Study: Birth control pills may offer long-term protection against endometrial and ovarian cancer

IN-DEPTH REVIEW OF RESEARCH

Study background

Research has suggested that oral contraceptives alter the risks of breast, endometrial and ovarian cancer.

Research results regarding breast cancer have been conflicting. One study showed that oral contraceptives slightly increased the risk for breast cancer in women who used the medicines within 10 years before the study. Other studies have shown no increase in the lifetime risk for breast cancer among women who have used oral contraceptives, even in women who have a family history of breast cancer or who began using the medicines at a young age.

Research showing that oral contraceptive use impacts endometrial and ovarian cancer has been more consistent, indicating that birth control pills lower a woman’s risk for these cancers.

However, it is unknown how varying durations of oral contraceptive use impact such cancer risks and how cancer risk is affected when women stop using these medications. It is also unclear whether these results apply to people from different racial or ethnic groups.

Researchers of this study wanted to know

The researchers wanted to know:

• how the duration of oral contraceptive use impacts a woman’s risk of ovarian, endometrial and breast cancer, and
• how long oral contraceptives impact the risk of endometrial, ovarian and breast cancer after a woman stops using them.

Populations in this study

Researchers examined the health data of more than 256,661 women in the United Kingdom who were born between 1939 and 1970. Data was collected between 2006 and 2010 when the participating women were ages 36 to 71. The data included extensive information on the participants’ medical histories, including the use and duration of oral contraceptives and any diagnosis or death that was related to endometrial, ovarian or breast cancer. However, this study lacked information on racial and ethnic diversity.

Study design

Researchers assessed the chance of an endometrial, ovarian, or breast cancer diagnosis by comparing women who had ever used oral contraceptives to those who had never used oral contraceptives. They also looked at the varying duration of oral contraceptive use during the following intervals:

• <2 years
• >2 to <5 years
• >5 to <10 years
• >10 to <15 years
• >15 to <20 years
• >20 years

Finally, the researchers observed the risk of cancer after discontinuation among women who had ever used oral contraceptives.

Study findings

• Women who used oral contraceptives had a 32% lower risk (OR = 0.68) of endometrial cancer compared with women who never used oral contraceptives.
• Women who used oral contraceptives had a 28% lower risk (OR = 0.72) of ovarian cancer compared to those who never used oral contraceptives.
• Long-term use of oral contraceptives was linked with greater risk reductions of endometrial and ovarian cancer. For example, women who used contraceptives for less than 2 years had a decreased risk for endometrial and ovarian cancer by 20 percent and 16 percent, respectively, compared with a risk reduction of 64% (endometrial cancer) and 40% (ovarian cancer) in women who used the medicines for more than 20 years.

• Protective effects of oral contraceptives against endometrial and ovarian cancer lasted for up to 35 years after use was discontinued.
• Compared with women who had never used oral contraceptives, oral contraceptive use among the entire group was not linked to an increased risk of breast cancer. Nor did duration of use affect breast cancer risk. There was no difference in breast cancer risk between women who used oral contraceptives for a shorter or longer time.
• This result differs from other studies which have reported an increased risk of breast cancer during and shortly after discontinuation of oral contraceptives; these studies only followed women from age 49 for 10 years. In contrast, this study followed women from the time they began using oral contraceptives until they reached age 71.
  • In this study, a 10% increase risk of breast cancer was linked to oral contraceptive use among women who used oral contraceptives and were followed only to age 55 and this increased risk only within 2 years of discontinuation. This suggests that if there is an increase in risk, it is relatively small and temporary.

Strengths and limitations

Strengths

• This large study of more than 250,000 women allowed the researchers to be confident that they would observe any differences that existed.
• The data collected spanned more than 50 years and allowed researchers to observe links between oral contraceptives and cancer risks over longer times, as well as the long-term impact on cancer risk after oral contraceptive use was discontinued.
• This study looked at endometrial, ovarian and breast cancer in the same group of women.

Limitations

• There are different types of oral contraceptives (e.g., combined estrogen-progesterone medicines, progesterone-only medicines, etc.). This study did not look at the type of oral contraceptives used and could not determine the impact of specific contraceptives.
• The type and dose of oral contraceptives have changed over the years. It is not clear how these differences may impact the results.
• The study lacked information on racial and ethnic diversity. This is important because other studies have shown that medical outcomes may differ among racial and ethnic groups. 
• There was no information known about the inherited mutation status of the women who participated. Whether this data applies to women at increased risk of breast, ovarian or endometrial cancer due to an inherited mutation is unknown.

• The study only included women who were receiving care and being administered medicines in the United Kingdom. This is information is also important because medication approval, as well as the dosage used, differ by country and could result in different health outcomes.

• The study highlighted that oral contraceptive use was not linked to increased risk for breast cancer. This differs from other studies that suggest the use of oral contraceptives may increase the risk of breast cancer, at least during or soon after use is discontinued. The researchers suggest that this is due to following participants for a longer-term after oral contraceptive use ended, although this needs to be confirmed.
• Many differences were observed among women who used oral contraceptives and those who never did, including average age, weight, smoking and menopausal status. The same results were found even when researchers compared models that factored in these differences. However, because of these differences between the two groups, factors other than oral contraceptive use may also contribute to the changes in cancer risk.

Context

Previous studies have shown that the use of oral contraceptives reduced the risk of endometrial and ovarian cancer. These results are consistent across most studies. In contrast, oral contraceptive use has at times been associated with an increased risk of breast, ovarian and endometrial cancer. One of the largest studies so far suggested that women who have used oral contraceptives during the previous 10 years have a slightly increased risk of breast cancer compared with never-users. Conversely, a study performed with women ages 35 to 64 found no association between current or former oral contraceptive use and an increased risk of breast cancer.

Research supports the use of oral contraceptives to reduce the risk of endometrial cancer. Additionally, hormonal IUDs may be a possible treatment for endometrial precancer and early-stage endometrial cancer. Results presented at the Society of Gynecologic Oncology (SGO) 2021 Virtual Annual Meeting on Women’s Cancer showed that six months after insertion of a hormonal IUD, biopsy results showed no signs of cancer or precancer in two-thirds of 165 women with stage I endometrial cancer or atypical endometrial hyperplasia a precancerous condition of the endometrium.

Conclusions

In this study, oral contraceptives were linked to a reduced risk of endometrial and ovarian cancer. This benefit lasted for up to 35 years after oral contraceptive use. The risk of breast cancer was not increased, except for the time during and two years after use.

This study adds to prior research that may help women make more informed decisions about oral contraceptive use, especially those with a previous or family history of certain cancers. However, more research is needed to further investigate the impact of long-term oral contraceptive use on breast cancer.

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posted 6/1/21