- Email: [email protected]
Emergency contraception: WHO Task Force study
CORRESPONDENCE
hypothesis that meconium aspiration is an inflammatory condition. Much remains to be learned about the mechanisms underlying inflammation in meconium aspiration and many proinflammatory and antiinflammatory mediators are probably involved. Hopefully, further research will give new insights into the role of IL-8 and other mediators in the pathogenesis of this complex syndrome. A J de Beaufort Neonatal Unit, Department of Pediatrics, Leiden University Medical Center, PO Box 9600, 2300RC Leiden, Netherlands 1
2
3
4
5
Olah KS, Vince GS, Neilson JP, Deniz G, Johnson PM. Interleukin-6, interferongamma, interleukin-8, and granulocytemacrophage colony stimulating factor levels in human amniotic fluid at term. J Reprod Immunol 1996; 32: 89–98. Smith JB, Kunjummen RD, Kishimoto TK, Anderson DC. Expression and regulation of L-selectin on eosinophils from human adults and neonates. Pediatr Res 1992; 32: 465–71. Burgess AM, Hutchins GM. Inflammation of the lungs, umbilical cord and placenta associated with meconium passage in utero. Review of 123 autopsied cases. Pathol Res Pract 1996; 192: 1121–28. Perlman EJ, Moore GW, Hutchins GM. The pulmonary vasculature in meconium aspiration. Hum Pathol 1989; 20: 701–06. Wiswell TE, Henley MA. Intratracheal suctioning, systemic infection, and the meconium aspiration syndrome. Pediatrics 1992; 89: 203–06.
Effect of early American results on patients in a tamoxifen prevention trial (IBIS) Sir—After a report that tamoxifen after surgery for breast cancer prevented new cancers in the contralateral breast,1 a pilot prevention trial was set up in the UK under the auspices of the United Kingdom Co-ordinating Committee for Cancer Research (UKCCCR) (July 11, p 98). 2 A definitive trial, The International Breast Cancer Intervention Study (IBIS), was begun in the UK, Europe, and Australia in 1992. The study requires a sample of 7000 women. So far 4536 women have been randomised to 5 years of either tamoxifen or placebo. Other prevention trials were also initiated in America and Italy.3,4 In April, 1998, the results from the first three and a half years of the American trial were outlined on the Internet. Researchers reported a 45% decrease in new breast cancers in women taking tamoxifen and an increase in endometrial cancer and thrombotic or
1222
embolic events.3 In view of the positive results on rate of breast cancer, the study was terminated. Following our standard practice all women in IBIS were immediately informed of the American results by post. To assess the effects of these preliminary positive results on women who participated in IBIS in Manchester, a twenty-item questionnaire was circulated. The questionnaire asked whether there were any beneficial or adverse effects of the publicity and whether it interfered with willingness to continue in the trial. 236 of 318 (74%) questionnaires were returned. Most women 206 (87%) had read the IBIS circular and were aware of the national publicity. Surprisingly, 86 (36%) were now even more willing to take part in the trial and almost all 226 (96%) felt that IBIS should continue. All respondents said that they wished to continue treatment, although three women did not answer this question. However, almost a third (75) had increased concerns about the toxicity of tamoxifen highlighted by the American results and a quarter (61) felt that the publicity would be detrimental to further recruitment into IBIS. To our knowledge none of the participants have left the trial as a result of the American Internet release. They were aware of the need for longer follow-up and results from other studies to be certain about the riskbenefit ratio of tamoxifen preventive treatment.5 Published early negative results from the Royal Marsden and Italian studies support this view.2,4 What effect these new results will have on trial participation remains to be seen. The IBIS Working Party and Data monitoring committee have both recommended that recruitment should continue and that no results on efficacy be released at this time. These questionnaire data indicate the continued commitment of women to IBIS. However, the attitudes of the 82 women who did not respond to the questionnaire are unknown. Respondents were pleased that the IBIS trial organisers were quick to provide clear information to aid decision-making, rather than leave them with media interpretations and speculation. Owen Hutchings, Gareth Evans, *Lesley Fallowfield, Jack Cuzick, Anthony Howell CRC Department of Medical Oncology and Department of Medical Genetics, Christie Hospital, Manchester, ICRF Department of Mathematics, Statistics and Epidemiology, London; and *CRC Psychosocial Oncology Group, University College Hospital Medical School, London W1P 7PL, UK
1
2
3
4
5
Cuzick J, Baum M. Tamoxifen and contralateral breast cancer. Lancet 1985; 2: 282. Powles T, Eeles R, Ashley S, et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 1998; 352: 98–101. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant and Bowel Project P-1 study. J Natl Cancer Inst 1998; 90: 1371–88. Veronesi U, Maisonneuve P, Costa A, et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Lancet 1998; 352: 93–97. Paolo Bruzzi. Tamoxifen for the prevention of breast cancer. Important questions remain unanswered, and existing trials should continue. BMJ 1998; 316: 1181–82.
