Joanne Hoover

Effect of Estrogen/Progestin Potency on Lipid/Lipoprotein Cholesterol

We studied 374 women taking oral contraceptives, 284 women taking estrogen preparations after menopause, and 1086 women taking no hormones, to determine the relation of plasma lipids and lipoprotein cholesterol concentrations to various types of estrogen/progestin formulations. Premenopausal women, using oral contraceptives containing a relatively low dose of estrogen combined with a medium or high dose of progestin (Norlestrin, Ovral, or Demulen) had a 24 per cent higher median concentration of low-density-lipoprotein cholesterol than did those not using hormones (P less than 0.05). Women using oral contraceptives that are high in estrogen and low in progestin (Enovid or Oracon) had significantly higher concentrations of high-density-lipoprotein cholesterol than did nonusers; those using Ovral, a low-estrogen and high-progestin formulation, had significantly lower levels of high-density-lipoprotein cholesterol. In postmenopausal women the use of estrogen was associated with concentrations of low-density-lipoprotein cholesterol that were 11 to 19 per cent below the levels in postmenopausal women who did not use hormones. The effects of estrogen-progestin balance on low-density and high-density lipoproteins may underlie the increased incidence of stroke and myocardial infarction in women of childbearing age who take oral contraceptives.

Quantitation of apolipoprotein A-I of human plasma high density lipoprotein.

High density lipoproteins (HDL) may be controlled via their major apolipoprotein, A-I. To study this apolipoprotein, a simple, precise, and accurate immunodiffusion assay for A-I was developed and applied in a sample of Bell Telephone Company employees. A-I showed a slight increase with age in men (r=0.11, n=263) and women (r=0.15, n=257). A-I correlated closely with HDL cholesterol (r=0.72). It was weakly related to total triglyceride in women (r=0.24) but was inversely related in men (r=-0.17). Women on estrogen had the highest A-I levels (149 mg/dl +/- 26, x +/- S.D., n=29, p is less than 0.05), followed by women on combination oral contraceptives (141 +/- 26, n=80) whereas women on no medication had lower levels (129 +/- 25, n=99, p is less than 0.01) but men had the lowest levels (120 +/- 20, p is less than 0.01) In a separate group of 14 women given estrogen for 2 wks (1 mug/kg/day), A-I increased by 24%. Thus A-I is increased by exogenous and, most likely, endogenous estrogen, Among hyperlipidemic referral subjects, those with hypercholesterolemia (n=43) and hypertriglyceridemic women (n=33) had normal A-I levels. Among hypertriglyceridemic men both A-I and HDL cholesterol values were decreased (115 +/- 20, p is less than 0.01 and 37 +/- 3, p is less than 0.01, respectively, n=68) but were significantly lower among a group of myocardial infarction survivors (107 +/- 16, p is less than 0.01, and 27 +/- 6, p is less than 0.01, respectively, n=24). High density lipoprotein levels and the content of cholesterol in HDL associated with A-I appear to be decreased in coronary heart disease.

ALTERED PLASMA LIPID AND LIPOPROTEIN LEVELS ASSOCIATED WITH ORAL CONTRACEPTIVE AND ŒSTROGEN USE: Report from the Medications Working Group of the Lipid Research Clinics Program

In a study of women attending ten North American Lipid Research Clinics plasma total cholesterol, triglyceride, low density (L.D.L.), very low density (V.L.D.L.), and high density (H.D.L.) lipoprotein levels in those taking oral contraceptives (O.C.) and in those taking oestrogens for menopausal symptoms were compared with those in women not taking gonadal hormones, after adjustment for age, educational attainment, and body-mass index, O.C. and oestrogen users were leaner than non-users. Compared with controls, O.C. users showed increased cholesterol, triglyceride, and L.D.L.-cholesterol and V.L.D.L.-cholesterol levels, but H.D.L.-cholesterol levels were similar. Cholesterol, triglyceride, and H.D.L.-cholesterol and V.L.D.L.-cholesterol levels were positively associated with the quantity of the oestrogen component of the O.C. preparations. Compared with non-users, menopausal oestrogen users had slightly lower cholesterol and triglyceride levels, significant decreases in L.D.L.-cholesterol and V.L.D.L.-cholesterol, and a significant increase in H.D.L.-cholesterol.

Type III Hyperlipoproteinemia: Diagnosis in Whole Plasma by Apolipoprotein-E Immunoassay

Because the cholesterol-rich very low density (VLD) lipoproteins of subjects with type III hyperlipoproteinemia are distinctively enriched in apolipoprotein E, a radial immunodiffusion assay for apolipoprotein E in whole plasma was developed. Its diagnostic usefulness was tested in randomly selected (n = 174) and hyperlipidemic (n = 61) subsets of an adult employee population and a hyperlipidemia clinic referral group (n = 63), which included 18 patients with well-documented type III hyperlipoproteinemia. Apolipoprotein-E levels were normally distributed among the random population subset, were equal between the two sexes, and increased little with age. The mean and 99th percentile values were 24.6 and 40.1 mg/dl, respectively. All subjects with type III patterns as assigned by standard criteria from both population (n = 4) and referral sources exceeded this 99th percentile (chi +/- SD = 54.7 +/- 9.7 mg/dl). Hence a plasma apolipoprotein-E concentration exceeding 40 mg/dl appears diagnostic of type III hyperlipoproteinemia, representing the first application of an apolipoprotein immunoassay to improved diagnosis of the hyperlipoproteinemias.

