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Clinical Science (198 1) 61,649-65 1
SHORT COMMUNICATION
Associations between sex hormones, thyroid hormones and
lipoproteins
R . F. H E L L E R ' , N . E. M I L L E R ' , B. L E W I S ' , A. V E R M E U L E N 4 , A N G E L A
F A I R N E Y 3 , V. H . T. J A M E S 3 A N D A . V. S W A N '
Departments of 'Community Medicine and 'Chemical Pathology, St Thomas' Hospital Medical School, London, =Department
of Chemical Pathology, St Mary's Hospital Medical School, London, and 4Department of Endocrinology, Akademisch
Ziekenhuis, Ghent. Belgium
(Received 30 March 1981; accepted 19 May 1981)
Summary
Introduction
1. A study of 150 middle-aged male industrial
employees has shown significant positive correlations between plasma levels of high-density-lipoprotein (HDL) cholesterol and both
serum testosterone and alcohol intake, and
significant negative correlations between HDL
cholesterol and both serum thyroxine and
obesity. These associations persist when examined by multiple linear regression, indicating
their independence.
2. Significant positive correlations are also
shown between plasma triglyceride levels and
both obesity and serum thyrotropic hormone
(TSH) levels.
3. There are no evident relationships between
serum oestrone or oestradiol and either HDL
cholesterol or triglyceride levels, nor between any
of the hormones and either total or low-densitylipoprotein (LDL) cholesterol.
4. Because of the potential importance in
relation to coronary heart disease prevention,
further studies are needed to try and understand
the mechanisms of the associations between
HDL cholesterol and obesity, alcohol intake and
thyroid and sex hormone levels.
After a suggestion that testosterone might be a
risk factor for coronary heart disease in men 111,
a case-control study indicated that men with
coronary heart disease had slightly higher testosterone levels than control subjects (although
the difference was not significant) [2]. Previous
studies had shown that injections of synthetic
androgens alter plasma lipid levels, producing a
reduction in high-density-lipoprotein (HDL)
cholesterol 131. Since low HDL cholesterol levels
are associated with a high risk of coronary heart
disease [4]we considered the possibility that any
adverse influence of testosterone on coronary
heart disease might be mediated through an effect
on HDL cholesterol. The present study was set
up to explore any relationship between sex
hormone levels and lipid levels in a sample of
middle-aged men. Measurements were also made
of thyroid function, in view of evidence that
patients with both hypo- and hyper-thyroidism
have altered lipoprotein metabolism 151.
Key words: lipoproteins, sex hormones, thyroid
hormones.
Abbreviations: HDL, high-density-lipoprotein;
LDL, low-density-lipoprotein; TSH, thyrotropic
hormone.
Correspondence: Dr R. F. Heller, Department of
Community Meditine, St Thomas' Hospital Medical
School, London S.E. 1.
0143-5221/81/110649-03%01.50/1/1
Methods
Participants in one of the industrial groups in a
study of the prevention of coronary heart disease
[ 6 ] were eligible to take part if they were still in
employment (8 years after the start) and if they
had attended a cardiovascular screening examination 2 years before the present study. Those
who were free of coronary heart disease at this
examination (having no past history or chest pain
symptoms and a normal ECG) were asked to
visit the factory medical department in the
0 1 9 8 1 The Biochemical Society and the Medical Research Society
R.F. Heller et al.
650
morning after having either fasted or had a
breakfast free of fat and dairy produce. A blood
sample was taken, spun and separated the same
day; 5 ml of serum was stored at -2OOC until
total testosterone, oestrone, oestradiol, thyrotropic hormone (TSH) and thyroxine measurements were made by radioimmunoassay as
described previously [7-101. A 5 ml sample of
plasma was stored at 4°C until total cholesterol,
HDL cholesterol, low-density-lipoprotein (LDL)
cholesterol and triglycerides were measured
(within a week of venepuncture) as described
previously [ 111. A self-administered questionnaire, completed before venepuncture, included a
question about the amount of alcoholic drinks
consumed during the previous week; this was
converted to grams of alcohol.
Statistical analyses involved simple regression
techniques to assess the relationships between the
different variables measured. In addition, multiple
linear-regression models were fitted to the data,
with the GLIM package programme [12], to
assess the independence of the relationships
between the different measured variables.
Results
Of the 253 men who had attended the screening
examination 2 years previously, 38 had died or
left employment by the time of this survey and
150 men attended (70% of the possible attenders). Those who attended this survey were
significantly lighter, less likely to be cigarette
smokers and less likely to come from social
classes IV and V than those who were still in
employment but did not participate.
