- Email: [email protected]
Smoking habits of 411 women with histologically proven endometriosis and 567 unaffected women
Smoking habits of 411 women with histologically proven endometriosis and 567 unaffected women Smoking habits did not influence either the risk of any form of endometriosis (superficial peritoneal endometriosis, ovarian endometriomas, and deep infiltrating endometriosis) and did not correlate with the revised American Fertility Society stages or scores. (Fertil Steril 2010;94:2353–5. 2010 by American Society for Reproductive Medicine.) Key Words: Endometriosis, pathogenesis, deep endometriosis, smoking habits, cross-sectional
Endometriosis is characterized by the presence of endometrial tissue—epithelium and/or stroma—that develops outside the uterine cavity (1), causing pain and infertility (2). There are three types of endometriotic lesions: superficial peritoneal endometriosis (SUP), Charles Chapron, M.D.a,d,e Carlos Souza, M.D.a,f Dominique de Ziegler, M.D.a Marie-Christine Lafay-Pillet, M.D.a Charlotte Ng^o, M.D.a,b Gerard Bijaoui, M.D.a Franc xois Goffinet, M.D., Ph.D.c Bruno Borghese, M.D., Ph.D.a,d,e a Service de Gyn ecologie Obst etrique II et M edecine de la Reproduction (Professeur Chapron), Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, Groupe Hospitalier Universitaire Ouest, Assistance Publique– H^ opitaux de Paris, Universit e Paris Descartes, Paris, France b Facult e de M edecine, EA 1833, ERTi, Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, Groupe Hospitalier Universitaire Ouest, Assistance Publique– H^ opitaux de Paris, Universit e Paris Descartes, Paris, France c Maternit e Port-Royal (Professeur Cabrol), Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, Groupe Hospitalier Universitaire Ouest, Assistance Publique– H^ opitaux de Paris, Universit e Paris Descartes, Paris, France d Institut Cochin, CNRS UMR 8104, Paris, France e INSERM U1016, Paris, France f Servicxo de Ginecologia e Obstetricia, Hospital de Clınicas de Porto Alegre, Coordenacxa~o de Aperfeicxoamento de Pessoal de Nıvel Superior, Porto Alegre, Brazil Received December 7, 2009; revised March 29, 2010; accepted April 8, 2010; published online May 31, 2010. C.C. has nothing to disclose. C.S. has nothing to disclose. D.Z. has nothing to disclose. M.-C.L.-P. has nothing to disclose. C.N. has nothing to disclose. G.B. has nothing to disclose. F.G. has nothing to disclose. B.B. has nothing to disclose. cologie— Reprint requests: Charles Chapron, M.D., Service de Gyne trique II et Me decine de la Reproduction, CHU Cochin—Saint Obste Vincent de Paul, Pavillon Lelong, 82 avenue Denfert Rochereau, 75014 Paris, France (FAX: 33-1-58-41-18-70; E-mail: charles. [email protected]).
0015-0282/$36.00 doi:10.1016/j.fertnstert.2010.04.020
ovarian endometriomas (OMA), and deep infiltrating endometriosis (DIE). The pathogenesis of endometriosis remains controversial (3–5). Sets of risk factors (lifestyle, sociodemographic, environmental, reproductive, and genetic characteristics), including smoking, have been associated with endometriosis (6–8). Endometriosis being an estrogen-dependent process, it has been thought that cigarette smoking, which has antiestrogenic effects, could lower the risk (9). Yet the links between tobacco use and endometriosis are still debated (6, 8, 10–14). The divergent findings regarding smoking and endometriosis stem in part from methodologic issues that are prone to affect all clinical trials on endometriosis (15). In light of this enduring controversy, we elected to study the issue of smoking and endometriosis by comparing a control and affected population in whom endometriosis was either surgically excluded or proven and histologically graded. To our knowledge, this study is the first to assess the possible association between smoking habits and the degree of surgically proven histologically graded endometriosis (SUP, OMA, and DIE). We conducted a cross-sectional study including all nonpregnant patients <42 years of age who were operated on (by laparotomy or operative laparoscopy) in our institution between January 2004 and December 2008. Excluded from this cohort were women with cancer and/or who refused to sign a consent form. A total of 1,133 were visually diagnosed with the presence (n ¼ 566) or absence (n ¼ 567) of endometriosis. Patients visually diagnosed with endometriosis but without histologic confirmation (n ¼ 155) were considered to be ineligible to participate in the study. Depending on pathologic findings, endometriotic lesions were divided into SUP, OMA, and DIE. Because the three types of lesions are frequently associated (16), the ultimate staging was given by the worst lesion found in each patient (from least bad to worst: SUP, OMA, and DIE). The control group included 567 patients without any visual lesion of endometriosis, as checked at the time of surgery by a thorough examination of the abdominopelvic cavity. Data were collected by face-to-face standardized questionnaires conducted by the surgeon during the month before surgery. During surgery, extension of endometriosis was scored according to the revised American Fertility Society (rAFS) classification (17). For each patient, current and past smoking habits were evaluated
Fertility and Sterility Vol. 94, No. 6, November 2010 Copyright ª2010 American Society for Reproductive Medicine, Published by Elsevier Inc.
