- Email: [email protected]
The UK breast-screening programme should start at age 47 years
CORRESPONDENCE
medical specialists and on data from the Eindhoven Cancer Registry.2 Up to 82% of women with positive nodes would have received either adjuvant chemotherapy or hormonal treatment, depending on their menopausal status in 1984–91. However, the proportion of patients with involved axillary nodes receiving any form of adjuvant systemic therapy rose from 49% in 1984 to 82% in 1991.2 Of the node-positive patients younger than 55 years, 47% received adjuvant chemotherapy in 1984–85 and 73% in 1990–91. The proportion of node-positive patients aged 55 years or older on endocrine therapy rose from 0% in 1986–87 to 53% in 1990–91 in those with oestrogenreceptor-negative tumours, and from 50% in 1984–85 to 85% in 1990–91 when tumours were receptor-positive. Between 1991 and 2000, use of adjuvant systemic treatment remained rather stable, apart from a shift from short-term—ie, 1–2 years—to longterm use of tamoxifen. The mortality-lowering effect of the enhanced use of systemic treatment in the 1980s probably coincided with the introduction of the screening programme in the first half of the 1990s, and probably has continued ever since. Considering these figures, we believe that the reduction in mortality from breast cancer in the Netherlands in the first half of the 1990s can be largely attributed to widespread use of adjuvant systemic treatment. Screening seems a plausible explanation for the noted reductions in breast-cancer mortality in the late 1990s, 2000, and 2001, but to rule out an effect of improvements in use and quality of adjuvant chemotherapy and endocrine treatment is difficult. A later effect of mammography screening has been shown in the Swedish randomised trials,3 in which a reduction in breastcancer mortality started to take place about 4 years after randomisation. The effect would also be more in line with the clinical course of breast cancer, which is characterised by excess overall mortality 15–20 years after diagnosis and raised risk of dying from this disease more than 20 years after diagnosis.4 Considering the stepwise introduction of the Dutch screening programme between 1990 and 1997, the full effect cannot yet be seen. Further reductions of breast-cancer mortality, however, will most probably be diluted by the introduction of new guidelines for treatment of nodenegative breast cancer, which will cause a 50% rise in the proportion of patients who receive adjuvant systemic
246
treatment in Dutch hospitals.5 Thus, linkage with cause-of-death statistics and data of screening organisations and cancer registries is needed to get a reliable estimate of the true effect of mammography screening.
Peter C Gøtzsche Nordic Cochrane Centre, Rigshospitalet Dept 7112, Blegdamsvej 9, DK-2100 Copenhagen, Denmark (e-mail: [email protected]) 1
*Adri C Voogd, Jan Willem W Coebergh *Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, Netherlands (ACV); and Eindhoven Cancer Registry, Comprehensive Cancer Centre South, Eindhoven, Netherlands (JWWC) (e-mail: [email protected]) 1
2
3
4
5
Otto SJ, Fracheboud J, Looman CWN, et al. Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review. Lancet 2003; 361: 1411–17. Voogd AC, van Beek MW, Crommelin MA, Kluck HM, Repelaer van Driel OJ, Coebergh JW. Management of early breast cancer in southeast Netherlands since 1984: a population-based study. Acta Oncol 1994; 33: 753–57. Nyström L, Andersson I, Bjurstam N, Frisell J, Nordenskjöld B, Rutqvist LE. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet 2002; 359: 909–19. Louwman WJ, Klokman WJ, Coebergh JW. Excess mortality from breast cancer 20 years after diagnosis when life expectancy is normal. Br J Cancer 2001; 84: 700–03. Voogd AC, Louwman WJ, Coebergh JW, Vreugdenhil G. Impact of the new guidelines for adjuvant systemic treatment of breast cancer at hospital level [in Dutch]. Ned Tijdschr Geneeskd 2000; 144: 1572–74.
