pill use messages in the mass media can speak directly to men and their participation in better reproductive health, including telling them how they can help their partners use the pill effectively. (See Population Reports, New Perspectives on Men's Participation, Series J, No. 46, October 1998.)

• The pill works if you take it correctly.
  It is up to you to make pill use as effective as it can be. You must remember to take a pill every day as long as there are pills in the pill packet.
• Take action if pills are missed.
  It is important to make up missed pills, abstain from intercourse, or use a back-up method of contraception if you do not want to get pregnant. (See box, p. 6.)
• Vomiting, diarrhea, and certain medications can make the pill less effective. (See side-bar below, Pill Effectiveness: Unresolved Issues.)
• Be sure to start a new pill packet on time.
  If you start a new packet late, use a back-up method or abstain from intercourse until you have taken pills for seven days straight.
• The pill does not prevent sexually transmitted infections (STIs).
  If you are at risk for STIs, use condoms or abstain from intercourse. (You can use condoms and pills at the same time for extra protection against pregnancy.)
• Most common side effects do not mean something is wrong.
  Continue taking a pill each day. Skipping pills can make side effects worse. It may take a few months to adjust to the pills and for side effects to diminish or go away entirely.
• You should immediately see a health care provider if you experience:
  
  • Constant, severe pain in chest, legs, or abdomen;
  • Severe, recurring head pain, often on one side or pulsating, that can cause nausea and is often made worse by light and noise or moving about;
  • Brief loss of vision, or seeing flashing lights or zigzag lines in front of the eyes (with or without bad headache); or
  • Yellowing of eyes or skin.

Common side effects of pill use typically subside within the first three to six months of use (37, 163, 179). Breakthrough bleeding decreases dramatically over the first four months of pill use (84, 136).

How can providers help women with side effects? First, they can urge all OC users to tell them if side effects occur and assure them that usually something can be done to manage side effects. Often, simply letting women know that they can return to consult the provider at any time helps women use a method longer, despite side effects (93, 126). When a pill user returns for help with side effects, the strategies below can help to reduce them.

Breakthrough bleeding and spotting. Some women experience breakthrough bleeding or spotting when they miss pills or take them at different times during the day. For these women, taking the pill every day and at the same time can help reduce breakthrough bleeding and spotting.

Other women, however, have these side effects even when they take their pills consistently. For women whose breakthrough bleeding occurs early in the pill cycle, changing to a pill with more estrogen, if available, can help reduce bleeding (84, 136). Sometimes switching to another low-dose pill formulation can help.

Women with vomiting and diarrhea sometimes ex-perience breakthrough bleeding and spotting (84, 85). Interactions with specific drugs can cause breakthrough bleeding, too (72). Vomiting, diarrhea, and drug interactions affect how the body absorbs the hormones in the pill. Breakthrough bleeding may indicate that the pill is not being fully absorbed, and thus the pill's contraceptive effect may be compromised. These women should continue taking a pill every day, and for added protection they can use a back-up method or avoid intercourse during the period of vomiting, diarrhea, or drug use and for 7 to 14 days afterward (74).

Nausea. Feeling nauseous usually passes after the first few months of pill use, usually occurs on the first day or so of the pill pack, and is more common among women who are underweight (73). Taking the pill at night or with food can help reduce nausea, as can consistent pill-taking (84, 85).

Weight gain. In most cases, weight change among women using OCs is minimal and not related to pill use: As many women lose weight while taking the pill as gain weight (84). Some women may gain substantially, however.

While some women see weight gain as a benefit, others may not be pleased. Reducing the level of estrogen may help keep women from gaining weight (84).

Amenorrhea. A small number of pill users stop menstruating when using the pill. More often, a woman's bleeding may be so slight or so brief that she may think she is not bleeding at all. Such apparent or actual amenorrhea can upset women who believe that regular menstruation is necessary to remain healthy or have certain folk beliefs about menstruation (90, 195). Others may be worried that lack of menstruation indicates pregnancy.

Asking pill users several questions can help identify what steps can be taken. Is the woman having any bleeding at all? Perhaps she has just a small stain on her underclothes that she has not recognized as bleeding. If this is the case, these women can continue taking their pills every day, with reassurance that not menstruating is not harmful to their health.

Although amenorrhea is not usually a sign that a pill user is pregnant, providers can verify whether or not this is case by asking a woman a few questions. For example, in the last month has she taken a pill every day? If so, it is not likely that she is pregnant. She should continue taking her pills every day as usual. Also, some women using 21-day packs may have no bleeding if they start another pill packet immediately rather than waiting seven days between packs. Women who have done this also are not likely to be pregnant.

For a woman who has missed two or more hormonal pills in a row, a series of questions can assess whether or not she may be pregnant (see checklist below). A woman must be told if a provider suspects that she may be pregnant. This woman should stop using OCs, and she can use spermicide and condoms until her menstrual period starts or it becomes otherwise clear whether or not she is pregnant. Women who are not pregnant should feel free to start using OCs again if they wish.

