The combined oral contraceptive pill has been used by an estimated 300 million women worldwide since it was first developed. In recent years it has been linked with both an increased risk of some forms of cancer and as having a protective effect against other cancers – leading to considerable confusion for women. In order to provide much-needed clarity, Dr Richard Russell and Mr Charles Kingsland provide an overview of the risks and benefits of the combined oral contraceptive pill.

Key Points

1.   Oral contraceptive use is a highly effective form of contraception.
2.   The use of the combined oral contraceptive (COC) pill is associated with a significant reduction in the incidence of ovarian and endometrial cancer.
3.   The risk of breast cancer increases with the length of use of the COC pill.
4.   Venous thromboembolism increases in COC pill users and is influenced by the generation of pill and the constituent progesterone component.
5.   While evidence exists for an increased risk of thrombotic cerebrovascular disease, the cardiovascular risk is less clear.
6.   Gallstones occur more frequently in oral contraceptive pill users.

Declaration of interests: No conflict of interests declared.
The combined oral contraceptive (COC) pill is often credited with kick-starting the sexual revolution of the 1960s. Initially developed in the US and trialled in South America, the oral contraceptive pill remains an extremely effective reversible method of contraception, with a failure rate of 0.1–3/100 woman years (pearl index of 0.16).

The pearl index is a standardised measure of contraceptive effectiveness, calculated using the number of unintentional pregnancies in 100 woman years of use (for example, 100 women using contraception for one year, or ten women for ten years). A lower pearl index represents a lower chance of unintentional pregnancy.

Having been used by an estimated 300 million women worldwide and currently being used by 100 million women, the COC pill’s impact on public health, healthcare provision and healthcare cost is substantial. Although formulations and dosages have been modified over time, concerns for safety persist. Divergent perspectives have ranged from conferring a clean bill of health to proclaiming the pill the greatest iatrogenic risk to female health.

The contraceptive properties of the pill are irrefutable, and its use in the successful management of menstrual disorders and benign gynaecological conditions are far beyond the scope of this review article. Instead, we focus on the risks and benefits that have a significant impact on patient morbidity and mortality, as well as healthcare costs.

Benefits of combined oral contraception

Ovarian cancer
The association between the protective effect of the COC pill and ovarian cancer has long been established. A recent large study suggested that in high-income countries, ten years’ use of the COC pill is estimated to reduce the incidence of ovarian cancer (p <0.0001) before age 75 from 1.2 to 0.8 per 100 users, with a reduction in mortality from 0.7 to 0.5 per 100 users. That is to say for every 5,000 woman years of use, about two ovarian cancers and one death from the disease are prevented.

The protective effect of the pill becomes apparent after a short latency period and increases with duration of use, with each year of use conferring an estimated 5% reduction in risk. Women who take the COC pill for less than a year also have a reduced ovarian cancer risk (odds ratio, OR=0.45) compared with non-users. In women who use it for longer, a persistent associated risk reduction of more than three decades following cessation of use is observed, although this effect seems to reduce over time since the last use.

The proportional risk reduction for ovarian epithelial cancers with COC pill use is 29% for individuals who stopped using the pill less than ten years ago; 19% for those who stopped between 10 and 19 years previously, and 15% for those who stopped 20 to 29 years previously. Time since first and last use modifies the association between COC pill use and ovarian cancers independently of the duration of use, with histological type being unaffected with the exception of mucinous tumours.

A recent report suggested that oral contraceptive use has already prevented 200,000 ovarian cancers and 100,000 deaths from the disease. Over the next few decades, the number of cancers prevented is expected to rise to at least 30,000 per year.

Endometrial cancer
Several epidemiological studies have observed a protective effect from endometrial cancer conferred by use of the oral contraceptive pill, with benefit persisting for more than 25 years. The majority of current COC preparations are potent enough to have a beneficial influence, but it has been found that women with a lower Body Mass Index (BMI) (<22.1kg/m²) receive a greater protective effect than those with a higher BMI on formulations containing a low dose of progesterone.

Colorectal cancer
Following the publication of several studies regarding hormone replacement therapy, considerable interest has evolved regarding the role of exogenous hormones and bowel carcinogenesis. The use of the COC pill has been associated with a modest risk reduction of developing colorectal cancer (relative risk, RR=0.72), with a consistent effect on all tumour subsites within the rectum. However, no apparent correlation between duration of use and benefit has been observed. The current evidence suggests some support for a potential role of COC pills in reducing the risk of colorectal cancer.

Morbidity and mortality
We are often complacent when observing trends in mortality and morbidity figures related to pregnancy in the developed world. Pregnancy, particularly when repeated and complicated, presents a significant risk to female health. Although good healthcare provision contains this risk to some degree, many developing countries are unable to provide the required standard of care. Every year, eight million women will come to harm as a result of pregnancy-related complications, and more than half a million of these women will die as a result. By contrast, the 2000–2002 Confidential Enquiry into Maternal and Child Health found a total of 261 deaths in the UK related either directly or indirectly to pregnancy. In sub-Saharan Africa, a woman’s lifetime risk of dying related to pregnancy is one in 16, in comparison to one in 2,800 in the developed world.

Unsafe and often illegal abortions continue to be a leading cause of morbidity and mortality in developing countries, while many obstetric complications occur in pregnancies that are neither planned nor wanted. The introduction of the oral contraceptive pill has had a considerable positive effect on female health in the developed world: it is hard to imagine that it would not have a significant and dramatic effect were it more available in the developing world.