Sir–Suzie Otto and colleagues1 describe a significant fall in breastcancer mortality in the Netherlands after the introduction of mammography screening. However, this decrease in mortality was similar in women aged 45–49 years and in those aged 50–54 years, although only women aged 49 years and older were screened. Otto and colleagues point out that breast-cancer mortality is falling among women in the target agegroups in some countries that have introduced mammography screening. They do not, however, mention that the same decrease has been seen in other countries that do not have national screening programmes, such as Austria, Germany, and Switzerland.2,3 Between 1988 and 1998, the age-standardised fall in breast-cancer mortality in Europe was larger among women in those agegroups not invited for screening (women aged 20–49 years) than in those aged 50–69 years (16·3% vs 8·6%).3 These observations lend support to a statement in a 2002 WHO report4 that observational studies cannot provide evidence of an effect of screening on mortality from breast cancer.
2
3
4
Otto SJ, Fracheboud J, Looman CWN, et al. Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review. Lancet 2003; 361: 1411–17. Levi F, Lucchini F, Negri E, Boyle P, La Vecchia C. Cancer mortality in Europe, 1990–1994, and an overview of trends from 1955 to 1994. Eur J Cancer 1999; 35: 1477–516. Levi F, Lucchini F, Negri E, La Vecchia C. The fall in breast cancer mortality in Europe. Eur J Cancer 2001; 37: 1409–12. Vainio H, Bianchini F, eds. IARC handbooks of cancer prevention. Volume 7: breast cancer screening. Lyon: IARC Press, 2002: 1–229.
The UK breast-screening programme should start at age 47 years Sir—The UK National Health Services (NHS) Breast-Screening Programme invites women aged 50–64 years for screening every 3 years. This is being expanded to include women aged 65–70 years. However, there are no plans to lower the age at which women are first invited for mammographic screening. Decisions about lowering the starting age seem to be dependent on a trial that is still underway, in which 53 000 women aged 40–41 years were invited for screening between 1991 and 1996. That trial is not scheduled to report until the end of next year, and is not large enough to be able to identify a difference in efficacy for women aged 47–49 years compared with women in their early 40s. We argue that even before the results become available, the age at which women are first invited for screening should be lowered to age 47 years. The main argument rests on the age-specific incidence of breast cancer before the introduction of screening (1980–89) and the similar relative protection of screening at different ages. At age 40 years, the annual rate of breast cancer is 79 per 100 000 women, but rises substantially to 148 per 100 000 women at age 47 years and 152 per 100 000 women at age 48 years. Between age 48 and 54 years, the rates of breast cancer plateau before again increasing more slowly reaching 221 per 100 000 women by age 64 years. Thus, the incidence rate of breast cancer at age 48–49 years is
THE LANCET • Vol 362 • July 19, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
CORRESPONDENCE
as great as that at age 50–54 years, and the number of life-years that could be saved is potentially greater among these younger women. Evidence indicates that mammographic screening at age 47–49 years is no less sensitive than at age 50–54 years. Laszlo Tabar and colleagues (April 26, p 1405),1 who assessed the mammography service screening in Sweden, found the relative protection afforded by screening in women aged 40–49 years was as great as that in those aged 50–59 years. Hendrick and colleagues’ meta-analysis2 of eight randomised trials showed a significant reduction in mortality as a result of mammographic screening at age 40–49 years. Nystrom and colleagues’ combined analysis3 of Swedish randomised trials showed that the relative rate of death from breast cancer was similar in women aged 40–49 years and in those aged 50–59 years (0·80 vs 0·84), although it was somewhat less in women aged 60–69 years (0·67). Furthermore, the relative risk of dying from breast cancer in women randomised to screening was lower in women aged 45–49 years than in those aged 50–54 years (0·78 vs 0·95), although this difference was not significant. Although it is justifiable not to screen women in their early 40s without additional evidence, the case for offering screening to women aged 47 years is as strong as the case for offering screening to women aged 50 years. Starting mammographic screening at age 47 years, rather than at age 48 years, allows for a 1 year lead-time for screen-detected cancers. We propose that it is time to begin screening at age 47 years in all women, with screening every 3 years thereafter. *Peter Sasieni, Jack Cuzick Cancer Research UK, Department of Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, London EC1M 6BQ, UK (e-mail: [email protected]) 1
2
3
Tabar L, Yen MF, Vitak B, Chen HH, Smith RA, Duffy SW. Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening. Lancet 2003; 361: 1405–10. Hendrick RE, Smith RA, Rutledge JH 3rd, Smart CR. Benefit of screening mammography in women aged 40–49: a new meta-analysis of randomized controlled trials. J Natl Cancer Inst Monogr 1997; 22: 87–92. Nystrom L, Andersson I, Bjurstam N, Frisell J, Nordenskjold B, Rutqvist LE. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet. 2002; 359: 909–19.
