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To the Editor
Peters and Woodward’s epidemiological study found that early menarche, early menopause, earlier age at first birth and a history of miscarriage, stillbirth or hysterectomy were each independently associated with a higher risk of CVD in later life.1 However, early menarche and early age of first birth could relate to younger starting age and longer use of progestogen and/or oestrogen contraception. Hysterectomy and early menopause can relate to younger starting age and longer use of menopausal oestrogens or progestogen/oestrogen combinations.
In my experience since 1960, the main risk factor for increases in vascular disease in women is the use of progestogens and oestrogens.2 Why does the UK Biobank not record this important information?
From 1968 to 1969, the RCGP oral contraceptive (OC) study enrolled 47 000 women. A total of 29 500 OC takers, including 5800 transferred controls, were compared with 17 800 never takers and only 36% of OC users were new takers.3 Deaths in 75% of the original cohort were flagged on the National Health Service Central Register but only from 1977. Average OC use was 44 months, 41% of women were lost and many deaths would have been missed. Takers had increases in deep venous thrombosis and pulmonary embolism (5.66×), heart disease (5.2×) and cerebrovascular disease (4.1×) compared with never takers and 120 months of OC use increased the risk of diabetes by 50%. Within the first 10 years, takers had significant excess mortality from all causes of death (1.2×), all circulatory diseases (2.2×) and cerebrovascular disease (2.7×). By 1994, the relative risk of death from heart disease was 7.3× for current users and 4.6× for former users compared with controls.
In a WHO study, average OC use was 3 years. After numerous exclusions, current OC users aged 15–49 years had 4.65× more risk of myocardial infarction than past or never users. OC users aged <35 years who also smoked had 35× more risk of myocardial infarction but non-smoking current OC users aged >35 years had a similar 31× increased risk.4
The elephant in the room for Biobank authors appears to be lack of contraceptive, fertility or menopausal hormone use data.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.