A few women experience amenorrhea after they stop using the pill. Sometimes it takes women a few months for their periods to return after using OCs. No medical management is needed. Women with irregular menstrual periods before using the pill may have irregular periods again once they stop using the pill (85). Assuring such women that the pill has not affected their fertility can reduce any anxiety about amenorrhea.

When Can a Woman Start the Pill

A woman who starts the pill more than seven days since menstrual bleeding began should use a back-up method such as condoms or spermicide or else avoid intercourse for the first seven days of taking the pill. Her usual menstrual pattern may change, but she should continue taking all the pills in the pack, regardless of when she next menstruates.

To make reasonably certain a client is not pregnant, a provider can ask a series of questions (see checklist, right). A pregnancy test is not necessary. There is no need to ask a woman to return when she is menstruating, for the pill or any other method.

If pregnancy cannot be ruled out—in other words, if the woman cannot answer yes to any of these questions—she can take pills home with her and start them as soon as her menstrual period begins or any time within the first seven days after menstruation starts.

When is the best day to start? The first day of menstrual bleeding may be easiest to remember, and starting on the first day requires no counting of days. Recent research, however, suggests that starting later reduces breakthrough bleeding and spotting in the first month. This could be an advantage because breakthrough bleeding is a common reason that women quit OC use in the first month (247, 248).

Two studies compared starting on the first day of menstrual bleeding with starting on the fifth day. In the first study 26% of the 50 women starting their pills on the first day of menstruation had breakthrough bleeding compared with 8% of the 50 women starting on the fifth day (248). In a second study 24% of 100 women starting on day 1 and 10% of 100 women starting OCs on day 5 experienced breakthrough bleeding in the first month (247). Because fewer of these women experienced breakthrough bleeding, fewer of the day 5 starters discontinued use during the first pill cycle (247, 248).

Some instructions for pill use in some developed countries have told women to start on a Sunday. This guidance has become somewhat less common because many pharmacies in these countries are closed on Sunday, making it difficult for women to obtain pills.

Drug Interactions

Broad-Spectrum Antibiotics

Nevertheless, some pill users who became pregnant report taking antibiotics around the time of conception. For example, 21% of women seeking abortions in New Zealand reported taking antibiotics at this time (207). Based on providers' questioning and assessment, the women in this study are not thought to have missed pills at the time of conception (207). In other studies 4% to as many as 34% of women seeking abortions after OC failure report concurrent antibiotic use, although these studies do not report on other factors that may have played a part in pill failure (47, 255).

One reason that concurrent antibiotic use appears to be so common among women experiencing pill failure may be the widespread use of antibiotics: Some women will become pregnant because they missed pills, and, by chance, be using antibiotics at the same time (74).

Other women, however, are affected physiologically by antibiotic use. Some pill users' bodies absorb less ethinyl estradiol than others. Such women rely on gut flora to consume the ethinyl estradiol and recirculate it through the small intestine. Broad-spectrum antibiotics, however, remove these flora, leaving no mechanism to redistribute the ethinyl estradiol (10, 201). Some researchers conclude that only these women experience pill failure as a result of using antibiotics (10, 201, 234). Unfortunately, there is no way to identify these women in advance (201).

Pill users should not stop taking antibiotics before finishing the full course prescribed to them, even if they are afraid it will make the pill less effective. A growing number of disease organisms are becoming resistant to widely used antibiotics because people are not finishing their full course of antibiotics (257).

Vomiting and Diarrhea

Vomiting and diarrhea can interfere with absorption of both estrogen and progestin. Although the hormones in OCs are absorbed in the upper intestinal tract, the increased movement of the intestines during bouts of illness seems to reduce hormonal absorption (63). Many pill users, however, are not aware that vomiting and/or diarrhea may make the pill less effective (19, 47).

What Advice to Give?

Among the advice that has been offered are the following:

• Pill users taking broad-spectrum antibiotics do not need to use a back-up method, since pharmacological studies do not show an increased risk of pill failure (84).
• Pill users can use an additional method of contraception if they want extra protection from pregnancy (7, 234, 241).
• Pill users can omit the seven-day hormone-free interval between pill packs while taking antibiotics (72).
• Long-term users of antibiotics can increase their contraceptive protection by switching to higher-dose pills, such as those containing 50 µg of ethinyl estradiol (72).
• Women with illnesses causing vomiting and/or diarrhea can use an additional method or abstain from sexual intercourse for 7 to 14 days after the illness (85, 120, 135, 194, 206).
• Women should take another pill if vomiting or diarrhea occurs within two hours after taking a pill. Two hours is sufficient time for the hormones in the pill to be absorbed and maintain contraceptive effectiveness (8).