Should we encourage exclusive breastfeeding at all cost? Sir—Nita Bhandari and colleagues (April 26, p 1418)1 note that exclusive breastfeeding in infants until age 6 months in a developing country is feasible, reduces the risk of diarrhoea, and does not lead to growth faltering. This statement fits what is known about the advantages of breastfeeding, which is also a protective factor against malnutrition and parasitic diseases (such as malaria) in developing countries. Bhandari and co-workers also note that WHO guidelines2 recommend exclusive breastfeeding in infants for the first 6 months of life. In view of this recommendation and on the basis of their findings, they argue that behaviour change in mothers toward feeding habits of young children is desirable and possible on a large scale. However, these same guidelines2 also indicate that some mothers will be unable to, or will choose not to, follow this recommendation. In developing countries, for example, where HIV-1 prevalence in the general population and specifically in pregnant women is high, encouraging exclusive breastfeeding in infants could pose a serious threat to the child’s health. United Nations Programme on HIV/AIDS (UNAIDS)3 estimates that 800 000 children were newly infected with HIV-1 in 2002, and that 90% of these new infections occurred in subSaharan Africa. Almost all HIV-1infected children acquire HIV-1 from their mothers. Transmission can arise during pregnancy, at delivery, and after birth through breastfeeding. Mother-to-child transmission rates, without any antiretroviral intervention, range from 15% to 30% in the absence of breastfeeding, from 25% to 35% if there is breastfeeding through 6 months, and from 30% to 45% if there is breastfeeding through 18–24 months.4 Thus, the risk of HIV-1 transmission through breastfeeding is high in early infancy and persists as long as breastfeeding continues. Health education programmes aimed at encouraging exclusive breastfeeding in developing countries should, therefore, not be undertaken lightly. They should be implemented at community level and take into account HIV-1 prevalence in the general population, the global burden of infectious disease and malnutrition, and the availability of treatment. In other words, policies aimed at encouraging breastfeeding should be
cautiously tailored to the existing epidemiological context, at a local level, and on a small scale. Hugo Pilkington Department of Geography, University of Paris (Saint-Denis), 93526 Saint-Denis Cedex 02, Paris, France (e-mail: [email protected]) 1
2
3
4
Bhandari N, Bahl R, Mazumdar S, et al. Effect of community-based promotion of exclusive breastfeeding on diarrhoeal illness and growth: a cluster randomised controlled trial. Lancet 2003; 361: 1418–23. WHO. The optimal duration of exclusive breastfeeding: report of an expert consultation, Geneva, Switzerland, March 28–30, 2001. Geneva: World Health Organization, 2002. UNAIDS/WHO. AIDS epidemic update, December, 2002. Geneva: UNAIDS/WHO, 2002. De Cock KM, Fowler MG, Mercier E, et al. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA 2000; 283: 1175–82.
