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Positioning Statements & Guidelines

SOGC Position Statement - The Birth Control Pill and Cancer

This position statement has been reviewed and approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada.

Principal Authors
Dr. André B. Lalonde, MD, FRCS(C), FRCOG, FSOGC, FACS, Ottawa, ON
Dr. Robert Reid, MD, FRCS(C), FACOG, FSOGC, Kingston, ON

Contributing Authors
Dr. Jennifer Blake, MD, MSc, FRCSC, FACOG, FSOGC, Toronto, ON
Dr. Michael Helewa, MD, FRCS(C), FACOG, Winnipeg, MB
Dr. Guylaine Lefebvre, MD, FRCS(C), FACOG, FSOGC, Toronto, ON
Dr. Vyta Senikas, MD, MDCM, FRCS(C),FSOGC, CSPQ, Ottawa, ON

This guideline reflects emerging clinical and scientific advances as of the date issued and are subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be reproduced in any form without prior written permission of the SOGC.

Summary Statements Review of relevant studies by SOGC experts indicates that oral contraceptives reduce the risk of ovarian and uterine cancer while slightly increasing the risk for cervical cancer and premenopausal breast cancer. For the majority of women, the benefits of oral contraception outweigh the risks. The risk for premenopausal breast cancer is slightly increased in oral contraceptive users compared to non users, an effect that is seen largely in women who use the pill before first full term pregnancy. Compared to other reproductive and lifestyle factors that affect breast cancer risk, the increase in risk associated with the oral contraceptive is very small. The public health impact of this slight increase in risk is small due to the very low background rates of breast cancer in women of this age group. There is evidence that the use of oral contraceptives in women with a positive family history for breast cancer, or a known BRCA gene mutation, does not increase their risk for breast cancer above that related to their genetic risk. In women with BRCA gene mutations, use of an oral contraceptive will reduce the risk of ovarian cancer. There is evidence that cervical cancer may progress more rapidly in women infected with the cancer-causing strains of HPV (the human papillomavirus) if they are also oral contraceptives users. This emphasizes the importance of comprehensive cervical cancer screening programs and the usefulness of HPV vaccines. In developed countries where effective screening has been in place for years and rates of cervical cancer are low, this is likely to have little public health impact. Oral contraceptives have been proven to reduce rates of endometrial and ovarian cancer by 50% or more. This benefit increases with duration of use and persists for up to 20 years after oral contraceptives are stopped. In addition to providing reliable contraception, oral contraceptives have numerous non-contraceptive benefits which have afforded relief to millions of women suffering from dysmenorrhea (painful menstruation), menorrhagia (heavy menstrual flow), premenstrual syndrome, acne, unwanted hair growth, pelvic pain due to endometriosis, and iron deficiency anemia.

The SOGC is a major stakeholder in the counseling and provision of contraception. Its members are actively involved in addressing the reproductive health concerns of Canadian women.

The SOGC shares the concern of many in the scientific community that the International Agency for Research on Cancer (IARC) is walking a slippery slope with its decision to label natural reproductive hormones -- estrogen and progesterone -- as carcinogens.¹ Lifetime exposure to these naturally occurring hormones, estrogen and progesterone, is known to be a risk factor for breast cancer. Simply stated, early onset of menstruation or a later menopause are known to increase a woman’s lifetime risk for breast cancer. The relationship between exposure to naturally occurring hormones and cancer is complex, however, because early pregnancy (which is associated with higher than normal production of these hormones) is known to have a protective effect on breast cancer.

To declare a naturally occurring hormone as a carcinogen raises the question: Are all other endogenous hormones growth factors that play a role in the development of cancers now to be labeled as carcinogens? Estrogen causes growth of epithelial cells in the breast and uterine lining. This stimulation increases the number of cell divisions and indirectly may increase the likelihood of cell mutations that lead to cancer. Whether these hormones should be classified as carcinogens suggesting that they cause the cancer is clearly debatable.¹

To term any substance a carcinogen, let alone a naturally occurring hormone over which women have little control, has the potential to generate fear and misunderstanding. In the case of oral contraceptives, a statement about carcinogenicity is sure to overshadow any references to the positive benefits of oral contraceptive of which there are many.

