This chapter should be cited as follows: This chapter was last updated:
Dardano, K, Burkman, R, Glob. libr. women's med.,
(ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10392
September 2008


Clinical Aspects of Oral Contraceptive Use

Kristin L. Dardano, MD
Associate Professor of Obstetrics and Gynecology, Tufts University, Baystate Medical Center, Springfield, Massachusetts, USA
Ronald T. Burkman, MD
Professor, Department of Obstetrics and Gynecology, Tufts University School of Medicine, Division of General Obstetrics and Gynecology, Baystate Medical Center, 759 Chestnut Street, Springfield, Massachusetts 01199, USA


The turn of this past century coincided with the 40th anniversary of the oral contraceptive pill. More than 90 million women worldwide now use combination (estrogen plus progestin) oral contraceptives.1 During the past four decades, the pill has probably been one of the most studied medications in the history of medicine, with the data clearly documenting overall safety and efficacy. However, despite 40 years of experience with oral contraceptives, adequate knowledge about additional health benefits and compliance with prescribed regimens continues to be a substantial problem.

In the United States, the National Center for Health Statistics has been conducting, at varying intervals, national fertility surveys known as the National Survey of Family Growth. Recent surveys presented data for 1994, 1995, and 2002.2, 3, 4 The number of women using contraception in the 15–44 years age group increased from 30 to 39 million users compared with results in 1982. Unfortunately, this overall increase in use of contraception was accompanied by a modest decrease in the use of oral contraceptives. Further, despite improved overall use of contraception, there remained approximately 5% of women in this age group, or 3 million women, who were not using contraception and were at risk for unintended pregnancy. Among the pregnancies occurring in this timeframe, 49% were unintended, yet approximately one half of these women reported use of contraception. A secondary analysis from the survey also supported the concept that inconsistent use of contraception is a significant contributor to unintended pregnancy.5 For example, among oral contraceptive users, 16% of women indicated they missed three or more pills within a three month period. Factors associated with inconsistent use included new users, Hispanic and black ethnicity, low income status, and having had a previous unintended pregnancy. Although there was a trend for teenaged women to have a greater likelihood of inconsistent use compared with other age groups, the differences among various age groups were not statistically significant. These findings clearly suggest that there is a substantial need to improve the ability of women to obtain contraception, select an appropriate method, and use the selected contraceptive method correctly.


This section outlines the benefits related to oral contraceptive use. Health benefits not related to contraceptive use are summarized in Table 1.


Table 1. Health benefits of oral contraceptives

Condition Approximate level of risk
reduction or improvement
Reasonably established  
   Ovarian cancer protection 40–80%
   Endometrial cancer protection 50%
   Ectopic pregnancy 90%
   Pelvic inflammatory disease 50–80%
   Menstrual disorders  
     Abnormal bleeding 30–50%
     Dysmenorrhea 60%
   Benign breast disease 30–50%
   Ovarian cysts Variable
   Acne 50%
   Bone mineral density Improvement in many studies
   Colorectal cancer 40%
   Rheumatoid arthritis Less progression


Contraceptive Effects


Combined oral contraceptives suppress ovulation by diminishing the frequency of gonadotropin-releasing hormone pulses and eliminating the luteinizing hormone surge at midcycle. They also change the consistency of cervical mucus, resulting in less sperm penetration, make the endometrial lining less receptive to implantation, and alter tubal transport of both sperm and oocytes. When used correctly and consistently, combination oral contraceptives confer a better than 99% method-effectiveness (theoretic effectiveness assuming perfect use) for prevention of pregnancy.6 Unfortunately, myths regarding increased cancer risks and problems with compliance have led to a significant reduction in use effectiveness (effectiveness that occurs in actual practice). Incorrect pill usage, unfortunately, leads to contraceptive failure and an increase in abnormal or breakthrough bleeding and, ultimately, pill discontinuation. Other factors that also affect use effectiveness include perceived convenience, cost, and motivation. Overall use effectiveness, because of these factors, ranges between 94% and 97%.6

Efficacy is reported either as a Pearl Index or as a life-table analysis. The former is calculated by taking the total number of unintended pregnancies as the numerator, with the denominator being the total months or cycles of exposure.7 This ratio is then multiplied by 1200 if months are used and 1300 if menstrual cycles are used. Although relatively simple to perform, the index does not account for duration of exposure, such that studies with different durations of exposure cannot be accurately compared. The life-table analysis is preferable because it does account for duration of use and can be used more accurately for direct comparisons between studies.8 Regardless of the method used to calculate efficacy, a number of factors influence results of clinical trials including characteristics of the study population; for example, fertility, sexual activity, and methodological issues such as frequency of pregnancy testing and follow-up of subjects. Finally, there has been one recent study suggesting that women weighing more than 155 pounds using oral contraceptives are at increased risk for contraceptive failure.9 Previous studies with contraceptive implants and the transdermal contraceptive patch have also indicated that women heavier than certain weights may experience more contraceptive failures than women who weigh less.

Ectopic Pregnancy

The rate of ectopic pregnancy has shown a steady increase since 1970 in the United States, such that between one and two ectopic gestations occur for every 100 term deliveries in this country. Although mortality associated with ectopic pregnancy is relatively low, morbidity related to future fertility and the consequences of an acute rupture persists. Based on results of various epidemiologic studies, oral contraceptives convey approximately a 90% reduction in risk of ectopic pregnancy.10 The likely mechanism is through suppression of ovulation, an effect that obviously prevents all types of pregnancy.

