Weighing the risks and benefits of contemporary hormonal contraception

The contraceptive pill, a convenient and effective method for women to control their fertility, has been trumpeted as a major development of the modern world. Nearly 800 million married or in-union women of reproductive age are expected to be using contraception by 2030 worldwide^[1]
. In Great Britain, 76% of women aged 16–49 years have used at least one form of contraception^[2]
.

Oestrogen (E) and progestin (P) combinations constitute contemporary hormonal contraception (CHC), taken with 21- and 28-day regimens. The use of E alone results in breakthrough bleeding. A combination of the appropriate type and dose of E and P has been adopted. Thromboembolic complications are one serious side effect to CHC.

The largest study to date exploring the correlation between CHC use and risk of breast cancer in women aged 15–49 years enrolled 1.8 million Danish women who were recently or currently using CHC. They were followed for up to an average of 11 years^[3]
. The study concluded:

• All forms of CHC lead to a 20% higher risk of breast cancer;
• The longer the CHC use, the higher the risk of breast cancer;
• The risk of breast cancer remains for around five years after the cessation of CHC use;
• The association of CHC and breast cancer was significant after accounting for confounding factors (such as age at first birth, among others that can influence risk of breast cancer);
• The association of CHC and breast cancer was particularly prominent in women who were aged under 35 years and nulliparous (had never given birth).

Women using CHC with P (gestodene, which is used in Denmark but not in the United States), showed a notable trend of ‘the longer the use, the higher the risk of breast cancer’. In 1992, Jeng et al. demonstrated that 19-nortestosterone derivatives, such as levonorgestrel (a type of P), are oestrogenic (they act through the oestrogen receptor [ER]) and facilitate human breast cancer cell growth^[4]
. In 1993, Catherino and et al. demonstrated that levonorgestrel and gestodene facilitate human breast cancer cell growth through the ER^[5]
. The newer P, gestodene, was reported to carry twice the risk of blood clots compared with the older P levonorgestrel^[6]
. However, the World Health Organization and the International Planned Parenthood Federation declared that the incidence of blood clots is very low in women of reproductive age across the world^[6]
,[7]
.

In perspective, the absolute increase in risk of breast cancer for women using CHC is small. This is because the risk of breast cancer increases rapidly with age, and this study looked at a young patient population. Furthermore, CHC is effective in preventing pregnancy, managing dysmenorrhea, menorrhagia, hirsutism and acne vulgaris, and substantially reducing ovarian, endometrial, and colorectal cancers after 10–15 years of use, with a small reduction in overall risk of cancer.

Women can defer to other birth-control methods such as condoms, and older women or those at risk of thromboembolic complications can substitute oral contraceptives or the levonorgestrel-releasing intrauterine device with non-hormonal, reversible, and long-acting contraception.

This study is a reminder that we need to optimise CHC, but the overall reduction of cancer risk remains in favour of CHC.

Balkees Abderrahman,

Postdoctoral fellow, University of Texas MD Anderson Cancer Center