Effective contraception is underutilized in Canada. Estimates suggest that last year in Canada there were 300,000 unplanned pregnancies and of these, approximately 106,000 women chose pregnancy termination. The risks of pregnancy are substantial and failure to use contraception due to unfounded, ill-advised fears about the side effects of hormones may do far more harm to women than any of the purported adverse effects of the contraceptive method.

When widespread media reports about an apparent increased risk of blood clots in women using a popular new oral contraceptive occurred in the UK in the 1990s, women panicked and stopped taking the pill resulting in many thousands of unplanned pregnancies (with the attendant risk of blood clots associated with pregnancy). The medical and social ramifications of this public relations disaster are summarized in an excellent article by Angela Mills.² Nine months later, London hospitals reported 25% more deliveries and an additional 10,000 women sought pregnancy termination. Women became so fearful of hormonal contraception that many opted for hysterectomy rather than use oral contraceptives to control excessive menstrual bleeding in the later reproductive years.

What is the evidence regarding the effects of oral contraceptives on cancer?

Breast Cancer
Endometrial Cancer
Cervical Cancer
Ovarian Cancer
Colorectal Cancer

Breast Cancer

La Vecchia et al provides a comprehensive summary of the issues and evidence related to breast cancer in users of oral contraception.³ These authors conclude that more recent studies from the USA and Norway (Marchbanks, Althuis, Dumeaux) suggest that more recent low dose oral contraceptives are not materially related to breast cancer.^4,5,6 They also caution that available data make it impossible to discern whether oral contraceptives are initiating new cancers (carcinogenic) or are merely advancing the detection of pre-existing cancers (cancer promotion) as might be expected with an agent that leads to increased epithelial cell division. Recent research suggests no association between oral contraceptive use and precancers in the breast –so-called ductal carcinoma in situ.⁷

Several studies have indicated a small but significant increase in the risk of breast cancer in women using the pill at a young age before first pregnancy but emphasize that an increased relative risk in this age group has little public health impact because the absolute risk of disease in this population is so low.

Table showing the low incidence of breast cancer per (100,000) in young women under 35 years old compared to older women.

Age	Incidence
<20	---
20-24	1.4
25-29	7.8
30-34	26.9
35-39	61.6
40-44	120.1
45-49	196.3
50-54	258.3
55-59	334.1
60-64	388.9
65-69	437.6
70-74	480.0
75-79	499.2
80-84	475.8

Figure #1: Risk of breast cancer in women who use OCs 1) ever 2) before first full term pregnancy (FFTP) and 3) after (FFTP) In a recent meta analysis of case-control studies (Kahlenborn et al. 2006) examining the association between premenopausal breast cancer and oral contraceptive use. This report examined 6 additional studies that had not been reported at the time of the collaborative re-analysis in 1996. This report examines findings in light of new prescribing patterns for oral contraceptives and focuses on premenopausal women. These authors also conclude that the relative risk for breast cancer identified in the analysis is “small” and because baseline rates of breast cancer in premenopausal women are so low that the absolute risk is “very small” . The numbers shown here are the absolute increased risks (attributable risks) risks of breast cancer in oral contraceptive users according to 1) ever use, 2) ever use before first full term pregnancy and 3) ever use after first full term pregnancy calculated by multiplying the baseline risk of premenopausal breast cancer (estimated in the introduction of the paper at 40/100,000 women) by the Odds Ratios reported in this paper and subtracting the background risk. Kahlenborn c et al. Oral contraceptive use as a risk factor for premenopausal breast cancer: A meta-analysis. Mayo Clin Proc 2006; 81(10):1290-1302