Over the age-range represented by the study
participants (47-64 years) there is no significant
association between age and any of the hormone
or lipid levels, nor is there any suggestion of an
effect on hormone or lipid levels of cigarette
smoking or social class. There are, however,
associations between obesity (measured as bodymass index, weight/height') and serum testosterone, oestradiol, HDL cholesterol and triglyceride concentrations (Table 1). Fatter people
have higher levels of oestradiol and triglycerides
and lower levels of testosterone and HDL
cholesterol. Table 1 also shows that increasing
alcohol intake is associated with high HDL
cholesterol and low thyroxine levels. Those
consuming an average of more than 60 g of
alcohol/day (9% of these men) also have raised
plasma triglyceride levels, but a relationship is not
seen over the whole range of alcohol intake.
The crude correlations between lipid and
hormone levels (Table 1) indicate a positive
association between testosterone and HDL
cholesterol levels and a negative association
between thyroxine and HDL cholesterol. TSH
also shows a negative correlation with HDL
cholesterol, but this does not reach statistical
significance. In each case there is a correlation
between hormone and triglyceride levels which is
in the opposite direction to that with HDL
cholesterol, but significance is reached only in the
case of TSH.
Entering each of the hormones, age, bodymass index and alcohol intake into a multiple
linear-regression model, with each of the lipids in
turn as the dependent variable, confirms that
body-mass index, alcohol intake and testosterone and thyroxine levels each have a significant and independent association with HDL
cholesterol, whereas body-mass index and TSH
have an independent association with triglyceride
levels.
Oestrone and oestradiol do not show an
association with HDL cholesterol or triglycerides;
nor do they affect the association with testosterone. None of the hormones appears to be
correlated with total or LDL cholesterol levels.
Nearly half of the variance in HDL cholesterol
(42%) and nearly a third of the variance in
TABLE1. Simple correlation coeflcients
Two outliers have been excluded from all analyses: one with a TSH level of 27 m-unit/l and one with a triglyceride level 6f
9.5 nmol/l. In addition. measurements were not available for lipids in 10 of the 150 subjects, for testosterone in five subjects,
oestrone. oestradiol and TSH in seven subjects and for thyroxine in 25 subjects. Significance of differences: * P < 0.05;
** P < 0.01.
~~~
Total cholesterol
LDL cholesterol
HDL cholesterol
Triglycerides
Body-mass index
Alcohol intake
Age
~~~~
~
Testosterone
Oestrone
Oestradiol
TSH
Thyroxine
-0.03
-0.02
-0.11
-0.03
0.11
-0.04
0.15
0.01
0.15
0.02
0.04
0.10
0.20*
-0.02
-0.04
-0.02
-0.01
0.02
-0.28"
0.12
0.12
-0.30..
0.06
0.02
0.28.'
-0. I6
-0.17'
0.09
0.13
-0.04
-0.16
0.19.
0.01
-0.08
0.12
Body-mass
index
0.12
0.05
-0.31**
0.26..
-
-0.10
-0.06
Alcohol
intake
Age
-0.00
-0.10
0.26**
-0.02
0.00
-0.09
-
-0.07
0.02
0.08
-
Hormones and lipoproteins
triglycerides (32%) can be explained by the eight
variables entered into the multiple regression
model.
65 1
importance in relation to coronary heart disease
prevention.
Acknowledgments
Discussion
The results of the present study relate to male
middle-aged industrial employees, working in the
same factory for at least 8 years, who were
thought to be free of coronary heart disease.
Under-represented in this study are smokers, the
overweight and those of social classes IV and V,
and the possibility of generalizing from these
results should be influenced by this. Smoking and
social class do not influence any other measured
variables, but obesity is strongly related to many
of the measured lipids and hormones: in the
statistical analyses we have tried to take account
of this.
We confirm previous observations on the
relationship of obesity with H D L cholesterol [41
and triglyceride levels [13], and of alcohol intake
with HDL cholesterol [141 (and with triglycerides at high alcohol intake). We also find an
inverse association between plasma thyroxine
and both alcohol intake and HDL cholesterol.
Neither of these relationships with thyroxine were
predicted before the study and both need independent confirmation.
The positive association between testosterone
and HDL cholesterol is in the opposite direction
to the one predicted, but has been found
elsewhere [ 151. This finding weakens the original
hypothesis that the serum testosterone concentration is a risk factor for coronary heart
disease [ l ] in view of the ‘protective’ effect of
high HDL cholesterol levels [41. It is also
surprising in view of the higher HDL levels in
women than in men 141: in this male population
oestrogens had no influence on HDL cholesterol
nor on the testosterone/HDL relationship.
These cross-sectional associations do not allow
an inderstanding of any possible mechanisms;
nor of whether a change in any of the variables
would be followed by a change in lipid levels
within individuals. HDL cholesterol does,
however, appear to have a close association with
obesity, alcohol intake, and thyroid and sex
hormone levels. Further studies are indicated to
elucidate the metabolic mechanisms underlying
these associations, in view of their potential
We are grateful to Dr Bernard Watney and his
staff of the Guinness Brewery Medical Centre,
Park Royal, for their help with the survey and to
the St Thomas’ Hospital Research Endowments
Fund for financial support. We also thank the
MRC for the gift of standard TSH.
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