Hormone Replacement Therapy and Its Relationship to Lipid and Glucose Metabolism in Diabetic and Nondiabetic Postmenopausal Women Results from the Third National Health and Nutrition Examination Survey (NHANES III)

Abstract

Among postmenopausal women, those with diabetes experience more cardiovascular diseases than those without diabetes. We examine the relationship of hormone replacement therapy (HRT) with indicators of lipid and glucose metabolism using a national sample of diabetic and nondiabetic postmenopausal women.
We used data from the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1994. A total of 2,786 postmenopausal women aged 40-74 years participated in an oral glucose tolerance test, had blood drawn for lipid assessment, and responded to HRT questions.
Our results show that postmenopausal women with diabetes had increased dyslipidemia compared with nondiabetic women. Among diabetic women, current users of HRT had significant different lipid and glucose control levels than never users of HRT for the following variables: total cholesterol (225 vs. 241 mg/dl), non-HDL (169 vs. 188 mg/dl), apoA (171 vs. 147 mg/dl), fibrinogen (306 vs. 342 mg/dl), glucose (112 vs. 154 mg/dl), insulin (16.81 vs. 22.6 uU/ml), and GHb (6.03 vs. 7.13 mg/dl).
Diabetic and nondiabetic postmenopausal women currently taking HRT had better lipoprotein profile than never or previous users of HRT. Diabetic women currently taking HRT had better glycemic control than never or previous users of HRT.

Full text

Hormone Replacement Therapy and Its
Relationship to Lipid and Glucose
Metabolism in Diabetic and Nondiabetic
Postmenopausal Women
Results from the Third National Health and Nutrition Examination Survey
(NHANES III)
CARLOS J. CRESPO,
D
R
PH, MS
1
ELLEN SMIT,
PHD, RD
1
ANASTACIA SNELLING,
PHD
2
CHRISTOPHER T. SEMPOS,
PHD
1
ROSS E. ANDERSEN,
PHD
3
OBJECTIVE — Among postmenopausal women, those with diabetes experience more car-
diovascular diseases than those without diabetes. We examine the relationship of hormone
replacement therapy (HRT) with indicators of lipid and glucose metabolism using a national
sample of diabetic and nondiabetic postmenopausal women.
RESEARCH DESIGN AND METHODS — We used data from the Third National
Health and Nutrition Examination Survey, conducted from 1988 to 1994. A total of 2,786
postmenopausal women aged 40–74 years participated in an oral glucose tolerance test, had
blood drawn for lipid assessment, and responded to HRT questions.
RESULTS — Our results show that postmenopausal women with diabetes had increased
dyslipidemia compared with nondiabetic women. Among diabetic women, current users of HRT
had significant different lipid and glucose control levels than never users of HRT for the following
variables: total cholesterol (225 vs. 241 mg/dl), non-HDL (169 vs. 188 mg/dl), apoA (171 vs. 147
mg/dl), fibrinogen (306 vs. 342 mg/dl), glucose (112 vs. 154 mg/dl), insulin (16.81 vs. 22.6
uU/ml), and GHb (6.03 vs. 7.13 mg/dl).
CONCLUSIONS — Diabetic and nondiabetic postmenopausal women currently taking
HRT had better lipoprotein profile than never or previous users of HRT. Diabetic women
currently taking HRT had better glycemic control than never or previous users of HRT.
Diabetes Care 25:1675–1680, 2002
S
ome studies have found the use of
hormone replacement therapy
(HRT) to be associated with a better
cardiovascular health profile in healthy
postmenopausal women, whereas others
have found no benefits (1–6). Epidemio-
logical research on the potential benefits
of HRT use in postmenopausal women
with diabetes is also inconclusive (7–11).
Diabetes is a group of metabolic diseases
characterized by hyperglycemia resulting
from defects in insulin secretion, insulin
action, or both. Most cases of diabetes fall
into two categories: type 1 and type 2 di-
abetes. In type 1 diabetes, the cause is an
absolute deficiency of insulin secretion.
In type 2 diabetes, the most common
form of diabetes, the cause is a combina-
tion of resistance to insulin action and in-
adequate compensatory insulin secretory
response. Risk factors for diabetes include
age, family history, obesity, and physical
inactivity. Moreover, diabetic individuals
are also at higher risk for coronary heart
disease, dyslipidemia, hypertension, reti-
nopathy, and renal disorders (7,8,10,12–
14).