Figure #2. Graph showing how different lifestyle factors compare to OC use as risk factors for breast cancer This figure depicts the relative risks for premenopausal breast cancer among oral contraceptive users and compares the level of risk to other well known breast cancer risk factors. References: Collaborative Group on Hormonal Factors and Breast Cancer. Breast feeding. Lancet 2002; 360:187-195 Newcomb, P A. et al. Lactation and a reduced risk of premenopausal breast cancer. NEJM 1994; 330(2):81-7 Tavani A et al. Risk factors for breast cancer in women under 40. European J Cancer 1999; 35(9): 1361-1367 MacMahon B et al. Age at first birth and breast cancer risk. Bull Wld Hlth Org 1970; 43:203-221 Kahlenborn c et al. Oral contraceptive use as a risk factor for premenopausal breast cancer: A meta-analysis. Mayo Clin Proc 2006; 81(10):1290-1302

Surveillance Epidemiology and End Results [SEER] Data USA 1997-2001

An extensive review of all available research data on oral contraceptives and breast cancer published in 1996 estimated the number of extra cancers that might be expected if 10,000 women used oral contraceptives for 5 years and were then followed for an additional 10 years after stopping the oral contraceptives. The estimates suggested that for 10,000 pill users between 16 and 19 years of age there would be an additional 0.5 breast cancers, between ages 20-24 an additional 1.5 breast cancers, and between 25-29 an additional 4.7 cancers. These numbers represent a very small increase above the baseline risk for breast cancer in these populations. Ten years later a review of available evidence (Kahlenborn et al. 2006) has confirmed these findings.⁸ These authors included 6 additional studies that had not been reported at the time of the 1996 analysis. This research, however, was able to examine the relationship between oral contraceptives and premenopausal breast cancer in light of new dosages and prescribing patterns of oral contraceptives. Once again absolute increase in risk for premenopausal breast cancer among oral contraceptive users is noted to be “very small” (0.7 additional premenopausal breast cancer cases per 10,000 users overall and 1.76 cases in women using the pill before having a full term pregnancy.⁹

Many women and their physicians assume that OC use in women with a family history of breast cancer or in those with BRAC gene mutations would be ill advised because it could increase the risk of breast cancer. This is unfortunate because available evidence does not support this view. Oral contraceptives do not appear to increase the risk for breast cancer in such women beyond the risk attributed to their genetic makeup yet the evidence that oral contraceptives will reduce the risk for ovarian cancer in such women is compelling.^10,11,12 Oral contraceptives are currently recommended as a form of ovarian cancer “chemoprevention” in women with the BRAC gene mutations.^13,14 It is estimated that 10 years of OC use by women with a positive family history for ovarian cancer can reduce their risk of ovarian cancer to a level below that for women whose family history is negative and who never use OCs.¹⁵

Endometrial Cancer

The incidence of endometrial cancer in developing countries has fallen dramatically since the introduction of combined oral contraceptives.

In a meta analysis of published studies examining the effect of oral contraceptives on endometrial cancer, Schlesselman produces these estimates of the effects of oral contraceptives:

Cumulative incidence of endometrial cancer in 100,000 U.S. women
by OC status (non-users vs users for 4, 8, or 12 years)

OC Use category	Estimated number of cases
OC Use category	Ages 20-54	Ages 20-74
Never	471	2396
Users
4 y	283	1696
8y	241	1522
12y	213	1417

- adapted from Table V Schlesselman JJ.
(Human Reproduction 1997)

This effect persists well after OC use is stopped with estimated relative risks of 0.32, 0.40 and 0.51 at 5, 10, and 20 years after cessation of use.

This benefit persists despite the substantial lowering of hormone dosages in modern oral contraceptives.¹⁶

The absolute risk of remaining free of endometrial cancer through to age 74 in U.S. women is estimated to be 97.6%. With the use of oral contraceptives for 12 years, the likelihood of remaining free of endometrial cancer would increase by 1% to 98.6%.