Ovarian Cancer

Although ovarian cancer is a relatively uncommon tumor type, unfortunately methods to detect tumors early are ineffective such that only approximately one half of women survive for five years after treatment. At least 22 case-control studies and three cohort studies have examined the relationship between oral contraceptive use and ovarian cancer.11, 12, 13, 14 All but two of these studies have shown a protective effect for oral contraceptives. Overall, between 40% and 80% decrease in risk prevails among users. The protection begins approximately one year after initiating use and conveys approximately a 10–12% decrease in risk for each year of use. In addition, protection persists for 15–20 years after the patient has discontinued use of oral contraceptives. This protective effect primarily involves epithelial tumors of the ovary. Two case-control studies have evaluated whether oral contraceptives provide protection against ovarian cancer for carriers of BRCA1 and BRCA2 mutations.15, 16 One study showed a protective effect for carriers of the BRCA1 mutation15 and the other study showed no protective effect of oral contraceptives for either type of BRCA carrier.16 However, because both studies have methodological problems, including small sample sizes, it is clear that the issue is not yet settled.

The mechanisms by which oral contraceptives may produce their protective effects include suppression of ovulation, thus resulting in a reduced frequency of injury to the ovarian capsule and the suppression of gonadotropins. Although the gonadotropin theory remains controversial, proponents cite data that high levels are associated with ovarian cancer in animals, and that gonadotropins have been shown to stimulate some human ovarian cancer cell lines. A recent primate study of contraceptive steroids suggests that induction of ovarian apoptosis which in turn eliminates surface epithelium inclusion cysts may also play a role in reducing ovarian cancer risk.17

Endometrial Cancer

Endometrial cancer is almost twice as frequent as ovarian cancer, with better five-year survival rates because of earlier appearing symptoms. At least 12 case-control studies and two cohort studies have demonstrated that use of oral contraceptives conveys protection against endometrial cancer.18, 19, 20 Overall, these studies suggest up to a 50% reduction in risk that begins approximately one year after initiation of use. Protection appears to increase with duration of use, indeed, some data indicate that the protection persists up to 20 years after oral contraceptive use is discontinued. Protection has been demonstrated for adenocarcinoma, adenosquamous tumors, and adenoacanthomas. However, the strength of the protective effect varies in studies for women with potential risk factors, such as obesity and nulliparity. The purported protective mechanism is a reduction in the mitotic activity of endometrial cells by the action of the progestin component.

Pelvic Inflammatory Disease

Pelvic inflammatory disease or salpingitis is still a major cause of morbidity for reproductive-aged women. It has been established in several epidemiologic studies that use of oral contraceptives reduces the risk of salpingitis by 50–80% compared with findings in women who are not using contraception or who use a barrier method.10, 21, 22 Interestingly, there is no protective effect against the acquisition of lower genital tract sexually transmitted diseases including Chlamydia trachomatis and Neisseria gonorrhoeae infections of the uterine cervix. Purported mechanisms by which oral contraceptives exert protection include progestin-induced changes to cervical mucus, making it thick and viscous such that ascent of bacteria is substantially inhibited. Additional theories include reduced menstrual flow such that there is less retrograde menstrual flow to the fallopian tubes and less of an environment that would promote growth of bacterial organisms and possible changes in uterine contractility such that ascent of organisms is less likely.

Menstrual Disorders

Abnormal uterine bleeding is a common symptom of reproductive aged women. Combined oral contraceptive pills are frequently used for the treatment of heavy menstrual bleeding and irregular cycles. According to a recent systematic review, there is a paucity of data regarding the use of oral contraceptive pills for the treatment of heavy menstrual bleeding.23 Until recently, there were several case series and reported anecdotal experience to suggest that oral contraceptive users have improved cycle control and decreased overall bleeding when using the pill regularly.24, 25, 26 In 2000, a multicenter, randomized trial compared the efficacy of a triphasic combination oral contraceptive containing norgestimate and ethinyl estradiol to a placebo for the treatment of metrorrhagic, menometrorrhagic, oligomenorrheic, and polymenorrheic dysfunctional uterine bleeding.27 The combination pill proved to be an effective treatment for a variety of irregular bleeding patterns, based on both patient perceptions and investigator's overall assessment in the improvement of bleeding.

The combination of estrogen and progesterone essentially stabilizes the lining over time. Because progestins are 19-nortestosterone derivatives, they are highly potent in regard to their endometrial activity. Continuous combined oral contraceptives without a hormone-free interval results in amenorrhea for many women.28, 29 Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptom appears to be high.

Dysmenorrhea is also a common symptom among reproductive aged women. Approximately 60–90% of all adolescents experience dysmenorrhea and up to one-quarter miss school or work as a result of pain.30 A recent review regarding the combined oral contraceptives as treatment for primary dysmenorrhea concluded that no recommendations can be made regarding the efficacy of modern combined oral contraceptives for this disorder.31 The reviewers did note that there is some evidence from four randomized, controlled trials that combined oral contraceptive pills with medium-dose estrogen and the progestins levonorgestrel, norgestimate, and desogestrel are more effective than placebo in decreasing dysmenorrhea.