2353
TABLE 1 Smoking habit characteristics of control subjects and endometriosis patients. Endometriosis type
Age began smoking (y) No. of cigarettes per day No. of years of smoking No. of cigarette pack Interval free from smoking
Endometriosis (n [ 411)
Control (n [ 567)
P valuea
SUP
OMA
DIE
P valueb
17.91 4.48 10.27 6.63 12.51 6.67 7.5 7.33 4.32 3.94
17.51 3.94 11.51 7.65 12.49 6.68 9.52 23.65 5.86 5.32
.43 .14 .98 .33 .08
17.53 4.25 8.87 5.95 11.43 7.14 6.87 6.35 9.13 8.60
17.11 3.99 10.32 5.69 12.06 6.89 6.26 5.53 3.97 3.46
18.38 4.74 10.52 7.20 12.92 6.54 8.203 8.18 3.94 3.19
.39 .44 .84 .77 .06
Note: DIE ¼ deep infiltrating endometriosis; OMA ¼ ovarian endometrioma; SUP ¼ superficial endometriosis. a Student t test. b One-way analysis of variance. Chapron. Correspondence. Fertil Steril 2010.
as follows: 1) never or ever (currently or in the past) a smoker; 2) age at onset of smoking; 3) number of cigarettes per day; 4) number of years smoking; 5) number of pack-years (18); and 6) interval free of smoking (past smokers). In accordance to earlier studies, we defined ‘‘ever a smoker’’ as anyone who answered ‘‘yes’’ to the following question: ‘‘During your lifetime, have you smoke more than 100 cigarettes?’’ ‘‘Current smoker’’ was defined as a patient who answered ‘‘yes’’ to the following question: ‘‘Did you smoke a cigarette during the past 30 days?’’ (19–20). Statistical analyses were performed using SPSS 13.0 (SPSS, Chicago, IL). Continuous data were presented as mean SD. Student t test and one-way analysis of variance were carried out when necessary. The chi square and Fisher exact test were used for categoric data. We used odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) to compare the smoking habits between the different types of endometriosis. We also performed an unconditional logistic regression to control for potential confounding factors, such as age, ethnicity, gravidity, parity, infertility, and body mass index (BMI). We performed a stepwise logistic regression analysis, in which a P value of .5 was used as entry criteria and a P value of .2 was the threshold for the covariate to stay in the model (21). A P value of < .05 was considered to be statistically significant. The power of the study was calculated based on the following assumptions: 1) sample size (n ¼ 978); 2) prevalence of smoking in control subjects of 35% (22); 3) expected difference of 10% between the groups (11); and 4) type I and II errors of .05 and .12, respectively. The local Ethics Committee (Comite Consultatif de Protection des Personnes dans la Recherche Biomedicale) at our institution approved the study protocol, and each of the included patients signed an informed consent form. Patients with histologically proven endometriotic lesions (group A: n ¼ 411; 42%) were distributed as follows: SUP: 47 patients (11.4%); OMA: 120 patients (29.2%), and DIE: 244 patients (59.4%). Classification according to the rAFS stages was: stage I: 56 patients (13.6%); stage II: 85 patients (20.7%); stage III: 112 patients (27.2%); and stage IV: 158 patients (38.5%). The control group (group B) consisted of 567 patients (58%) without endometriosis at the time of surgery. The number of ‘‘ever smokers’’ was 184 in group A (SUP: 19 patients; OMA: 54 patients; DIE: 111 patients) and 207 in group B. Smoking habits were similar in the operative and laparoscopy/laparotomy groups (OR 1.28,
2354
Chapron et al.
