Many women worry that hormonal contraceptives have dangerous side-effects, including increased cancer risk. But this perception is often out of proportion with the actual risks, say the experts.
Writing in The Conversation, Susan Jordan, Karen Tuesley and Penny Webb ask what the research actually says about cancer risk for contraceptive users, and whether a woman’s cancer risk is different if, instead of the pill, she uses long-acting reversible contraceptives. These include intrauterine devices or IUDs (such as Mirena), implants under the skin (such as Implanon), and injections (such as Depo Provera).
They write:
Our new study – by the University of Queensland and QIMR Berghofer Medical Research Institute and published by the Journal of the National Cancer Institute – looked at this question, and found that long-acting contraceptives seem to be as safe as the pill when it comes to cancer risk (which is good news) but not necessarily any safer than the pill.
How does the contraceptive pill affect cancer risk?
The International Agency for Research on Cancer, which compiles evidence on cancer causes, has concluded that oral contraceptives have mixed effects on cancer risk.
Using the oral contraceptive pill:
• slightly increases the risk of breast and cervical cancer in the short term, but
• substantially reduces the risk of cancers of the uterus and ovaries in the longer term.
Our earlier work showed the pill was responsible for preventing far more cancers overall than it contributed to.
In previous research we estimated that in 2010, oral contraceptive pill use prevented more than 1 300 cases of endometrial and ovarian cancers in Australian women.
It also prevented almost 500 deaths from these cancers in 2013. This is a reduction of around 25% in the deaths that could have occurred that year if women hadn’t taken the pill.
In contrast, we calculated the pill may have contributed to around 15 deaths from breast cancer in 2013, which is less than 0.5% of all breast cancer deaths in that year.
What about long-acting reversible contraceptives and cancer risk?
Long-acting reversible contraceptives – which include intrauterine devices or IUDs, implants under the skin, and injections – release progesterone-like hormones.
These are very effective contraceptives that can last from a few months (injections) up to seven years (intrauterine devices).
Notably, they don’t contain the hormone oestrogen, which may be responsible for some of the side effects of the pill (including perhaps contributing to a higher risk of breast cancer).
Use of these long-acting contraceptives has doubled over the past decade, while the use of the pill has declined. So it’s important to know whether this change could affect cancer risk for Australian women.
Our new study of more than 1m Australian women investigated whether long-acting, reversible contraceptives affect risk of invasive cancers. We compared the results to the oral contraceptive pill.
We used de-identified health records for Australian women aged 55 and under in 2002.
Among this group, about 176 000 were diagnosed with cancer between 2004 and 2013 when the oldest women were aged 67. We compared hormonal contraceptive use among these women who got cancer to women without cancer.
We found that long-term users of all types of hormonal contraception had around a 70% lower risk of developing endometrial cancer in the years after use. In other words, the risk of developing endometrial cancer is substantially lower among women who took hormonal contraception than those who didn’t.
For ovarian cancer, we saw a 50% reduced risk (compared with those who took no hormonal contraception) for women who were long-term users of the hormone-containing IUD.
The risk reduction was not as marked for the implants or injections, however, few long-term users of these products developed these cancers in our study.
As the risk of endometrial and ovarian cancers increases with age, it will be important to look at cancer risk in these women as they get older.
What about breast cancer risk?
Our findings suggest that the risk of breast cancer for current users of long-acting contraceptives is similar to users of the pill.
However, the contraceptive injection was only associated with an increase in breast cancer risk after five years of use and there was no longer a higher risk once women stopped using them.
Our results suggested that the risk of breast cancer also reduces after stopping use of the contraceptive implants.
We will need to follow-up the women for longer to determine whether this is also the case for the IUD.
It is worth emphasising that the breast cancer risk associated with all hormonal contraceptives is very small.
About 30 in every 100 000 women aged 20 to 39 develop breast cancer each year, and any hormonal contraceptive use would only increase this to around 36 cases per 100 000.
What about other cancers?
Our study did not show any consistent relationships between contraceptive use and other cancers types. However, we only at looked at invasive cancers (meaning those that start at a primary site but have the potential to spread to other parts of the body).
A recent French study found that prolonged use of the contraceptive injection increased the risk of meningioma (a type of benign brain tumour).
However, meningiomas are rare, especially in young women. There are around two cases in every 100 000 in women aged 20-39, so the extra number of cases linked to contraceptive injection use was small.
The French study found the hormonal IUD did not increase meningioma risk (and they did not investigate contraceptive implants).
There are benefits and side effects for all medicines, including contraceptives, but most very serious side effects are rare.
Susan Jordan – Professor of Epidemiology, The University of Queensland; Karen Tuesley – Postdoctoral Research Fellow, School of Public Health, The University of Queensland; Penny Webb – Distinguished Scientist, Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute.
Study details
Long-acting, progestin-based contraceptives and risk of breast, gynecological, and other cancers
Karen Tuesley, Katrina Spilsbury, Sallie-Anne Pearson et al.
Published in Journal of the National Cancer Institute on 14 January 2025
Abstract
Background
Use of long-acting, reversible contraceptives has increased over the past 20 years, but an understanding of how they could influence cancer risk is limited.
Methods
We conducted a nested case-control study among a national cohort of Australian women (n = 176 601 diagnosed with cancer between 2004 and 2013; 882 999 matched control individuals) to investigate the associations between the levonorgestrel intrauterine system, etonogestrel implants, depot-medroxyprogesterone acetate and cancer risk and compared these results with the oral contraceptive pill. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI).
Results
Levonorgestrel intrauterine system and etonogestrel implant use was associated with breast cancer risk (OR = 1.26, 95% CI = 1.21 to 1.31, and OR = 1.24, 95% CI = 1.17 to 1.32, respectively), but depot-medroxyprogesterone acetate was not, except when used for 5 or more years (OR = 1.23, 95% CI = 0.95 to 1.59). Reduced risks were seen for levonorgestrel intrauterine system (≥1 years of use) in endometrial cancer (OR = 0.80, 95% CI = 0.65 to 0.99), ovarian cancer (OR = 0.71, 95% CI = 0.57 to 0.88), and cervical cancer (OR = 0.62, 95% CI = 0.51 to 0.75); for etonogestrel implant in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34) and ovarian cancer (OR = 0.76, 95% CI = 0.57 to 1.02); and for depot-medroxyprogesterone acetate in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34). Although levonorgestrel intrauterine system, etonogestrel implant and depot-medroxyprogesterone acetate were all associated with increased cancer risk overall, for etonogestrel implant, the risk returned to baseline after cessation, similar to the oral contraceptive pill. We were unable to adjust for all potential confounders, but sensitivity analyses suggested that adjusting for parity, smoking, and obesity would not have materially changed our findings.
Conclusion
Long-acting, reversible contraceptives have similar cancer associations to the oral contraceptive pill (reduced endometrial and ovarian cancer risks and short-term increased breast cancer risk). This information may be helpful to women and their physicians when discussing contraception options.
See more from MedicalBrief archives:
Breast cancer risk upped by contraceptive pill use – UK meta-analysis
Newer oral contraceptives linked to reduced ovarian cancer risk
IUDs may cut cervical cancer risk by a third — US systematic review
Prolonged use of some hormone drugs tied to tumour risk
Injectable contraceptive may raise HIV infection risk by 40%