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Combined estrogen-progestogen for contraception and menopausal therapy: is there a cancer risk?

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Context - Combined estrogen-progestogen pills are used both as oral contraceptives and for hormone therapy in menopausal women.

Their use has been linked to an increase in some cancers, and a decrease of others. This report present the conclusions reached by the International Agency for Research on Cancer (IARC) – associated to the WHO - on the topic.

No more recent international assessment on the subject was identified since the IARC monograph publication.

A summary of this monograph is available in Lancet Oncology 

This is a faithful summary of the leading report produced in 2007 by the International Agency for Research on Cancer (IARC): " Combined Estrogen−Progestogen Contraceptives and Combined Estrogen−Progestogen Menopausal Therapy" 

  • Source document:IARC (2007)
  • Summary & Details: GreenFacts
Latest update: 7 March 2017

What are the conclusion of this report?

The conclusion made in this report is that combined estrogen–progestogen contraceptives can increase the risk for cervical cancer in women who have a human papillomavirus infection.

The authors recommend thus that women who suffer from papillomavirus infection and use this form of hormonal contraception over a long period of time participate in cervical cancer screening programmes.

What is the evidence that contraceptive combining estrogen and progestogen hormones are carcinogenic?

There is sufficient evidence , according to the IARC report, to conclude for the carcinogenicity in humans of combined oral estrogen–progestogen contraceptives (Group 1 classification of IARC). This evaluation was made on the basis of increased risks:

On the contrary the report concludes that there is evidence in humans suggesting a lack of carcinogenicity of combined oestrogen-progestagens for colorectum and even convincing evidence for their protective effect against carcinogenicity indn the endometrium (the lining of the uterus) and the ovary.

More specifically:

  • For breast cancer, the evidence suggests an increase in the relative risk among current and recent users, and that 10 years after cessation of use the risk goes back to baseline level.
  • For cervical cancer, the totality of the evidence indicated that, overall, the risk increased with increasing duration of use of combined hormonal contraceptives.
  • For uterine (endometrial), the risk is approximately reduced by half in women who had taken these medications. The risk reduction was generally greater with a longer duration of use and persisted for at least 15 years after cessation of use, although the extent of the protective effect may wane over time.
  • For colorectal cancer, most studies did not show an increase in risk in women who had ever used contraceptives or in relation to duration of use.

Is the use of combined estrogen−progestogen hormones for menopausal therapy beneficial or presenting a risk?

The beneficial effects of combined hormonal menopausal therapy have been established unambiguously. However, there is a possibility that women who use both combined estrogen– progestogen contraceptives and menopausal therapy during their lifetime may experience effects that are greater than those experienced by women who use either contraceptives or menopausal therapy but not both.

There is in particular unambiguous evidence for an increase in breast density, breast tenderness and vaginal bleeding. For breast and uterine, the combined estrogen– progestogen menopausal treatment increases the cancer risk:

  • For breast cancer the increased risk is largely confined to current or recent users with increasing duration of use of the combined hormonal therapy.
  • For uterine cancer, an increased risk is observed only if progestogens are taken for less than 10 days per month and not observed when progestogens are taken daily. The risk is thus decreasing inversely to the number of days per month of hormone therapy.

For colorectal cancer , there is evidence suggesting lack of carcinogenicity in humans associated to a combined estrogen– progestogen therapy.

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