Correspondence
95% CI 0.67–2.42). Raw data indicated that smokers had an increased overall risk of endometriosis (OR 1.41, 95% CI 1.08–1.82; P¼.009). However, when controlling for confounding factors (age, ethnicity, gravidity, parity, infertility, and BMI) in a regression model, no independent association remained between ever smoking and endometriosis (OR 1.17, 95% CI 0.89–1.55; P¼.25). When comparing current and past smokers to never smokers, adjusted for confounding factors, we also failed to find any association (respectively: OR 1.45, 95% CI 0.94–2.23; P¼.09; and OR 1.07, 95% CI 0.79–1.47; P¼.61). Smoking habits were correlated neither with the different types of endometriotic lesions (SUP, OMA, or DIE) nor with the rAFS stages and mean rAFS scores. ‘‘Never’’ and ‘‘ever’’ smokers presented similar mean rAFS total scores (38.3 32.42 and 35.47 29.41, respectively; P¼.36), mean rAFS implant scores (15.22 11.75 and 16.22 12.73, respectively; P¼.41), and mean rAFS adhesion scores (23.54 26.03 and 19.43 22.75, respectively; P¼.09). Smoking habits characteristics were similar in endometriotic and control groups and between the subtypes of endometriotic lesions (Table 1). The present study, the first to examine smoking and histologically proven endometriosis or lack of disease by using control subjects, did not reveal any link between smoking habits and endometriosis. Moreover, in women with endometriosis, there were no differences in smoking between the various groups based on disease extension and grade (SUP, OMA, and DIE). Studying the risk factors for endometriosis is challenging. The strength of the present study lies in the following points. 1) The endometriosis group included only patients with histologically proven endometriosis whose surgical procedure aimed at totally excising of all the endometriotic lesions. The high percentage of DIE was due to the fact that the department is a referral center for severe endometriosis. For the first time, this methodologic approach allowed studying smoking habits in different forms of the disease scored according the rAFS classification and categorized without any ambiguity into SUP, OMA, and DIE groups. In contrast, other studies based on visual recognition of endometriotic lesions as appearing during laparoscopy were likely to report different prevalences of the disease (7, 23–24). 2) Our study included a large sample size of severe endometriosis, the subgroup whose treatment is most problematic and most likely
Vol. 94, No. 6, November 2010
to require extensive surgery. 3) The control group constituted patients in whom endometriosis had been surgically excluded. 4) In this study, the control group underwent the same questioning before surgery and had surgery performed at the same hospital. Therefore, all of the control women had a complete visual evaluation of the pelvic cavity performed by the same team of surgeons experienced in treating endometriosis as operated on the ‘‘study’’ patients. And 5) Our analysis used a detailed review of smoking habits. We provided not only the smoking status but also the conditions of ‘‘ever,’’ ‘‘past,’’ and ‘‘current’’ smoker as well as the age of first smoking, the number of cigarettes per day, the number of years of smoking, and the number of cigarette packs per year. This design allowed us to individually test each of these facets of smoking, looking for association with endometriosis and/or the degree of it. The extent of this survey therefore adds weight to the finding that there seemed to be no association between smoking habits and endometriosis. In spite of all the precautions taken, we concede that the present study may be subject to various possible biases (15, 25). First, this study may indeed suffer from reporting errors owing to the retrospective manner with which epidemiologic data (such as
age at onset of smoking, duration of smoking, and so on) were obtained based on the patients’ own recollection at the time of surgery. These, however, are likely to similarly affect control subjects and women with all stages of endometriosis. Second, recruitment biases can affect control subjects because other gynecologic pathologies may be associated with increased smoking habits (26). Yet any effect of such biases is likely to be limited, because the incidence of smoking in the control group was similar to that encountered in the general female population in France (35%) (22). In conclusion, the present study constitutes a first attempt at assessing the impact of smoking habits on degree of endometriosis, as expressed by the type of the worst lesions (SUP, OMA, or DIE) found. Our data indicated that smoking does not stand as an independent risk factor for endometriosis in a population of histologically proven mostly severe endometriosis. Acknowledgments: The authors warmly thank staff members from our department operating room for their expert assistance with data collection. The authors also thankfully acknowledge Nathalie Girma for unabatedly managing the patient database.