Postmenopausal women experience
more type 2 diabetes and cardiovascular
diseases than their premenopausal coun-
terparts. One hypothesis concerning the
increased prevalence of type 2 diabetes
and cardiovascular diseases in postmeno-
pausal women is that it may be related to
age-related changes in sex-steroid hor-
mones. Although sex hormones do not
appear to play a primary role in the etiol-
ogy of type 2 diabetes, they may be related
to other metabolic factors. After meno-
pause there is an increase in dyslipidemia,
especially reduced levels of HDL. In addi-
tion to HDL changes, menopause is also
accompanied by changes in apolipopro-
tein (apo)A and apoB, fibrinogen, and hy-
perinsulinemia (1–3,5,8).
HRT may be effective in lowering the
risk of cardiovascular disease in healthy
menopausal women, and although post-
menopausal HRT is recommended to pre-
vent disease and prolong life, little data
are available to examine the association
between HRT and emerging hyperlipid-
emic indicators separately for diabetic
●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●
From the
1
Department of Social and Preventive Medicine, School of Medicine and Biomedical Sciences,
University at Buffalo, State University of New York, Buffalo, New York; the
2
Department of Health and
Fitness, American University, Washington, DC; and the
3
Department of Geriatric Medicine and Gerontol-
ogy, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Address correspondence and reprint requests to Carlos J. Crespo, Associate Professor, University at
Buffalo, State University of New York, School of Medicine and Biomedical Sciences, Department of Social and
Preventive Medicine, 270 Farber Hall, 3435 Main St., Buffalo, NY 14214. E-mail: ccrespo@buffalo.edu.
Received for publication 25 February 2002 and accepted in revised form 2 July 2002.
Abbreviations: apo, apolipoprotein; HRT, hormone replacement therapy; Lp(a), lipoprotein(a);
NHANES III, Third National Health and Nutrition Examination Survey; OGTT, oral glucose tolerance test.
A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion
factors for many substances.
See accompanying editorial by Buse and Raftery, p. 1876
Clinical Care/Education/Nutrition
ORIGINAL ARTICLE
DIABETES CARE,VOLUME 25, NUMBER 10, OCTOBER 2002 1675

subjects and nondiabetic postmeno-
pausal women. In this study, we exam-
ined the relationship of HRT use with
dyslipidemic indicators in a national
sample of diabetic and nondiabetic
postmenopausal women 40–74 years of
age.
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 represen-
tative data regarding the civilian, non-
institutionalized U.S. population aged 2
months and older. NHANES III was con-
ducted between 1988 and 1994, and con-
sisted of a home interview and a detailed
clinical examination performed in a mo-
bile 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 pro-
vided 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 question-
naires. Body measurements and blood
chemistries were obtained during a sub-
sequent visit to the mobile examination
center (15–18). For this study, postmeno-
pausal women 40–74 years of age were
selected, and our findings are only appli-
cable to the analytic sample studied.
Reproductive health
A trained interviewer collected informa-
tion 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 pe-
riod? Have you had a hysterectomy? Has
your uterus/womb been removed? How
old were you when you had your (hyster-
ectomy/uterus/womb removed)? Have
you had one or both of your ovaries re-
moved? Postmenopause was defined as a
woman who has not had a menstrual pe-
riod in the past 12 months. We only re-
port 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 hor-
mones in the form of patches that are
placed on the skin? Not counting any time
when you stopped using the female hor-
mone patches, for how many years alto-
gether 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, vag-
inal cream, suppository, injection, or
patches and who were also currently us-
ing HRT. Previous users of HRT were
women who answered “yes”to any of the
above questions, but who were not cur-
rently using HRT. Never users of HRT re-
fers to women who answer no to all of the
above questions about usage of HRT.
Oral glucose tolerance test
During NHANES III, an oral glucose tol-
erance test (OGTT) was conducted on
participants aged 40–74 years who at-
tended the mobile examination part of the
survey. Participants were randomly as-
signed 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 sub-
sample most closely conformed to the
World Health Organization criteria for
OGTTs to identify diabetes (12,19,20).