Emergency contraception: WHO Task Force study Sir—The World Health Organization Task Force on Postovulatory Methods of Fertility Regulation (Aug 8, p 428)1 concluded that “the earlier emergency contraceptive treatment was given, the greater its efficacy, with a downward gradient in efficacy from treatment within 24 h to treatment within 49–72 h (p=0·01)”. Specifically, the efficacy of each of the two most common treatment regimens (the standard Yuzpe regimen and the levonorgestrel-only regimen) dropped significantly as time elapsed between unprotected intercourse and the start of treatment. This issue is important because of its implications for public awareness campaigns about emergency contraception, for the current prescription-only status of the drugs, and for tailoring the therapy to be user friendly by letting women wait to start treatment at a time when the second dose, taken 12 h after the first, would be convenient. As the investigators note, their results contrast with the result of an analysis2 of nine published reports of the efficacy of the Yuzpe regimen. That review found that timing of treatment did not affect efficacy; the treatment worked equally well when started 1, 2, or 3 days after unprotected intercourse. The WHO investigators “suspect that the discrepancy is due to the lack of bias in randomised controlled trials as compared with observational studies”. However, this explanation clearly cannot be correct. The only random assignment in the WHO trial was to one of the two treatment regimens. For this reason, comparisons made across other patient characteristics are just as vulnerable to bias as would be comparisons in an
THE LANCET • Vol 352 • October 10, 1998
CORRESPONDENCE
observational study. With respect to the timing of treatment after unprotected intercourse, therefore, the WHO study should not automatically be accorded any more weight than the nine previous studies, despite its different result. Nevertheless, with the conflicting evidence, I agree with the conclusion that “women should receive treatment as soon as practicable after unprotected coitus”, provided that it is interpreted to mean that treatment could be delayed by a few hours to avoid having to take the second dose at a very inconvenient time (such as 0300 h) and provided that women are not denied treatment after 24 h, or after 48 h, or even after 72 h with proper informed consent, especially when the option of insertion of a copper intrauterine device is not available or appropriate. James Trussell Office of Population Research, Princeton University, Princeton, NJ 08544, USA 1
2
Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet 1998; 352: 428–33. Trussell J, Ellertson C, Rodríguez G. The Yuzpe regimen of emergency contraception: how long after the morning after? Obstet Gynecol 1996; 88: 150–54.
Sir—The use of progestagens alone for emergency contraception is attractive in terms of safety and efficacy over the Yuzpe regimen, as the Task Force on Postovulatory Methods of Fertility Regulation pointed out.1 This regimen may be useful for over-the-counter, emergency contraception since it has fewer contraindications than the oestrogen-progestagen combined regimen commonly used. However, this is not so in every European country or in the USA. It is perplexing that levonorgestrel is indicated in women with thromboembolic disease, as John Guillebaud points out quite rightly in his commentary 2 accompanying the WHO report, and yet previous thromboembolism is regarded as the number one cointraindication clearly spelled out in the drug leaflet for all progestagens, irrespective of dose and route of administration, sold in Italy and I believe in other countries too. Two cases that I have come across illustrate quite well this dilemma. A 42-year-old woman with lupus erythematosus (SLE) and a previous deep-vein thrombosis followed by pulmonary embolism came to me requesting contraception and relief of her heavy menstrual periods.
