- Email: [email protected]
Oral contraceptives, nuns, and cancer
Correspondence
systems, takes time, is complicated, and requires skilled researchers. This brings me back to the students: what of their future? Imagine that the requirement to be qualified for a science degree is nothing more than a laptop. Students will be taught in computer clusters with no recourse to science laboratories. We will produce students who are computer literate and can find their way around even the most complicated spreadsheet or database. But what happens when the students are required to take a patient’s blood pressure, understand where their data come from, or even do their own experiments? Research-led teaching in areas such as physiology is fundamental to science departments and too important to lose. We urge the decision makers to listen to all sides (including those whose futures will be most affected) and think very carefully about the consequences before axeing subjects. I declare that I have no conflicts of interest.
Rachel Ashworth [email protected] School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK 1
Allen JF, Missirlis F. Queen Mary: nobody expects the Spanish Inquisition. Lancet 2012; 379: 1785.
Oral contraceptives, nuns, and cancer Although we agree with Kara Britt and Roger Short (June 23, p 2322)1 that studying Catholic nuns could yield important information on the potential health effects of nulliparity and celibacy, we do not agree with their suggestion that the Catholic Church should encourage all its nuns to take the oral contraceptive pill on the grounds that it decreases lifetime risk of reproductive cancers. We propose that a personalised approach and screening might be more sensible. The recommendation that the contraceptive pill should be freely www.thelancet.com Vol 379 June 23, 2012
available to nuns is based on the study by Fraumeni and colleagues,2 who in 1969 reported that Catholic nuns are at increased risk of breast, uterine, and ovarian cancers. However, a study in 2000 by the same group3 reported that professionally active nuns have in fact favourable mortality rates compared with the general population, which the authors ascribed to the “healthy worker effect”. Further, a recent exhaustive literature search on mortality in members of the clergy4 found that Catholic nuns have a mortality advantage of roughly 20–25% over the general population. Nevertheless, a survey of breast cancer prevention in nuns found a need for increased engagement of breast-related health practices, including breast examination and mammography.5 Celibacy renders the risk of cervical cancer very low;2,3 thus, with improved information on breast cancer prevention, Catholic nuns are already in a favourable position to avoid death from gynaecological cancer, without a need for the oral contraceptive pill. We declare that we have no conflicts of interest.
*Ivo Brosens, Giuseppe Benagiano [email protected] Catholic University of Leuven, 3000 Leuven, Belgium (IB); and Department of Gynecology, Obstetrics and Urology, University of Rome “La Sapienza”, Rome, Italy (GB) 1 2
3
4
5
Britt K, Short R. The plight of nuns: hazards of nulliparity. Lancet 2012; 379: 2322–23. Fraumeni JF, Lloyd JW, Smith EM, Wagoner JK. Cancer mortality among nuns: role of marital status in etiology of neoplastic disease in women. J Natl Cancer Inst 1969; 42: 455–68. Doody MM, Mandel JS, Lubin JH, Boice JD Jr. Mortality among United States radiologic technologists, 1926–90. Cancer Causes Control 1998; 9: 67–75. Flanelly KJ, Weaver AJ, Larson DB, Koenig HG. A review of research on clergy and other religious professionals. J Religion Health 2002; 41: 57–68. Thiel L. Breast health of US women religious (nuns). Breast J 2008; 14: 581–83.
