Who can take the OC?

In women with certain medical conditions or risk factors, oral contraceptive (OC) use may be associated with an increased risk of complications. The World Health Organization (WHO) recently updated their list of contraindications for contraceptive use.¹ Absolute contraindications (WHO Category 4) are conditions that represent an unacceptable health risk if the contraceptive method is used. With relative contraindications (WHO Category 3), the theoretical or proven risks usually outweigh the advantages.¹ See Table 1 for a list of absolute contraindications. Age itself is not a contraindication to the OC. Experts agree that healthy, non-smoking women may continue to take the OC until menopause.

Is menstrual suppression with the pill safe?

Traditionally, women taking the pill have had a monthly withdrawal bleed by taking active pills for 21 days and then having a 7-day hormone-free interval (a 21/7 regimen). But there’s no evidence that a monthly withdrawal bleed is medically necessary, and women are increasingly choosing to extend use of their active hormonal pills in order to delay or prevent menstruation. Extended or continuous OC use has been used to successfully treat many medical conditions, including dysmenorrhea, menorrhagia, endometriosis, hormone withdrawal symptoms, premenstrual dysphoric disorder (PMDD), and perimenopausal symptoms. The current SOGC guidelines on continuous/extended hormonal contraception use state that in the absence of contraindications, continuous or extended OC regimens may be considered for any woman who for medical reasons, contraceptive purposes, or personal preference may benefit from this regimen.²

Disadvantages of extended use include a slightly higher cost for medication, possible delay in the recognition of pregnancy, and little information on long-term safety (although there are long-term data for comparable total estrogen-progestin doses per month). While the short-term safety of extended regimens is similar to that of cyclic regimens, we don’t have direct evidence of long-term safety of extended regimens. However, we do have extensive reassuring evidence on the long-term safety of OCs over the past 50 years. If there is a greater risk associated with long-term use of extended regimens compared to long-term use of cyclic regimens, it’s likely to be minimal.²

Although any OC can be used in a continuous or extended fashion to suppress menstruation, there is only one pill in Canada that has the official indication for extended use. This OC uses a 91-day regimen (84 days of active pills containing 30-mcg EE/0.15-mg levonorgestrel and a 7-day HFI). A 1-year continuous OC regimen containing 20 mcg EE/0.09 mg levonorgestrel has been submitted to Health Canada for approval.

What’s the risk of venous thromboembolism (VTE) among OC users? Should women be screened prior to starting the OC?

The risk of VTE in healthy non-pregnant women is low but the incidence increases with age, from 3/100,000 per year at age 20-24 to 6/100,000 per year at age 40-44. The risk of VTE in OC users is increased 3- to 4-fold, which translates into an absolute risk of 10 to 25/100,000 per year. Therefore, VTE associated with OC use is still a rare event and the risk is lower than that of VTE in pregnancy (60/100,000 per year). The risk is much higher during the first year of OC use than subsequently.^3,4 The case fatality rate of VTE is 1-2%.

The available evidence doesn’t suggest a further decrease in VTE risk with further reductions in EE below 50 mcg. There is some controversy, however, over the effect of progestin type on VTE risk. Initial evidence suggested an increased risk of VTE in users of OCs containing 3^rd generation progestins (norgestimate, desogestrel, gestodene) and cyproterone acetate. A 2001 meta-analysis suggested there would be 15 extra cases of VTE per 100,000 women per year with the use of 3^rd generation OCs compared to 2^nd generation OCs. More recent evidence, though, suggests a comparable risk of VTE in all OCs, including those containing 3^rd generation progestins, cyproterone acetate, and drosperinone.^4,5

The risk of VTE associated with thrombophilias is further increased with OC use. The effect is greater with severe thrombophilias (deficiencies of antithrombin III, protein C, protein S, and homozygous thrombophilias) than with milder thrombophilias (heterozygous forms). The most common is the Factor V Leiden (FVL) mutation, which has a prevalence of 5% in Caucasians. Heterozygous FVL increases the risk of VTE 5- to 7-fold and heterozygous prothrombin gene mutation by 2- to 3-fold. Compared with women who aren’t OC users and don’t have the FVL mutation, the risk of VTE among OC users with the FVL mutation is between 10 and 35 times higher. This translates to an absolute risk of up to 285 events/100,000 women/year. The WHO recommends that OCs should not be used by women with a thrombophilia.¹

Even with the increased risk of VTE seen with thrombophilias, the majority of carriers that use the OC will never develop a clinical VTE. At this time, screening for inherited thrombophilias before starting OCs is recommended only in women with a personal or significant family history of VTE. More than 20,000 women would need to be screened to prevent one episode of VTE and more than two million women would need to be screened to prevent one death from pulmonary embolism.³

Women having elective surgery may be at increased risk of VTE, particularly with surgeries for malignancy or those followed by prolonged periods of immobilization. The decision to stop the OC prior to elective surgery is controversial and must take into account the risk of unintended pregnancy. Given that the procoagulant effects of the OC take four weeks to return to baseline, if the OC is to be stopped it should be discontinued at least 4 weeks prior to surgery. OC users who have major surgery associated with an increased risk of VTE should receive perioperative anti-thrombotic prophylaxis.³

Should women with a history of migraine headaches use OCs? What about smokers?

