Oral Contraceptives: What you need to know about the latest formulations

Key Points

A 27-year-old woman, MB, comes to your clinic to discuss starting to use birth control pills. She reports heavy periods and mild acne, but is otherwise healthy. She has seen ads in magazines for a new brand of pill and asks you how this new pill differs from older formulations. She asks whether there are benefits that might warrant a higher copay at the pharmacy and what risks are associated with the new pill. Are you prepared to answer her questions?

An estimated 12 million women in the United States use the oral contraceptive (OC) pill, making it the most popular reversible method of birth control.¹ Many new hormonal delivery systems offer benefits superior to those of the pill. The vaginal ring, injection, and patch allow less-frequent dosing, which may improve compliance. The intrauterine device and implant are significantly more effective than the pill, with failure rates rivaling those of sterilization.² Nevertheless, the pill remains the method of choice for the majority of women, and pharmaceutical companies are therefore eager to develop new formulations. Since the pill was first introduced more than 50 years ago, many of these new formulations have been little more than updated packaging. However, several new brands have emerged recently that are advertised as having noncontraceptive benefits beyond those of older pill formulations, as well as improved bleeding and side-effect profiles.

Many gynecologists hesitate to prescribe newer OC formulations because they want to ensure that their patients have the pill with the most extensive efficacy and safety data, or one with an inexpensive generic version. Cost is certainly an important consideration. Although few studies have directly compared different brands, some evidence suggests that certain newer formulations may offer advantages to patients in terms of efficacy, cycle control, treatment of heavy bleeding, and other undesired menstrual symptoms, and potentially even a decreased risk of metabolic effects. On the other hand, evidence suggests that certain formulations may be riskier than others.

Shortening or eliminating the hormone-free interval

Extended dosing refers to a 28-day cycle with a shortened hormone-free interval, generally between 2 and 4 days. Extended cycle refers to a schedule with a delayed hormone-free interval, such as regimens with 84 active pills and 7 placebo pills. Continuous dosing refers to regimens without a hormone-free interval.

It is well known that extended and continuous OC regimens are associated with shorter and lighter periods.^3,4 The total number of bleeding days is decreased; however, an increase in unscheduled bleeding episodes also is seen. Fortunately, this appears to improve over time.⁵ In addition, these nontraditional regimens offer clear benefits for women with menstrual symptoms such as bloating, dysmenorrhea, and headaches.^6,7 It makes sense that eliminating or minimizing the hormone-free interval helps alleviate these common complaints. Most important, such regimens do not appear to have greater metabolic effects than standard 21/7 formulations.⁸

For many years, researchers hypothesized that a shorter hormone-free interval would lead to higher efficacy in terms of pregnancy prevention. A study showed that the follicle-stimulating hormone concentration rose and follicles developed after 4 hormone-free days, suggesting that ovulation may occur with a longer hormone-free interval, particularly if there is a delay in starting a new pack of pills.⁹ A recent large cohort study confirmed the greater efficacy of extended-cycle regimens.¹⁰ This important new study determined contraceptive failure rates associated with OCs containing ethinyl estradiol and various progestins. Comparison of those containing ethinyl estradiol and either drospirenone or norethisterone in 21-day regimens versus 24-day regimens showed that the extended regimens had lower failure rates.

Pharmaceutical companies are paying attention to these data, and the newest pill formulations have decreased the hormone-free interval to 2 or 4 days or eliminated it altogether. Some brands have replaced the placebo pills with estrogen-only pills. Direct comparisons to other formulations are lacking, but these regimens aim to offer the benefits of an extended cycle or continuous pill while potentially improving efficacy and minimizing unscheduled bleeding episodes.¹¹ Only one formulation (20 mcg ethinyl estradiol/90 mcg levonorgestrel) approved by the US Food and Drug Administration (FDA) is packaged and labeled for continuous dosing. No studies have compared this product to the off-label continuous use of generic 20 mcg ethinyl estradiol/100 mcg levonorgestrel products.

Discarding the placebo pills of any 21/7 OC is another way for patients to achieve extended or continuous dosing. However, comparative studies of this off-label use are lacking, and this strategy often requires patients to make more frequent visits to the pharmacy.