- Email: [email protected]
FORMULATION-DEPENDENT EFFECT OF ORAL CONTRACEPTIVES ON H.D.L.-CHOLESTEROL
677 value of improving control is weakened by this lack of significant correlation in single-sex groups. As control improved in insulin-treated patients so the plasma-H.D.L.-cholesterol concentration rose. We agree with Boucher and Yudkin that our findings and theirs may reflect differences in clinic populations. We tend to discharge maturity-onset diabetics who are well-controlled or see them annually, retaining only those whose control is difficult because of dietary problems or who have diabetic complications or social difficulties. For this reason we think the data on patients matched for age, sex, weight, and HbA1 concentration are more important in that variables associated with patient selection are largely eliminated. Other differences between clinic populations may reflect differences in dietary advice. Some clinics restrict carbohydrate intake and allow an uncontrolled fat intake, so long as bodyweight is controlled. We concentrate on total caloric intake in all mature-onset diabetics, and calories from saturated fat are therefore also restricted, as we attempt to maintain a balanced diet in these Dr Durrington (July 22, p. 206) asks about alcohol intake. We advise all diabetics to give up alcohol. Alcohol consumption tends to increase H.D.L.-cholesterol. If any of our diabetic groups had a higher alcohol intake than any other we think it would be those on sulphonylureas, but this group had a H.D.L.cholesterol concentration than the others. We have not sought data on alcohol, smoking, or adiposity (as distinct from bodyweight). We found no correlation between plasma-total-cholesterol and either HbA, or H.D.L.-cholesterol concentrations, and we reported a positive correlation (r<001, overlooked by between and Durrington) plasma-triglyceride concentraHbA1 tions in the whole group of patients. We do not understand Durrington’s criticisms of the way we matched characteristics of groups receiving different therapies. Groups were matched for sex as well as age, weight, and HbA,. The mean weight of the sulphonylurea-treated group was not statistically different from that of the diabetics treated with insulin or diet only, as shown in table 11. We agree with Durrington that the subject of cholesterol and lipoprotein metabolism in diabetics is complex, and we look forward to publication of his results and those of Boucher and Yudkin.
patients.
baseline when a progestin was added. Thus, the net effect on H.D.L.-cholesterol of the use of combination oral contraceptives is dependent on the contraceptive’s formulation. The formulation of the contraceptives studied by Schade et al. (50 fLg mestranol and 1 mg norethisterone; and 30 µg ethinyloestradiol and z 15 mg levonorgestrel) and by Krauss et al. are consistent with the Bradley study and the formulations used by Roosner show an improvement with increased oestrogen and a worsening with increased progestin. The formulations studied by Arntzenius et al are not given. Because of the inverse relationship between H.D.L.-cholesterol and coronary disease6-8 the epidemiological evidence linking coronary-artery disease and oral contraceptive use should be reexamined with regard to the specific preparations of oral contraceptives used. For the two most prominent of these studies9 10 (which were carried out in the U.K.) we cannot find precise data but there is some fragmentary evidence to suggest that the combined oral contraceptives commonly available in the U.K. at the time of these studies tended to be high in progestin."12 The formulation-dependent effect of oral contraceptives on H.D.L.-cholesterol use may mean that the risk of coronary disease in users varies from preparation to preparation and from country to country. Only 14% of oral-contraceptive users in the Walnut Creek California Study used preparations which were associated with a significant reduction in H.D.L.-cholesterol level. Clearly, other pathophysiological mechanisms besides that reflected by H.D.L.-cholesterol may also affect the relationship between combined oral contraceptives and myocardial infarction. Nevertheless, in settings such as the U.S., where oral contraceptive progestin potency appears to be lower, it seems reasonable to expect that the relationship between use and myocardial infarction may be weaker or even nonexistent. Research Division, Office of Population, Agency for International Development,
Washington, 20523, U.S.A. Family Planning Evaluation Division, Center for Disease Control, Atlanta, Georgia, 30333
JAMES D. SHELTON DIANA PETITTI
Department of Clinical Biochemistry and Medicine, Flinders Medical Centre, Bedford Park, South Australia 5042.
