sex hormone alterations and systemic inflammation in chronic obstructive pulmonary disease

Sex hormone alterations and systemic inflammation inchronic obstructive pulmonary disease

F. Karadag,1 H. Ozcan,1 A. B. Karul,2 M. Yilmaz,2 O. Cildag1

Introduction

Decreased anabolic hormone levels are commonly

described in several chronic or critical illnesses,

including chronic respiratory diseases (1,2). Periph-

eral muscle wasting, osteoporosis, sexual dysfunc-

tion, immunological alterations, memory loss,

diminished energy and vitality are among the clin-

ical consequences of hypogonadal state (1,3,4). Per-

ipheral muscle wasting in chronic obstructive

pulmonary disease (COPD) is associated with

decreased exercise capacity, impaired quality of life

and even decreased survival (5–7). The wasting

process is too complex to explain by disturbance in

a single component of this system, so investigating

anabolic and catabolic factors together may be

more convenient.

A dysfunctioning hypothalamic-pituitary-gonadal

axis has been reported in COPD in previous studies

(8–12). Moreover, a decreased response to adminis-

tered gonadotrophin-releasing hormone was detected

in chronic airway diseases (13). However, in most of

these studies, there was no comparison of sex hor-

mones of COPD patients and age-matched subjects

with normal pulmonary function. The mechanisms

of these alterations are not clear yet, but hypoxia,

disease severity, smoking, corticosteroid therapy and

underlying chronic inflammatory illness were sugges-

ted to contribute to low testosterone levels (3).

Chronic diseases, including COPD, lead to

increased levels of circulatory proinflammatory

cytokines resulting in a shift towards catabolism

(14,15). Proinflammatory cytokines, interleukin-6

(IL-6) and tumour necrosis factor alpha (TNF-a),

SUMMARY

Objective: Decreased anabolic hormone levels are described in chronic obstructive

pulmonary disease (COPD), leading to important clinical consequences. The aim of

this study was to evaluate the alterations in sex hormone levels in men with COPD

to compare with age-matched control subjects, the determinants of these altera-

tions, the relationship between hypogonadism and markers of systemic inflamma-

tion [interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-a)] and the

androgen status during an acute exacerbation of COPD. Methods: A total of 103

COPD patients and 30 control subjects were admitted to the study. 83 stable

COPD patients and 30 control subjects were evaluated as outpatients. 20 patients

with COPD exacerbation were hospitalised and evaluated before discharge and

after 1 month. Results: Testosterone and dehydroepiandrosteronesulphate

(DHEAS) levels of both COPD groups were lower than that of the control group.

Luteinizing hormone (LH), follicle stimulating hormone (FSH) levels were increased

during exacerbation. Testosterone and DHEAS levels increased and LH decreased in

follow-up measurements of COPD exacerbation group. Testosterone and DHEAS

levels were lower in severe COPD [forced expiratory volume in 1 s (FEV1) < 50%],

in patients with severe hypoxaemia (PaO2 < 60 mmHg) and in hypercapnic

patients. Circulating IL-6 and TNF-a concentrations were higher in both stable and

exacerbation phase COPD groups than controls. There was no correlation between

sex hormones and TNF-a or IL-6. Conclusion: The alterations in sex hormone lev-

els in COPD are particularly related to FEV1, hypoxaemia and hypercapnia. There

are significant differences in hormone levels during stable and exacerbation phases

of COPD; the hormonal changes are marked during exacerbation and partially

regress after 1 month when the disease is stabilised.

What’s knownA dysfunctioning hypothalamic-pituitary-gonadal

axis has been reported in chronic obstructive

pulmonary disease (COPD). However, there was no

comparison of sex hormones of COPD patients and

age-matched subjects with normal pulmonary

function. The mechanisms of these alterations are

not clear yet, but hypoxia, disease severity,

smoking, corticosteroid therapy and underlying

chronic inflammatory illness were suggested to

contribute to low testosterone levels. There appears

to be a regulatory loop between proinflammatory

cytokines and anabolic steroids.

What’s newThe sex hormones of COPD patients were

compared to age-matched subjects with normal

pulmonary function. The alterations in sex hormone

levels in COPD are particularly related to FEV1,

hypoxaemia and hypercapnia. There are significant

differences in hormone levels during stable and

exacerbation phases of COPD; the hormonal

changes are marked during exacerbation and

partially regress when the disease is stabilised.