REFERENCES 1. Sampson JA. Perforating hemorragic (chocolate) cysts of the ovary. Arch Surg 1921;3:69. 2. Giudice LC, Kao LC. Endometriosis. Lancet 2004;364:1789–99. 3. Borghese B, Mondon F, Noel JC, Fayt I, Mignot TM, Vaiman D, et al. Gene expression profile for ectopic versus eutopic endometrium provides new insights into endometriosis oncogenic potential. Mol Endocrinol 2008;22: 2557–62. 4. Bulun SE. Endometriosis. N Engl J Med 2009;360: 268–79. 5. Ngo C, Chereau C, Nicco C, Weill B, Chapron C, Batteux F. Reactive oxygen species controls endometriosis progression. Am J Pathol 2009;175: 225–34. 6. Heilier JF, Donnez J, Nackers F, Rousseau R, Verougstraete V, Rosenkranz K, et al. Environmental and host-associated risk factors in endometriosis and deep endometriotic nodules: a matched case-control study. Environ Res 2007;103:121–9. 7. Hediger ML, Hartnett HJ, Louis GM. Association of endometriosis with body size and figure. Fertil Steril 2005;84:1366–74. 8. Parazzini F, Cipriani S, Bianchi S, Gotsch F, Zanconato G, Fedele L. Risk factors for deep endometriosis: a comparison with pelvic and ovarian endometriosis. Fertil Steril 2008;90:174–9. 9. Baron JA, La Vecchia C, Levi F. The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol 1990;162:502–14.
Fertility and Sterility
10. Cramer DW, Wilson E, Stillman RJ, Berger MJ, Belisle S, Schiff I, et al. The relation of endometriosis to menstrual characteristics, smoking, and exercise. JAMA 1986;255:1904–8. 11. Darrow SL, Vena JE, Batt RE, Zielezny MA, Michalek AM, Selman S. Menstrual cycle characteristics and the risk of endometriosis. Epidemiology 1993;4:135–42. 12. Calhaz-Jorge C, Mol BW, Nunes J, Costa AP. Clinical predictive factors for endometriosis in a Portuguese infertile population. Hum Reprod 2004;19:2126–31. 13. Buck Louis GM, Hediger ML, Pena JB. Intrauterine exposures and risk of endometriosis. Hum Reprod 2007;22:3232–6. 14. Vessey MP, Villard-Mackintosh L, Painter R. Epidemiology of endometriosis in women attending family planning clinics. BMJ 1993;306:182–4. 15. Zondervan KT, Cardon LR, Kennedy SH. What makes a good case-control study? Design issues for complex traits such as endometriosis. Hum Reprod 2002;17:1415–23. 16. Somigliana E, Vercellini P, Gattei U, Chopin N, Chiodo I, Chapron C. Bladder endometriosis: getting closer and closer to the unifying metastatic hypothesis. Fertil Steril 2007;87:1287–90. 17. American Fertility Society. Revised American Fertility Society classification of endometriosis: 1985. Fertil Steril 1985;43:351–2. 18. Bernaards CM, Twisk JW, Snel J, Van Mechelen W, Kemper HC. Is calculating pack-years retrospectively a valid method to estimate life-time tobacco
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smoking? A comparison between prospectively calculated pack-years and retrospectively calculated pack-years. Addiction 2001;96:1653–61. Signorello LB, Harlow BL, Cramer DW, Spiegelman D, Hill JA. Epidemiologic determinants of endometriosis: a hospital-based case-control study. Ann Epidemiol 1997;7: 267–74. Warren CW, Jones NR, Eriksen MP, Asma S. Patterns of global tobacco use in young people and implications for future chronic disease burden in adults. Lancet 2006;367:749–53. Nick TG, Campbell KM. Logistic regression. Methods Mol Biol 2007;404:273–301. Peretti-Watel P, Constance J, Seror V, Beck F. Cigarettes and social differentiation in France: is tobacco use increasingly concentrated among the poor? Addiction 2009 Aug 4. [Epub ahead of print]. Howard FM. The role of laparoscopy in chronic pelvic pain: promise and pitfalls. Obstet Gynecol Surv 1993;48:357–87. Bonte H, Chapron C, Vieira M, Fauconnier A, Barakat H, Fritel X, et al. Histologic appearance of endometriosis infiltrating uterosacral ligaments in women with painful symptoms. J Am Assoc Gynecol Laparosc 2002;9:519–24. Holt VL, Weiss NS. Recommendations for the design of epidemiologic studies of endometriosis. Epidemiology 2000;11:654–9. Grodstein F, Rothman KJ. Epidemiology of pelvic inflammatory disease. Epidemiology 1994;5: 234–42.