Effects of oral contraceptives on lipoprotein triglyceride and cholesterol: Relationships to estrogen and progestin potency

Hormone formulation and estrogen/progestin potency were evaluated in relation to triglyceride and cholesterol concentrations in total plasma and lipoprotein fractions and in relation to lipid composition among a random sample of female telephone company personnel. Triglyceride concentrations in whole plasma, very low-density lipoprotein, and high-density lipoprotein (HDL) were elevated in response to increasing estrogen potency as were triglyceride concentrations in low-density lipoprotein (LDL). LDL cholesterol rose with increasing estrogen potency in contraceptive users but was slightly lower in postmenopausal estrogen-treated women. Plasma HDL cholesterol varied according to estrogen and progestin levels. The LDL cholesterol/triglyceride ratio was reduced for all combination oral contraceptives examined. Sequential oral contraceptives of postmenopausal estrogens did not significantly alter the cholesterol/triglyceride ratio in any lipoprotein fraction. Potential arteriosclerotic risk from sex hormone use may vary among oral contraceptive formulations.

Distribution of lipoprotein triglyceride and lipoprotein cholesterol in an adult population by age, sex, and hormone use: The pacific northwest bell telephone company health survey☆

This report describes the distribution of lipoprotein triglyceride and lipoprotein cholesterol in employees of the Pacific Northwest Bell Telephone Company. Means, medians, and selected percentiles are presented for very low, low, and high density lipoproteins (VLDL, LDL, and HDL, respectively) in 606 randomly selected white subjects aged 20-59. Results are specific for age decade, sex, and female sex hormone usage. Women who use sex hormones have significantly higher concentrations of triglycerides in all of the fractions across all age decades from 20 to 59 than do women not taking hormones. The average VLDL, LDL, and HDL triglyceride levels in women taking hormones are 69, 25 and 18 mg/dl which are considerably higher than the corresponding averages of 44, 17 and 12 mg/dl noted in women not taking hormones. Men have the highest average VLDL triglyceride value (85 mg/dl) but their average triglyceride concentrations in the LDL and HDL fractions (18 and 12 mg/dl) approximate those of women not taking hormones. This study in a well-defined population provides references standards for lipoprotein triglyceride concentrations. These results can be used to evaluate the effect of sex hormone treatment on the lipoprotein triglyceride content in VLDL, LDL and HDL, and to assess triglyceride content as a potential risk factor in men and older women.

Lipid and lipoprotein triglyceride and cholesterol interrelationships: Effects of sex, hormone use, and hyperlipidemia

The interrelationships of lipid and lipoprotein cholesterol and triglyceride concentrations in normolipidemic and hyperlipidemic employees of the Pacific Northwest Bell Telephone Company were examined bivariately using correlation analysis and multivariately by factor analysis. Application of the latter resulted in the identification of three distinct lipoprotein lipid clusters, which succinctly describes their metabolic relationships. Among normolipidemic subjects, the interrelationships were found to be similar in male and female subjects, but hormone use by women considerably altered interrelationships that involved high-density lipoprotein cholesterol (HDL-C) and triglyceride. Among hyperlipidemic subjects, we found that elevation in cholesterol level alone rarely altered relationships, but elevation in triglyceride level either alone or in conjunction with an elevation in cholesterol concentration was associated with substantial changes in relationships involving the low-density lipoprotein (LDL) fraction. In many instances, positive relationships between LDL cholesterol (LDL-C) and other lipoprotein lipids became inverse in the presence of triglyceride elevation. We conclude that hormone use by women and hypertriglyceridemia with or without an elevation in cholesterol level clearly alter lipoprotein relationships, whereas pure hypercholesterolemia does not. These alterations provide a basis for investigating pathophysiologic mechanisms in hypertriglyceridemia.

ALTERED PLASMA-LIPIDS ASSOCIATED WITH ORAL CONTRACEPTIVE OR ŒSTROGEN CONSUMPTION: The Lipid Research Clinic Program

Mean plasma cholesterol and triglyceride concentrations were measured in White female users and non-users of oral contraceptives and oestrogens in 10 diverse, demographically defined North American populations. About 50% of the younger women (20-24 years old) were taking oral contraceptives. In these women mean triglyceride concentrations were up to 48% higher and mean cholesterol concentrations were about 5% higher than in non-users. The 95% percentile of the total lipid distribution among non-users was used to define hyperlipidaemia. In young women on oral contraceptives hypercholesterolaemia was up to three times more common and hypertriglyceridaemia was up to five times more common than in non-users. 37% of older women (50-54 years) (presumably intramenopausal and postmenopausal) were hormone users, and in this group there were small, inconsistent alterations in plasma-triglyceride and a modest but consistent reduction in mean cholesterol concentration.

Alteration in blood pressures associated with combined alcohol and oral contraceptive use--the Lipid Research Clinics Prevalence Study.

Alterations in systolic and diastolic blood pressure levels associated with combined oral contraceptive (OC) and alcohol use were investigated in white women 20-49 years of age from 10 North American Lipid Research Clinics study populations. OC users had systolic pressures 2-3 mm Hg higher than non-users, but no difference was noted for diastolic pressures. Among non-OC users, both systolic and diastolic blood pressures were positively associated with reported alcohol consumption, though participants reporting no alcohol use had blood pressures slightly higher than those reporting minimal intake. The blood pressure correlates of OCs and alcohol appeared to be independent, and systolic pressures levels were over 8 mm Hg higher in those reporting heavier alcohol intake and OC use than among those reporting minimal alcohol intake and no OC use.

Cholesterol and triglyceride distributions in an adult employee population: The Pacific Northwest Bell Telephone Company health survey

Plasma cholesterol and triglyceride are presented for 4503 adult employees of the Pacific Northwest Bell Telephone Company. Cross-sectional age and sex specific means and percentiles are shown. Females are classified by use or nonuse of exogenous sex hormones. Comparisons are examined among these groups, between blacks and whites, and among education and occupation categories. In these cross-sectional data, cholesterol and triglyceride generally increase with age and exhibit distinct differences by sex and by hormone use.