There is no correlation between sex hormones and

TNF-a or IL-6.

Departments of 1Chest Diseases

and 2Biochemistry, School of

Medicine, Adnan Menderes

University, Aydin, Turkey

Correspondence to:

Fisun Karadag,

Department of Chest Diseases,

Faculty of Medicine, Adnan

Menderes University, 09010

Aydin, Turkey

Tel.: + 90 256 4441256/150

Fax: + 90 256 2146495

Email:

[email protected]

Disclosures

The authors have declared that

they have no interests which

might be perceived as posing a

conflict or bias.

OR IG INAL PAPER

ª 2007 The AuthorsJournal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, February 2009, 63, 2, 275–281doi: 10.1111/j.1742-1241.2007.01501.x 275

play a role in muscle wasting and cachexia (16,17).

IL-6 is able to initiate catabolism by activating pro-

teolysis (18). Experimental data showed that TNF-aadministration induced testicular atrophy with

decreased testosterone and increased gonadotrophin

levels in male rats, and a 50% decrease in serum

total testosterone in healthy males (19,20).

There appears to be a regulatory loop between

proinflammatory cytokines and anabolic steroids.

Increased levels of proinflammatory cytokines reduce

testosterone secretion by interfering with Leydig-cell

function (19). Furthermore, anabolic hormone defi-

ciency contributes to elevated IL-6 levels as the

expression of this cytokine is downregulated by tes-

tosterone and dehydroepiandrosteronesulphate

(DHEAS) (15). Moreover, low anabolic hormone

level may synergize the catabolic effects of proinflam-

matory cytokines, or, conversely, high anabolic hor-

mone level may protect against negative effects of

cytokines (15).

The present cross-sectional study was designed to

evaluate:

• Serum sex hormone levels as markers of hypotha-

lamic-pituitary-gonadal axis dysfunction in men with

stable moderate-to-severe COPD to compare with

those of age-matched control subjects with normal

pulmonary function

• The hormonal status during an acute exacerbation

of COPD and follow-up after exacerbation phase

• The determinants of the alterations in sex hor-

mones in COPD (smoking, body mass index, pul-

monary function, exacerbation of disease, severity of

hypoxaemia and hypercapnia)

• The relationship between markers of systemic

inflammation (IL-6 and TNF-a) and hypogonadism

in COPD

Methods

PatientsA total of 138 consecutive male COPD patients who

attended chest diseases outpatient clinic were asked to

participate in the study. Of these, 112 were reluctant

to participate, but nine were excluded because of drug

use which may interfere with serum hormone levels,

infections, malignancy, significant cardiac, renal, hep-

atic, endocrine or metabolic disturbance and prior

diagnosis or treatment of urogenital disease. Thirty

age-matched subjects with normal pulmonary func-

tion, and without any above-mentioned exclusion cri-

teria were admitted as control group. The diagnosis

and severity of COPD had been established by a respir-

atory physician on the basis of international guidelines

(21). 83 of the patients had been clinically stable for at

least 3 months, and 20 had clinical signs of COPD

exacerbation (22). Stable COPD patients had been

receiving inhaled bronchodilator therapy in the form

of long-acting b2-agonists and/or anticholinergic

agents. Severe/very severe COPD patients were on

inhaled corticosteroids (budesonide 1600 lg/day).

Antibiotics and systemic steroids (methylprednisolone

40 mg/day) were added to therapy in exacerbation

period. After an overnight fast, height and nude weight

were measured in all subjects and body mass index

(BMI) was calculated. BMI between 19 and 25 was

accepted as normal (23).

The study was approved by the institutional ethics

committee and written consent was obtained in each

case.

Pulmonary function testsForced vital capacity (FVC) and forced expiratory

volume in 1 s (FEV1) were measured with standard

spirometric techniques according to the ATS criteria

(Minato AutoPal Spirometry, Osaka, Japan) (24).

Patients with FEV1 < 50% of predicted value were

considered to have severe and 50% £ FEV1 < 80% as

moderate COPD (21). Arterial blood sample was

obtained while the subjects were breathing room air

for at least 30 min, and analysed with a blood gas

analyzer immediately (OMNIC; Roche, Vienna,

Austria).