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Endometriosis is characterized by the presence of endometrial tissue—epithelium and/or stroma—that develops outside the uterine cavity (1), causing pain and infertility (2). There are three types of endometriotic lesions: superficial peritoneal endometriosis (SUP), Charles Chapron, M.D.a,d,e Carlos Souza, M.D.a,f Dominique de Ziegler, M.D.a Marie-Christine Lafay-Pillet, M.D.a Charlotte Ng^o, M.D.a,b Gerard Bijaoui, M.D.a Franc xois Goffinet, M.D., Ph.D.c Bruno Borghese, M.D., Ph.D.a,d,e a Service de Gyn ecologie Obst etrique II et M edecine de la Reproduction (Professeur Chapron), Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, Groupe Hospitalier Universitaire Ouest, Assistance Publique– H^ opitaux de Paris, Universit e Paris Descartes, Paris, France b Facult e de M edecine, EA 1833, ERTi, Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, Groupe Hospitalier Universitaire Ouest, Assistance Publique– H^ opitaux de Paris, Universit e Paris Descartes, Paris, France c Maternit e Port-Royal (Professeur Cabrol), Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, Groupe Hospitalier Universitaire Ouest, Assistance Publique– H^ opitaux de Paris, Universit e Paris Descartes, Paris, France d Institut Cochin, CNRS UMR 8104, Paris, France e INSERM U1016, Paris, France f Servicxo de Ginecologia e Obstetricia, Hospital de Clınicas de Porto Alegre, Coordenacxa~o de Aperfeicxoamento de Pessoal de Nıvel Superior, Porto Alegre, Brazil Received December 7, 2009; revised March 29, 2010; accepted April 8, 2010; published online May 31, 2010. C.C. has nothing to disclose. C.S. has nothing to disclose. D.Z. has nothing to disclose. M.-C.L.-P. has nothing to disclose. C.N. has nothing to disclose. G.B. has nothing to disclose. F.G. has nothing to disclose. B.B. has nothing to disclose. cologie— Reprint requests: Charles Chapron, M.D., Service de Gyne trique II et Me decine de la Reproduction, CHU Cochin—Saint Obste Vincent de Paul, Pavillon Lelong, 82 avenue Denfert Rochereau, 75014 Paris, France (FAX: 33-1-58-41-18-70; E-mail: charles. [email protected]).
0015-0282/$36.00 doi:10.1016/j.fertnstert.2010.04.020
ovarian endometriomas (OMA), and deep infiltrating endometriosis (DIE). The pathogenesis of endometriosis remains controversial (3–5). Sets of risk factors (lifestyle, sociodemographic, environmental, reproductive, and genetic characteristics), including smoking, have been associated with endometriosis (6–8). Endometriosis being an estrogen-dependent process, it has been thought that cigarette smoking, which has antiestrogenic effects, could lower the risk (9). Yet the links between tobacco use and endometriosis are still debated (6, 8, 10–14). The divergent findings regarding smoking and endometriosis stem in part from methodologic issues that are prone to affect all clinical trials on endometriosis (15). In light of this enduring controversy, we elected to study the issue of smoking and endometriosis by comparing a control and affected population in whom endometriosis was either surgically excluded or proven and histologically graded. To our knowledge, this study is the first to assess the possible association between smoking habits and the degree of surgically proven histologically graded endometriosis (SUP, OMA, and DIE). We conducted a cross-sectional study including all nonpregnant patients <42 years of age who were operated on (by laparotomy or operative laparoscopy) in our institution between January 2004 and December 2008. Excluded from this cohort were women with cancer and/or who refused to sign a consent form. A total of 1,133 were visually diagnosed with the presence (n ¼ 566) or absence (n ¼ 567) of endometriosis. Patients visually diagnosed with endometriosis but without histologic confirmation (n ¼ 155) were considered to be ineligible to participate in the study. Depending on pathologic findings, endometriotic lesions were divided into SUP, OMA, and DIE. Because the three types of lesions are frequently associated (16), the ultimate staging was given by the worst lesion found in each patient (from least bad to worst: SUP, OMA, and DIE). The control group included 567 patients without any visual lesion of endometriosis, as checked at the time of surgery by a thorough examination of the abdominopelvic cavity. Data were collected by face-to-face standardized questionnaires conducted by the surgeon during the month before surgery. During surgery, extension of endometriosis was scored according to the revised American Fertility Society (rAFS) classification (17). For each patient, current and past smoking habits were evaluated
Fertility and Sterility Vol. 94, No. 6, November 2010 Copyright ª2010 American Society for Reproductive Medicine, Published by Elsevier Inc.
