Researchers in a 2022 study found no differences in colorectal cancer rates in over 130,000 women who took IVF medications between 1995 and 2017, with the exception of clomid which reduced rates.
The use of fertility drugs to modify hormone levels in IVF might influence the development of hormone-sensitive cancers, and there are few studies on the impact of these drugs on colorectal cancer.
Møller et al. (2022) compared the incidence of colorectal cancer in 148,036 women with infertility who were treated with fertility drugs (131,173) or weren’t (16,863) in Denmark between 1995 and 2017.
The data from this study was from the Danish Infertility Cohort, a registry that combines records of infertile women in Denmark over the years, including IVF data from the Danish IVF Register. Women aged 20-45 entered the Cohort at different times between 1995 and 2017, depending on when they were diagnosed with infertility and started using fertility drugs. Those who developed colorectal cancer during this time were identified using the Danish Cancer Register.
The median age of women who were first included in the Cohort was 31.1 and at the end of follow-up the median age was 43.4 years. The median follow-up time was 11.3 years.
They looked at a number of fertility drugs including:
- Clomiphene citrate (clomid)
- Gonadotropins (including FSH and hMG)
- hCG
- GnRH
- Progesterone
To be clear, these women didn’t take these medications for the whole study period. They started taking them at some point in their life, at which point they were entered into the Cohort, and then they were followed up with until 2017. They weren’t necessarily still taking any fertility drugs by 2017.
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Incidence of colorectal cancer didn’t change with fertility drugs, except clomid
In total there were 205 women diagnosed with colorectal cancer, including 64 with rectal cancer and 141 with colon cancer. The median age of diagnosis was 48.2 years.
They grouped women based on the type of fertility drug used and calculated hazard ratios. In this study, the hazard ratio represents the chance of getting colorectal cancer after taking a fertility drug, divided by the chance of getting colorectal cancer without taking a fertility drug.
After statistical adjustment to control for confounders (calendar year for entry, level of education, obesity, etc.), they found no statistical differences in the incidence of colorectal cancer in women who used any fertility drug, except for the clomid group (hazard ratio [95% CI]: 0.68 [0.50-0.93]). This means that the chance of developing colorectal cancer in those who used clomid was 32% lower compared to those who didn’t use the medication (1.00-0.68 = 0.32 or 32%).
Colorectal cancer includes both colon cancer and rectal cancer. When they separated these cancers and reanalyzed the data, they found no differences in their incidence among all the different medication groups.
Longer first exposure to fertility drugs have no difference in colorectal cancer rates
Since cancer takes time to develop, it’s possible that women who started fertility drugs a longer time ago had a higher rate of colorectal cancer development, so they grouped women as either having <8 years or ≥8 years since first exposure to a fertility medication.
The only statistically significant difference was in the ≥8 year group with clomid, which showed a decrease (hazard ratio [95% CI]: 0.52 [0.36-0.75]). This means that women who first took clomid 8 or more years ago, had a 48% reduced chance of having colorectal cancer.
They found no statistical differences with the other medications.
Women who take more fertility drugs are not more likely to develop colorectal cancer
Some women in the study may have taken more fertility drugs compared to other, and this may have increased their chances of getting colorectal cancer.
In another analysis, the researchers looked at the cumulative dose of fertility drugs used over the course of the study and found no differences in the incidence of colorectal cancer.
Conclusions
There were no differences in the incidence of colorectal cancer between women who used fertility medications and those who didn’t, with the exception of clomid. Use of clomid reduced the rate of colorectal cancer, and this was only in women who had first used it 8 or more years prior.
The authors are unclear on how clomid may reduce the incidence of colorectal cancer, and state that this finding may be related to underlying conditions in the women who are prescribed the drug (clomid is often used to treat ovarian dysfunction in PCOS patients), or simply due to chance.
The major limitation of this study, and all studies that investigate cancer and IVF, is the follow-up time. Cancer takes time to develop, and most women who develop colorectal cancer are around 70. The median age at the end of follow-up in this study was 43.4 years. There simply may not have been enough time to see any differences, and the authors conclude that these results mostly apply to premenopausal women. More studies, and more time, are needed to address the long-term impact of fertility medications and colorectal cancer.
Reference
About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
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