Clitoral surgery and sexual outcome in intersex individuals Sir—We agree with Catherine Minto and colleagues (April 12, p 1252)1 that individuals with ambiguous genitalia who are reared as females and undergo surgical removal of parts of the clitoris may later have compromised sexual function. However, to blame clitoral surgery alone for these difficulties seems excessive. Minto and colleagues’ cohort includes patients with congenital adrenal hyperplasia, partial androgen insensitivity, gonadal dysgenesis, and true hermaphrodism. These conditions are so different that grouping such individuals together hardly allows for any meaningful generalisations to be made. For example, unlike the patients in whom castration limits endogenous longterm hormonal influences, those with adrenal hyperplasia not only keep their gonads but also their secreting adrenals, which may produce androgens along the circadian cycle despite well monitored corticosteroid treatment.2 The fairly high number of iterative resections after regrowth of the clitoris in Minto and colleagues’ series illustrates this point. Those individuals with intersex conditions who are exposed to prenatal androgen influence—for example, those with adrenal hyperplasia—might have their gender attitudes, and hence their sexual
THE LANCET • Vol 362 • July 19, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
247
medical specialists and on data from the Eindhoven Cancer Registry.2 Up to 82% of women with positive nodes would have received either adjuvant chemotherapy or hormonal treatment, depending on their menopausal status in 1984–91. However, the proportion of patients with involved axillary nodes receiving any form of adjuvant systemic therapy rose from 49% in 1984 to 82% in 1991.2 Of the node-positive patients younger than 55 years, 47% received adjuvant chemotherapy in 1984–85 and 73% in 1990–91. The proportion of node-positive patients aged 55 years or older on endocrine therapy rose from 0% in 1986–87 to 53% in 1990–91 in those with oestrogenreceptor-negative tumours, and from 50% in 1984–85 to 85% in 1990–91 when tumours were receptor-positive. Between 1991 and 2000, use of adjuvant systemic treatment remained rather stable, apart from a shift from short-term—ie, 1–2 years—to longterm use of tamoxifen. The mortality-lowering effect of the enhanced use of systemic treatment in the 1980s probably coincided with the introduction of the screening programme in the first half of the 1990s, and probably has continued ever since. Considering these figures, we believe that the reduction in mortality from breast cancer in the Netherlands in the first half of the 1990s can be largely attributed to widespread use of adjuvant systemic treatment. Screening seems a plausible explanation for the noted reductions in breast-cancer mortality in the late 1990s, 2000, and 2001, but to rule out an effect of improvements in use and quality of adjuvant chemotherapy and endocrine treatment is difficult. A later effect of mammography screening has been shown in the Swedish randomised trials,3 in which a reduction in breastcancer mortality started to take place about 4 years after randomisation. The effect would also be more in line with the clinical course of breast cancer, which is characterised by excess overall mortality 15–20 years after diagnosis and raised risk of dying from this disease more than 20 years after diagnosis.4 Considering the stepwise introduction of the Dutch screening programme between 1990 and 1997, the full effect cannot yet be seen. Further reductions of breast-cancer mortality, however, will most probably be diluted by the introduction of new guidelines for treatment of nodenegative breast cancer, which will cause a 50% rise in the proportion of patients who receive adjuvant systemic
246
treatment in Dutch hospitals.5 Thus, linkage with cause-of-death statistics and data of screening organisations and cancer registries is needed to get a reliable estimate of the true effect of mammography screening.
Peter C Gøtzsche Nordic Cochrane Centre, Rigshospitalet Dept 7112, Blegdamsvej 9, DK-2100 Copenhagen, Denmark (e-mail: [email protected]) 1
*Adri C Voogd, Jan Willem W Coebergh *Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, Netherlands (ACV); and Eindhoven Cancer Registry, Comprehensive Cancer Centre South, Eindhoven, Netherlands (JWWC) (e-mail: [email protected]) 1
2
3
4
5
Otto SJ, Fracheboud J, Looman CWN, et al. Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review. Lancet 2003; 361: 1411–17. Voogd AC, van Beek MW, Crommelin MA, Kluck HM, Repelaer van Driel OJ, Coebergh JW. Management of early breast cancer in southeast Netherlands since 1984: a population-based study. Acta Oncol 1994; 33: 753–57. Nyström L, Andersson I, Bjurstam N, Frisell J, Nordenskjöld B, Rutqvist LE. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet 2002; 359: 909–19. Louwman WJ, Klokman WJ, Coebergh JW. Excess mortality from breast cancer 20 years after diagnosis when life expectancy is normal. Br J Cancer 2001; 84: 700–03. Voogd AC, Louwman WJ, Coebergh JW, Vreugdenhil G. Impact of the new guidelines for adjuvant systemic treatment of breast cancer at hospital level [in Dutch]. Ned Tijdschr Geneeskd 2000; 144: 1572–74.