Kara Britt and Roger Short1 recommend that nuns should take oral contraceptives to prevent reproductive cancers. Besides nulliparity, nuns might have more repro-
ductive cancers than other women owing to deficiencies of vitamin D or other essential nutrients because of lack of sunlight or sparse diets. Any use of oral contraceptives is claimed to protect from ovarian cancer. This claim could be mistaken. A 2008 meta-analysis of 45 studies2 found that slightly fewer women with ovarian cancer had taken oral contraceptives, and for slightly fewer months, almost 20 years previously, than had women without ovarian cancer; the median age of cancer diagnosis was 56 years. By this age, many women would have taken fertility drugs or hormone replacement therapy (HRT), both of which increase cancer risks, including ovarian cancer.3,4 Adding HRT takers to never-takers of oral contraceptives would have falsely reduced risk estimates in oral contraceptive studies. It does not make scientific sense that progestagens and oestrogens can cause ovarian cancer when called HRT whereas the same hormones are claimed to prevent ovarian cancer when given for contraception. Also, women who die young might be missing from studies of older women or from studies with large losses to follow-up such as the Royal College of General Practitioners’ Oral Contraception Study.5 In that study, although most use started before enrolment in 1968, deaths were not flagged nationally until 1977. Most deaths were from cancer, especially breast cancer. 75% of deaths were notified 30–40 years after enrolment, when HRT use was likely but unrecorded, and oral contraceptive use was long past. However, nearly three times more ever-takers of oral contraceptives died before age 30 years than never-takers. Cancer prevention by oral contraceptives must be an illusion due to confusion in epidemiological studies.
See Comment page 2322
We declare that we have no conflicts of interest.
*Ellen C G Grant, Elizabeth H Price [email protected] 20 Coombe Ridings, Kingston-upon-Thames KT2 7JU, UK (ECGG); and London NW11 6SG, UK (EHP)
2339
Correspondence
1 2
3
Corbis
4
5
Britt K, Short RV. The plight of nuns: hazards of nulliparity. Lancet 2012; 379: 2322–23. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23 257 women with ovarian cancer and 87 303 controls. Lancet 2008; 371: 303–14. van Leeuwen FE, Klip H, Mooij TM, et al. Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort. Hum Reprod 2011; 12: 3456–65. Beral V, Bull D, Green J, Reeves G, for the Million Women Study Collaborators. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 2007; 69: 1703–10. Hannaford PC, Iversen L, Macfarlane TV, et al. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study. BMJ 2010; 340: c927.
Authors’ reply We agree with Ivo Brosens and Giuseppe Benagiano that a personalised approach is needed in the use of the oral contraceptive pill to protect against reproductive cancers, together with a proactive educational programme for nuns and other nulliparous women about the benefits of regular breast examinations and mammograms; a woman’s medical history should always be considered. We agree that nuns have a favourable overall mortality rate compared with the general population.1,2 However, the 20–25% decrease is specific to younger nuns, and older nuns are significantly less protected (8% at 80–84 years). The 20% increased risk of breast cancer in older nuns compared with the general population will affect these agespecific changes in mortality.3 Ellen Grant and Elizabeth Price are concerned that the confounding effects of hormone-replacement therapy (HRT) are not considered when the benefits of the oral contraceptive pill for ovarian and uterine cancer risk are considered. The Hannaford study4 reported that ever-users of the oral contraceptive pill were more likely to have used HRT (13·1% compared with 10% in never-users), so the increased risk of cancer in non-users of the oral contraceptive pill is very unlikely to 2340
result from an over-representation of HRT users. The epidemiological research that showed that the oral contraceptive pill can reduce ovarian and uterine cancers was first published in 2010. We need to know exactly how the oral contraceptive pill affects the reproductive tract, and whether age, duration of exposure, and dose affect its protective effects. To help define this effect, the Hannaford and Vessey data4,5 could be stratified by age at use, dose, parity, and HRT use. Assessment of the effects of progestagens and oestrogens on the reproductive tract premenopausally versus postmenopausally might also reveal why hormonal regimens have opposing effects in women of different reproductive status. Assessment of mortality by age in the Hannaford study would explain why young women (<30 years) had an adjusted relative risk of death of 2·85 when taking the oral contraceptive pill compared with never-users, and would help to define the optimum age window for protection. The latest epidemiological research suggests that the oral contraceptive pill might protect against ovarian cancer by reducing the monthly trauma of ovulation, and reduction of the frequency of menstruation might similarly protect the uterus. We hope that these observations will stimulate further research into how different hormonal regimens might help to protect women from ovarian and uterine cancers. And if we could emulate the proven protective effects of pregnancy and lactation against breast cancer, this might allow all women in the future to enjoy the benefits of healthy infertility. We declare that we have no conflicts of interest.