THE LANCET • Vol 352 • October 10, 1998
Medroxyprogesterone acetate (DepoProvera 150 mg, Pharmacia Upjohn, Kalamazoo, MI, USA) a progestagen only injectable form of contraceptive, was, I believed, the drug of choice both for its effectiveness and for the amenorrhoea that it produces, until the patient pointed out the contraindications mentioned in the drug leaflet. Needless to say, a progesterone-only pill would not have fared any better in her case: the leaflet for Microlut (levonorgestrel 0·030 mg, Schering, Berlin, Germany), the only progesterone-only pill sold in Italy has the same contraindication. A 45-year-old patient was advised by her ophthalmologist against the use of cyclical norethisterone acetate given to control menorrhagia. The patient had had severe retinal detachment secondary to myopia, and her ophthalmologist feared that the increased risk of thrombosis associated with the use of progestagen, as highlighted in the drug leaflet (Primolut-Nor, Schering), might compromise further her eyesight. These two cases represent, in my opinion, the multitude of women that can become victims of dubious, hardly supported scientifically, and most variously interpreted, contraindications reported in drug leaflets for progestagens. Sadly, the patients are left with the short end of the stick. The women who are at real risk of thromboembolism and for whom oestrogen certainly is contraindicated are thus deprived of the only class of drugs previously available to them both for contraception and menstrual cycle control. In these patients, unreliable contraception and surgery put them at even higher risk of thrombosis, and yet they are the only choice left to them. Surely, no doctor or patient in his or her right mind would use a drug after having read the contraindication so clearly spelled out on the box. It is unfortunate that such a useful and inexpensive medication, a potential solution to so many gynaecological problems, is no longer available for patients who would need it most, and this, in all likelihood, is attributable to some obscure medical legal hitch.
Low carbohydrate intake and oral glucose-tolerance tests Sir—Takashi Kaneko and colleagues (July 25, p 289)1 discuss the importance of carbohydrate intake before an oral glucose-tolerance tests (OGTT). They conclude that the impaired glucose tolerance after a low-carbohydrate meal is due to the proportionally less insulin release in response to glycaemic stimulus, and that the decrease in insulin secretion is associated with the Randle effect.2 The insulinogenic index was significantly decreased after the low-carbohydrate intake, but no significant difference in the insulin concentrations before and 30 min after OGTT was found between patients on the low-carbohydrate intake and highcarbohydrate intake. Therefore, we think that the impaired glucose tolerance after the low-carbohydrate intake reflects insulin resistance rather than decreased insulin secretion, since free fatty acids inhibit use of insulinstimulated glucose in muscle via the Randle effect.3 A fasting plasma glucose test is superior to OGTT to diagnose and classify diabetes mellitus in terms of screening and cost peformance.4 However, it is inappropriate to conclude the OGTT is diagnostically inferior to a fasting plasma glucose test because individuals with impaired fasting glucose may include both impaired glucose tolerance and diabetes when OGTT is done, although particular attention should be paid to the last carbohydrate intake. *Keiji Yoshioka, Sadayoshi Yokoh, Toshihide Yoshida *First Department of Internal Medicine, Matsushita Memorial Hospital, Osaka 570, Japan; and First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto 1
2
3
Paola Albertazzi Ospedale Maternità, 40123 Bologna, Italy 1
2
Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet 1998; 352: 428–33. Guillebaud J. Time for emergency contraception with levonorgestrel alone. Lancet 1998; 352: 416–17.
4
Kaneko T, Wang P-Y, Tawata M, Sato A. Low carbohydrate intake before oral glucosetolerance tests. Lancet 1998; 352: 289. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty acid cycle; its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963; i: 785–89. Randle PJ, Kerbey AL, Espinal J. Mechanisms decreasing glucose oxidation in diabetes and starvation: role of lipid fuels and hormones. Diabetes Metab Rev 1988; 4: 623–38. Expert Commirty of the Diagnosis and Classidication of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183–97.