Sir–Suzie Otto and colleagues1 describe a significant fall in breastcancer mortality in the Netherlands after the introduction of mammography screening. However, this decrease in mortality was similar in women aged 45–49 years and in those aged 50–54 years, although only women aged 49 years and older were screened. Otto and colleagues point out that breast-cancer mortality is falling among women in the target agegroups in some countries that have introduced mammography screening. They do not, however, mention that the same decrease has been seen in other countries that do not have national screening programmes, such as Austria, Germany, and Switzerland.2,3 Between 1988 and 1998, the age-standardised fall in breast-cancer mortality in Europe was larger among women in those agegroups not invited for screening (women aged 20–49 years) than in those aged 50–69 years (16·3% vs 8·6%).3 These observations lend support to a statement in a 2002 WHO report4 that observational studies cannot provide evidence of an effect of screening on mortality from breast cancer.
2
3
4
Otto SJ, Fracheboud J, Looman CWN, et al. Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review. Lancet 2003; 361: 1411–17. Levi F, Lucchini F, Negri E, Boyle P, La Vecchia C. Cancer mortality in Europe, 1990–1994, and an overview of trends from 1955 to 1994. Eur J Cancer 1999; 35: 1477–516. Levi F, Lucchini F, Negri E, La Vecchia C. The fall in breast cancer mortality in Europe. Eur J Cancer 2001; 37: 1409–12. Vainio H, Bianchini F, eds. IARC handbooks of cancer prevention. Volume 7: breast cancer screening. Lyon: IARC Press, 2002: 1–229.
The UK breast-screening programme should start at age 47 years Sir—The UK National Health Services (NHS) Breast-Screening Programme invites women aged 50–64 years for screening every 3 years. This is being expanded to include women aged 65–70 years. However, there are no plans to lower the age at which women are first invited for mammographic screening. Decisions about lowering the starting age seem to be dependent on a trial that is still underway, in which 53 000 women aged 40–41 years were invited for screening between 1991 and 1996. That trial is not scheduled to report until the end of next year, and is not large enough to be able to identify a difference in efficacy for women aged 47–49 years compared with women in their early 40s. We argue that even before the results become available, the age at which women are first invited for screening should be lowered to age 47 years. The main argument rests on the age-specific incidence of breast cancer before the introduction of screening (1980–89) and the similar relative protection of screening at different ages. At age 40 years, the annual rate of breast cancer is 79 per 100 000 women, but rises substantially to 148 per 100 000 women at age 47 years and 152 per 100 000 women at age 48 years. Between age 48 and 54 years, the rates of breast cancer plateau before again increasing more slowly reaching 221 per 100 000 women by age 64 years. Thus, the incidence rate of breast cancer at age 48–49 years is
THE LANCET • Vol 362 • July 19, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
CORRESPONDENCE
as great as that at age 50–54 years, and the number of life-years that could be saved is potentially greater among these younger women. Evidence indicates that mammographic screening at age 47–49 years is no less sensitive than at age 50–54 years. Laszlo Tabar and colleagues (April 26, p 1405),1 who assessed the mammography service screening in Sweden, found the relative protection afforded by screening in women aged 40–49 years was as great as that in those aged 50–59 years. Hendrick and colleagues’ meta-analysis2 of eight randomised trials showed a significant reduction in mortality as a result of mammographic screening at age 40–49 years. Nystrom and colleagues’ combined analysis3 of Swedish randomised trials showed that the relative rate of death from breast cancer was similar in women aged 40–49 years and in those aged 50–59 years (0·80 vs 0·84), although it was somewhat less in women aged 60–69 years (0·67). Furthermore, the relative risk of dying from breast cancer in women randomised to screening was lower in women aged 45–49 years than in those aged 50–54 years (0·78 vs 0·95), although this difference was not significant. Although it is justifiable not to screen women in their early 40s without additional evidence, the case for offering screening to women aged 47 years is as strong as the case for offering screening to women aged 50 years. Starting mammographic screening at age 47 years, rather than at age 48 years, allows for a 1 year lead-time for screen-detected cancers. We propose that it is time to begin screening at age 47 years in all women, with screening every 3 years thereafter. *Peter Sasieni, Jack Cuzick Cancer Research UK, Department of Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, London EC1M 6BQ, UK (e-mail: [email protected]) 1
2
3
Tabar L, Yen MF, Vitak B, Chen HH, Smith RA, Duffy SW. Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening. Lancet 2003; 361: 1405–10. Hendrick RE, Smith RA, Rutledge JH 3rd, Smart CR. Benefit of screening mammography in women aged 40–49: a new meta-analysis of randomized controlled trials. J Natl Cancer Inst Monogr 1997; 22: 87–92. Nystrom L, Andersson I, Bjurstam N, Frisell J, Nordenskjold B, Rutqvist LE. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet. 2002; 359: 909–19.