*Kara Britt, Roger Short [email protected] Prostate and Breast Cancer Research Program, Department of Anatomy and Developmental Biology, Monash University, VIC 3800, Australia (KB); and Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, VIC, Australia (RS)
1
2
3
4
5
Doody MM, Mandel JS, Linet MS, et al. Mortality among Catholic nuns certified as radiologic technologists. Am J Industrial Med 2000; 37: 339–48. Flannelly KJ, Weaver AJ, Larson DB, Koenig HG. A review of mortality research on clergy and other religious professionals. J Religion Health 2002; 41: 57–68. Butler SM, Snowdon DA. Trends in mortality in older women: findings from the Nun Study. J Gerontol 1996; 51B: S201–08. Hannaford PC, Iversen L, Macfarlane TV. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study. BMJ 2010; 340: 927–35. Vessey M, Yeates D, Flynn S. Factors affecting mortality in a large cohort study with special reference to oral contraceptive use. Contraception 2010; 82: 221–29.
Tackling breast cancer in India Priya Shetty’s World Report “India faces growing breast cancer epidemic” (March 17, p 992)1 rightly highlights an important problem, but Shetty does not question the evidence for some of the opinions expressed— eg, use of ultrasound or breast selfexamination screening. Ultrasound-based breast screening in the general population has not been sufficiently investigated, and breast self-examination has not shown any benefit.2 Clinical breast examination is being assessed in a large cluster-randomised trial3 in India; it seems to be a personnelintensive intervention that might be difficult to implement. And it is not only the question of resources for mammography screening, but also of its effectiveness, since the benefit of mammography screening is doubtful in women younger than 50 years,4 and almost 60% of breast cancer patients in India are younger than 55 years.5 Early detection in any form will not realise its potential if the treatment offered is not optimal; it could even be morally wrong if a patient is diagnosed early but then has limited or no access to treatment—a worst-case scenario that is presently quite possible in India. The cancer treatment given in non-specialty treatment facilities is www.thelancet.com Vol 379 June 23, 2012
systems, takes time, is complicated, and requires skilled researchers. This brings me back to the students: what of their future? Imagine that the requirement to be qualified for a science degree is nothing more than a laptop. Students will be taught in computer clusters with no recourse to science laboratories. We will produce students who are computer literate and can find their way around even the most complicated spreadsheet or database. But what happens when the students are required to take a patient’s blood pressure, understand where their data come from, or even do their own experiments? Research-led teaching in areas such as physiology is fundamental to science departments and too important to lose. We urge the decision makers to listen to all sides (including those whose futures will be most affected) and think very carefully about the consequences before axeing subjects. I declare that I have no conflicts of interest.
Rachel Ashworth [email protected] School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK 1
Allen JF, Missirlis F. Queen Mary: nobody expects the Spanish Inquisition. Lancet 2012; 379: 1785.
Oral contraceptives, nuns, and cancer Although we agree with Kara Britt and Roger Short (June 23, p 2322)1 that studying Catholic nuns could yield important information on the potential health effects of nulliparity and celibacy, we do not agree with their suggestion that the Catholic Church should encourage all its nuns to take the oral contraceptive pill on the grounds that it decreases lifetime risk of reproductive cancers. We propose that a personalised approach and screening might be more sensible. The recommendation that the contraceptive pill should be freely www.thelancet.com Vol 379 June 23, 2012
available to nuns is based on the study by Fraumeni and colleagues,2 who in 1969 reported that Catholic nuns are at increased risk of breast, uterine, and ovarian cancers. However, a study in 2000 by the same group3 reported that professionally active nuns have in fact favourable mortality rates compared with the general population, which the authors ascribed to the “healthy worker effect”. Further, a recent exhaustive literature search on mortality in members of the clergy4 found that Catholic nuns have a mortality advantage of roughly 20–25% over the general population. Nevertheless, a survey of breast cancer prevention in nuns found a need for increased engagement of breast-related health practices, including breast examination and mammography.5 Celibacy renders the risk of cervical cancer very low;2,3 thus, with improved information on breast cancer prevention, Catholic nuns are already in a favourable position to avoid death from gynaecological cancer, without a need for the oral contraceptive pill. We declare that we have no conflicts of interest.