Sir—Takashi Kaneko and colleagues1 conclude that when an OGTT is used to classify patients’ glucose tolerance as
1223
hypothesis that meconium aspiration is an inflammatory condition. Much remains to be learned about the mechanisms underlying inflammation in meconium aspiration and many proinflammatory and antiinflammatory mediators are probably involved. Hopefully, further research will give new insights into the role of IL-8 and other mediators in the pathogenesis of this complex syndrome. A J de Beaufort Neonatal Unit, Department of Pediatrics, Leiden University Medical Center, PO Box 9600, 2300RC Leiden, Netherlands 1
2
3
4
5
Olah KS, Vince GS, Neilson JP, Deniz G, Johnson PM. Interleukin-6, interferongamma, interleukin-8, and granulocytemacrophage colony stimulating factor levels in human amniotic fluid at term. J Reprod Immunol 1996; 32: 89–98. Smith JB, Kunjummen RD, Kishimoto TK, Anderson DC. Expression and regulation of L-selectin on eosinophils from human adults and neonates. Pediatr Res 1992; 32: 465–71. Burgess AM, Hutchins GM. Inflammation of the lungs, umbilical cord and placenta associated with meconium passage in utero. Review of 123 autopsied cases. Pathol Res Pract 1996; 192: 1121–28. Perlman EJ, Moore GW, Hutchins GM. The pulmonary vasculature in meconium aspiration. Hum Pathol 1989; 20: 701–06. Wiswell TE, Henley MA. Intratracheal suctioning, systemic infection, and the meconium aspiration syndrome. Pediatrics 1992; 89: 203–06.
Effect of early American results on patients in a tamoxifen prevention trial (IBIS) Sir—After a report that tamoxifen after surgery for breast cancer prevented new cancers in the contralateral breast,1 a pilot prevention trial was set up in the UK under the auspices of the United Kingdom Co-ordinating Committee for Cancer Research (UKCCCR) (July 11, p 98). 2 A definitive trial, The International Breast Cancer Intervention Study (IBIS), was begun in the UK, Europe, and Australia in 1992. The study requires a sample of 7000 women. So far 4536 women have been randomised to 5 years of either tamoxifen or placebo. Other prevention trials were also initiated in America and Italy.3,4 In April, 1998, the results from the first three and a half years of the American trial were outlined on the Internet. Researchers reported a 45% decrease in new breast cancers in women taking tamoxifen and an increase in endometrial cancer and thrombotic or
1222
embolic events.3 In view of the positive results on rate of breast cancer, the study was terminated. Following our standard practice all women in IBIS were immediately informed of the American results by post. To assess the effects of these preliminary positive results on women who participated in IBIS in Manchester, a twenty-item questionnaire was circulated. The questionnaire asked whether there were any beneficial or adverse effects of the publicity and whether it interfered with willingness to continue in the trial. 236 of 318 (74%) questionnaires were returned. Most women 206 (87%) had read the IBIS circular and were aware of the national publicity. Surprisingly, 86 (36%) were now even more willing to take part in the trial and almost all 226 (96%) felt that IBIS should continue. All respondents said that they wished to continue treatment, although three women did not answer this question. However, almost a third (75) had increased concerns about the toxicity of tamoxifen highlighted by the American results and a quarter (61) felt that the publicity would be detrimental to further recruitment into IBIS. To our knowledge none of the participants have left the trial as a result of the American Internet release. They were aware of the need for longer follow-up and results from other studies to be certain about the riskbenefit ratio of tamoxifen preventive treatment.5 Published early negative results from the Royal Marsden and Italian studies support this view.2,4 What effect these new results will have on trial participation remains to be seen. The IBIS Working Party and Data monitoring committee have both recommended that recruitment should continue and that no results on efficacy be released at this time. These questionnaire data indicate the continued commitment of women to IBIS. However, the attitudes of the 82 women who did not respond to the questionnaire are unknown. Respondents were pleased that the IBIS trial organisers were quick to provide clear information to aid decision-making, rather than leave them with media interpretations and speculation. Owen Hutchings, Gareth Evans, *Lesley Fallowfield, Jack Cuzick, Anthony Howell CRC Department of Medical Oncology and Department of Medical Genetics, Christie Hospital, Manchester, ICRF Department of Mathematics, Statistics and Epidemiology, London; and *CRC Psychosocial Oncology Group, University College Hospital Medical School, London W1P 7PL, UK
1
2
3
4
5
Cuzick J, Baum M. Tamoxifen and contralateral breast cancer. Lancet 1985; 2: 282. Powles T, Eeles R, Ashley S, et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 1998; 352: 98–101. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant and Bowel Project P-1 study. J Natl Cancer Inst 1998; 90: 1371–88. Veronesi U, Maisonneuve P, Costa A, et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Lancet 1998; 352: 93–97. Paolo Bruzzi. Tamoxifen for the prevention of breast cancer. Important questions remain unanswered, and existing trials should continue. BMJ 1998; 316: 1181–82.
