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Impact of Gender and Life Cycle on Triglyceride Levels

Authors: Vera Bittner, MD, MSPHFaculty and Disclosures



Cardiovascular disease is the most common cause of death in women. The American Heart Association estimates that 42.7 million women have cardiovascular disease, with an annual mortality of nearly half a million.[1] Cardiovascular disease morbidity and mortality increase with advancing age and are higher among African American than among white women.[1] Cardiovascular risk factors such as obesity, physical inactivity, metabolic syndrome, diabetes, hypertension, and dyslipidemia are highly prevalent not only among middle-aged and older women, but increasingly among younger individuals.[1] This brief review will focus on the impact and treatment of hypertriglyceridemia throughout the female life cycle.

Childhood and Adolescence

Determinants of neonatal lipid levels have been reviewed recently by Bansal and colleagues.[2] Neonates have triglyceride levels that are about one half of those seen in adults. Ethnic and gender differences have been reported in some but not all studies. When differences are observed, female newborns tend to have higher triglyceride levels than their male counterparts. Triglyceride levels in the newborn are in part determined by maternal diet. Infants born to mothers who consume a high-fat diet tend to have higher triglyceride levels than infants born to mothers who have lower fat intake, and macrosomic offspring of obese mothers tend to be hypertriglyceridemic.

In the Third National Health and Nutrition Examination Survey (NHANES), the mean triglyceride level among adolescents age 12 to 15 years was 91 mg/dL, and the mean triglyceride level among those age 16 to 19 years was 95 mg/dL (respective 50th percentiles were 74 mg/dL and 78 mg/dL).[3] Non-Hispanic black teenagers had significantly lower levels than their white and Hispanic counterparts; no sex differences were apparent.[3] Similar data for younger children were not included in the survey.

Childhood obesity is increasing in prevalence, resulting in increasing rates of metabolic syndrome. In NHANES, rates of metabolic syndrome were 6.8% among overweight adolescents and 28.7% among obese adolescents.[4] As in adults, hypertriglyceridemia and low high-density lipoprotein (HDL) cholesterol are key features of the metabolic syndrome in children; these features tend to track from childhood to adulthood.[5]


In young adulthood, men tend to have higher triglyceride levels than women. In NHANES, for example, triglyceride levels among men vs women were for age 20 to 29: 103 mg/dL vs 97 mg/dL; for age 30 to 39:
122 mg/dL vs 102 mg/dL; and for age 40 to 49: 153 mg/dL vs 104 mg/dL.[6] During the reproductive years, lipid and lipoprotein levels among women vary cyclically with the menstrual cycle; the highest triglyceride levels are generally seen at midcycle.[7] Triglyceride increases are characteristic of the late phases of pregnancy because of increased secretion of very low-density lipoprotein (VLDL) particles and decreased activity of adipose tissue lipoprotein lipase.[8]

The loss of estrogen with menopause is associated with an increase in abdominal adiposity and the development of features reminiscent of the metabolic syndrome.[9] Triglyceride levels increase during the menopausal transition. A longitudinal study of the menopausal transition reported an increase of 16% in triglyceride values.[10] In NHANES, the gap in triglyceride levels between men and women narrowed in the
50- to 59-year age group, and from 60 years onward, women had higher levels than men.[6]

Hormone Therapy: Postmenopausal Therapy and Oral Contraceptives

Triglyceride levels increase during oral hormone therapy. This triglyceride increase tends to be more pronounced with higher estrogen doses. Concomitant progestin therapy attenuates this triglyceride increase. The Figure shows triglyceride increases observed during selected key trials of postmenopausal hormone therapy published in recent years.[11-15]



The figure shows baseline levels and trial levels of triglycerides in the major postmenopausal hormone trials in the United States. Oral hormone therapy resulted in statistically significant triglyceride elevations in each group but varied in magnitude by hormone preparation. The highest increase (25%) was seen in the estrogen-only group of the Women's Health Initiative.
TG = triglycerides;PEPI = the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial; CEE = conjugated equine estrogen; MPA = medroxy progesterone acetate; cycl = cyclic; con = consecutive; MP = micronized progesterone; HERS = Heart and Estrogen/progestin Replacement Study; PERT = combined estrogen progestin therapy; WHI= Women's Health Initiative; ERT = oral estrogen therapy

Whereas there is heterogeneity in age, cardiovascular risk, and baseline triglyceride levels among the women enrolled in these trials, an increase in triglycerides is seen in all groups, ranging from a mean of 6.9% to a mean of 15%. Therapy with transdermal estrogens tends to be lipid neutral.[16] Switching from oral supplementation to transdermal supplementation can alleviate postmenopausal hypertriglyceridemia without having to resort to additional pharmacologic lipid-lowering therapy. The effects of oral contraceptives are qualitatively similar to those of postmenopausal oral hormone treatment regimens, with specific lipoprotein effects dependent on type and dose of estrogen and progestogen.[17] Among women in whom significant hypertriglyceridemia develops while on oral contraceptives, changes in formulation should be considered before resorting to specific antihyperlipidemic therapy.

Triglycerides and Coronary Heart Disease Risk

Both fasting and nonfasting triglyceride levels are related to coronary heart disease risk in both genders.[18-21] Nonfasting triglycerides appear to be more closely linked with coronary heart disease, consistent with a
long-standing hypothesis that atherosclerosis is a postprandial phenomenon.[22] Most studies suggest a closer link between coronary heart disease risk and hypertriglyceridemia among women than among
men.[18-20] A recent meta-analysis by Sarwar and colleagues[21] suggests, however, that the risk is similar among men and women. To date, clinical trials of lipid-lowering therapy have focused on lowering LDL cholesterol. Statins, fibrates, and niacin, which have been used in these trials, have concomitantly lowered triglycerides, but it is unknown whether this triglyceride lowering has contributed to improvement in cardiovascular disease risk.

Treatment Recommendations

Treatment recommendations for individuals with hypertriglyceridemia are outlined in detail in the Adult Treatment Panel III Report.[23] Approaches vary by triglyceride level, but there are several common elements across treatment strata. Secondary and acquired causes of hypertriglyceridemia (eg, related to obesity, poorly controlled diabetes, excess alcohol, very high carbohydrate consumption, or medications such as unopposed estrogen therapy) should be identified and treated if possible. Implementation of therapeutic lifestyle changes, including smoking cessation, regular physical activity, appropriate diet, reduction in alcohol consumption as indicated, and weight management, is critical in all categories of hypertriglyceridemia. Drug therapy is not indicated for individuals with borderline triglyceride elevations (151-199 mg/dL). For individuals with high triglyceride levels (200-500 mg/dL), LDL cholesterol remains the primary treatment target and
non-HDL cholesterol is the secondary target, with cut-off points 30 mg/dL above those set for LDL cholesterol. Statins, fibrates, niacin, or combinations of these drugs are appropriate, with monitoring for toxicity if combination therapy is used. When triglyceride levels are very high (above 500 mg/dL), triglyceride lowering to prevent pancreatitis becomes the first priority, with prevention of coronary heart disease as a secondary goal. Statins are not first-line agents in this group of patients, and bile acid binding resins are contraindicated because of their triglyceride-raising effects. Fish oil, fibrates, and niacin are appropriate pharmacologic choices.

This activity is supported by an independent educational grant from Reliant Pharmaceuticals.

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