Oral contraceptives, smoking and nodular hyperplasia of the liver

Case studies of 4 women (aged 21, 40, 44, and 45) who smoked, had used oral contraceptives, and had nodular hyperplasia of the liver are reviewed, with an emphasis on vascular changes. It is suggested that the natural history of focal nodular hyperplasia is a progressive occlusion of hepatic lobular arteries as a result of either recurrent thrombosis or stimulation of intimal proliferation by contraceptive steroids. Ischemia, infarction, and hemorrhage may occur, followed by rapid development of collateral vessels and nodular regeneration about a central scar. The process is not primarily neoplastic, when contraceptive steroids are withdrawn the lesions will regress. Women with the condition who smoke are urged to stop.     

Oral contraceptives and breast cancer: a national study

In a population based case-control study 433 New Zealand women aged 25-54 with newly diagnosed breast cancer were compared with 897 women selected at random from the electoral rolls. The relative risk of breast cancer in women who had ever used oral contraceptives was 0.94 (95% confidence interval 0.70 to 1.25). The relative risk in women aged 25-34 at diagnosis was estimated to be 2.2 (95% confidence interval 0.47 to 9.9) and in older women less than 1. Analyses of risk by duration of use of oral contraceptives, age at first use, and time since first use showed no adverse effect of the pill. In particular, there was no increased risk in women who had used oral contraceptives before the age of 25 or before their first pregnancy, even for prolonged periods. Given the high prevalence of use in New Zealand, this study provides strong evidence against the hypothesis that use of oral contraceptives at young ages increases the risk of breast cancer.     

Oral contraceptives and hepatocellular carcinoma

A series of 26 white women aged under 50 who developed hepatocellular carcinoma in a non-cirrhotic liver were studied for the possible role of oral contraceptives. Eighteen of the women had used the "pill" for a median of eight years. Over 1300 women whose use of the pill had been determined in another study served as controls. Patients and controls were divided into five age and four calendar groups and the relative risks associated with oral contraceptives calculated by multivariate analysis. Short term use of the pill was not associated with an increased risk of tumour development; nevertheless, use for eight years or more was associated with a 4.4-fold increased risk (p less than 0.01). When patients with markers of hepatitis B virus infection were excluded the relative risk was 7.2 (p less than 0.01). In both instances the absolute risk for developing hepatoma remained low.     

Oral contraceptives, pregnancy, and focal nodular hyperplasia of the liver

There is uncertainty regarding the role, if any, of oral contraceptive steroids in the development of focal nodular hyperplasia of the liver. In a 36-year-old woman, a large left hepatic lobe tumor developed that was detected after 11 years of using these drugs. The tumor regressed when administration of the drug was stopped but began to increase in size during a subsequent pregnancy. A left hepatic lobectomy during the second trimester disclosed focal nodular hyperplasia. Both contraceptive steroids and pregnancy, with high levels of endogenous sex steroids, favored tumor growth in this patient, suggesting that focal nodular hyperplasia can be steroid related.     

Oral contraceptives and blood pressure

Both cross-sectional and longitudinal analysis of data from 13,358 women showed that oral contraceptive use is associated with a slight but statistically significant (P lesser than .05) rise in mean blood pressure, which is reversible. The age-adjusted proportion of oral contraceptive users with a blood pressure over 140/90 mm Hg was about three times that on nonusers. These findings are caused by a uniform upward shift in the blood pressure distribution of oral contraceptive users compared to nonusers. Women continuing oral contraceptive use had no appreciably greater change in blood pressure between two visits than persistent nonusers. The clinical implications of a mild contraceptive-induced blood pressure elevation (systolic, 5 to 6 mm Hg; diastolic, 1 to 2 mm Hg) remain unsettled but disturbing.