Therefore, those who attended the morn-
ing subsample of the NHANES III were
used to estimate the prevalence of diabe-
tes as recommended by National Center
for Health Statistics guidelines. People
who reported a medical history of diabe-
tes but who were not using insulin ther-
apy 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 chal-
lenge and second venipuncture were can-
celed. 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 ex-
cluded from venipuncture. Examinees
who reported that they used insulin ther-
apy 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 veni-
punctures were performed.
Diabetes
The Expert Committee on Diagnosis and
Classification of Diabetes (12) recom-
mends that for epidemiological studies,
estimates of diabetes prevalence and inci-
dence should be based on a fasting plasma
glucose of 126 mg/dl. This recommenda-
tion is made in the interest of standardiza-
tion and also to facilitate field work.
However, the committee concedes that
this approach can lead to slightly under-
estimate prevalence that would be ob-
tained from the combined use of fasting
plasma glucose and OGTT (19–21). For
this study, the prevalence of diabetes is
defined as fasting (at least 8 h) plasma
glucose ⱖ126 mg/dl, plasma glucose val-
ues ⱖ200 mg/dl after a 2-h postload glu-
cose (OGTT), currently taking
antihyperglycemic medication (such as
insulin), or a (self-reported) medical his-
tory of diabetes.
Lipids
Assessment of lipid levels was conducted
using the following variables: total serum
cholesterol levels, HDL cholesterol, non-
HDL cholesterol (calculated by subtract-
ing 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 signifi-
cantly greater triglyceride levels than non-
diabetic 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 lipopro-
tein(a) [Lp(a)] were ascertained instead
(16,22).
HRT and lipid and glucose metabolism
1676 DIABETES CARE,VOLUME 25, NUMBER 10, OCTOBER 2002

Statistical analysis
Statistical analyses were carried out using
SAS, SUDAAN, and STATA statistical
software. All analyses incorporated the
sampling weights and the complex sam-
ple 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 us-
ing the survey procedure to calculate
means in the STATA software.
RESULTS —Table 1 describes se-
lected characteristics according to diabe-
tes status. The percent of women with less
than a high-school education was greater
among diabetic women (59%) than
among nondiabetic women (43%). The
percent of current smokers was higher
among nondiabetic menopausal women
(24%) than among diabetic women
(15%). Obesity was more prevalent
among diabetic (47%) than nondiabetic
(31%) women. Current use of HRT was
60% lower among diabetic women than
among nondiabetic women (10 and
16%, respectively). The most common
form of HRT administration among
women who reported ever taking HRT
were pills (90%).
We found a poorer lipid profile and,
as expected, glucose metabolism among
diabetic women compared with their
nondiabetic counterparts. The differences
in lipid and glucose profile between dia-
Table 1—Descriptive characteristics of postmenopausal women according to diabetes status
All Diabetic Nondiabetic
Sample size* % Sample size* % Sample size* %
Age-groups (years) 2,786 100 830 30 1,956 70
40–49 374 13 59 7 315 16
50–59 805 29 191 23 614 31
60–69 1,088 39 381 46 707 36
70–74 519 19 199 24 320 16
Race/ethnicity
Non-Hispanic white 1,309 47 315 38 994 51
Non-Hispanic black 739 27 219 26 520 27
Mexican-Americans 629 23 268 32 361 18
Other race/ethnicity 109 4 28 3 81 4
Education
Less than high school 1,322 48 488 59 834 43
High school 879 32 226 27 653 33
More than high school 585 21 116 14 469 24
Body weight categories (kg/m
2
)
Underweight (BMI ⬍18.5) 73 3 13 2 60 3
Normal weight (BMI 18.5–24.9) 768 28 151 18 617 32
Overweight (BMI 25–29.9) 948 34 280 34 668 34
Obesity (BMI 30⫹) 997 36 386 47 611 31
Smoking status
Current smokers 592 21 125 15 467 24
Previous smokers 667 24 224 27 443 23
Never smokers 1,527 55 481 58 1,046 53
HRT
Currently using HRT 388 14 84 10 304 16
Previously used HRT 700 26 184 23 516 27
Never used HRT 1,639 60 542 67 1,097 57
*Unweighted sample sizes.
