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

Introduction

These IARC Monographs contain evaluations of the carcinogenic hazard to humans of combined estrogen–progestogen contraceptives and combined estrogen–progestogen menopausal therapy. The hormonal drugs reviewed in this monograph involve co-administration of an estrogen and a progestogen.

These evaluations identified specific forms of cancer for which the risk is increased or decreased by such combined estrogen–progestogen contraceptives and provide information that help address the health concerns and well-being of hundreds of millions of women worldwide.

The report concluded that there is sufficient evidence in humans for the carcinogenicity of combined oral estrogen–progestogen used either as contraceptives or as menopausal therapy (Group 1 classification of IARC).

The report underlines that there is some concordance in the tumour sites at which the risks for cancer are increased by combined contraceptives and by combined menopausal therapy. Consequently, says the report further, 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.

Implications for cervical cancer screening

The conclusion made in this report that combined estrogen–progestogen contraceptives can increase the risk for cervical cancer in women who have a human papillomavirus infection led the authors to state that women who use this form of hormonal contraception over a long period of time should be encouraged to participate in cervical cancer screening programmes.

Use of Combined Estrogen−Progestogen as contraceptives: results of the risk evaluation

The report concluded that there is sufficient evidence in humans for the carcinogenicity of combined oral estrogen–progestogen contraceptives (Group 1 classification of IARC).

This evaluation was made on the basis of increased risks for cancer of the breast among current and recent users only, for cancer of the cervix and for cancer of the liver in populations that are at low risk for hepatitis B viral infection.

On the contrary the reports concludes that there is evidence suggesting lack of carcinogenicity in humans for combined oral estrogen–progestogen contraceptives in the endometrium, ovary and colorectum. There is convincing evidence in humans, says the report, for their protective effect against carcinogenicity in the endometrium and ovary.

In particular for breast cancer and based on studies on over 60 000 women, the reports says that the totality of the evidence suggested an increase in the relative risk for breast cancer among current and recent users. This effect was noted particularly among women under 35 years of age at diagnosis who had begun using contraceptives when young (< 20 years), whereas the increased risk declined sharply with older age at diagnosis. By 10 years after cessation of use, says the report, the risk in women who had used combined hormonal contraceptives appeared to be similar to that in women who had never used them.

For endometrial cancer, the results of the studies available consistently showed that the risk for endometrial cancer in women who had taken these medications is approximately halved. The reduction in risk was generally greater with longer duration of use of combined hormonal contraceptives and persisted for at least 15 years after cessation of use, although the extent of the protective effect may wane over time.

For cervical cancer, the totality of the evidence indicated that, overall, the risk increased with increasing duration of use of combined hormonal contraceptives, and was somewhat greater for in-situ than for invasive cancer. The relative risk appeared to decline after cessation of use. The results, says the report, were broadly similar regardless of adjustment for the number of sexual partners, cervical screening, tobacco smoking and the use of barrier contraceptives. The association between combined hormonal contraceptives use and cervical cancer was found in studies conducted in both developed and developing countries.

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. The results were generally similar for colon and rectal cancer when examined separately, and two case–control studies showed a significant reduction in risk.

For more detailed information on these and other types of cancer risks related to these hormonal associations, consult the full monograph.

Use of combined Estrogen−Progestogen for menopausal therapy: results of the risk evaluation

For vasomotor symptoms, osteoporosis and fractures, the beneficial effects of combined hormonal menopausal therapy have been established unambiguously with moderate evidence for a reduced risk for non-insulin-dependent diabetes. The evidence for an increase in breast density and an increase in the prevalence of breast tenderness and vaginal bleeding is also unambiguous.

With regards to carcinogenicity the reports concludes that there is sufficient evidence in humans for the carcinogenicity of combined estrogen– progestogen menopausal therapy (category 1A of the IARC classification) in the breast and also in the endometrium when progestogens are taken for fewer than 10 days per month.

On the contrary, in the colorectum, there is evidence suggesting lack of carcinogenicity in humans for combined estrogen– progestogen menopausal therapy and in the endometrium when progestogens are taken daily. The risk for endometrial cancer, says the report, is inversely associated with the number of days per month that progestogens are added to the regimen.

For breast cancer, the studies consistently reported an increased risk in users of combined estrogen–progestogen therapy compared with non-users. The increased risk was greater than that in users of estrogen alone. The available evidence was inadequate to evaluate whether or not the risk for breast cancer varies according to the progestogenic content of the therapy or its dose, or according to the number of days each month that the progestogens are added to the estrogen therapy. The increase in the risk for breast cancer was largely confined to current or recent users, and the risk increased with increasing duration of use of the combined hormonal therapy

For endometrial cancer, the risk was inversely associated with the number of days per month that progestogens were added to the regimen. The addition of progestogens to estrogen therapy for less than 10 days per month was associated with a significantly higher risk for endometrial cancer than never use of hormonal therapy, and the risk increased with increasing duration of use of that regimen.

Estrogen therapy with daily progestogens was associated with a risk of endometrial cancer similar to, and possibly lower than, that found in women who had never used hormonal therapy. In contrast, the use of estrogens alone was associated with a considerably higher risk than that of any combined estrogen–progestogen regimen.

For gallbladder disease, there is also consistent evidence for an increase in the risk.

For more detailed information on these and other types of cancer risk, see the full monograph.

Note : the shorts excerpts of summaries or conclusions of scientific reports prepared for the blog of GreenFacts are not reviewed by its Scientific Board