Hormone Replacement Therapy and Its Relationship to Lipid and Glucose Metabolism in Diabetic and Nondiabetic Postmenopausal Women

Carlos J. Crespo, DrPH, MS, Ellen Smit, PHD, RD, Anastacia Snelling, PHD, Christopher T. Sempos, PHD and Ross E. Andersen, PHD


Diabetes Care. 2002;25(10) 

In This Article

Research Design and Methods

The Third National Health and Nutrition Examination Survey (NHANES III) was conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention. NHANES III is designed to produce nationally representative data regarding the civilian, noninstitutionalized U.S. population aged 2 months and older. NHANES III was conducted between 1988 and 1994, and consisted of a home interview and a detailed clinical examination performed in a mobile examination center. Subjects signed a consent form, and approval was obtained from a human subjects committee in the U.S. Department of Health and Human Service. Self-reported information provided the basis for the identification of race ethnicity and allowed for the over-sampling of Mexican-Americans and non-Hispanic blacks. A total of 18,885 adults 20 years of age or older responded to the household adult and family questionnaires. Body measurements and blood chemistries were obtained during a subsequent visit to the mobile examination center.[15,16,17,18] For this study, postmenopausal women 40-74 years of age were selected, and our findings are only applicable to the analytic sample studied.

A trained interviewer collected information on reproductive health, use of HRT, time on HRT, and mode of administration of HRT. Some of the questions asked by the interviewer were as follows: Have you had a period in the past 12 months? How old were you when you had your last period? Have you had a hysterectomy? Has your uterus/womb been removed? How old were you when you had your (hysterectomy/uterus/womb removed)? Have you had one or both of your ovaries removed? Postmenopause was defined as a woman who has not had a menstrual period in the past 12 months. We only report data on postmenopausal women.

The interviewer also asked about past and current use of female hormone pills, including birth control pills and estrogen pills. Some of the questions asked were: Have you ever taken estrogen or female hormone pills by mouth other than oral contraceptive pills? Have you ever taken or used estrogen or female hormones in the form of vaginal cream, suppository, or injection? Have you ever used female hormones in the form of patches that are placed on the skin? Not counting any time when you stopped using the female hormone patches, for how many years altogether have you used them?

Current users of HRT were those who answered yes to the use of estrogen or female hormones in the form of pills, vaginal cream, suppository, injection, or patches and who were also currently using HRT. Previous users of HRT were women who answered "yes" to any of the above questions, but who were not currently using HRT. Never users of HRT refers to women who answer no to all of the above questions about usage of HRT.

During NHANES III, an oral glucose tolerance test (OGTT) was conducted on participants aged 40-74 years who attended the mobile examination part of the survey. Participants were randomly assigned to receive an OGTT in the morning after an overnight fast. Almost half of the OGTT examinees received the morning OGTT after an overnight fast. This subsample most closely conformed to the World Health Organization criteria for OGTTs to identify diabetes.[12,19,20] Therefore, those who attended the morning subsample of the NHANES III were used to estimate the prevalence of diabetes as recommended by National Center for Health Statistics guidelines. People who reported a medical history of diabetes but who were not using insulin therapy were asked to conform to the fasting instructions for their examination session and were eligible for an OGTT if the age criteria were satisfied.

Participants aged 40-74 years who used insulin were excluded from the OGTT. A first venipuncture was obtained on these individuals, but the glucose challenge and second venipuncture were canceled. In these cases, NHANES III data report values for fasting glucose, but the results for the second glucose values from the second venipuncture are blank-filled to indicate a medical exclusion. Those who answered "yes" to the hemophilia question or who received chemotherapy within the past 4 weeks were also excluded from venipuncture. Examinees who reported that they used insulin therapy on their examination day were also excluded from the OGTT. If an examinee was between the ages of 40 and 74 years and received the OGTT, two timed venipunctures were performed.

The Expert Committee on Diagnosis and Classification of Diabetes[12] recommends that for epidemiological studies, estimates of diabetes prevalence and incidence should be based on a fasting plasma glucose of 126 mg/dl. This recommendation is made in the interest of standardization and also to facilitate field work. However, the committee concedes that this approach can lead to slightly underestimate prevalence that would be obtained from the combined use of fasting plasma glucose and OGTT.[19,20,21] For this study, the prevalence of diabetes is defined as fasting (at least 8 h) plasma glucose ≥126 mg/dl, plasma glucose values ≥200 mg/dl after a 2-h postload glucose (OGTT), currently taking antihyperglycemic medication (such as insulin), or a (self-reported) medical history of diabetes.

Assessment of lipid levels was conducted using the following variables: total serum cholesterol levels, HDL cholesterol, non-HDL cholesterol (calculated by subtracting HDL from total cholesterol levels), triglyceride level, and the ratio of total cholesterol to HDL. LDL in NHANES III was calculated and not measured, thus, participants with triglycerides >300 mg/dl do not have LDL levels reported. Because diabetic subjects had significantly greater triglyceride levels than nondiabetic subjects, we decided not to report LDL levels but to use non-HDL. During phase 1 (1988-1991), levels of apoA and apoB were measured as part of the lipid profile, whereas in phase 2 (1991-1994) measurements of lipoprotein(a) [Lp(a)] were ascertained instead.[16,22]

Statistical analyses were carried out using SAS, SUDAAN, and STATA statistical software. All analyses incorporated the sampling weights and the complex sample design unless otherwise specified. Prevalence estimates and 95% CIs were calculated taking into account the design effect of a multistage stratified complex sample design. Differences between groups are determined based on the prevalence estimates and their 95% CIs. Multivariate adjustments for other confounders (e.g., age, BMI, race/ethnicity, smoking, and education) were made using the general linear model procedure and the least square means option in SAS callable SUDAAN, and 95% CIs were obtained using the survey procedure to calculate means in the STATA software.


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