RE: "RISK FACTORS FOR UTERINE LEIOMYOMA: A PRACTICE-BASED CASE-CONTROL STUDY. II. ATHEROGENIC RISK FACTORS AND POTENTIAL SOURCES OF UTERINE IRRITATION"

Riitta Luoto

Tampere School of Public Health University of Tampere Medisiinarinkatu 3 FIN-33014 Tampere, Finland

The study by Faerstein et al. in the January 2001 issue of the Journal (1Go) was very interesting and demonstrated the importance of uterine leiomyomas (UL), or fibroids, in women's health. The epidemiology of UL has for too long been understudied.

Faerstein et al. stated that the coexistence of UL with hypertension was noted in some studies conducted between the 1930s and the 1970s (1Go). However, the study by Faerstein et al. failed to refer to relevant studies carried out since the 1970s that have also noted a correlation between hysterectomy with ovarian preservation and hypertension (2GoGoGo–5Go). The rationale of these studies has been the indication for hysterectomy, UL, which explains the correlation of UL with hypertension rather than with the operation itself.

In our Finnish population-based cohort study (n = 3,895), women with a history of hysterectomy (n = 163) had an increased risk of high diastolic blood pressure and diagnosis of hypertension (odds ratio (OR) = 2.2, 95 percent confidence interval (CI): 1.5, 3.1), even if their ovaries had been preserved (3Go). Women with UL as an indication for surgery especially had an increased risk of diagnosis of hypertension (adjusted OR = 2.5, 95 percent CI: 1.6, 3.9). We concluded that UL as an indication for hysterectomy may share a common pathogenic mechanism with hypertension.

In another study, we obtained the medical records of all women who had undergone hysterectomy at Helsinki University Hospital in the years 1984 and 1994 (6Go). Hyper-tension was defined on the basis of a previously established diagnosis or preoperatively measured blood pressure. Women with UL according to the pathology reports were significantly more likely to be hypertensive (age-adjusted OR = 1.8, 95 percent CI: 1.2, 2.7). The age-adjusted association between UL and hypertension was strongest among women who underwent hysterectomy for benign adnexal tumors (OR = 3.6, 95 percent CI: 1.2, 10.9). Local growth factors found in UL (7Go, 8Go) may be involved in the cellular proliferation and hypertrophy leading to the development of UL. These factors, as well as obesity and nutritional considerations, are also involved in the regulation of smooth muscle cells and blood pressure, which may be part of a common pathogenic mechanism of UL and hypertension.

Thus, the atherogenesis hypothesis has more evidence than that suggested in the conclusion by Faerstein et al. (1Go) and other hypotheses evidenced in that study. The finding that the adjusted association was confined to women who had been hypertensive for 5 or more years supports the view that UL and hypertension have a common pathogenesis. Therefore, the order of causality may be difficult to establish without longitudinal data.

REFERENCES

  1. Faerstein E, Szklo M, Rosenshein NB. Risk factors for uterine leiomyoma: a practice-based case-control study. II. Atherogenic risk factors and potential sources of uterine irritation. Am J Epidemiol 2001;153:11–19.[Abstract/Free Full Text]
  2. Palmer JR, Rosenberg L, Shapiro S. Reproductive factors and risk of myocardial infarction. Am J Epidemiol 1992;136:408–16.[Abstract]
  3. Gordon T, Kannel WB, Hjortland MC, et al. Menopause and coronary heart disease: The Framingham Study. Ann Intern Med 1978;89:157–61.[ISI][Medline]
  4. Luoto R, Kaprio J, Reunanen A, et al. Cardiovascular morbidity in relation to ovarian function after hysterectomy. Obstet Gynecol 1995;85:515–22.[Abstract/Free Full Text]
  5. Ritterband AB, Jaffee IA, Densen PM, et al. Gonadal function and the development of coronary heart disease. Circulation 1963;27:237–51.[ISI][Medline]
  6. Luoto R, Rutanen E-M, Auvinen A. Fibroids and hypertension—a cross-sectional study of women undergoing hysterectomy. J Reprod Med 2001;46:359–64.[ISI][Medline]
  7. Shimomura Y, Matsuo H, Samoto T, et al. Up-regulation by progesterone of proliferating cell nuclear antigen and epidermal growth factor expression in human uterine leiomyoma. J Clin Endocrinol Metab 1998;83:2192–8.[Abstract/Free Full Text]
  8. Dawood MY, Sabir N. Growth factors and leiomyomas. Infertil Reprod Med Clin North Am 1996;7:5–18.

 

TWO AUTHORS REPLY

Eduardo Faerstein and Moyses Szklo

Department of Epidemiology Institute of Social Medicine State University of Rio de Janeiro Rio de Janeiro, RJ 20550-900, Brazil
Department of Epidemiology Bloomberg School of Public Health Johns Hopkins University Baltimore, MD 21202-6709

We thank Dr. Luoto for her comments (1Go) on our paper (2Go), in which an atherogenesis hypothesis regarding the development of uterine leiomyomas (UL) was postulated. More specifically, we suggested that hyperinsulinemia may play a pivotal role linking hormone-related and atherogenic determinants (e.g., hypertension) in the UL causal web.

We appreciate Dr. Luoto's reference to her own work (3Go, 4Go), which also supports the existence of an association between UL and hypertension. However, after reviewing other reports mentioned by her as also providing earlier findings of that association (5GoGo–7Go), we concluded that those reports do not address exactly the same topic.

We agree that longitudinal data, when available, will help in establishing the causal nature of a hypertension-UL association. We hope that prospective research will be conducted to investigate both hormone-related and non-hormone-related potential risk factors (e.g., sources of local irritation (2Go)) for this understudied and important medical condition.

REFERENCES

  1. Luoto R. Re: "Risk factors for uterine leiomyoma: a practice-based case-control study. II. Atherogenic risk factors and potential sources of uterine irritation." (Letter). Am J Epidemiol 2002;155:187.[Free Full Text]
  2. Faerstein E, Szklo M, Rosenshein NB. Risk factors for uterine leiomyoma: a practice-based case-control study. II. Atherogenic risk factors and potential sources of uterine irritation. Am J Epidemiol 2001;153:11–19.[Abstract/Free Full Text]
  3. Luoto R, Kaprio J, Reunanen A, et al. Cardiovascular morbidity in relation to ovarian function after hysterectomy. Obstet Gynecol 1995;85:515–22.[Abstract/Free Full Text]
  4. Luoto R, Rutanen E-M, Auvinen A. Fibroids and hypertension—a cross-sectional study of women undergoing hysterectomy. J Reprod Med 2001;46:359–64.[ISI][Medline]
  5. Palmer JR, Rosenberg L, Shapiro S. Reproductive factors and risk of myocardial infarction. Am J Epidemiol 1992;136:408–16.[Abstract]
  6. Gordon T, Kannel WB, Hjortland MC, et al. Menopause and coronary heart disease: The Framingham Study. Ann Intern Med 1978;89:157–61.[ISI][Medline]
  7. Ritterband AB, Jaffee IA, Densen PM, et al. Gonadal function and the development of coronary heart disease. Circulation 1963;27:237–51.[ISI][Medline]