Ovarian Cancer

One theory about the causation of ovarian cancer is that recurrent disruption to the surface epithelium occasioned by repeated ovulation provides the stimulus for epithelial mutations that lead to ovarian cancer. Oral contraceptives have been shown to reduce the risk of future ovarian cancer by 10-12% after 1 yr, by 50% after 5 yr, and by 80% after 10 years of use. This beneficial effect persists for at least 20 years after last use.¹⁵

Ovarian cancer is often detected at an advanced stage and overall five year survival is less than 50%. Lifetime risk of ovarian cancer is 1.44% so that a reduction of 50-80% would bring this number to 0.7 -0.3% of women.

Cervical Cancer

Attempts to investigate the relationship between cervical cancer and oral contraceptive use have been confounded by the general lack of barrier protection among OC users and the effects of oncogenic strains of the human papillomavirus (HPV). Of all cervical cancers, 99.5% are found in association with HPV.

Oral contraceptives have not been found to increase the incidence of preinvasive cervical cancer; however there has been a significant association between the long term use of oral contraceptives and the presence of invasive cervical cancer possibly suggesting a promoting effect rather than a carcinogenic action of oral contraceptives on established cervical neoplasia.^3,17,18

A review of 28 studies found a 10% increase in risk with oral contraceptive use of less than 5 yrs and a doubling of risk with 10 or more years of use.¹⁹ OC users are not more likely to convert to HPV positivity than non-users.

In developed countries with widespread and effective cervical surveillance programs, this effect is likely to have minimal public health impact. The incidence of invasive cervical cancer has fallen dramatically in North America at a time when oral contraceptive usage approaches 80% of the population at some time. Vaccines against HPV are now a reality so that rates of cervical cancer will likely fall dramatically in the next century.

Colorectal Cancer

The combined oral contraceptive may reduce the risk of colorectal cancer. A meta-analysis found a pooled RR of colorectal cancers for ever use of oral contraceptives from eight case control studies of 0.81, the pooled estimate from 4 cohort studies was 0.84 and from all studies combined 0.82.²⁰ This area is less well understood and further research is needed to establish risk profile with duration of use, recentness of use , and careful consideration of possible confounders.²¹

All Cause Mortality in OC Users

If the reported carcinogenic effect of oral contraceptives were of significant public health impact an effect on cancer related mortality would be expected. Two large follow-up studies have examined mortality in oral contraceptive users.

Beral et al in 1999 presented the results from 25 years of follow-up of a cohort of women in the Royal College of General Practitioners data base. Over that time period 1599 deaths had been reported. Oral contraceptive users were no more likely than non users to have died. [OR 1.0 (95% CI 0.9-1.1)]. Subgroup analysis revealed a reduced death rate for ovarian cancer [OR 0.2 (95% CI 0.1-0.8)] and an increased death rate from cervical cancer [OR 2.5 (95% CI 1.1-6.1)]. Overall there were fewer cancer deaths in the OC users which were offset by a slightly greater risk for death due to cardiovascular diseases [OR 1.9 (95% CI 1.2-3.1)]. Modern low dose pills used by non-smokers have minimal effect on cardiovascular disease.

Vessey in 2003 examined records of 17,032 women aged 25-39 at enrollment into the Oxford Family Planning Study looking for causes of death. Again the death rate among oral contraceptive users was not increased [OR 0.82 (95% CI 0.77-1.02)]confirming no harmful effect of oral contraceptive usage on all-cause mortality.

