Traitement Hormonal de Substitution: nouvelle guerre de l'information ?
(L'express du 1/06/2000 p 56 par Vincent Olivier)
Nouvelle guerre de l'information autour du Traitement Hormonal de Substitution (THS) ?
Cancérigène pour les américains, pas pour les français, le traitement hormonal de substitution évolue.
Le Traitement Hormonal Substitutif (THS) destiné aux femmes ménopausées provoque t-il le cancer ?
Voici le dossier et l'analyse réalisés par l'équipe d'infoguerrre.com:
"Our results suggest that the combined estrogen-progestin regimen is associated with greater increases in breast cancer risk than estrogen alone"
L'étude américaine réalisée par le JAMA sous entend que les prescriptions de Traitements Hormonaux de Substitution associant oeustrogènes et progestine sont plus dangereux pour la femme que les THS prescrits aux Etats-Unis composés uniquement d'oestrogènes.
Est-ce un vrai débat scientifique, ou au contraire, est-ce une véritable manipulation de l'information à objectif purement commercial ?
| L'étude complète du JAMA Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk | http://jama.ama-assn.org/issues/v283n4/full/joc91096.html#ABSTRACT |
| THS : rassurer les femmes | www.quotimed.com |
| THS | www.quotimed.com travail dirigé par Brigitte Séradour (Marseille) |
| Ménopause : l'hormonothérapie substitutive augmente-t-elle le risque de cancer du sein ? | www.quotimed.com par le Dr Christian Jamin |
| THS et risque cardio-vasculaire : difficile de conclure | www.quotimed.com Dr Annie DUMONCEAU |
Lire l'étude complète du JAMA ci-après
| Vol. 283 No. 4, January 26, 2000 sources : http://jama.ama-assn.org/issues/v283n4/full/joc91096.html#ABSTRACT Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk Catherine Schairer, PhD; Jay Lubin, PhD; Rebecca Troisi, ScD; Susan Sturgeon, DrPH; Louise Brinton, PhD; Robert Hoover, MD Context Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown. Objective To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone. Design Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. Setting Twenty-nine screening centers throughout the United States. Participants A total of 46,355 postmenopausal women (mean age at start of follow-up, 58 years). Main Outcome Measure Incident breast cancers by recency, duration, and type of hormone use. Results During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval {CI}, 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin–only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin–only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only. Conclusion Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone. JAMA. 2000;283:485-491 1 Unresolved issues include the extent to which the findings were due to a biological effect of hormones rather than issues of screening and ascertainment. The data were also insufficient to determine whether a combined estrogen-progestin regimen increased risk beyond that associated with estrogen alone. METHODSFollow-up Study Study subjects were participants in the Breast Cancer Detection Demonstration Project (BCDDP) conducted between 1973 and 1980. We previously described a follow-up study begun in 1979 involving a subset of BCDDP participants.2 In brief, the follow-up study included (1) all screening participants who underwent breast surgery during the screening period, with no evidence of malignant disease (n = 25,114); (2) all subjects who had recommendations by the project for a surgical consultation but did not have either a biopsy or aspiration performed (n = 9628); and (3) a sample of women who had neither surgery nor recommendation for surgical consultation during screening participation (n = 25,165). The follow-up study was approved by the Institutional Review Board at the National Cancer Institute. Informed consent was obtained from participants. 2 The current analysis includes data from these earlier phases as well as from the latest phase of the study, during which 1 mailed questionnaire was administered between 1993 and December 1995 to study subjects not known to be deceased and who completed a questionnaire in 1987-1989. Nonrespondents to the mailed questionnaire were interviewed by telephone, if possible. Information collected from phase 1 of the study included recognized breast cancer risk factors; breast cancer screening practices, including number of mammograms for a routine reason or because of a problem since the last interview; and breast procedures undergone since the last examination by the screening program or the last interview. In addition, information was collected on age at first use and duration of use of female hormones (excluding creams) other than oral contraceptives. Information was not obtained on type of hormone used. During phase 2 of the study, information on breast procedures and previously collected risk factors was updated. Information was obtained on use of menopausal hormones in the form of shots, creams, patches, or pills since the last interview; those who had used pills provided information on ever use of menopausal estrogens and progestins in the same month, duration of use of estrogens and progestins, and number of days in the month progestins were used. Information on breast cancer screening practices was not collected during phase 2. In phase 3 of follow-up, previously collected information, including use of estrogens and progestins, was updated; information was also collected on mammographic and physical examinations of the breast for a routine reason or because of a problem in the 5 years prior to the interview. Level of education was recorded on a form completed at entry to the screening program. Height and weight measurements were recorded on forms