No abstract

To determine the associations between high-density-lipoprotein cholesterol levels and use of oral contraceptives or of noncontraceptive estrogens and progestins we analyzed the serum levels of this lipid in 4978 women, 21 to 62 years of age. In estrogen users, the mean level was 6.7 to 15.1 mg per deciliter above the nonuser level (P less than 0.001), whereas in a group of progestin users it was 15.8 mg per deciliter below (P less than 0.001). In women using combination oral contraceptives, the level varied with the type and dose of the component steroids, in general increasing with increasing dose of estrogen and decreasing with increasing dose or potency of progestin. Thus, the net effect of use of a combination oral contraceptive on high-density-lipoprotein cholesterol depends on its formulation.

Summary.-Women who had used oral contraceptives, particularly long-term users, were found to have higher rates of malignant melanoma and of a past history of skin cancer than those who had never used oral contraceptives. This excess was confined to lesions of the lower limb. The association between oral contraceptive use and melanoma was noted in 3 separate sets of data, although it was statistically significant only in one. The possibility that this relationship is indirect because, for example, oral contraceptive users are more likely than never-users to be exposed to sunlight and thus to develop malignant melanoma, cannot be excluded.

Methods suitable for the estimation of urinary metabolites of aldosterone and of cortisol are described. The excretion of 3H and of 14C in various urinary fractions after the simultaneous injection of 7-3H aldosterone and 4-14C cortisol have been investigated, and the secretion rates of these steroids were estimated. Factors affecting the accuracy of the methods and their suitability for routine use are discussed. Considerable difference was found in the pattern of excretion of 3H and of 14C. In particular, a much larger proportion of the injected tritium was released on extraction at pH. 1. Further, while the total excretion of glucuronide as a percentage of the injected dose was greater for 14C than for 3H, about 72 % of the total tritium in the glucuronide fraction of the first 24 hour urine collection was eluted as a single chromatographic peak, whereas about 60 % of the 14C in the glucuronide fraction was eluted as tetrahydrocortisone, tetrahydrocortisol and allotetrahydrocortisol combined. Excretion values for aldosterone released at pH 1 were obtained for nine normal men after addition of tritiated aldosterone to the urine, and for five normal women and one normal man after injection of the isotope. Excretion values for cortisol metabolites are reported for six normal subjects after injection of 4-14C cortisol. Secretion rates for cortisol were calculated for six normal subjects from the specific activity of the tetrahydro metabolites. The values were 12.2 to 20.5, mean 17.2 mg/d, and agreed with those reported by other workers. The secretion rates for aldosterone, based on the specific activity of the aldosterone released at pH 1 were 50 to 118, mean 77 μg/d.

High density lipoprotein (HDL) levels are known to be higher in women than in men, and to increase with estrogen use. To assess the effects of estrogens on HDL subspecies, analytic ultracentrifuge measurements of HDL were compared in 11 menopausal estrogen users and 16 controls. The difference in mean schlieren patterns between the groups showed a significantly higher level of HDL with flotation rate (F1.20o)>1.5 (predominantly HDL2) in the users. This was similar to the difference in HDL seen between nonusers of hormones and age‐matched males. A previous study had shown that users of combination oral contraceptives had increased levels of HDL with F1.20o≤3.5 (primarily HDL3) suggesting that the estrogen effect on HDL is altered by the presence of added progestin. The progrestin effect was studied here in more detail in two women with type V hyperlipoproteinemia treated with norethindrone acetate. Reduction in serum triglyceride was accompanied by a reduction in HDL, predominantly in the less dense species (HDL2). Among groups of oral contraceptive and noncontraceptive estrogen and progestin users whose HDL‐cholesterol levels have been reported recently, there was a direct correlation (r=0.86, p<.001) between mean HDL‐cholesterol and triglyceride levels. Endogenous hormonal influences on HDL were assessed by serum hormone and lipoprotein measurements at weekly intervals during two consecutive menstrual cycles in four healthy females. An increase in HDL of highest flotation rate (F1.20o 5–9) was seen, which corresponded with the time of ovulation raising the possibility of pituitary as well as gonadal hormone effects on HDL.