Oral contraceptives reduce pain associated with menstruation through two possible mechanisms. First, there are data to suggest that the prostaglandin content of menstrual fluid is reduced, leading to less local endometrial vasoconstriction and ischemia.32 Second, it has also been shown in oral contraceptive users that uterine contractile activity is reduced.33 In summary, a trial of combined oral contraceptive pills should be considered a safe and effective treatment for menstrual disorders.

Benign Breast Disease

Benign breast conditions encompass fibrocystic change, fibroadenoma, galactorrhea, intraductal papilloma, fat necrosis, duct ectasia, lobular hyperplasia, and sclerosing/fibrosing adenosis. Results of several studies reveal a significant decrease in the incidence of benign fibrocystic conditions with oral contraceptive use, with a 30–50% decrease overall.34, 35 The occurrence of fibroadenomas, specifically, decreases among women younger than age 45 years. These effects are mainly seen in current and recent long-term users of oral contraceptives. The likely mechanism is through suppression of ovulation; therefore, inhibition of the breast cell proliferation that normally occurs in the first half of an ovulatory menstrual cycle. Oral contraceptive use has also been demonstrated to decrease incidence of galactorrhea.

Ovarian Cysts

It has been reported that ovarian cysts are the fourth leading cause of gynecologic admission in the United States.36 The incidence of ovarian cysts among oral contraceptive users depends heavily on the steroid dosages in oral contraceptive formulations. Although data are somewhat inconsistent, a clear suggestion is present that higher-dose contraceptives (e.g. 50 μg or greater of ethinyl estradiol) protect against cyst formulation. In contrast, current lower-dose formulations appear to have no effect on ovarian cyst formation.37, 38 However, it is important to recognize that many recent studies evaluating this issue use ultrasound definitions of cysts as opposed to clinical definitions in which some type of therapy might be indicated. Further, many of these cysts identified in such studies regress over time. Thus, it appears that current low-dose oral contraceptives reduce the frequency of ovulation but may still allow early recruitment of follicles that do not progress to the stage of ovulation. Finally, no data support use of oral contraceptives in the treatment of existing cysts, although higher-dose formulations can be used as a means to prevent cyst formation for women who are plagued by recurrent symptoms caused by ovarian cyst formation. A recent study reported that ever-use of oral contraceptives was associated with a decreased risk of benign ovarian tumors.39 The decreased risks observed were greatest for women with endometriosis.


At least 25% of reproductive-aged women are affected by acne to a varying degree. The progestins and their doses contained in initial combined oral contraceptives had significant androgenic properties and contributed to acne in many women. Newer progestins such as norgestimate, desogestrel, and drospirenone have more affinity for the progestin receptor and less for the androgen receptors and help to reduce overall acne lesions. Oral contraceptives reduce acne by several purported mechanisms. Oral contraceptives increase the level of sex hormone-binding globulin, which binds and decreases available free testosterone. They also suppress gonadotropins, which can lead to decreased ovarian production of androgens. Two multicenter, double-blind, placebo-controlled clinical trials demonstrated that the formulation of 35 μg of ethinyl estradiol and triphasic norgestimate reduced total acne lesions.40, 41 The newest progestin marketed, drospirenone, a spironolactone analogue, has demonstrated decreases in acne symptoms as well.42 Further, it is likely that many other oral contraceptives may be effective in the treatment of acne despite lack of clinical trial data.

Bone Mineral Density

One of every two women experiences an osteoporotic fracture during her lifetime. Bone mineral density in women peaks between the ages of 20–25 years, then stays constant for approximately 10 years, and then progressively decreases in the later reproductive years.22, 43, 44 Accelerated bone loss then occurs in the perimenopausal/menopausal years and during all hypoestrogenic states including premature ovarian failure, gonadal dysgenesis, hypothyroidism, hyperprolactinemia, anorexia nervosa, and exercise-induced amenorrhea. Nineteen studies have revealed a positive effect on bone mineral density and 13 indicated no effect on bone mineral density among oral contraceptive users.43 No studies have demonstrated a negative effect on bone mineral density. It appears that oral contraceptives are most effective at preventing bone loss during times of low estrogen and have a further protective effect with increased duration of use. Women who have used oral contraceptives for 5–10 years or longer are afforded the greatest protection. Most important, a population-based control study revealed a 25% reduction in hip fracture risk.45 Estrogens act on bone by increasing calcium absorption, decreasing calcium loss, and directly inhibiting bone reabsorption through inhibition of osteoclasts.

Potential Health Benefits: Colorectal Cancer and Rheumatoid Arthritis Protection

Colorectal cancer is the third commonest cancer in women, second only to lung and breast cancer. Five case-control46, 47, 48, 49, 50 and two cohort studies51, 52 have evaluated the relationship between oral contraceptives and colorectal cancer, with four of the studies showing either a protective effect of approximately 40% or a trend toward protection, and three showing no effect or a possible increased risk for rectal cancer but not colon cancer. Potential mechanisms of action leading to the protective effect include reduction of bile acid production and concentration, and effects on colonic mucosa or flora.53 A large metaanalysis of nine hospital and population-based studies suggested that oral contraceptives may prevent progression of rheumatoid arthritis to the more severe varieties.54 However, this protective effect was noted in the hospital-based studies, but not the population-based studies, which suggests the possibility of confounding or bias.