Emergency contraception: WHO Task Force study Sir—The World Health Organization Task Force on Postovulatory Methods of Fertility Regulation (Aug 8, p 428)1 concluded that “the earlier emergency contraceptive treatment was given, the greater its efficacy, with a downward gradient in efficacy from treatment within 24 h to treatment within 49–72 h (p=0·01)”. Specifically, the efficacy of each of the two most common treatment regimens (the standard Yuzpe regimen and the levonorgestrel-only regimen) dropped significantly as time elapsed between unprotected intercourse and the start of treatment. This issue is important because of its implications for public awareness campaigns about emergency contraception, for the current prescription-only status of the drugs, and for tailoring the therapy to be user friendly by letting women wait to start treatment at a time when the second dose, taken 12 h after the first, would be convenient. As the investigators note, their results contrast with the result of an analysis2 of nine published reports of the efficacy of the Yuzpe regimen. That review found that timing of treatment did not affect efficacy; the treatment worked equally well when started 1, 2, or 3 days after unprotected intercourse. The WHO investigators “suspect that the discrepancy is due to the lack of bias in randomised controlled trials as compared with observational studies”. However, this explanation clearly cannot be correct. The only random assignment in the WHO trial was to one of the two treatment regimens. For this reason, comparisons made across other patient characteristics are just as vulnerable to bias as would be comparisons in an
THE LANCET • Vol 352 • October 10, 1998
CORRESPONDENCE
observational study. With respect to the timing of treatment after unprotected intercourse, therefore, the WHO study should not automatically be accorded any more weight than the nine previous studies, despite its different result. Nevertheless, with the conflicting evidence, I agree with the conclusion that “women should receive treatment as soon as practicable after unprotected coitus”, provided that it is interpreted to mean that treatment could be delayed by a few hours to avoid having to take the second dose at a very inconvenient time (such as 0300 h) and provided that women are not denied treatment after 24 h, or after 48 h, or even after 72 h with proper informed consent, especially when the option of insertion of a copper intrauterine device is not available or appropriate. James Trussell Office of Population Research, Princeton University, Princeton, NJ 08544, USA 1
2
Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet 1998; 352: 428–33. Trussell J, Ellertson C, Rodríguez G. The Yuzpe regimen of emergency contraception: how long after the morning after? Obstet Gynecol 1996; 88: 150–54.
Sir—The use of progestagens alone for emergency contraception is attractive in terms of safety and efficacy over the Yuzpe regimen, as the Task Force on Postovulatory Methods of Fertility Regulation pointed out.1 This regimen may be useful for over-the-counter, emergency contraception since it has fewer contraindications than the oestrogen-progestagen combined regimen commonly used. However, this is not so in every European country or in the USA. It is perplexing that levonorgestrel is indicated in women with thromboembolic disease, as John Guillebaud points out quite rightly in his commentary 2 accompanying the WHO report, and yet previous thromboembolism is regarded as the number one cointraindication clearly spelled out in the drug leaflet for all progestagens, irrespective of dose and route of administration, sold in Italy and I believe in other countries too. Two cases that I have come across illustrate quite well this dilemma. A 42-year-old woman with lupus erythematosus (SLE) and a previous deep-vein thrombosis followed by pulmonary embolism came to me requesting contraception and relief of her heavy menstrual periods.
