Newer oral contraceptives linked to reduced ovarian cancer risk

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ContraceptivesNew types of combined oral contraceptives (containing both lower doses of oestrogens and newer progestogens) are associated with a reduced risk of ovarian cancer, in young women, finds a large study. The results show that this positive effect strengthened with longer periods of use and persisted for several years after stopping, providing important reassurance for women, say the researchers.

At least 100m women worldwide are using hormonal contraception every day. Previous research has shown a reduced risk of ovarian cancer in women who take combined oral contraceptives, but most of the evidence relates to the use of older products, containing higher levels of oestrogen and older progestogens.

Women who use newer oral contraceptives and other hormonal contraceptive methods also want to know whether they are likely to experience the same benefit. So, researchers at the University of Aberdeen in Scotland and the University of Copenhagen in Denmark investigated the influence of newer hormonal contraceptives (combined and progestogen-only products) on overall and specific types of ovarian cancer in women of reproductive age.

Using national prescribing and cancer registers, they analysed data for nearly 1.9m Danish women aged 15-49 years between 1995 and 2014. Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (up to one year after stopping use), or former users (more than one year after stopping use) of different hormonal contraceptives.

Most (86%) of the hormonal contraceptive use related to combined oral products. After taking account of several factors, including age and parity, the researchers found that the number of cases of ovarian cancer were highest in women who had never used hormonal contraception (7.5 per 100,000-person years), whereas among women who had ever used hormonal contraception, the number of cases of ovarian cancer were 3.2 per 100,000-person years.

There was no firm evidence to suggest any protective effect among women who used progestogen-only products, although the researchers point out that few women were exclusive users of these products. This limits the ability to detect an effect.

The reduced risk for combined products was seen with nearly all types of ovarian cancer, and there was little evidence of important differences between products containing different types of progestogens.

Similar results were also found among women followed up to their first switch in contraceptive type.

Based on these figures, the researchers say that hormonal contraception prevented an estimated 21% of ovarian cancers in this group of women.

This is an observational study, so no firm conclusions can be drawn about cause and effect, but they do support the findings of studies of older products. The researchers point out that they did not study older women, among whom most cases of ovarian cancer occur. However, this was a large study with a long follow-up period, and the researchers were able to adjust for a range of potentially influential factors.

“Based on our results, contemporary combined hormonal contraceptives are still associated with a reduced risk of ovarian cancer in women of reproductive age, with patterns similar to those seen with older combined oral products,” say the authors.

“The reduced risk seems to persist after stopping use, although the duration of benefit is uncertain. Presently, there is insufficient evidence to suggest similar protection among exclusive users of progestogen-only products,” they conclude.

Abstract
Objectives: To investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer.
Design: Prospective, nationwide cohort study.
Setting: Denmark, 1995-2014.
Participants: All women aged 15-49 years during 1995-2014 were eligible. Women were excluded if they immigrated after 1995, had cancer (except non-melanoma skin cancer), had venous thrombosis, or were treated for infertility before entry (final study population included 1 879 227 women). Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (≤1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives.
Main outcome measures: Poisson regression was used to calculate relative risk of ovarian cancer among users of any contemporary combined hormonal contraceptives and by progestogen type in combined preparations and all progestogen-only products, including non-oral preparations. Separate analyses examined women followed up to their first contraception type switch and those with full contraceptive histories. Duration, time since last use, and tumour histology were examined and the population prevented fraction were calculated.
Results: During 21.4 million person years, 1249 incident ovarian cancers occurred. Among ever users of hormonal contraception, 478 ovarian cancers were recorded over 13 344 531 person years. Never users had 771 ovarian cancers during 8 150 250 person years. Compared with never users, reduced risks of ovarian cancer occurred with current or recent use and former use of any hormonal contraception (relative risk 0.58 (95% confidence interval 0.49 to 0.68) and 0.77 (0.66 to 0.91), respectively). Relative risks among current or recent users decreased with increasing duration (from 0.82 (0.59 to 1.12) with ≤1 year use to 0.26 (0.16 to 0.43) with >10 years’ use; P<0.001 for trend). Similar results were achieved among women followed up to their first switch in contraceptive type. Little evidence of major differences in risk estimates by tumour type or progestogen content of combined oral contraceptives was seen. Use of progestogen-only products were not associated with ovarian cancer risk. Among ever users of hormonal contraception, the reduction in the age standardised absolute rate of ovarian cancer was 3.2 per 100 000 person years. Based on the relative risk for the never use versus ever use categories of hormonal contraception (0.66), the population prevented fraction was estimated to be 21%—that is, use of hormonal contraception prevented 21% of ovarian cancers in the study population.
Conclusions: Use of contemporary combined hormonal contraceptives is associated with a reduction in ovarian cancer risk in women of reproductive age—an effect related to duration of use, which diminishes after stopping use. These data suggest no protective effect from progestogen-only products.

Authors
Lisa Iversen, Shona Fielding, Øjvind Lidegaard, Lina S Mørch, Charlotte W Skovlund, Philip C Hannaford

 

Dr Channa Jayasena, a clinical senior lecturer in reproductive endocrinology at Imperial College London who was not involved in the study, noted hormonal contraceptives – particularly the combined pill – have previously been linked to a small increased risk of breast cancer. However, Jayasena stressed in a report in The Guardian that the pill remains an important tool for women.

“(The study) shows that the combined pill which is thought of by patients and GPs as the one with more risks actually has some benefits too, over (progestin-only) methods,” he said.

Fiona Osgun, from Cancer Research UK, said: “The good news is that this confirms what we know, so there’s no need to swap your prescription. But the risk of other types of cancer can be affected, so if you’re thinking about starting or stopping the pill, make sure you speak to your doctor who can talk you through the pros and cons for your individual situation to help you make a decision.”

BMJ material
BMJ abstract
The Guardian report


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