Cardiovascular Disease

The major cardiovascular risks identified in association with oral contraceptive use include venous thromboembolism, myocardial infarction, and stroke.55, 56 Use of most current oral contraceptives approximately triples a user's risk of venous thromboembolism, although some studies of formulations containing specific progestins suggest that the risk could increase as high as seven-fold.1, 57 However, it is important to recognize that even with the worst situations, the attributable risk annually is approximately 18 additional events per 100,000 users compared with nonusers. This risk is enhanced by risk factors such as recent leg trauma, pelvic surgery, stasis (but not varicose veins), and the presence of hemostatic changes such as factor V Leiden. Although the presence of this latter clotting abnormality markedly increases a user's risk, the absolute risk is still low such that routine screening for the disorder among all potential oral contraceptive users would not be cost-effective.58, 59 Obesity is also inconsistently cited as a risk factor; smoking, hypertension, and diabetes are not risk factors that increase the risk of venous thromboembolism among oral contraceptive users.

Myocardial infarction is a rare condition in the reproductive age group.57 This disorder occurs among oral contraceptive users only in the presence of risk factors such as hypertension, diabetes, severe dyslipidemia, and, in particular, cigarette smoking.1 In fact, it has been estimated that 80% of the cases of myocardial infarction among oral contraceptive users are directly attributable to cigarette smoking. Age older than 35 years and smoking also act synergistically to increase risk further such that it is not recommended that one prescribe oral contraceptive to women older than 35 who smoke. However, even with a 20–30-fold relative risk of myocardial infarction among smoking oral contraceptive users, this risk only equates to a maximum of 500–600 events per 1 million woman-years. However, unlike venous thromboembolism in which the case-fatality rate in this age group is lower than 1%, the case-fatality rate for myocardial infarction is approximately 50%.

Stroke is also a rare condition among women in the reproductive age group, with hemorrhagic stroke being somewhat more common than ischemic stroke.57 Among nonsmoking women, the rates range from 6–46 events per 1 million women-years; oral contraceptive use increases that risk only if risk factors are present.1 The major risk factors include age, cigarette smoking, migraine headaches (for ischemic but not hemorrhagic stroke), and especially hypertension. Overall, the relative risk varies between two-fold and 10-fold depending on the number of risk factors present.

Breast Cancer

For several decades, concern has been expressed regarding the possible association between oral contraceptive use and breast cancer. Unfortunately, many epidemiologic studies reported conflicting results with the discrepancies probably related to how well potential biases and confounding were addressed in the individual studies. This is particularly important because many calculated relative risks were small, such that an unrecognized significant bias could essentially weight a study toward a positive association or risk when in fact none existed. In addition, with the changes in dosages and hormones in the formulations against a backdrop of a cancer with a latency period of several years, it has often been difficult to interpret the results of individual studies in the context of current practice. In 1996, a collaborative project representing a meta-analysis of most of the better epidemiologic studies in the literature was published.60, 61 This project gives perhaps the most valuable and up-to-date data that we have on this issue. In total, 54 studies were included in the analysis representing 53,297 women with breast cancer and 100,239 control subjects. To be included, studies had to have had at least 100 women in the study with a diagnosis of breast cancer and the original data had to be available for reanalysis. In all, there were 11 cohort studies, 28 case-control studies with population-based controls, and 15 case-control studies with hospital-based control subjects. In addition, approximately one third of these cancers were diagnosed in women younger than age 45 years and approximately one-half after 1985. Thus, the data probably provide clinicians with the best information that can be applied to their current oral contraceptive users. For current users of oral contraceptives, the relative risk of breast cancer for them compared with those who had never used them was 1.24. This small increase in risk persisted for approximately 10 years after oral contraceptive use was discontinued, with the risk essentially disappearing after that time. In addition, there was no overall effect of oral contraceptive use by dosage, specific formulation, duration of use, age at first use, age at time of cancer diagnosis, or by family history of breast cancer. The comparison of ever-users of oral contraceptives with never-users revealed that the relative risk for tumors that had spread as opposed to localized disease was 0.88. Thus, although oral contraceptive users face a modest increase in risk for breast cancer, the disease tends to be localized. In addition, the pattern of disappearance of risk after 10 years coupled with the tendency toward localized disease suggests that the overall effect may represent detection bias or perhaps a promotional effect. For example, if oral contraceptive users undergo more frequent breast examinations because they are required to see a clinician to get their prescriptions refilled compared with users of other methods, the findings may be caused by, to a certain degree, users having a better chance of earlier detection of cancer. A promotional effect would occur if the hormones in oral contraceptives, especially estrogen, cause growth of cells that have already been transformed into a neoplasia. In such a situation, the cancer would be detected earlier than if such women were not exposed to agents that might promote neoplastic cell growth. More recently, a large population-based case-control study conducted in the United States analyzed risk of breast cancer among women aged 35–64 years.62 The results indicated that neither current nor past use of oral contraceptives increased the risk of breast cancer compared with population-based controls. Further, the results did not vary according to a number of potential risk factors such as estrogen dose, duration of use, family history of breast cancer, or time of initiation of use. Thus this recent study also indicates that breast cancer risk related to oral contraceptive use appears to be negligible for most women.