G. D. CALVERT
ADIPOSE TISSUE AND ÆTIOLOGY OF BREAST
J. J. GRAHAM
FORMULATION-DEPENDENT EFFECT OF ORAL CONTRACEPTIVES ON H.D.L.-CHOLESTEROL
SiR,-The influence of oral contraceptives on high-densitylipoprotein (H.D.L.)-cholesterol is controversial. Krauss et al.l found slightly but not significantly higher levels in oral contraceptive (o.c.) users, Arntzenius et al .2 found significantly lower levels among users, and Schade et al. found similar levels before and after use. Dr Roosner (July 29, p. 209) reported a decrease in H.D.L.-cholesterol after oral contraceptive began. Bradley et al.4 may have shed light on this inconsistency. Their cross-sectional data comparing numerous hormone and oral contraceptive preparations show that oestrogens increase H.D.L.-cholesterol while progestins decrease it. This result is supported by Goldzieher5 who observed an increase in H.D.L.cholesterol when an oestrogen alone was given, and a return to
CANCER
SIR,-Professor Beer and Dr Billingham (Aug. 5, p. 296) suggest that the adipose tissue of the breast, by acting as a depot for lipid-soluble carcinogens, might account for the high risk of cancer borne by this organ. This hypothesis is supported by epidemiological and experimental findings (discussed elsewhere’) and we tested one aspect of it in a community-wide case-controJ study based on 179 unselected breast-cancer cases and 179 age-matched controls selected from a population register. We found a very close agreement between patients and controls not only in height, weight, and indices of overweight (Quetelet’s and Broca’s) but also with regard to breast size as assessed by the woman herself and by her surgeon (see table). The results do not support the hypothesis that the amount of adipose tissue, as reflected in breast size, is related to breastcancer risk. 6.
293.
Gordon, T., Castelli, W. P., Hjortland, M. C., Kannel, W. B., Dawber, T. R. Am. J. Med, 1977, 62, 707. 8. Miller, N. E., Forde, A. H., Thelle, D. S., M)os, O. D. Lancet, 1977, i, 965. 9. Royal College of General Practitioners, ibid. ii, 727. 10. Vessey, M. P., McPherson, K., Johnson, B. ibid. p. 731. 11. Inman, W. H. W., Vessey, M. P., Westerholm, B., Engelund, A. Br. med. J. 1970, ii, 203. 12. Royal College of General Practitioners, Lancet, 1977, i, 624. 1. Adami, H. O., Rimsten, A., Stenkvist, B., Vegelius, J. Br. J. Cancer, 1977, 36, 787. 7.
1.
Krauss, R. M., Lindgren, F. T., Silvers, A., Jutagir, R., Bradley, D. D. Clin. chim. Acta, 1977, 80, 465. 2. Arntzenius, A. C., van Gent, C. M., van der Voort, H., Stegerhuch, C. I., Styblo, K. Lancet, 1978, i, 1221. 3. Schade, R. W. D., Meuwese, J. P. M., Thoben, A. J. N., Demacker, P. N.M. ibid. ii, 40. 4. Bradley, D. D., Wingerd, J., Petitti, D. B., Krauss, R. M., Ramcharan, S. New Engl. J Med. 1978, 291, 170. 5. Goldzieher, J. Fert. Steril. 1978, (in the press).
Rhoads, G. G., Gulbrandsen, S. L., Kagan, A. New Engl. J. Med. 1976, 294,
patients.
baseline when a progestin was added. Thus, the net effect on H.D.L.-cholesterol of the use of combination oral contraceptives is dependent on the contraceptive’s formulation. The formulation of the contraceptives studied by Schade et al. (50 fLg mestranol and 1 mg norethisterone; and 30 µg ethinyloestradiol and z 15 mg levonorgestrel) and by Krauss et al. are consistent with the Bradley study and the formulations used by Roosner show an improvement with increased oestrogen and a worsening with increased progestin. The formulations studied by Arntzenius et al are not given. Because of the inverse relationship between H.D.L.-cholesterol and coronary disease6-8 the epidemiological evidence linking coronary-artery disease and oral contraceptive use should be reexamined with regard to the specific preparations of oral contraceptives used. For the two most prominent of these studies9 10 (which were carried out in the U.K.) we cannot find precise data but there is some fragmentary evidence to suggest that the combined oral contraceptives commonly available in the U.K. at the time of these studies tended to be high in progestin."12 The formulation-dependent effect of oral contraceptives on H.D.L.-cholesterol use may mean that the risk of coronary disease in users varies from preparation to preparation and from country to country. Only 14% of oral-contraceptive users in the Walnut Creek California Study used preparations which were associated with a significant reduction in H.D.L.-cholesterol level. Clearly, other pathophysiological mechanisms besides that reflected by H.D.L.-cholesterol may also affect the relationship between combined oral contraceptives and myocardial infarction. Nevertheless, in settings such as the U.S., where oral contraceptive progestin potency appears to be lower, it seems reasonable to expect that the relationship between use and myocardial infarction may be weaker or even nonexistent. Research Division, Office of Population, Agency for International Development,
Washington, 20523, U.S.A. Family Planning Evaluation Division, Center for Disease Control, Atlanta, Georgia, 30333
JAMES D. SHELTON DIANA PETITTI
Department of Clinical Biochemistry and Medicine, Flinders Medical Centre, Bedford Park, South Australia 5042.
