Abstract

PIP: Arterial hypertension (AH) was reported for the 1st time as a side effect 5 years after the introduction of oral contraceptives (OCs) in the early 1960s. Most of the information associated with the risks of OC use was derived from the UK Royal College of General Practitioner's (RCGP) Oral Contraception Study of 1968, the UK Oxford/Family Planning Associates Contraceptive Study of 1968, and the US Walnut Creek/Kaiser Permanente Study of 1968 and 1977. These studies showed that AH and the risk of cardiovascular morbidity and mortality was significantly higher in women over 35 and who smoked because of the increased estradiol metabolism. In the 1960s the estrogen content in OCs was 50-150 mcg and the prostagen content was 10-10 mg. An average of 50 mcg estrogen and 1.5 mg of progestogen has been used since 1969. Low dose preparations in use since 1973 contain 30 mcg of estrogen and an equal dose of progestogen. The RCGP study of 1977 implicated norethisterone acetate (1, 3, and 4 mg used with 50 mcg of ethinyl estradiol EE), a progestogen, in hypertension. In a study of 78 women 15 were using an OC with 30 mcg of EE with 150 or 250 mcg of norgestrel and 63 women used a pill with 50 mcg of EE or mestranol with 1, 3, or 4 mg of norethisterone. The lower EE dose produced higher arterial pressure attributable to norgestrel. In 9 women taking OCs with 30 mcg of EE blood pressure dropped in a 1978 study of 50 women taking such low-dose pills, while the pressure increased in 100 other women taking on OC with 50 mcg of EE. Most relevant studies indicated a dose-response or type-response relationship between the progestogen component and arterial pressure. The estrogen component was also a major factor in OC-induced AH. The data implicate the involvement of the renin-angiotensin-aldosterone system, the direct effects of mineralocorticoids, and the adrenergic nervous system in the etiology of high blood pressure under OC use.