Oral contraceptive compliance has recently been examined in various patient populations. Some studies have focused on various patient characteristics and behaviors from the standpoint of likelihood of not using pills correctly and the effect of various side effects on overall continuation.63, 64, 65, 66, 67, 68, 69 In a study of 6676 European women aged 16–30 years using oral contraceptives, several factors were associated with poor compliance.69 For example, the risk of missing one or more pills in a cycle was highest among women who did not use their pills at the same time each day, who had read but understood little or nothing of the package insert information, or who had not received adequate information or help from their health care provider. Although the side effects of breast tenderness, nausea, and irregular bleeding were modestly associated with poor pill-taking compliance, abnormal hair growth was the side effect associated with the greatest risk for failure to take oral contraceptive pills properly. In one of the largest studies performed in the United States, 1657 oral contraceptive users nationwide were surveyed at two and six months after initiating or switching to the use of a new oral contraceptive preparation.65, 66 In the study, 56% of the women were enrolled through their private physicians, 42% from Planned Parenthood clinics, and 2% through a health maintenance organization, resulting in a sample with varied demographic characteristics. Although interpretation of the results is somewhat hampered by the low rate of return of the questionnaires, 65% at two months and 54% at six months, the results still provide some insight about issues that affect oral contraceptive compliance. Similar to the previously described European study, failure to take one's pill at the same time every day and not fully understanding the package insert information was associated with missing two or more pills per cycle. In particular, having a totally inconsistent pill-taking time and taking the pill right before bed was associated with the greatest risk of missing pills during a cycle. Spotting and heavy or prolonged menstrual periods were also associated with missing pills during a cycle. Overall in this study, 47% of oral contraceptive users reported missing one or more pills during a cycle and 22% missed two or more. Side effects were the most important reason women stopped taking oral contraceptives in this study. Thirty-seven percent of women stopped their preparation for this reason; this percentage increases to 46% when physicians' recommendation to discontinue, presumably for some side effect, is included in the total. Bleeding irregularity was the side effect most frequently cited as being associated with oral contraceptive discontinuation. Somewhat disconcerting was the finding that among study participants who elected to discontinue oral contraceptives but did not desire to become pregnant, 19% adopted no method and approximately 60% selected a less effective method (e.g. barrier method, spermicides, or withdrawal). Although the level of response to the study questionnaire needs to be taken into account, approximately 32% of women who were new start oral contraceptive users and approximately 17% of women switching to another oral contraceptive had discontinued by the end of the six month study. Further, among all women who elected to stop oral contraceptive use, 42% discontinued without first contacting their health care provider.

Patient recollection of missing oral contraceptive pills is also a problem. In a study of 103 students who kept a pill-taking diary and who also were provided with an electronic pill pack to record when pills were removed from the pack, the electronic pack recorded missed pills at rates two to three times higher than those study subjects recorded in their diaries.70 Obviously, such problems of recollection can contribute to reduced efficacy, because doubling-up strategies cannot be adopted if one does not remember that an oral contraceptive pill has been missed that day. Finally, older women compared with adolescents have lower rates of discontinuation and missed pills. The reasons that adolescents are less successful are complex. In a study that examined the beliefs that 345 adolescent women had regarding the possible sequelae associated with oral contraceptive use, beliefs that the pill would affect physical appearance or would have major or minor effects on health were related to a reduced likelihood that the women would use oral contraceptives consistently.71 In summary, recent oral contraceptive compliance studies continue to confirm previous studies that inconsistent pill-taking is prevalent and that side effects can affect both pill-taking and overall continuation. How material regarding efficacy, side effects, risks, and benefits is presented to patients appears to have some effect on compliance. However, several authors suggest that developing a better understanding of the health beliefs and preferences of patients and their decision-making processes may ultimately be more effective in designing strategies that improve compliance.64, 72, 73, 74

Table 2 outlines some methods that can be used to improve compliance. From the standpoint of systems improvements, methods that improve access to care are important. Such improvements could include varying times of office hours, making practice locations more convenient to patients (e.g. school-based clinics for adolescents and providing better coverage for contraceptives by health insurance companies). Educational materials also need to be examined to ensure that they are at an appropriate level for the patients being served. In addition, consideration should be given to customizing materials for patients based on age, sociodemographic background, and even health beliefs and perceptions. The patient's interaction with her health care providers is also critical to achieving compliance. Patients need to feel that providers will listen to them and actually care about their problems. Accordingly, the therapeutic relationship must be built on rapport, trust, and respect. Given that the patient's decision-making process is important relative to changing health behaviors, ascertaining her beliefs and perceptions about contraception, and her knowledge and past experience is a key task of the patient interaction. The interview process should use open-ended questions that allow women to express their views and concerns; this process also helps build rapport. One also uses reflective listening, which uses the interview to validate the patient's knowledge, concerns, and understanding of the issues through the interactive process. It is also critically important when educating patients that one tries to ascertain how a patient actually learns and remembers. For example, for a patient who is more visual, magnet reminders may be useful for encouraging regular oral contraceptive pill-taking. For the patient who is more verbal in her orientation, use of a diary or other written materials may be more useful. It also may be a useful approach to enlist patients in modifying some aspects of the interview process and to assist in designing more useful educational materials.


