Safety concerns and health benefits associated with oral contraception☆

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Abstract

Since the introduction of hormonal contraceptives in the 1960s, there have been a variety of both health benefits and safety concerns attributed to their use. In most instances, the noncontraceptive benefits of oral contraceptives (OCs) outweigh the potential cardiovascular risks. In fact, the probability of a patient experiencing a cardiovascular event while taking a low-dose OC is very low. However, smoking, hypertension, obesity, and diabetes are risk factors that must be taken into account when prescribing OCs. The neoplastic effects of hormonal contraceptives have been extensively studied, and recent meta-analyses indicate that there is a reduction in the risk of endometrial and ovarian cancer, a possible small increase in the risk for breast and cervical cancer, and an increased risk of liver cancer. Finally, many women will experience noncontraceptive health benefits with OCs that expand far beyond pregnancy prevention. Some of these benefits include reduction in menstrual-related symptoms, fewer ectopic pregnancies, a possible increase in bone density, and possible protection against pelvic inflammatory disease.

Section snippets

Cardiovascular effects of oral contraceptives

As recently as 20 years ago, the cardiovascular effects of hormonal contraceptives—and OCs in particular—were the subject of widespread scrutiny. In recent years, the public health impact of these safety-related issues has diminished considerably, as the focus has shifted to helping women successfully use the many different types of OCs as well as the newer methods of hormonal contraception that are now available.

It is also useful to differentiate the cardiovascular events associated with the

OCs and the risk of VTE

There has been a steady decline in the estrogen content of combination OCs since early reports appearing in the mid to late 1960s described a several-fold times higher risk of thromboembolic events among OC users than among nonusers, a finding that was subsequently found to be dose-related. On the basis of pharmacy data collected from 1960 to 1986 in Michigan, it has now been shown that there was a 10-fold increase in the rate of VTE among women using OC formulations containing more than 50 μg

OCs and the risk of MI

As is the case with VTE, the incidence of MI in women is age-related, rarely occurring in nonsmoking, nondiabetic women under the age of 35 and increasing to only about 2 events per 100,000 woman-years in women between the ages of 40 and 44 years.3 Deaths caused by MI among nonsmoking women are even more rare.3 Although current or prior OC use is not associated with an increased risk of MI in nonsmokers, several observational studies have shown that by far the most important independent risk

OCs and the risk of stroke

Although the incidence of ischemic or hemorrhagic stroke in young (ie, aged <45 years), nonsmoking women is almost as high as that of VTE, stroke is still a very rare event in this population and follows a similar, age-related pattern.3 In common with MI, stroke is rarely a cause of death in young, nonsmoking women, but the mortality rate in women who experience a stroke can be as high as 20% to 30%. Also in common with MI, there are several prominent risk factors for ischemic stroke, including

Summary of cardiovascular effects

Although there are cardiovascular effects associated with OCs, fortunately most patients will experience the benefits as opposed to the adverse events that come with their use. The introduction of low-dose OCs has made this possible, along with the reduction of modifiable risk factors such as smoking and obesity. The reduction of the estrogen component in OCs has also played a viable role in the incidence of VTE. The risk of MI and stroke in OC users is rare with those formulations that contain

Neoplastic effects of hormonal contraceptives

Use of combined OCs is associated with a reduced risk of cancer of the ovary and endometrium, and an increased risk of cancer of the liver and uterine cervix.36., 37. In all 4 instances, the estimated effect is related to length of use. Plausible biologic mechanisms exist for the OC-associated reductions in risk of ovarian and endometrial cancer, which are thought to result from cause-effect.36 Although bias and confounding have not been ruled out as explanations for the OC association with

Summary of neoplastic effects

In summary, the results of this analysis suggest that the effect of oral contraception in US women is to slightly reduce their risk of invasive cancer by age 60. This is inclusive of both white and black women between the ages of 20 to 59 in the United States. Obviously, the public health impact varies by site of invasive cancer. Therefore, with regard to specific organ sites, there is likely to be a reduced risk of endometrial and ovarian cancer with the use of low-dose OCs. Second, there is a

Established and emerging noncontraceptive health benefits

Combination oral contraceptives (COCs) bestow many benefits on users related to their contraceptive effects, including reduced risk of unintended pregnancy, less demand for abortion, decreased need for surgical sterilization, reduced maternal mortality, and less risk of other maternal or child complications. However, a growing number of noncontraceptive health benefits of COCs have become clear, including several only recently recognized (Table VI). The well-established noncontraceptive health

Dysmenorrhea

Primary dysmenorrhea is a significant issue for many young women during the menses. The pain of dysmenorrhea has been linked to prostaglandin release in the uterus, which is associated with increased uterine activity and responsivity to vasopressin and leukotrienes.56 Several studies have documented that COCs reduce menstrual prostaglandin release and thereby decrease uterine contractility to alleviate dysmenorrhea.56., 57., 58. Dysmenorrhea is one of the few disorders in which the data include

Benefits related to inhibition of ovulation

The frequency of ovarian cysts may be dependent on the hormone dose in OC pills. Because COCs inhibit ovulation and protect against pregnancy, they also protect against ectopic pregnancy. Both of these established benefits of COC use are reviewed here.

Other known protective effects of COCs

Among the other recognized noncontraceptive benefits of COC use are reductions in ovarian and endometrial cancers, pelvic inflammatory disease, benign breast disease (BBD), and benign breast conditions.

Emerging benefits associated with OC use

There is a growing number of emerging noncontraceptive health benefits associated with COCs. These effects include everything from protection from the infrequent but serious diseases (colorectal cancer) to the commonplace conditions (acne and perimenopausal symptoms) and carry important public health implications.

Noncontraceptive benefits of additional methods of hormonal contraception

Some noncontraceptive benefits of recently introduced methods of hormonal contraception have been reported, but few well-planned, placebo-controlled trials have been conducted to confirm positive health effects. These newer methods include progestin-releasing IUDs, progestin implants, monthly combined (estrogen + progestin) injectables, a combination transdermal method, and a combination vaginal ring; in addition, an OC with a new progestin (drospirenone) has been introduced that has been

Summary of noncontraceptive health benefits

OCs are now entering their fifth decade of clinical use, in a landscape that has changed enormously in a relatively short period. Dosages of both progestins and estrogens have decreased, side effects minimized, and new hormonal delivery systems developed. The aforementioned methods are extremely safe and effective forms of birth control.

In this short time it has also become clear that there are a variety of noncontraceptive benefits associated with these drugs. A number of these effects are so

Comment

The low-dose hormonal contraceptive formulations available today afford women not only highly effective contraceptive protection, but also protection against many forms of cancers as well as numerous noncontraceptive health benefits. Cardiovascular effects associated with the original high-dose formulations have been significantly minimized by reductions in the hormonal content; in addition, potential hormonal contraceptive candidates can be screened to exclude those women at demonstrated

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