ArticlesProspective study of exogenous hormones and risk of pulmonary embolism in women
Introduction
Current use of oral contraceptives (OCs) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism (PE)1, 2, 3, 4, 5 but little is known about possible residual effects of past OC use. Nevertheless, on the basis of the apparently increased risk of PE for OC users, a commonly held view among physicians is that a similar danger is posed by postmenopausal hormone therapy,6 although the oestrogen dose in such treatment is about a sixth of that in OCs. Whether postmenopausal hormones are associated with an increased risk of PE remains unclear; few epidemiological studies have assessed the relation between postmenopausal hormones and thrombotic disease,7, 8, 9, 10 and most of those available were too small to provide any clear conclusions. The largest of these studies included six cases of PE among users of postmenopausal hormones.9 In addition, the strong interaction between OC use, cigarette smoking, and heart disease11, 12 suggests the possibility of such associations for exogenous hormones and PE. Because use of hormone therapy is widespread, assessment of any possible risk of adverse effects is important.
We, therefore, assessed the associations of OCs and postmenopausal hormones with PE, as well as interactions with cigarette smoking, in a prospective cohort of 112 593 women aged 30–55 years at baseline in 1976.
Section snippets
Methods
The Nurses' Health Study began in 1976. 121 700 female registered nurses in 11 states completed a mailed questionnaire that included items about their medical history and cardiovascular risk factors such as height, weight, cigarette smoking, diabetes, hypertension, serum cholesterol, parental myocardial infarction, parity, menopause, and the use of exogenous hormones. Height and weight were used to calculate body-mass index. Every 2 years, follow-up questionnaires were sent so that information
Results
Documented primary PE was uncommon in this cohort (table 1). The highest rate was only 36 per 100 000 person-years among current OC users aged 30–39, based on five observed cases. For primary and secondary PE together, the highest rate was also in that category (57 per 100 000 person-years, based on eight cases).
Among postmenopausal women, 68 cases of primary PE occurred during 633 817 person-years of follow-up. The relative risk of PE associated with current postmenopausal hormone use,
Discussion
In this large prospective study, women currently using postmenopausal hormones had a significantly increased risk of primary PE. There were few current OC users in the cohort, but their risk of PE was also increased. Past use of exogenous hormone preparations was not associated with primary PE. Cigarette-smoking status did not affect the findings.
Because information on exogenous hormone use was collected from the women themselves, misclassification is possible. We believe the self-reports of
References (32)
- et al.
Oral contraceptives and cardiovascular disease: a critique of the epidemiologic studies
Am J Obstet Gynecol
(1985) Estrogen and risk of coagulopathy
Am JMed
(1992)- et al.
Estrogen replacement therapy and the risk of venous thrombosis
Am J Med
(1992) Risks and mechanisms of cardovascular events in users of oral contraceptives
Am J Obstet Gynecol
(1988)- et al.
Oral contraceptives and venous thromboembolic disease: the effect of oestrogen dose
Maturitas
(1988) - et al.
Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen
Lancet
(1995) - et al.
Thromboembolic disease and the steroidal content of oral contraceptives: a report to the Committee on Safety of Drugs
BMJ
(1970) - et al.
Investigation of relation of use of oral contraceptives and thromboembolic disease
BMJ
(1968) Oral contraception and risk of a cerebral thromboembolic attack
BMJ
(1993)Venous thromboembolic disease and combined oral contraceptives: results of an international multicentre case-control study
Lancet
(1995)
Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy: a report
N Engl J Med
Risk of vascular disease in women: smoking, oral contraceptives, noncontraceptive estrogens, and other factors
JAMA
A prospective investigation of pulmonary embolism in women and men
JAMA
Myocardial infarction and cigarette smoking in women younger than 50 years of age
JAMA
Oral contraceptives and risk of cardiovascular disease: epidemiologic evidence on acute and long-term effects
Test of the National Death Index
Am J Epidemiol
Cited by (569)
Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis
2018, Thrombosis ResearchCitation Excerpt :Therefore, a meta-analysis of progestin subgroups was not possible. Seven studies [7,27,30,33,37,38,40] compared never-HT users with past HT users (oral route only). Six of them did not report changes in VTE risk when never users and past users were compared (Supplemental Table).
Endometrial hyperplasia, estrogen therapy, and the prevention of endometrial cancer
2018, Clinical Gynecologic OncologyVenous Thromboembolism
2018, Hematology: Basic Principles and PracticeThrombosis and anticoagulation in women
2018, Revista Colombiana de CardiologiaVenous Thromboembolism
2017, Hematology: Basic Principles and Practice