Some studies have demonstrated an up to 6-fold increased risk of ischemic stroke in women who have migraine headaches with aura (reversible visual symptoms including flickering zigzag lines and scintillating scotomata) compared to women without migraines. The risk of stroke may be further increased by the presence of other risk factors such as hypertension, smoking and OC use. Some studies have found that migraineurs who use the OC have a 2-4 fold greater risk of stroke than migraineurs who don’t use the pill. While some studies suggest that the risk of stroke associated with OCs is no different in women with simple migraine vs classic migraine, others have found a significantly higher risk of stroke in OC users with classic migraines. At this time, OCs shouldn’t be used by women who have migraine headaches associated with visual aura or focal neurological deficits, nor should they be used by migraine sufferers without aura aged 35 and over because they may be at significantly increased risk of ischemic stroke.¹

Age and smoking are the major risk factors for myocardial infarction (MI) in women who may consider the OC. Although not all studies agree, the use of low-dose OCs may be associated with a very small increase in the absolute risk of MI (0.4 events/100,000 women age 30-34/year). Smoking increases the risk of MI in pill users, an effect that is more noticeable over age 35. The absolute risk of cardiovascular death in smokers who use the OC is 3.3/100,000 women between ages 15-34 but increases sharply to 29.4/100,000 women between ages 35 and 44. Thus, OCs are not recommended for women over age 35 who smoke.¹

Is the Pill associated with an increased risk of cancer?

Because the OC has a dominant progestational effect on the endometrium, the risk of endometrial cancer in Pill users is almost 50% lower than in women who never used the OC. This beneficial effect grows with increasing duration of OC use and persists long after the OC is stopped. Similarly, the risk of ovarian cancer decreases with increasing duration of use and the effect persists long after OC discontinuation. Risk of ovarian cancer is decreased by up to 50% after five years of use and by as much as 80% after 10 years of use. The protective effects are seen with as little as 3 to 6 months of use and continue for up to 20 years after discontinuation. The protective effect is also seen in women at risk of hereditary ovarian cancer (the BRCA gene mutations, which increase risk of ovarian as well as breast cancer). There’s growing evidence that OCs may protect against colorectal cancer, too, with a 54% decreased risk of colorectal cancer seen in women who had used OCs in the past 10 years.

A 2002 meta-analysis found that longer durations of OC use potentially increase the risk of cervical dysplasia and cervical cancer. This is most likely because the OC acts as a cofactor for human papillomavirus (HPV) rather than due to a direct effect of the OC itself. Women who use the OC may also be less likely to use condoms. More recently,
a large American randomized controlled trial concluded that OCs had little or no impact on having an oncogenic HPV infection.⁶

Breast cancer is very rare in young women (42 cases/100,000 women/year); however, the possible effect of OCs on breast cancer is the focus of much debate. A 1996 meta-analysis suggested that there was a small but significant increase in risk of breast cancer in women who were current OC users (RR 1.24), and in the first 10 years after discontinuing it. By age 50, there was no difference in risk of breast cancer between ever-users of OCs and controls. A 2002 case-control study found no significant association between current or past OC use and breast cancer. The risk didn’t increase with longer periods of OC use. A 2006 meta-analysis estimated a small increased risk of premenopausal breast cancer in former OC users (OR 1.19) but couldn’t account for duration of OC use. A more recent study found that short-term OC use was not associated with breast cancer risk (OR 1.0). Overall, if there is an increased risk of premenopausal breast cancer in OC users, the absolute risk is likely to be very small. Other lifestyle variables such as excessive alcohol ingestion, obesity, delayed first full-term pregnancy, and reduced breastfeeding may in fact be associated with a greater increase in breast cancer risk than OC use itself.⁷

The OC pill already has a strong record of safety and tolerability, and newer formulations have sought to maintain contraceptive efficacy while further decreasing unwanted side effects and risks, and improving its non-contraceptive benefits. The pill continues to evolve as researchers look at different synthetic hormonal components and doses, new dosing regimens, and ways to improve contraceptive adherence.