Table 2. Approaches to improve oral contraceptive compliance

Systems Issues
   Improve access to care
   Greater availability of multiple contraceptive methods
   Develop educational materials that are better designed for patients' educational levels
Patient Interaction
   Establish a therapeutic relationship built on rapport, trust, and respect
   Ascertain patient's:
      Health beliefs
Use structured encounters that include:
   Open-ended questions
   Reflective listening
Interact in the context of the patient's age and sociodemographic status
Understand how the patient learns and remembers, then use educational cues built on this information

(Modified from Burkman RT: Compliance and other issues in contraception. Intl J Fertil 44:234–240, 1999.)


Although many long-term medications, such as those taken for treatment of high blood pressure, are dispensed in three-month units, oral contraceptives are often dispensed one pill pack at a time. The history of this tradition is unclear, but it certainly compounds the issue of compliance. Most users start their 28-day cycle pack on a Sunday, which is when their physician's office is closed and thus unavailable to call in for a refill. To compensate for this, patients must be reminded of the method of action of the birth control pill and informed about routine prescription refills through the office. It is unfortunate that many women taking this well-studied and safe medication are required to make monthly visits to the pharmacy.


Oral contraceptives continue to be a highly safe and effective form of birth control and offer a multitude of noncontraceptive benefits. Patients presenting for initiation of oral contraceptives should undergo a thorough personal medical, social, and family history. Particular attention should be given to patients with histories of uncontrolled hypertension, migraines with neurologic components, or personal or family histories of thrombosis. A complete physical examination should be performed including the pelvic examination in women with gynecologic symptoms, those at risk for sexually transmitted diseases, and those due for their screening Pap smear. Patients who have never been sexually active who are requesting oral contraceptive pills for such indications as the treatment of acne or premenstrual syndrome may delay having their first pelvic examination for several visits. Never sexually active adolescents with pelvic symptoms such as dysmenorrhea or abnormal uterine bleeding should undergo a pelvic examination to assess for pathology during the initiation of oral contraceptives.

On initiating treatment with oral contraceptives, much of the visit should consist of counseling, including emphasizing the positive effects of oral contraceptives when they are used correctly and consistently. Missed pills and back-up methods of contraception and the prevention of sexually transmitted infections by barrier methods should also be discussed. Anticipatory guidance regarding side effects, especially the potential for irregular menstrual bleeding on beginning the pills, must be included. Patients should be encouraged to read provided written material and call with questions before discontinuing oral contraceptives on their own. If patients are scheduled and do not come in for a 15-minute follow-up visit after three months, they may have stopped the pill on their own and need a phone call for counseling regarding other methods of birth control. Healthy women using low-dose oral contraceptive formulations can have their blood pressure measured annually. Offices should adapt a patient-friendly and efficient system for refilling prescriptions for compliant patients

Abnormal Bleeding

Whether women start oral contraceptives for prevention of pregnancy or regulation of their menstrual cycles, a significant proportion has abnormal bleeding after initiation. Women with previously normal cycles may have immediate bleeding, midcycle spotting, or absence of menses. Women with a history of anovulation may have an immediate increase in irregular and heavy bleeding. More than 50% of women who discontinue oral contraceptives because of abnormal bleeding do so with the first two months.65 Abnormal bleeding patterns with oral contraceptives are strongly associated with poor compliance, although compliant patients also experience changes in bleeding patterns. Patients need to be counseled to expect some change in their bleeding and be reassured that it does not indicate a gynecologic cancer. Patients may stop pills in an attempt to not stimulate bleeding and therefore compound the irregular cycle and increase the likelihood of an unplanned pregnancy. As is always the difficulty in assessing vaginal bleeding, women's perceptions and tolerances vary widely, and again counseling must be individualized.

Patients must be instructed on the mechanism of action of pills that contain estrogen and progesterone. Progesterone alone is sufficient to prevent ovulation; however, the estrogen component helps to maintain cycle control. Lower doses of estrogen have been associated with an increase in breakthrough bleeding.75 Therefore, in patients with a particular concern about abnormal bleeding, a 30–35 μg ethinyl estradiol content may be indicated. No data indicate that reducing the ethinyl estradiol dose below 30–35 μg reduces the risk of stroke, or that the 20 μg pill is any safer in women who smoke. This benefit of potentially less bleeding with higher estrogen must be weighed with other potential side effects of a higher estrogen dose. One study has demonstrated that a flexible starting schedule for oral contraceptives reduced the incidence of breakthrough bleeding.76 Women who started the pill on the last day of menses, but no later than day five of their menstrual cycle, reported less breakthrough bleeding and better compliance than women who started the pill on day one of their cycle, without an effect of contraceptive efficacy. This method of initiation of oral contraceptives is made simpler with flexible pill dispenser packs and by not using the traditional Sunday start. Women who have a history of anovulation may benefit from a withdrawal bleed with progesterone before starting oral contraceptives. Persistent abnormal uterine bleeding on oral contraceptives should be investigated. The initial evaluation should include assessment for cervicitis or neoplasia. The evaluation may also include an endometrial biopsy, sonohysterography, diagnostic hysteroscopy, or dilation and curettage.


