Women with endometriosis show higher risk for heart disease
BMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i1851 (Published 01 April 2016) Cite this as: BMJ 2016;353:i1851All rapid responses
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The Nurses’ Health Study authors report that women with endometriosis who had a hysterectomy or oophorectomy had a 51% higher risk of combined coronary heart disease than those not having had such surgical treatment, especially at younger ages.1 The study claims to have accounted for oral contraceptive (OC) and hormone replacement therapy use (HRT) but not other hormonal treatments of endometriosis. How was that possible?
The 36 year follow up of the Nurses' Health Study revealed that only 13.7% (16,670/121,577) of women included had never used OCs or HRT. “All Cause” mortality was claimed to be unaltered by ever use of OCs although OC use had increased rates of violent or accidental death and breast cancer.2 My Rapid Response commentated that OC mortality was underestimated because recent HRT users were incorrectly added to controls if they had never used OCs.3 Eugene Breen responded that the study was seriously flawed because the mean age of participants at intake in 1976 was 42 years and 61 years at mid-point in 1994. Therefore a significant number of deaths due to OCs use had occurred before the study was started and were missed by studying mortality in older women.4
In the beginning years of OC studies the main cause of death are from accidents and violence, cancers, venous thromboembolic disease and strokes. Coronary artery disease becomes a main cause of death in older women, especially in women who have smoked for over 20 years and taken also taken HRT. Longer OC follow up studies confuse if the effects of HRT use are included in their so called never user control groups.
An increasingly high hysterectomy rate in young women has been another important confounding factor in OC studies. The Walnut Creek contraceptive drug study found that women under 40 years of age taking OCs were significantly more likely to have hysterectomies and more reasons for hysterectomy; with increased hospital admissions for cervical cancer, fibroids, menstrual irregularities, anaemia from blood loss, pelvic inflammatory disease and adenomyosis.5
1 Mu F, Rich-Edwards J, Rimm EB, Spiegelman D, Missmer SA. Endometriosis and risk of coronary heart disease. Circ Cardiovasc Qual Outcomes 2016; published online 29 Mar,doi:10.1161/CIRCOUTCOMES.115.002224.
2 Charlton BM, Rich-Edwards JW, Colditz GA, Missmer SA, Rosner BA, Hankinson SE, Speizer FE, Michels KB. Oral contraceptive use and mortality after 36 years of follow-up in the Nurses’ Health Study: prospective cohort study. BMJ 2014;349:g6356.
3 Grant ECG. Re: Oral contraceptive use and mortality after 36 years of follow-up in the Nurses’ Health Study: prospective cohort study. BMJ 2014; 349/bmj.g6356/rapid-responses 1 November 2014.
4 Breen EG. Re: Oral contraceptive use and mortality after 36 years of follow-up in the Nurses’ Health Study: prospective cohort study. BMJ 2014; 349/bmj.g6356/rapid-responses 3 November 2014.
5 Ramcharan S, Pellegrin FA, Ray RM, Hsu JP. The Walnut Creek Contraceptive Drug Study. A prospective study of the side effects of oral contraceptives. Volume III, an interim report: A comparison of disease occurrence leading to hospitalization or death in users and nonusers of oral contraceptives. J Reprod Med. 1980 Dec;25(6 Suppl):345-72.
Competing interests: No competing interests
Suffering women who sign informed consent forms to undergo hysterectomies and bilateral oophorectomies at such a young age, surely have Stage III or IV endometriosis.
More advanced peritoneal and intestinal endometriotic loci are associated with severe chronic inflammation, heightened oxidative stress, and worse atherogenic lipid profile.
Thus, women with advanced endometriosis are inherently at increased risk for Coronary Heart Disease, compared to women with early endometriosis (Stages I-II) who do not need or opt for hysterectomies and oophorectomies.
Stating in that research study that hysterectomies per se are causative risk factors for Coronary Heart Disease is incorrect and not evidence based.
Reference
http://circoutcomes.ahajournals.org/content/early/2016/03/29/CIRCOUTCOME...
Competing interests: No competing interests
Hormone use can increase oxidative stress and cause heart disease
Women with endometriosis show higher risk for heart disease
Jacqui Wise reviewed the findings of the Nurses’ Health Study II that women with endometriosis increased risk of heart disease.1 Was this because women who were enrolled with endometriosis were three times more likely to be taking menopausal hormones than women without confirmed endometriosis?
The Nurses’ Health Study II is a prospective cohort study which enrolled 116,430 nurses aged 25 to 42 with a mean age of 35 years in 1989. At enrolment 89% of the 5295 women with laparoscopically confirmed endometriosis had used oral contraceptives (OCs), 32% had used postmenopausal hormones and 21% had a history of hysterectomy. In contrast, although 83% of 109,161 women without confirmed endometriosis had used OCs, only 10% had used postmenopausal hormones and only 4% had a history of hysterectomy.2
Chan and Kotani found that levels of derivatives of reactive oxygen metabolites, which they used to measure the overall oxidative stress burden by analysing the oxidation of various components such as lipids, proteins and nucleic acids, positively correlated with the level of C-reactive protein, a marker of chronic inflammation in OC users. They proposed that OC use might increase breast cancer by increasing inflammation.3 Also Krintus and colleagues found that use of second and third generation OCs increased C-reactive protein levels.4 Progestogens and oestrogens use can lower zinc and raise copper levels which impairs superoxide dismutase activities and liver clearance of carcinogens.5
Use of progestogens and oestrogens, whether used for contraception or menopausal therapy can cause chronic inflammation with heightened oxidative stress and increase the risk of endometriosis and coronary artery disease and also breast and other types of cancer. It is unfortunate for women that the fact that use progestogens and oestrogens can increase oxidative stress is usually ignored with potentially serious consequences.
1 Jacqui Wise. Women with endometriosis show higher risk for heart disease 353:doi10.1136/bmj.i1851
2 Mu F, Rich-Edwards J, Rimm EB, Spiegelman D, Missmer SA. Endometriosis and risk of coronary heart disease. Circ Cardiovasc Qual Outcomes 2016; published online 29 Mar,doi:10.1161/CIRCOUTCOMES.115.002224
3 Chen JT, Kotani K. Oral contraceptive therapy increases oxidative stress in pre-menopausal women. Int J Prev Med 2012;3:893-6.
4 Krintus M, Sypniewska G, Kuligowska-Prusinska M. Effect of second and third generation oral contraceptives on C-reactive protein, lipids and apolipoproteins in young, non-obese, non-smoking apparently healthy women. Clin Biochem 2010;43:626-8.
5 Grant ECG. The pill, hormone replacement therapy, vascular and mood over-reactivity and mineral imbalance. J Nutr Environ Med 1998:8:789-91. DOI:10.1080/13590849862131
Competing interests: No competing interests