Table 2—Indicators of lipid and glucose metabolism according to HRT in diabetic postmenopausal women aged 40–74 years: NHANES III,
1988–1994
HRT use status in diabetes
Current Previous Never
Sample size* Mean (95% CI) Sample size* Mean (95% CI) Sample size* Mean (95% CI)
Total cholesterol (mg/dl) 83 225 (217–233) 178 247 (238–256) 524 241 (235–246)
HDL (mg/dl) 82 56 (50–62) 175 52 (49–56) 516 51 (48–53)
Non-HDL (mg/dl) 82 169 (158–180) 175 192 (182–201) 516 188 (182–194)
Total cholesterol–to–HDL ratio 82 4.40 (3.85–4.94) 175 5.09 (4.69–5.49) 516 5.15 (4.89–5.39)
Triglycerides (mg/dl) 83 219 (167–270) 177 249 (194–304) 524 224 (201–246)
Lp(a) (mg/dl) 54 22 (10–33) 92 24 (15–32) 289 22 (17–27)
ApoA (mg/dl) 29 171 (158–185) 84 151 (142–161) 232 147 (143–150)
ApoB (mg/dl) 29 117 (109–125) 85 135 (127–143) 234 125 (120–130)
Fibrinogen (mg/dl) 82 306 (285–327) 172 336 (309–363) 515 342 (331–353)
C-reactive protein (mg/dl) 82 0.97 (0.58–1.35) 177 0.66 (0.48–0.83) 522 0.84 (0.70–0.98)
Fasting glucose (mg/dl) 83 112 (104–120) 180 151 (137–166) 528 154 (141–166)
Fasting insulin (␮U/ml) 82 16.7 (13.4–20.1) 178 20.6 (16.5–24.7) 523 22.6 (19.4–25.8)
GHb (mg/dl) 84 6.03 (5.70–6.35) 180 6.91 (6.46–7.36) 525 7.13 (6.81–7.44)
*Unweighted sample sizes.
Crespo and Associates
DIABETES CARE,VOLUME 25, NUMBER 10, OCTOBER 2002 1677

betic and nondiabetic subjects did not
change drastically after adjusting for age,
race/ethnicity, BMI, smoking, and educa-
tional attainment (data not shown). Of
note, fibrinogen and C-reactive protein
were also higher in diabetic subjects
(336 and 0.81 mg/dl) than among non-
diabetic women (310 and 0.48 mg/dl,
respectively).
Tables 2 (diabetic subjects) and 3
(nondiabetic subjects) show indicators of
lipid and glucose metabolism according
to HRT status. Table 2 shows that among
women with diabetes, serum cholesterol
levels were significantly lower (225 mg/
dl) among those currently taking HRT
than among previous or never users of
HRT (⬎240 mg/dl). Non-HDL levels
were significantly lower among diabetic
as well as nondiabetic women currently
taking HRT (Tables 2 and 3). HDL levels
were not significantly different among di-
abetic women on HRT and previous or
never users of HRT (Table 2). In nondia-
betic women, however, HDL levels were
significantly higher in those taking HRT
than in those who have never used HRT
or who previously used HRT (Table 3).
Similar divergent results were observed
for the total cholesterol–to–HDL ratio.
Thus, although HDL and total choles-
terol–to–HDL ratios were significantly
different among nondiabetic women cur-
rently taking HRT compared with previ-
ous HRT users or never HRT users, these
results were not observed in diabetic
women.
Diabetic women currently taking
HRT had significantly lower fasting glu-
cose levels (112 mg/dl) than previous or
never HRT users (⬎150 mg/dl) (Table 2).
Among diabetic and nondiabetic women,
however, fasting insulin levels were not
significantly different when compared
across HRT use category (Tables 2 and 3).
Never users of HRT had higher fibrinogen
levels than current users for both diabetic
and nondiabetic postmenopausal women
(Tables 2 and 3). Adjustment for age,
BMI, smoking, and education did not al-
ter the above findings.
CONCLUSIONS —We examined
lipid profiles and indicators of glucose
metabolism in a nationally representative
sample of postmenopausal diabetic and
nondiabetic women from NHANES III.
Although HDL was found to be signifi-
cantly higher among nondiabetic women
who were currently taking HRT than
among never or previous users of HRT,
this finding was not observed among dia-
betic women. Total cholesterol and non-
HDL levels, however, were significantly
lower among diabetic women currently
on HRT than among never or previous
users of HRT. Furthermore, these find-
ings were not observed in nondiabetic
women. This divergent result may be in-
dicative of a different effect of HRT on
lipid metabolism in diabetic compared
with nondiabetic women.