*Ivo Brosens, Giuseppe Benagiano [email protected] Catholic University of Leuven, 3000 Leuven, Belgium (IB); and Department of Gynecology, Obstetrics and Urology, University of Rome “La Sapienza”, Rome, Italy (GB) 1 2
3
4
5
Britt K, Short R. The plight of nuns: hazards of nulliparity. Lancet 2012; 379: 2322–23. Fraumeni JF, Lloyd JW, Smith EM, Wagoner JK. Cancer mortality among nuns: role of marital status in etiology of neoplastic disease in women. J Natl Cancer Inst 1969; 42: 455–68. Doody MM, Mandel JS, Lubin JH, Boice JD Jr. Mortality among United States radiologic technologists, 1926–90. Cancer Causes Control 1998; 9: 67–75. Flanelly KJ, Weaver AJ, Larson DB, Koenig HG. A review of research on clergy and other religious professionals. J Religion Health 2002; 41: 57–68. Thiel L. Breast health of US women religious (nuns). Breast J 2008; 14: 581–83.
Kara Britt and Roger Short1 recommend that nuns should take oral contraceptives to prevent reproductive cancers. Besides nulliparity, nuns might have more repro-
ductive cancers than other women owing to deficiencies of vitamin D or other essential nutrients because of lack of sunlight or sparse diets. Any use of oral contraceptives is claimed to protect from ovarian cancer. This claim could be mistaken. A 2008 meta-analysis of 45 studies2 found that slightly fewer women with ovarian cancer had taken oral contraceptives, and for slightly fewer months, almost 20 years previously, than had women without ovarian cancer; the median age of cancer diagnosis was 56 years. By this age, many women would have taken fertility drugs or hormone replacement therapy (HRT), both of which increase cancer risks, including ovarian cancer.3,4 Adding HRT takers to never-takers of oral contraceptives would have falsely reduced risk estimates in oral contraceptive studies. It does not make scientific sense that progestagens and oestrogens can cause ovarian cancer when called HRT whereas the same hormones are claimed to prevent ovarian cancer when given for contraception. Also, women who die young might be missing from studies of older women or from studies with large losses to follow-up such as the Royal College of General Practitioners’ Oral Contraception Study.5 In that study, although most use started before enrolment in 1968, deaths were not flagged nationally until 1977. Most deaths were from cancer, especially breast cancer. 75% of deaths were notified 30–40 years after enrolment, when HRT use was likely but unrecorded, and oral contraceptive use was long past. However, nearly three times more ever-takers of oral contraceptives died before age 30 years than never-takers. Cancer prevention by oral contraceptives must be an illusion due to confusion in epidemiological studies.
See Comment page 2322
We declare that we have no conflicts of interest.
*Ellen C G Grant, Elizabeth H Price [email protected] 20 Coombe Ridings, Kingston-upon-Thames KT2 7JU, UK (ECGG); and London NW11 6SG, UK (EHP)
2339
Correspondence
1 2
3
Corbis
4
5
Britt K, Short RV. The plight of nuns: hazards of nulliparity. Lancet 2012; 379: 2322–23. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23 257 women with ovarian cancer and 87 303 controls. Lancet 2008; 371: 303–14. van Leeuwen FE, Klip H, Mooij TM, et al. Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort. Hum Reprod 2011; 12: 3456–65. Beral V, Bull D, Green J, Reeves G, for the Million Women Study Collaborators. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 2007; 69: 1703–10. Hannaford PC, Iversen L, Macfarlane TV, et al. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study. BMJ 2010; 340: c927.