Gastrointestinal side effects are noted with oral contraceptives, hormone replacement therapy, and the increased hormone levels of early pregnancy. The etiologies are unclear but may be related to an estrogen effect on the central nervous system and a progestin effect on smooth muscle. Combination of these hormones leads to further symptoms. Up to half of women report a feeling of nausea on initiation of combined oral contraceptives, with many fewer experiencing vomiting. Incidence of these side effects has decreased with the decrease in the estrogen content of the pill less than 50 μg, but it is still frequently experienced. Anecdotal reports suggest a 50 mg daily dose of vitamin B6 may be effective for amelioration of symptoms. Other strategies include taking the pill with meals or at bedtime, decreasing the dose to 20 μg, or switching to a progesterone-only contraceptive. Reassuring the patient of the likely transient nature of the nausea is an important part of contraceptive counseling.

Premenstrual Symptoms

Premenstrual symptoms such as irritability, bloating, and breast tenderness are troublesome for many women. Anecdotally, some women report improvement with oral contraceptives while others indicate no improvement or worsening of their symptoms. Since spironolactone has been used to treat premenstrual symptoms, the new oral contraceptive containing drospirenone, an analogue of spironolactone, theoretically could be used successfully for these symptoms. Although uncontrolled trials have suggested some benefit,77, 78 longer studies, and a randomized placebo-controlled trial have only shown limited benefit.42, 79 Such results suggest there is a significant placebo response associated with treatments for this disorder.

Weight Gain

There is no evidence that combined oral contraceptives directly cause weight gain. Estrogens and progestins may act as appetite stimulants or have anabolic steroid effects. They can also cause water retention that can lead to a sensation of bloating. Although some women actually lose weight while using the pill, a significant number discontinue the pill for the simple fear of weight gain. The perceived alteration in body image appears to have a much stronger impact on pill-taking practices than the fear of an unintended pregnancy, whereas pregnancy is associated with a 25–35 pound weight gain. Patients should be counseled that the pills themselves contain no calories, and that they should maintain a healthy, well-balanced diet while using the pill.

Breast Tenderness

As experienced with hormone replacement therapy, estrogens are known to stimulate breast tissue and lead to increased growth and tenderness. This side effect seems to ameliorate with continued use as endogenous levels of estrogen and progesterone are suppressed. Lower levels of ethinyl estradiol, as in the 20 μg combination pills, could theoretically decrease this side effect. If patients are experiencing increased breast tenderness immediately before the pill-free interval, they may actually benefit with a higher-dose estrogen combination pill that more effectively inhibits ovulatory cycles. Patients should be reassured that the tenderness is not evidence of growth of a breast cancer, and that with time the overall incidence of benign breast disease will decrease.


Headache is a common symptom among reproductive-aged women. Unfortunately, there are few controlled data on the incidence of headache in oral contraceptive users or on the potential interaction with dose, formulation, or duration of use. One study indicated that the frequency of headache overall has not changed with the introduction of the new lower-dose formulations, suggesting that the occurrence of many headaches is independent of oral contraceptive use. However, migraine headaches have undergone significant study in relationship to oral contraceptive use.80 As noted previously, some data indicate that the presence of migraine headache among oral contraceptive users increases the risk of ischemic stroke by two fold to three fold compared with nonusers. However, the clinician still needs to keep in mind that the attributable risk still would equate only to 10–35 events per 1 million woman-years of use.1 However, if other risk factors such as smoking or high blood pressure are present, then the risk goes up in a multiplicative fashion.

From an overall management standpoint, careful history taking should allow one to differentiate between tension-like headache and migraine headache. If one suspects migraine headache, oral contraceptives should be used with care. Although there are no conclusive data on differences in stroke risk for migraine with or without aura, oral contraceptive use in the former circumstance should be considered only if other contraceptive methods cannot be used and only after detailed counseling. If migraine occurs without aura, and if other risk factors are not present, then most women can be administered a trial of oral contraceptives. Follow-up should be initiated within the first two to three months to assess frequency and severity of headaches. If there is a slight increase in frequency during the trial, a change in formulation might be considered. If headache occurs more frequently in the hormone-free interval, the physician might consider the use of daily continuous oral contraceptives without a hormone-free interval. However, if the headaches become significantly more severe or frequent, oral contraceptives should be discontinued and other contraceptive approaches used.

Diabetes Mellitus

Diabetes mellitus affects approximately 6% of the United States population with approximately 10% of cases being type 1 diabetes or insulin-dependent, with the remainder being noninsulin-dependent or type 2 diabetes. There are substantial pregnancy and gynecologic-related risks associated with this condition. Relative to oral contraceptives, no evidence confirms that they increase the risk of either type of diabetes.81 Although users of oral contraceptives may have slight increases in glucose or insulin values when glucose tolerance tests are performed, there is no evidence that among individuals with diabetes, the use of oral contraceptives leads to any deterioration of their condition.82, 83 Accordingly, women who have had previous gestational diabetes, or who have type 1 or type 2 diabetes without evidence of vascular complications, are candidates for this method of contraception. If such patients with diabetes have coexisting nephropathy, retinopathy, neuropathy, or vascular disease, contraceptive care needs to be individualized. If possible, consideration should be given to use of nonhormonal methods, although little evidence suggests that there is an increase in cardiovascular or cerebrovascular disease among oral contraceptive users with diabetes, particularly if the disease is well controlled.