Our findings confirm that glucose
metabolism among diabetic women who
were currently taking HRT as evidenced
by lower fasting glucose, fasting insulin,
and GHb is superior to those who were
not on HRT. This may indicate that
women who take HRT are also in better
control of their diabetes and may be in-
dicative of other favorable health behav-
iors among women who use HRT. Not
only were fasting glucose and GHb lower
among diabetic current users of HRT
compared with never or previous users of
HRT, but also among nondiabetic women
users of HRT compared with nonusers.
Current users of HRT in both diabetic
and nondiabetic postmenopausal women
also had significantly higher levels of
apoA levels than never users of HRT.
ApoA is the major protein component of
HDL and an important coenzyme for the
enzyme lecithin:cholesterol acyltrans-
ferase, which attaches a free fatty acid on
the cholesterol molecule, forming a cho-
lesterol ester that will later remove cho-
lesterol via the bile acids (23). Therefore,
higher levels of apoA are considered to be
beneficial. ApoB is an atherogenic com-
ponent of the lipoproteins and is more
closely linked to non-HDL cholesterol.
ApoB levels in both diabetic and nondia-
betic postmenopausal women appear to
be lower in current users of HRT when
compared with women who previously or
never used HRT, but it only approached
statistical significance because the 95%
CIs overlapped slightly. Other research-
ers have found that HRT reduced apoB in
postmenopausal women with type 2 dia-
Table 3—Indicators of lipid and glucose metabolism according to HRT in nondiabetic postmenopausal women aged 40 –74 years: NHANES III,
1988–1994
HRT use status in nondiabetic women
Current Previous Never
Sample size* Mean (95% CI) Sample size* Mean (95% CI) Sample size* Mean (95% CI)
Total cholesterol (mg/dl) 293 224 (218–230) 491 231 (227–235) 1,031 227 (223–231)
HDL (mg/dl) 292 64 (61–67) 488 57 (55–59) 1,027 55 (53–56)
Non-HDL (mg/dl) 292 160 (153–167) 487 174 (170–178) 1,027 172 (168–176)
Total cholesterol–to–HDL ratio 292 3.78 (3.55–3.99) 487 4.40 (4.21–4.58) 1,027 4.54 (4.31–4.76)
Triglycerides (mg/dl) 293 155 (142–167) 491 150 (139–160) 1,028 139 (132–147)
Lp(a) (mg/dl) 164 24 (19–29) 265 26 (20–31) 527 25 (20–29)
ApoA (mg/dl) 128 174 (168–181) 227 158 (153–162) 498 152 (148–156)
ApoB (mg/dl) 129 109 (103–115) 227 115 (110–120) 500 116 (113–118)
Fibrinogen (mg/dl) 292 297 (283–310) 488 301 (292–310) 1,019 320 (310–330)
C-reactive protein (mg/dl) 292 0.60 (0.50–0.68) 492 0.46 (0.37–0.54) 1,023 0.45 (0.40–0.51)
Fasting glucose (mg/dl) 300 92 (91–93) 501 94 (93–96) 1,047 96 (95–96)
Fasting insulin (␮U/ml) 297 8.59 (7.7–9.4) 497 10.30 (9.0–11.6) 1,043 10.38 (9.7–11.0)
GHb (mg/dl) 298 5.3 (5.21–5.33) 501 5.37 (5.32–5.42) 1,045 5.42 (5.36–5.48)
*Unweighted sample sizes.
HRT and lipid and glucose metabolism
1678 DIABETES CARE,VOLUME 25, NUMBER 10, OCTOBER 2002

betes (11,24). The difference may be due
to the smaller sample size in our study or
the cross-sectional design of our study
(11).
We found no significant differences
in Lp(a) among the groups studied. Lp(a)
is a complex of an LDL-like particle and
apoA. Elevations in Lp(a) have been asso-
ciated with coronary heart disease and
thrombotic stroke (25–27). The mecha-
nism of this relationship is not known,
but it is thought that because apoA and
plasminogen are homologous, elevated
levels of Lp(a) may interfere with fibronoly-
sis and therefore promote thrombosis (2).