2353
TABLE 1 Smoking habit characteristics of control subjects and endometriosis patients. Endometriosis type
Age began smoking (y) No. of cigarettes per day No. of years of smoking No. of cigarette pack Interval free from smoking
Endometriosis (n [ 411)
Control (n [ 567)
P valuea
SUP
OMA
DIE
P valueb
17.91 4.48 10.27 6.63 12.51 6.67 7.5 7.33 4.32 3.94
17.51 3.94 11.51 7.65 12.49 6.68 9.52 23.65 5.86 5.32
.43 .14 .98 .33 .08
17.53 4.25 8.87 5.95 11.43 7.14 6.87 6.35 9.13 8.60
17.11 3.99 10.32 5.69 12.06 6.89 6.26 5.53 3.97 3.46
18.38 4.74 10.52 7.20 12.92 6.54 8.203 8.18 3.94 3.19
.39 .44 .84 .77 .06
Note: DIE ¼ deep infiltrating endometriosis; OMA ¼ ovarian endometrioma; SUP ¼ superficial endometriosis. a Student t test. b One-way analysis of variance. Chapron. Correspondence. Fertil Steril 2010.
as follows: 1) never or ever (currently or in the past) a smoker; 2) age at onset of smoking; 3) number of cigarettes per day; 4) number of years smoking; 5) number of pack-years (18); and 6) interval free of smoking (past smokers). In accordance to earlier studies, we defined ‘‘ever a smoker’’ as anyone who answered ‘‘yes’’ to the following question: ‘‘During your lifetime, have you smoke more than 100 cigarettes?’’ ‘‘Current smoker’’ was defined as a patient who answered ‘‘yes’’ to the following question: ‘‘Did you smoke a cigarette during the past 30 days?’’ (19–20). Statistical analyses were performed using SPSS 13.0 (SPSS, Chicago, IL). Continuous data were presented as mean SD. Student t test and one-way analysis of variance were carried out when necessary. The chi square and Fisher exact test were used for categoric data. We used odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) to compare the smoking habits between the different types of endometriosis. We also performed an unconditional logistic regression to control for potential confounding factors, such as age, ethnicity, gravidity, parity, infertility, and body mass index (BMI). We performed a stepwise logistic regression analysis, in which a P value of .5 was used as entry criteria and a P value of .2 was the threshold for the covariate to stay in the model (21). A P value of < .05 was considered to be statistically significant. The power of the study was calculated based on the following assumptions: 1) sample size (n ¼ 978); 2) prevalence of smoking in control subjects of 35% (22); 3) expected difference of 10% between the groups (11); and 4) type I and II errors of .05 and .12, respectively. The local Ethics Committee (Comite Consultatif de Protection des Personnes dans la Recherche Biomedicale) at our institution approved the study protocol, and each of the included patients signed an informed consent form. Patients with histologically proven endometriotic lesions (group A: n ¼ 411; 42%) were distributed as follows: SUP: 47 patients (11.4%); OMA: 120 patients (29.2%), and DIE: 244 patients (59.4%). Classification according to the rAFS stages was: stage I: 56 patients (13.6%); stage II: 85 patients (20.7%); stage III: 112 patients (27.2%); and stage IV: 158 patients (38.5%). The control group (group B) consisted of 567 patients (58%) without endometriosis at the time of surgery. The number of ‘‘ever smokers’’ was 184 in group A (SUP: 19 patients; OMA: 54 patients; DIE: 111 patients) and 207 in group B. Smoking habits were similar in the operative and laparoscopy/laparotomy groups (OR 1.28,
2354
Chapron et al.