Drug Interactions

As with use of any pharmaceutical preparation, drug interactions can occur. For example, use of other medications may lead to gastrointestinal side effects such as nausea or diarrhea, leading to problems with compliance. Anecdotal reports suggest that concomitant use of antibiotics may interfere with the absorption of steroid hormones, although there have been no studies that have clearly documented this.84, 85 However, some practitioners suggest women use back-up methods such as condoms when using short-term antibiotic regimens. Data suggest that some drugs may interfere with the P450 microsomal liver enzymes that metabolize contraceptive steroids leading to increased breakdown.84 In particular, anticonvulsants with the exception of valproate, ethosuximide, vigabatrin, and lamotrigine may have this effect.86, 87 It has been suggested that use of a 50 μg estrogen combined pill as opposed to low-dose preparations will overcome this effect.88 Rifampin, a drug used to treat tuberculosis, and griseofulvin, an antifungal, also have enzyme-inducing effects to the extent that it has been suggested that nonhormonal alternatives be used instead of oral contraceptives.89 Oral contraceptives may also increase the clearance of benzodiazepines and aspirin while decreasing the clearance of corticosteroids, theophylline-like drugs, and caffeine.84, 86, 90 Accordingly, dosages may need to be adjusted on occasion to account for these effects.

Perimenopausal Use

Although approximately one half of pregnancies occurring among perimenopausal women are unintended, oral contraceptives are underused, with only 4% of women between the ages of 45 and 50 years using this method.2, 3, 91 Fear of serious immediate health risks such as cancer, myocardial infarction, stroke, and venous thromboembolism contributes, as does fear of potential sequelae with long-term use. There are a number of specific advantages associated with oral contraceptive use for women in this age group, in addition to contraception. A placebo-controlled trial evaluating oral contraceptive use as treatment for dysfunctional uterine bleeding demonstrated improvement for each subtype of bleeding as well as improvement in overall physical functioning.27 A study evaluating hip fracture risk for women older than age 40 years demonstrated a relative risk of 0.7, 95% confidence limits 0.5–0.9, for oral contraceptive users versus never-users.45 Finally, another randomized, double-blind, placebo-controlled trial has demonstrated that oral contraceptive users in this age group have reduced numbers and severity of hot flashes.92 Although most women in this age group are potential candidates for oral contraceptive use, cigarette smokers, women with uncontrolled hypertension, and women with diabetes with vascular manifestations are not. Use probably can be continued until women are in their mid 50s to ensure continued contraceptive protection. Although levels of follicle-stimulating hormone (FSH) were previously used to estimate when women were menopausal and thus candidates for conversion to hormone-replacement therapy, more recent data suggest that FSH levels in this situation may not be reliable.93



Progestin-only oral contraceptives are primarily used for women who are lactating to avoid the effects of estrogen on the lactation mechanism. Although few studies suggest that combined oral contraceptives lead to reduced weight gain of infants, there are studies indicating that lactating women using combined oral contraceptives may have less milk volume and may elect to discontinue breastfeeding earlier than other women.94 In general, progestin-only tablets are started at the six-week postpartum visit if the breastfeeding pattern is well-established because lactational amenorrhea alone is effective as a contraceptive during the first few weeks postpartum. At the time that the decision to wean is made or when additional foods are added to the infant's diet, the patient can then switch to combination oral contraceptives. In addition, progestin-only oral contraceptives are occasionally used when estrogen use is contraindicated, such as in patients with a past history of venous thromboembolism. Currently, the medication is available as either 0.35-mg norethindrone tablets or 0.75-mg norgestrel tablets. The major concerns with this type of formulation is a higher overall failure rate of approximately three pregnancies per 100 woman-years because of reduced effectiveness in preventing ovulation and an increased incidence of erratic bleeding.


Current oral contraceptive combinations have excellent cycle control and minimal estrogenic and androgenic side effects. This successful combination continues to improve with the latest combined formulations. While 30 μg and 35 μg ethinyl estradiol formulations have improved cycle control and 20 μg formulations have less estrogenic side effects, the newest 25 μg ethinyl estradiol and triphasic norgestimate and desogestrel combinations appear to address both of these issues. One large comparative trial indicated that the norgestimate-containing formulation is equivalent in efficacy to the comparative oral contraceptives, is well-tolerated, has less nuisance bleeding, and has an excellent safety profile.95 A triphasic desogestrel combined with 25 μg ethinyl estradiol formulation compared with a 35 μg triphasic norethindrone formulation also demonstrated equivalent contraceptive efficacy but less breakthrough bleeding and amenorrhea.96

Another oral contraceptive introduced in the 1990s contains 30 μg of ethinyl estradiol and 3 μg of drospirenone.97 Drospirenone, unlike progestins in most oral contraceptives, is not a 19-nortestosterone derivative but rather is an analogue of the weak diuretic spironolactone. It has properties quite similar to progesterone including antiandrogenic and antimineralocorticoid activity. Overall, it appears to have efficacy and a side effect profile similar to other oral contraceptives.79 Because of its recent introduction and unique progestin, it is not yet known whether over time there will be any significant differences with this preparation relative to noncontraceptive benefits or serious sequelae compared with other oral contraceptives.



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