at each screening visit. Current height and weight measurements were available from the 1987-1989 questionnaire. Analytic Data Set This analysis was limited to women who were menopausal before the start of the follow-up period or who became menopausal during the course of the study. Menopausal women were defined as those who did not have a menstrual period for at least 3 months prior to an interview because of natural menopause or a bilateral oophorectomy. In addition, women who stopped menstruating because of a hysterectomy but who retained at least 1 ovary or whose ovarian status was uncertain were considered to have reached menopause by age 57 years (the 75th percentile for age at menopause in the study population) or their age at hysterectomy, whichever was later. However, they were assigned an unknown value for their specific ages at menopause in the analyses. Those reporting prophylactic bilateral mastectomies or a diagnosis of breast cancer before the start of follow-up were excluded. Those reporting use of menopausal hormones in the form of shots, patches, or creams (n = 6212) were also excluded because detailed information regarding timing of use was not available. Most study subjects (86%) were white. There were small percentages of black (5%), Hispanic (2%), and Asian American (5%) women, as well as those with other or unknown race/ethnicity (1%). After all exclusions, 46,355 subjects were available for analysis. A total of 39,427 (85%) of these subjects completed a phase 2 questionnaire; 33,004 (84%) of those who completed a phase 2 questionnaire also completed a phase 3 questionnaire. Phase 3 questionnaires were not completed by those who completed phase 2 for reasons including death (6%); loss to follow-up (0.5%); and illness, refusal, or because contact with study subjects at a current telephone number was not made by the end of the study period (9.5%). 2 Pathology reports were obtained for 1713 of these cases (82%); reports were not obtained for 237 cases (11%) because they were not received before the end of the study period, because of nonresponse of physicians or hospitals, or because permission to retrieve medical records was not received from the study subject. Pathology reports for the 132 cases (6%) identified by death certificate also were not retrieved. A total of 255 (15%) cancers for which pathology reports were available were in situ and 1456 (85%) were invasive. It was uncertain whether 2 cases were in situ or invasive. Invasive tumors were further classified into 2 groups based on histology: (1) mucinous, medullary, tubular, or papillary carcinomas (n = 76) or (2) ductal or lobular carcinomas (n = 916). A total of 788 in the second group were ductal carcinomas, 104 were lobular carcinomas, and 24 were comedocarcinomas or Paget disease with infiltrating ductal carcinoma. Histology was not available for 464 invasive cases, largely from those whose disease was diagnosed during phase 1 of the study, because pathology reports were no longer available from which to code histology. Because the accuracy of self-reporting was high among those with pathology reports (97% were confirmed as cancers), cancers without pathology reports (n = 369) were included in the analyses but were not categorized as in situ or invasive. Nodal status was available for 1253 (86%) of the invasive cases; 903 (72%) were node negative and 350 were (28%) node positive. Tumor size was available for 1041 (71%) of invasive cases: 680 (65%) were smaller than 2 cm and 361 (35%) were 2 cm or larger. Analysis Follow-up began at the date of the baseline interview or date of menopause, whichever was later. Person-years accrued until the earliest of the following dates: diagnosis of breast cancer, a second prophylactic mastectomy, death (including cases identified by death certificate), or date of last contact. 4 Score tests were used to test for the statistical significance of trends and to assess quadratic departures from linearity in the linear ERR model. No such departures were detected. Tests of homogeneity of the effects of estrogen and estrogen-progestin were assessed by score tests in which the effects of the 2 regimens were first assumed to be the same and then were allowed to vary. Similarly, score tests were used to assess the homogeneity of hormonal effects by categories of body mass index (BMI). Variables included as time-dependent factors were attained age, BMI, use of female hormones for menopausal reasons, and mammographic examinations of the breast. Hormone use was calculated to 1 year prior to attained (or current) age to eliminate exposure that was most likely not causal. Data on BMI and mammographic examinations were calculated to attained age. Because information on progestin use was not collected until the 1987-1989 interview, progestin use was unknown for the 6928 subjects who did not answer this interview. For these subjects and those who were uncertain whether they had used progestins, person-years and cases associated with estrogen use were included in the estrogen (progestin unknown) category if the subject had undergone a natural menopause; otherwise, they were included in the estrogen only category because women with a surgical menopause were less likely to have used progestins. Information on episodes of hormone use that occurred before breast cancer diagnosis may have been reported by study subjects after diagnosis. For instance, a subject may have reported on a 1994 interview that she had been diagnosed as having breast cancer in 1993 and that she had used hormones between 1991 and 1992 (before diagnosis). For this same study subject, all hormone use that was reported on interviews completed prior to 1993 would have been reported before breast cancer diagnosis. An individual who responded to the 1994 interview but did not report breast cancer on that interview would have reported any hormone use in a manner similar to this hypothetical case. 5 A similar variable was created for clinical breast examinations by a health care professional during the follow-up period. For the follow-up period until the 1987-1989 questionnaire, we calculated BMI from information obtained from the screening visit closest in time to the baseline follow-up interview; for the subsequent period we calculated BMI from current height and weight from the 1987-1989 questionnaire. 