Fibrinogen is an important compo-
nent in platelet aggregation and is also a
risk indicator for cardiovascular disease,
including coronary heart disease, stroke,
and peripheral artery disease, and has
been closely linked to smoking, hyperten-
sion, and total cholesterol (28). We found
fibrinogen to be significantly lower
among current HRT users than women
who never used HRT for both diabetic
and nondiabetic women. Similar findings
were observed in a group of postmeno-
pausal women aged 52–65 years (n⫽
300), where HRT usage was associated
with significantly lower fibrinogen con-
centration (232 vs. 268 mg/dl) and de-
creased plasma viscosity (29). Results
from this study, however, were not pro-
vided separately for diabetic and nondia-
betic women.
C-reactive protein is an important in-
flammatory biomarker that has been sug-
gested to have an intermediary role in the
pathogenesis of cardiovascular disease in
individuals with type 2 diabetes (14). Our
results indeed confirm higher levels of C-
reactive protein among postmenopausal
diabetic women. Both diabetic and non-
diabetic women currently using HRT had
higher levels of C-reactive protein than
previous or never users, but these only
approached statistical significance.
We found lower fasting glucose and
GHb among diabetic women currently
using HRT than among never or previous
users of HRT. This may be due to higher
compliance in using glucose-controlling
medication among diabetic women cur-
rently using HRT than among with previ-
ous or never users of HRT and is not
necessarily an effect of HRT. However,
several studies support our findings using
prospective, observational, or random-
ized controlled trials (7,9,11). Also, the
fact that we observed a similar finding in
nondiabetic women confirms the possible
hypoglycemic effect of HRT or the fact
that women on HRT may have healthier
habits. Adjustment for smoking, BMI,
physical activity, education, and race/
ethnicity did not alter the lower fasting
glucose levels observed, especially among
diabetic women (data not shown).
One of the strengths of this analysis is
the inclusion of emerging cardiovascular
disease risk factors such as Lp(a), fibrino-
gen, apoA, and apoB in a national sample
of postmenopausal women according to
HRT use. Some of these measurements
were obtained during phase 1 (apoA and
apoB), while another [Lp(a)] was col-
lected during phase 2. One of the limita-
tions of this study was that to further
subdivide the analytic sample among di-
abetic and nondiabetic subjects by HRT
use, we reduced the sample size consid-
erably for some of these components, and
because of these smaller sample sizes, we
may have failed to see a difference when
there was one. We did, however, observe
statistically significantly different levels of
apoA between current HRT users com-
pared with never or previous HRT users
in both diabetic and nondiabetic women.
A possible limitation of this analysis
is that it is based on cross-sectional
data. However, this is a descriptive epide-
miological analysis based on a national
representative sample of the civilian non-
institutionalized population of post-
menopausal women 40–74 years of age
who underwent a rigorous lipid and glu-
cose metabolism assessment. Our find-
ings serve to confirm previous smaller
studies that have examined the relation-
ship of HRT with glucose and lipid me-
tabolism in diabetic and nondiabetic
postmenopausal women.
Our definition of diabetes is not a
clinical definition of diabetes, but rather
an epidemiological definition based on
clinical measurements, self-reported use
of medications to control glucose levels,
and previous diagnosis of diabetes by a
health professional. The prevalence of di-
abetes in the U.S. among individuals aged
40–74 years falls between 12 and 14%.
Since the prevalence of undiagnosed
diabetes (5–7%) can be as great as the
prevalence of diagnosed diabetes (7%),
our definition of diabetes allowed us to
more clearly separate postmenopausal
women without diabetes from those with
diabetes.
Although favorable lipid and glucose
profiles were observed among HRT users,
we caution that our findings are observa-
tional and may not be adequate to guide
lipid-altering therapy in postmenopausal
diabetic women. Nevertheless, our find-
ings at the population level suggest that
HRT use may be associated with increased
apoA and lower fasting glucose, GHb,
total cholesterol, and non-HDL in this
group of diabetic postmenopausal wom-
en. To what extent these differences are
explained by the fact that women who use
HRT are more health conscious is not en-
tirely clear. In our analyses we controlled
for BMI, education, race/ethnicity, smok-
ing, and age and the results did not
change substantively. A large and more
rigorous clinical trial is necessary to better
assess if the potential cardiovascular risk–
reducing benefits of HRT observed in
nondiabetic women are applicable to
women with diabetes.
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