Authors’ reply We agree with Ivo Brosens and Giuseppe Benagiano that a personalised approach is needed in the use of the oral contraceptive pill to protect against reproductive cancers, together with a proactive educational programme for nuns and other nulliparous women about the benefits of regular breast examinations and mammograms; a woman’s medical history should always be considered. We agree that nuns have a favourable overall mortality rate compared with the general population.1,2 However, the 20–25% decrease is specific to younger nuns, and older nuns are significantly less protected (8% at 80–84 years). The 20% increased risk of breast cancer in older nuns compared with the general population will affect these agespecific changes in mortality.3 Ellen Grant and Elizabeth Price are concerned that the confounding effects of hormone-replacement therapy (HRT) are not considered when the benefits of the oral contraceptive pill for ovarian and uterine cancer risk are considered. The Hannaford study4 reported that ever-users of the oral contraceptive pill were more likely to have used HRT (13·1% compared with 10% in never-users), so the increased risk of cancer in non-users of the oral contraceptive pill is very unlikely to 2340
result from an over-representation of HRT users. The epidemiological research that showed that the oral contraceptive pill can reduce ovarian and uterine cancers was first published in 2010. We need to know exactly how the oral contraceptive pill affects the reproductive tract, and whether age, duration of exposure, and dose affect its protective effects. To help define this effect, the Hannaford and Vessey data4,5 could be stratified by age at use, dose, parity, and HRT use. Assessment of the effects of progestagens and oestrogens on the reproductive tract premenopausally versus postmenopausally might also reveal why hormonal regimens have opposing effects in women of different reproductive status. Assessment of mortality by age in the Hannaford study would explain why young women (<30 years) had an adjusted relative risk of death of 2·85 when taking the oral contraceptive pill compared with never-users, and would help to define the optimum age window for protection. The latest epidemiological research suggests that the oral contraceptive pill might protect against ovarian cancer by reducing the monthly trauma of ovulation, and reduction of the frequency of menstruation might similarly protect the uterus. We hope that these observations will stimulate further research into how different hormonal regimens might help to protect women from ovarian and uterine cancers. And if we could emulate the proven protective effects of pregnancy and lactation against breast cancer, this might allow all women in the future to enjoy the benefits of healthy infertility. We declare that we have no conflicts of interest.
*Kara Britt, Roger Short [email protected] Prostate and Breast Cancer Research Program, Department of Anatomy and Developmental Biology, Monash University, VIC 3800, Australia (KB); and Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, VIC, Australia (RS)
1
2
3
4
5
Doody MM, Mandel JS, Linet MS, et al. Mortality among Catholic nuns certified as radiologic technologists. Am J Industrial Med 2000; 37: 339–48. Flannelly KJ, Weaver AJ, Larson DB, Koenig HG. A review of mortality research on clergy and other religious professionals. J Religion Health 2002; 41: 57–68. Butler SM, Snowdon DA. Trends in mortality in older women: findings from the Nun Study. J Gerontol 1996; 51B: S201–08. Hannaford PC, Iversen L, Macfarlane TV. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study. BMJ 2010; 340: 927–35. Vessey M, Yeates D, Flynn S. Factors affecting mortality in a large cohort study with special reference to oral contraceptive use. Contraception 2010; 82: 221–29.
Tackling breast cancer in India Priya Shetty’s World Report “India faces growing breast cancer epidemic” (March 17, p 992)1 rightly highlights an important problem, but Shetty does not question the evidence for some of the opinions expressed— eg, use of ultrasound or breast selfexamination screening. Ultrasound-based breast screening in the general population has not been sufficiently investigated, and breast self-examination has not shown any benefit.2 Clinical breast examination is being assessed in a large cluster-randomised trial3 in India; it seems to be a personnelintensive intervention that might be difficult to implement. And it is not only the question of resources for mammography screening, but also of its effectiveness, since the benefit of mammography screening is doubtful in women younger than 50 years,4 and almost 60% of breast cancer patients in India are younger than 55 years.5 Early detection in any form will not realise its potential if the treatment offered is not optimal; it could even be morally wrong if a patient is diagnosed early but then has limited or no access to treatment—a worst-case scenario that is presently quite possible in India. The cancer treatment given in non-specialty treatment facilities is www.thelancet.com Vol 379 June 23, 2012