Correspondence
95% CI 0.67–2.42). Raw data indicated that smokers had an increased overall risk of endometriosis (OR 1.41, 95% CI 1.08–1.82; P¼.009). However, when controlling for confounding factors (age, ethnicity, gravidity, parity, infertility, and BMI) in a regression model, no independent association remained between ever smoking and endometriosis (OR 1.17, 95% CI 0.89–1.55; P¼.25). When comparing current and past smokers to never smokers, adjusted for confounding factors, we also failed to find any association (respectively: OR 1.45, 95% CI 0.94–2.23; P¼.09; and OR 1.07, 95% CI 0.79–1.47; P¼.61). Smoking habits were correlated neither with the different types of endometriotic lesions (SUP, OMA, or DIE) nor with the rAFS stages and mean rAFS scores. ‘‘Never’’ and ‘‘ever’’ smokers presented similar mean rAFS total scores (38.3 32.42 and 35.47 29.41, respectively; P¼.36), mean rAFS implant scores (15.22 11.75 and 16.22 12.73, respectively; P¼.41), and mean rAFS adhesion scores (23.54 26.03 and 19.43 22.75, respectively; P¼.09). Smoking habits characteristics were similar in endometriotic and control groups and between the subtypes of endometriotic lesions (Table 1). The present study, the first to examine smoking and histologically proven endometriosis or lack of disease by using control subjects, did not reveal any link between smoking habits and endometriosis. Moreover, in women with endometriosis, there were no differences in smoking between the various groups based on disease extension and grade (SUP, OMA, and DIE). Studying the risk factors for endometriosis is challenging. The strength of the present study lies in the following points. 1) The endometriosis group included only patients with histologically proven endometriosis whose surgical procedure aimed at totally excising of all the endometriotic lesions. The high percentage of DIE was due to the fact that the department is a referral center for severe endometriosis. For the first time, this methodologic approach allowed studying smoking habits in different forms of the disease scored according the rAFS classification and categorized without any ambiguity into SUP, OMA, and DIE groups. In contrast, other studies based on visual recognition of endometriotic lesions as appearing during laparoscopy were likely to report different prevalences of the disease (7, 23–24). 2) Our study included a large sample size of severe endometriosis, the subgroup whose treatment is most problematic and most likely
Vol. 94, No. 6, November 2010
to require extensive surgery. 3) The control group constituted patients in whom endometriosis had been surgically excluded. 4) In this study, the control group underwent the same questioning before surgery and had surgery performed at the same hospital. Therefore, all of the control women had a complete visual evaluation of the pelvic cavity performed by the same team of surgeons experienced in treating endometriosis as operated on the ‘‘study’’ patients. And 5) Our analysis used a detailed review of smoking habits. We provided not only the smoking status but also the conditions of ‘‘ever,’’ ‘‘past,’’ and ‘‘current’’ smoker as well as the age of first smoking, the number of cigarettes per day, the number of years of smoking, and the number of cigarette packs per year. This design allowed us to individually test each of these facets of smoking, looking for association with endometriosis and/or the degree of it. The extent of this survey therefore adds weight to the finding that there seemed to be no association between smoking habits and endometriosis. In spite of all the precautions taken, we concede that the present study may be subject to various possible biases (15, 25). First, this study may indeed suffer from reporting errors owing to the retrospective manner with which epidemiologic data (such as
age at onset of smoking, duration of smoking, and so on) were obtained based on the patients’ own recollection at the time of surgery. These, however, are likely to similarly affect control subjects and women with all stages of endometriosis. Second, recruitment biases can affect control subjects because other gynecologic pathologies may be associated with increased smoking habits (26). Yet any effect of such biases is likely to be limited, because the incidence of smoking in the control group was similar to that encountered in the general female population in France (35%) (22). In conclusion, the present study constitutes a first attempt at assessing the impact of smoking habits on degree of endometriosis, as expressed by the type of the worst lesions (SUP, OMA, or DIE) found. Our data indicated that smoking does not stand as an independent risk factor for endometriosis in a population of histologically proven mostly severe endometriosis. Acknowledgments: The authors warmly thank staff members from our department operating room for their expert assistance with data collection. The authors also thankfully acknowledge Nathalie Girma for unabatedly managing the patient database.
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