Elsevier

The Lancet

Volume 348, Issue 9033, 12 October 1996, Pages 983-987
The Lancet

Articles
Prospective study of exogenous hormones and risk of pulmonary embolism in women

https://doi.org/10.1016/S0140-6736(96)07308-4Get rights and content

Summary

Background

Current use of oral contraceptives (OCs) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism (PE). Little is known about residual effects of past OC use. Furthermore, few epidemiological studies have assessed the relation between postmenopausal use of hormones and thrombotic disease.

Methods

In this prospective study information was obtained through questionnaires sent every 2 years (1976–92) to 112 593 women aged 30–55 in 1976. We excluded women with previously diagnosed cardiovascular disease or cancer in 1976 and at the beginning of each subsequent 2-year follow-up period.

Findings

From self-reports and medical records, we documented 123 cases of primary PE (no identified antecedent cancer, trauma, surgery, or immobilisation). Current users of postmenopausal hormones had an increased risk of primary PE (relative risk adjusted for multiple risk factors 2·1 [95% CI 1·2–3·8]). However, past use showed no relation to PE (1·3 [0·7–2·4]). In current users of OCs the risk of primary PE was about twice that in non-users (2·2 [0·8–5·9]), but this finding was based on only five cases who were current OC users. Users of OCs in the past had no increase in risk of PE (0·8 [0·5–1·2]). These relations were consistent irrespective of cigarette-smoking status.

Interpretation

Primary PE was uncommon in this cohort. The risk was increased by current though not past use of postmenopausal hormones or OCs.

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)

  • Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy: a report

    N Engl J Med

    (1974)
  • DB Pettiti et al.

    Risk of vascular disease in women: smoking, oral contraceptives, noncontraceptive estrogens, and other factors

    JAMA

    (1979)
  • DA Quinn et al.

    A prospective investigation of pulmonary embolism in women and men

    JAMA

    (1992)
  • L Rosenberg et al.

    Myocardial infarction and cigarette smoking in women younger than 50 years of age

    JAMA

    (1985)
  • MJ Stampfer

    Oral contraceptives and risk of cardiovascular disease: epidemiologic evidence on acute and long-term effects

  • MJ Stampfer et al.

    Test of the National Death Index

    Am J Epidemiol

    (1984)
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