Effect on hypertension and benign breast disease of progestagen component in combined oral contraceptives
Lancet 1(8012): 624
1977
ISSN/ISBN: 0140-6736 PMID: 66428 Document Number: 120234
The combined oral contraceptives consist of an estrogen (ethinylestradiol or mestranol) in varying doses, and 1 of several synthetic progestagens, also in varying doses. Attempts to assess the separate effects of the estrogen and the progestagen have previously been confounded by the varying potencies of both compounds, and the fact that they interact synergistically or antagonistically. Each oral-contraceptive preparation must be considered as a therapeutic entity which is different from the sum of its 2 components. A partial solution to the problem of assessing progestagen potency is afforded by the availability in the U.K. of 3 compounds 'Anovlar', 'Gynovlar', and 'Minovlar', which contain the same dose of a single estrogen and different doses of the same progestagen. They each contain ethinylestradiol 50 .mu.g and norethisterone acetate in respective doses of 4 mg, 3 mg, and 1 mg, and they are identically absorbed and dispersed in the body tissues. The frequency of reporting of benign breast disease is negatively associated with the dose of norethisterone acetate. A positive trend between the progestagen and hypertension is also shown. Since bias can virtually be excluded as an explanation of the relationships, the observations provide strong evidence that the effects are associated with the pharmacological properties of oral contraceptives. They provide new hypotheses for investigation of the mechanism of the actions.