Non Contraceptive Benefits of the Pill

While it is important to continue post-marketing surveillance of oral contraceptive users to detect the possible associations with rare adverse events (like cardiovascular disease) or diseases which have a long latency (like cancer), it is equally important to take into account the many non contraceptive benefits of the pill. Numerous reviews have addressed the significant public health impact that the oral contraceptive has had on two generations of women.^21,22,23

Dysmenorrhea

This condition affects 50-90% of women. Estimates from the USA suggest that dysmenorrheal accounted for 600 million lost hours and $2 billion of lost productivity annually. In the UK oral contraceptive users had 26 hospital admissions for dysmenorrheal per 100,000 women compared with 50 per 100,000 for non users. ²¹ There are data from RCTs, cross sectional surveys and non-comparative trials which all support the benefit of oral contraceptives including new lower dose pills for the reduction of dysmenorrheal.²¹

Menorrhagia

Approximately 10% of fertile women suffer from menorrhagia. The prevalence increases with increasing age and this remains a common cause for hysterectomy or endometrial ablative procedures for women in their 40s. Oral contraceptives now approved for use in non-smoking women until the age of menopause have had a major beneficial impact. Reduced blood loss is reported by 87% of oral contraceptive users.²¹

Hyperandrogenism/Polycystic ovary syndrome (PCOS)

Acne affects 40% of adolescents and 10% of adult women. Oral contraceptives in addition to providing cycle regulation for anovulatory women with PCOS also improve acne and unwanted hair growth through their effects on suppression of ovarian androgen production and augmentation of androgen binding in circulation.²¹

Premenstrual Syndrome/Premenstrual Dysphoric Disorder

This menstrual mood disorder is reported to severely affect 3-5% of the female population in reproductive years with another 20-30% reporting moderate symptoms. Oral contraceptives have been shown in RCTs to benefit PMS symptoms when taken cyclically or when taken continuously for menstrual cycle suppression.^24,25

Endometriosis

Pelvic pain is a common presentation for endometriosis and the long term management of women with recurrent pain after fertility preserving surgery is problematic. Continuous oral contraceptives have been shown to be highly effective in such women.²⁶ Oral contraceptive induced anovulation, decidualisation, amenorrhea and the establishment of a steady-state estrogen-progestin milieu contribute to disease quiescence.²¹

Other

Oral contraceptives reduce the risk of iron deficiency anemia and ectopic pregnancy. Although observational data suggest a possible benefit of the oral contraceptive on fibroids and benign breast disease, more research is needed to address these issues conclusively.²¹

Additional Resources:

References:

¹ Schneider HP. Mueck AO. Kuhl H. IARC monographs program on carcinogenicity of combined hormonal contraceptives and menopausal therapy.Climacteric.2005; 8(4):311-6

² Mills A. Combined oral contraception and the risk of venous thromboembolism. Human Reproduction 1997; 12(12):2595-2598

³ La Vecchia C, Bosetti C. Benefits and risks of oral contraceptives on cancer. European J Cancer prevention 2004; 13:467-470

⁴ Marchbanks PA, MacDonald JA, Wilson HG et al. Oral contraceptives and the risk of breast cancer. N Engl J Med 2002; 346:2025-2032

⁵ Althuis MD, Brogan DR, Coates RJ et al Hormonal content and potency of oral contraceptives and breast cancer risk among young women.Br J Cancer 2003; 88:50-57

⁶ Dumeaux V, Alsaker E, Lund E. Breast cancer and specific types of oral contraceptives: a large Norwegian cohort study. Int J Cancer 2003; 195:844-850

⁷Claus EB. Stowe M. Carter D. Oral contraceptives and the risk of ductal breast carcinoma in situ. Source Breast Cancer Research & Treatment. 2003; 81(2):129-36.

⁸Kahlenborn C, Modugno F, Potter DM, Severs WB.Oral contraceptive use and premenopausal breast cancer: A meta-analysis. Mayo Clinic Proc 81(10): 1290-1392

⁹ Cerhan JR. Oral contraceptive use and breast cancer: current status. Mayo Clinic Proc 81(10): 1288-1289

¹⁰ Milne RL. Knight JA. John EM. Dite GS. Balbuena R. Ziogas A. Andrulis IL. West DW. Li FP. Southey MC. Giles GG. McCredie MR. Hopper JL. Whittemore AS. Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiology, Biomarkers & Prevention 2005; 14(2):350-6