THE LANCET • Vol 352 • October 10, 1998
Medroxyprogesterone acetate (DepoProvera 150 mg, Pharmacia Upjohn, Kalamazoo, MI, USA) a progestagen only injectable form of contraceptive, was, I believed, the drug of choice both for its effectiveness and for the amenorrhoea that it produces, until the patient pointed out the contraindications mentioned in the drug leaflet. Needless to say, a progesterone-only pill would not have fared any better in her case: the leaflet for Microlut (levonorgestrel 0·030 mg, Schering, Berlin, Germany), the only progesterone-only pill sold in Italy has the same contraindication. A 45-year-old patient was advised by her ophthalmologist against the use of cyclical norethisterone acetate given to control menorrhagia. The patient had had severe retinal detachment secondary to myopia, and her ophthalmologist feared that the increased risk of thrombosis associated with the use of progestagen, as highlighted in the drug leaflet (Primolut-Nor, Schering), might compromise further her eyesight. These two cases represent, in my opinion, the multitude of women that can become victims of dubious, hardly supported scientifically, and most variously interpreted, contraindications reported in drug leaflets for progestagens. Sadly, the patients are left with the short end of the stick. The women who are at real risk of thromboembolism and for whom oestrogen certainly is contraindicated are thus deprived of the only class of drugs previously available to them both for contraception and menstrual cycle control. In these patients, unreliable contraception and surgery put them at even higher risk of thrombosis, and yet they are the only choice left to them. Surely, no doctor or patient in his or her right mind would use a drug after having read the contraindication so clearly spelled out on the box. It is unfortunate that such a useful and inexpensive medication, a potential solution to so many gynaecological problems, is no longer available for patients who would need it most, and this, in all likelihood, is attributable to some obscure medical legal hitch.
Low carbohydrate intake and oral glucose-tolerance tests Sir—Takashi Kaneko and colleagues (July 25, p 289)1 discuss the importance of carbohydrate intake before an oral glucose-tolerance tests (OGTT). They conclude that the impaired glucose tolerance after a low-carbohydrate meal is due to the proportionally less insulin release in response to glycaemic stimulus, and that the decrease in insulin secretion is associated with the Randle effect.2 The insulinogenic index was significantly decreased after the low-carbohydrate intake, but no significant difference in the insulin concentrations before and 30 min after OGTT was found between patients on the low-carbohydrate intake and highcarbohydrate intake. Therefore, we think that the impaired glucose tolerance after the low-carbohydrate intake reflects insulin resistance rather than decreased insulin secretion, since free fatty acids inhibit use of insulinstimulated glucose in muscle via the Randle effect.3 A fasting plasma glucose test is superior to OGTT to diagnose and classify diabetes mellitus in terms of screening and cost peformance.4 However, it is inappropriate to conclude the OGTT is diagnostically inferior to a fasting plasma glucose test because individuals with impaired fasting glucose may include both impaired glucose tolerance and diabetes when OGTT is done, although particular attention should be paid to the last carbohydrate intake. *Keiji Yoshioka, Sadayoshi Yokoh, Toshihide Yoshida *First Department of Internal Medicine, Matsushita Memorial Hospital, Osaka 570, Japan; and First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto 1
2
3
Paola Albertazzi Ospedale Maternità, 40123 Bologna, Italy 1
2
Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet 1998; 352: 428–33. Guillebaud J. Time for emergency contraception with levonorgestrel alone. Lancet 1998; 352: 416–17.
4
Kaneko T, Wang P-Y, Tawata M, Sato A. Low carbohydrate intake before oral glucosetolerance tests. Lancet 1998; 352: 289. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty acid cycle; its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963; i: 785–89. Randle PJ, Kerbey AL, Espinal J. Mechanisms decreasing glucose oxidation in diabetes and starvation: role of lipid fuels and hormones. Diabetes Metab Rev 1988; 4: 623–38. Expert Commirty of the Diagnosis and Classidication of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183–97.
Sir—Takashi Kaneko and colleagues1 conclude that when an OGTT is used to classify patients’ glucose tolerance as
1223