6 RESULTSThe mean duration of follow-up was 10.2 years, with a median of 12.3 years, a maximum of 16.0 years, and a minimum of less than 1 year. During follow-up, 473,687 person-years were accumulated for the 46,355 subjects. The average age at start of follow-up was 58 years. Forty-two percent of person-years were associated with no use of hormones, 38% with estrogen-only use, 4% with combined estrogen-progestin–only use, 6% with estrogen-progestin use among those who also used estrogen alone, 5% with estrogen use with uncertain or unascertained progestin use, 1% with progestin-only use or progestin use with uncertain estrogen use, and 5% with uncertain hormone use. The primary type of estrogen used was conjugated estrogens (Premarin) and the primary progestin was medroxyprogesterone acetate. Ever Use and Recency of Use Relative risks associated with ever use of different hormone regimens after adjustment for attained age, age at menopause, education, BMI, and mammographic screening are shown in Table 1. Adjustment for race, period of follow-up, age at first live birth, family history of breast cancer, history of benign breast disease, and clinical breast examinations did not alter these estimates. There were slight increases in risk associated with all regimens of use except progestin only. Most subsequent analyses are restricted to nonhormone use, use of estrogen only, and use of estrogen-progestin only. Table 1). Relative risks were 1.2 (95% CI, 1.0-1.4) and 1.4 (95% CI, 1.1-1.8), respectively. The mean person-year weighted duration of combined estrogen-progestin use among recent users was less than half that among recent users of estrogens alone (3.6 vs 10.3 years). Duration of Use Observed and predicted RRs associated with duration of estrogen-only use and estrogen-progestin–only use among recent users are shown in Figure 1. Based on the linear excess risk model, the RR of breast cancer increased by 0.01 (95% CI, 0.002-0.03) for each year of estrogen-only use (P = .01 for trend) and by 0.08 (95% CI, 0.02-0.16) for each year of estrogen-progestin–only use (P = .01 for trend). The P value for the test of homogeneity of these estimates was .02. Results were similar when analyses were restricted to the category of annual mammographic screening, which included 24% of the person-years in the study. To assess the impact of excluding women with an unknown age at menopause on the analysis, we restricted data to recent users with a known age at menopause. Relative risks were changed only slightly; in contrast with estimates of 0.01 and 0.08 for all data, the increase in RR for each year of estrogen-only use was 0.02 (95% CI, 0.002-0.04) and for each year of estrogen-progestin–only use was 0.06 (95% CI, -0.002 to 0.15). The P value for the test of homogeneity of these associations was .23. We also examined associations among women with a known age at menopause but unadjusted for age at menopause; the increase in RR for each year of estrogen-only use was 0.01 (95% CI, 0.002-0.24) and for estrogen-progestin–only use was 0.07 (95% CI, 0.001-0.16), suggesting that ignoring age at menopause entirely had little effect on the estimates. When analyses included all recent users of estrogen-progestin (ie, including those who also used estrogen alone and those with an unknown age at menopause), the RR increased by 0.05 (95% CI, 0.003-0.11) with each year of use. The P value associated with the test of homogeneity of this estimate and that associated with duration of use of estrogen alone was .07. There was no association between duration of use of estrogen alone and risk of breast cancer among past users. Duration by Days in the Month Progestins Were Used Among recent users who used progestins for fewer than 15 days per month, the RRs associated with less than 4 and 4 or more years of use of estrogen-progestin only were 1.1 (95% CI, 0.8-1.7) and 1.5 (95% CI, 1.0-2.4), respectively, based on 26 and 22 cases. The median number of days progestins were used in this group was 10. There were too few cases who had used progestins for 15 or more days per month (n = 12) to derive stable estimates according to duration of use. A substantial number of cases (n = 33) were uncertain how many days in the month they had used progestin. Variation by BMI Associations with duration of estrogen-only use among recent users varied significantly according to BMI (P = .002 for score test), with increases in risk evident only in women with a BMI of 24.4 kg/m2 or less (Table 2). The RRs increased by 0.03 (95% CI, 0.01-0.06) for each year of estrogen-only use in this group. Associations with duration of estrogen-progestin–only use among recent users did not vary significantly according to BMI (P = .42 for score test), although there was a significant increase in risk among lean women but not heavier women. The RR among lean women increased by 0.12 (95% CI, 0.02-0.25) for each year of use. The P value associated with the test of homogeneity of this estimate and that associated with estrogen-only use in lean