¹¹ Silvera S, Miller AN, Rohan AB, Thomas E. Oral contraceptive use and risk of breast cancer among women with a family history of breast cancer: a prospective cohort study. Cancer Causes & Control 2005; 16(9):1059-63

¹² Grenader T. Peretz T. Lifchitz M. Shavit L.BRCA1 and BRCA2 germ-line mutations and oral contraceptives: to use or not to use. Breast 2 005; 14(4):264-8

¹³ Henderson BE. Ross RK. Pike MC. Hormonal chemoprevention of cancer in women. Science 1993; 259(5095):633-8

¹⁴ Whittemore AS. Balise RR. Pharoah PD. Dicioccio RA. Oakley-Girvan I. Ramus SJ. Daly M. Usinowicz MB. Garlinghouse-Jones K. Ponder BA. Buys S. Senie R. Andrulis I. John E. Hopper JL. Piver MS. Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations. Br J Cancer 2004; 91(11):1911-5

¹⁵ Gross TP. Schlesselman JJ. The estimated effect of oral contraceptive use on the cumulative risk of epithelial ovarian cancer. Obstet Gynecol 1994; 83(3):419-24.

¹⁶ Weiderpass E. Adami HO. Baron JA. Magnusson C. Lindgren A. Persson I. Use of oral contraceptives and endometrial cancer risk (Sweden). Cancer Causes & Control 1999; 10(4):277-84

¹⁷ Castle PE, Wacholder S, Lorincz AT, et al. A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. Journal of the National Cancer Institute 2002; 94(18):14061414.

¹⁸ Moreno V, Bosch FX, Munoz N, et al. Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: The IARC multicentric case-control study. Lancet 2002; 359(9312):10851092.

¹⁹ Smith JS, Green J, de Gonzalez AB, et al. Cervical cancer and use of hormonal contraceptives: A systematic review. Lancet 2003; 361(9364):11591167.

²⁰ Fernandez E, LaVecchia C, Balducci A et al. Oral contraceptives and colorectal cancer risk: a meta-analysis. Br J Cancer 2001; 84:722-727

²¹ The ESHRE Capri Workshop Group. Noncontraceptive health benefits of combined oral contraception. Human Reproduction Update 2005; 11(5):513-25

²² Jensen JT. Speroff L. Health benefits of oral contraceptives. Obstet Gynecol Clinics of North America 2000; 27(4):705-21

²³ Dayal M. Barnhart KT. Noncontraceptive benefits and therapeutic uses of the oral contraceptive pill. Seminars in Reproductive Medicine. 19(4):295-303, 2001

²⁴ Yonkers KA, Brown C, Pearlstein TB, Foegh M, Sampson-Landers C, Rapkin A. Efficacy of a new low dose oral contraceptive with drospirenone in Premenstrual Dysphoric Disorder. Obstetrics and Gynecology 2005; 106(3): 492-501

²⁵ Freeman EW, Borisute H,Deal LS et al significant improvement in cycle-related symptoms following treatment with continuous LNG/EE, a low dose continuous oral contraceptive Abstract; ASRM Mtg Montreal Quebec Oct 2005

²⁶ Vercellini p, Frontino G De Giorgi O, Aimi G, Zaina B Crosignani PG. Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen. Fertil Steril 2003; 80:560-563

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Calle EE et al for the Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual dat on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347: 1713-1727

Schlesselman JJ. Risk of endometrial cancer in relation to use of combined oral contraceptives. A practitioner's guide to meta-analysis. Human Reproduction 1997; 12(9):1851-63

Beral V. Hermon C. Kay C. Hannaford P. Darby S. Reeves G. Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study. BMJ 1999; 318(7176):96-100

Vessey M, Painter R, Yeates D. Mortality in relation to oral contraceptive use and cigarette smoking. Lancet. 362(9379):185-91, 2003

Last Updated February 19, 2008