G. D. CALVERT
ADIPOSE TISSUE AND ÆTIOLOGY OF BREAST
J. J. GRAHAM
FORMULATION-DEPENDENT EFFECT OF ORAL CONTRACEPTIVES ON H.D.L.-CHOLESTEROL
SiR,-The influence of oral contraceptives on high-densitylipoprotein (H.D.L.)-cholesterol is controversial. Krauss et al.l found slightly but not significantly higher levels in oral contraceptive (o.c.) users, Arntzenius et al .2 found significantly lower levels among users, and Schade et al. found similar levels before and after use. Dr Roosner (July 29, p. 209) reported a decrease in H.D.L.-cholesterol after oral contraceptive began. Bradley et al.4 may have shed light on this inconsistency. Their cross-sectional data comparing numerous hormone and oral contraceptive preparations show that oestrogens increase H.D.L.-cholesterol while progestins decrease it. This result is supported by Goldzieher5 who observed an increase in H.D.L.cholesterol when an oestrogen alone was given, and a return to
CANCER
SIR,-Professor Beer and Dr Billingham (Aug. 5, p. 296) suggest that the adipose tissue of the breast, by acting as a depot for lipid-soluble carcinogens, might account for the high risk of cancer borne by this organ. This hypothesis is supported by epidemiological and experimental findings (discussed elsewhere’) and we tested one aspect of it in a community-wide case-controJ study based on 179 unselected breast-cancer cases and 179 age-matched controls selected from a population register. We found a very close agreement between patients and controls not only in height, weight, and indices of overweight (Quetelet’s and Broca’s) but also with regard to breast size as assessed by the woman herself and by her surgeon (see table). The results do not support the hypothesis that the amount of adipose tissue, as reflected in breast size, is related to breastcancer risk. 6.
293.
Gordon, T., Castelli, W. P., Hjortland, M. C., Kannel, W. B., Dawber, T. R. Am. J. Med, 1977, 62, 707. 8. Miller, N. E., Forde, A. H., Thelle, D. S., M)os, O. D. Lancet, 1977, i, 965. 9. Royal College of General Practitioners, ibid. ii, 727. 10. Vessey, M. P., McPherson, K., Johnson, B. ibid. p. 731. 11. Inman, W. H. W., Vessey, M. P., Westerholm, B., Engelund, A. Br. med. J. 1970, ii, 203. 12. Royal College of General Practitioners, Lancet, 1977, i, 624. 1. Adami, H. O., Rimsten, A., Stenkvist, B., Vegelius, J. Br. J. Cancer, 1977, 36, 787. 7.
1.
Krauss, R. M., Lindgren, F. T., Silvers, A., Jutagir, R., Bradley, D. D. Clin. chim. Acta, 1977, 80, 465. 2. Arntzenius, A. C., van Gent, C. M., van der Voort, H., Stegerhuch, C. I., Styblo, K. Lancet, 1978, i, 1221. 3. Schade, R. W. D., Meuwese, J. P. M., Thoben, A. J. N., Demacker, P. N.M. ibid. ii, 40. 4. Bradley, D. D., Wingerd, J., Petitti, D. B., Krauss, R. M., Ramcharan, S. New Engl. J Med. 1978, 291, 170. 5. Goldzieher, J. Fert. Steril. 1978, (in the press).
Rhoads, G. G., Gulbrandsen, S. L., Kagan, A. New Engl. J. Med. 1976, 294,