women was .06. When those with an unknown age at menopause were excluded, the RR increased by 0.05 for each year of estrogen-only use (95% CI, 0.02-0.08) among lean women; the increase in the RR for each year of estrogen-progestin–only use in lean women was 0.11 (95% CI, 0.01-0.27). The P value associated with the test of homogeneity of these estimates was .36. Extent of Disease and Tumor Histology In recent estrogen-only users with BMI of 24.4 kg/m2 or less, duration of use was associated with significant increases in risk of both early- and later-stage invasive disease (Table 3). Estrogen-progestin–only use was also associated with significant increases in risk of invasive cancer, but numbers were too small to draw conclusions regarding associations according to extent of invasive disease. There were no significant increases in risk of in situ disease associated with either regimen, but the number of cases was small. In recent users with BMI of 24.4 kg/m2 or less, use of estrogen only and estrogen-progestin only were both associated with significant increases in risk of invasive tumors with ductal and/or lobular histologies (Table 4). Similar associations were evident when analyses were limited to invasive tumors with ductal histology. There were too few cases with other histologies to examine these associations. COMMENT7 1 9 consistent with the current analysis. 12 Several methodological issues need to be considered in interpreting our results. The pattern of greater increases in risk associated with the estrogen-progestin regimen than with estrogen alone was evident when subjects with an unknown age at menopause were both included and excluded, although the disparity between the associations was slightly smaller when they were excluded. The lack of statistical significance for the test of the homogeneity of the associations of the 2 regimens after exclusion of those with an unknown age at menopause most likely resulted from the elimination of 17% of person-years and 20% of cases in the study, which reduced the information available for estimating increases in the RRs. We chose to present our main findings including women with an unknown age at menopause because age at menopause was not a substantial confounder of the hormone associations in these data and because excluding these women resulted in a substantial loss of information. Moreover, the estimates including and excluding these women were not meaningfully different, given the uncertainty in the estimates. 13 15 Our results, as well as those of others, suggest that in weighing the risks and benefits of menopausal HRT, it is important to consider the type of hormone regimen as well as individual characteristics of the woman, such as body mass index. Author/Article Information  Author Affiliations: National Cancer Institute, Division of Cancer Epidemiology and Genetics, Rockville, Md (Drs Schairer, Lubin, Troisi, Sturgeon, Brinton, and Hoover); Social and Scientific Systems Inc, Bethesda, Md (Dr Troisi); and the Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst (Dr Sturgeon). Corresponding Author and Reprints: Catherine Schairer, PhD, National Cancer Institute, Division of Cancer Epidemiology and Genetics, 6120 Executive Blvd, EPS Room 7080-MSC 7234, Rockville, MD 20852-7234 (e-mail: [email protected]). Acknowledgment: We are indebted to Leslie Carroll and Heather Clancey of IMS Inc, Rockville, Md, for computer support. |
Cette polémique est relancée en France par la lettre du Pr Barrat publiée par le Quotidien du Médecin (www.quotimed.com)
CHER Collègue, * Paris. |
| THS THS est la principale explication. THS », lit-on dans le rapport. Probable compensation par un meilleur pronostic Dr Béatrice VUAILLE Un congrès |
| Ménopause : l'hormonothérapie substitutive Récemment, le « JAMA » a publié une étude concernant l'hormonothérapie substitutive de la ménopause et le risque de cancer du sein. Dans l'article ci-dessous, le Dr Christian Jamin décortique ce travail et en fait l'analyse pour « le Quotidien » sur le thème : « L'hormonothérapie substitutive de la ménopause, en particulier lors de l'association estroprogestative, augmente-t-elle le risque de cancer du sein ? » THS, et que celui-ci comporte ou non un progestatif. Le traitement progestatif est indispensable à la protection endométriale et n'altère pas les bénéfices cardio-vasculaires apportés par les estrogènes, pour peu que les molécules soient bien choisies : son bien-fondé ne doit, à ce jour, aucunement être remis en cause par cette étude. Dr Christian JAMIN |
THS et risque cardio-vasculaire : difficile de conclure Les effets protecteurs des estrogènes sur le système cardio-vasculaire sont maintenant reconnus. Néanmoins, ces effets sont à nuancer selon les femmes, leurs facteurs de risque et leurs antécédents cardio-vasculaires. Les résultats des grandes études américaines restent relativement contradictoires. THS) de la ménopause ne fait plus de doute, notamment pour améliorer la qualité de vie de la femme et prévenir l'ostéoporose, de nombreuses questions restent encore en suspens concernant les bénéfices coronaires des traitements hormonaux. L'administration d'un traitement hormonal substitutif est-elle plus intéressante en prévention primaire, en prévention secondaire, chez les femmes présentant une dyslipidémie ou un diabète sucré ? Par ailleurs, faut-il préférer les estrogènes per os, les estrogènes percutanés et quels type de progestatifs ? Les nombreuses études américaines présentées au congrès de l'ACC n'ont pas résolu toutes ces questions, mais ont permis de comparer les effets cardio-vasculaires de différentes associations hormonales. En prévention primaire La progestérone naturelle |