Should we encourage exclusive breastfeeding at all cost? Sir—Nita Bhandari and colleagues (April 26, p 1418)1 note that exclusive breastfeeding in infants until age 6 months in a developing country is feasible, reduces the risk of diarrhoea, and does not lead to growth faltering. This statement fits what is known about the advantages of breastfeeding, which is also a protective factor against malnutrition and parasitic diseases (such as malaria) in developing countries. Bhandari and co-workers also note that WHO guidelines2 recommend exclusive breastfeeding in infants for the first 6 months of life. In view of this recommendation and on the basis of their findings, they argue that behaviour change in mothers toward feeding habits of young children is desirable and possible on a large scale. However, these same guidelines2 also indicate that some mothers will be unable to, or will choose not to, follow this recommendation. In developing countries, for example, where HIV-1 prevalence in the general population and specifically in pregnant women is high, encouraging exclusive breastfeeding in infants could pose a serious threat to the child’s health. United Nations Programme on HIV/AIDS (UNAIDS)3 estimates that 800 000 children were newly infected with HIV-1 in 2002, and that 90% of these new infections occurred in subSaharan Africa. Almost all HIV-1infected children acquire HIV-1 from their mothers. Transmission can arise during pregnancy, at delivery, and after birth through breastfeeding. Mother-to-child transmission rates, without any antiretroviral intervention, range from 15% to 30% in the absence of breastfeeding, from 25% to 35% if there is breastfeeding through 6 months, and from 30% to 45% if there is breastfeeding through 18–24 months.4 Thus, the risk of HIV-1 transmission through breastfeeding is high in early infancy and persists as long as breastfeeding continues. Health education programmes aimed at encouraging exclusive breastfeeding in developing countries should, therefore, not be undertaken lightly. They should be implemented at community level and take into account HIV-1 prevalence in the general population, the global burden of infectious disease and malnutrition, and the availability of treatment. In other words, policies aimed at encouraging breastfeeding should be
cautiously tailored to the existing epidemiological context, at a local level, and on a small scale. Hugo Pilkington Department of Geography, University of Paris (Saint-Denis), 93526 Saint-Denis Cedex 02, Paris, France (e-mail: [email protected]) 1
2
3
4
Bhandari N, Bahl R, Mazumdar S, et al. Effect of community-based promotion of exclusive breastfeeding on diarrhoeal illness and growth: a cluster randomised controlled trial. Lancet 2003; 361: 1418–23. WHO. The optimal duration of exclusive breastfeeding: report of an expert consultation, Geneva, Switzerland, March 28–30, 2001. Geneva: World Health Organization, 2002. UNAIDS/WHO. AIDS epidemic update, December, 2002. Geneva: UNAIDS/WHO, 2002. De Cock KM, Fowler MG, Mercier E, et al. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA 2000; 283: 1175–82.
Clitoral surgery and sexual outcome in intersex individuals Sir—We agree with Catherine Minto and colleagues (April 12, p 1252)1 that individuals with ambiguous genitalia who are reared as females and undergo surgical removal of parts of the clitoris may later have compromised sexual function. However, to blame clitoral surgery alone for these difficulties seems excessive. Minto and colleagues’ cohort includes patients with congenital adrenal hyperplasia, partial androgen insensitivity, gonadal dysgenesis, and true hermaphrodism. These conditions are so different that grouping such individuals together hardly allows for any meaningful generalisations to be made. For example, unlike the patients in whom castration limits endogenous longterm hormonal influences, those with adrenal hyperplasia not only keep their gonads but also their secreting adrenals, which may produce androgens along the circadian cycle despite well monitored corticosteroid treatment.2 The fairly high number of iterative resections after regrowth of the clitoris in Minto and colleagues’ series illustrates this point. Those individuals with intersex conditions who are exposed to prenatal androgen influence—for example, those with adrenal hyperplasia—might have their gender attitudes, and hence their sexual
THE LANCET • Vol 362 • July 19, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
247