Sex hormonesSerum levels of sex hormones [total testosterone,

DHEAS, follicle stimulating hormone (FSH) and

luteinizing hormone (LH)] were measured using

electrochemiluminescence immunoassay (Elecsys

2010; Roche, Tokyo, Japan). Sex hormones were meas-

ured once in stable COPD patients and controls, and

measured thrice in COPD exacerbation group; on the

first day of hospitalisation (admission), on the day of

discharge from hospital (after 10–14 days of treat-

ment) and 4 weeks after the discharge (recovery).

Cytokine assaysFasting blood samples were withdrawn between 7 and

8 am into plain tubes. Blood was centrifuged imme-

diately and serum was stored at )70 �C until analysis.

Serum TNF-a and IL-6 concentrations (pg/ml) were

measured by solid phase sandwich enzyme-linked

immunosorbent assay (ELISA) (BioSource Interna-

tional Inc., Camarillo, CA, USA).

Statistical analysisData were presented as mean value ± standard

deviation of the mean. Correlations between param-

eters were evaluated using Pearson’s rank correla-

tion analysis. Non-parametric data of study groups

were compared by Mann–Whitney U-test. One-way

276 Sex hormones in COPD

ª 2007 The AuthorsJournal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, February 2009, 63, 2, 275–281

analyses of variance (Kruskal–Wallis test) was used

to compare differences in COPD subgroups. Fried-

man test was used to compare baseline and subse-

quent control hormone and cytokine levels of

COPD patients. Significance was determined at 5%

level.

Results

Pulmonary function tests and arterial bloodgasesDemographic data, BMI, pulmonary function tests

and arterial blood gas values of COPD patients and

control subjects are shown in Table 1. There was sig-

nificant difference in pulmonary function and blood

gases of stable and exacerbation groups of COPD

patients. BMI of COPD patients was lower than that

of control subjects (p ¼ 0.042).

Sex hormonesSerum sex hormone levels of stable and exacerbation

phase COPD patients and control subjects are shown

in Table 2. Testosterone and DHEAS levels were

lower in stable COPD patients compared with con-

trol subjects; LH and FSH were similar in both

groups. In COPD exacerbation group, testosterone

and DHEAS levels were lower and LH, FSH were

higher compared with controls. Testosterone was

lower and LH was higher in exacerbation group

compared with stable COPD.

Sex hormone levels of moderate (FEV1 ‡ 50%)

and severe (FEV1 < 50%) stable COPD patients are

given in Table 3. Testosterone and DHEAS levels

were significantly lower in severe COPD.

Testosterone and DHEAS were lower and LH was

higher in stable COPD patients with severe hypoxae-

mia (PaO2 £ 60 mmHg) compared with those with

Table 1 Characteristics and pulmonary function tests of stable and exacerbation phase COPD patients and control

subjects

Stable Exacerbation Controls p*

Subjects (n) 83 20 30 –

Age (years) 65.54 ± 7.66 68.60 ± 5.87 64.10 ± 7.68 0.064

Smoking (pack-year) 53.58 ± 25.63 61.50 ± 22.05 16.77 ± 15.78 0.134

BMI 25.25 ± 4.84 24.00 ± 5.41 26.32 ± 3.07 0.154

FVC 75.78 ± 14.97 71.69 ± 12.25 89.40 ± 10.35 0.264

FEV1 46.41 ± 14.43 36.00 ± 9.92 85.09 ± 10.24 0.003

FEV1/FVC % 47.99 ± 12.24 39.43 ± 9.51 76.03 ± 6.21 0.006

pH 7.41 ± 0.02 7.37 ± 0.08 7.38 ± 0.04 0.048

PaO2 74.24 ± 10.39 54.21 ± 11.58 94.32 ± 4.62 0.000

PaCO2 41.46 ± 6.00 51.30 ± 14.03 38.23 ± 3.46 0.002

*p-value is obtained by comparison of stable and exacerbation phase COPD patients. COPD, chronic obstructive pulmonary disease;

BMI, body mass index (kg/m2); FVC, forced vital capacity (% predicted); FEV1, forced expiratory volume in 1 s (% predicted); PO2, oxy-

gen partial pressure (mmHg); PCO2, carbon dioxide partial pressure (mmHg).

Table 2 Serum sex hormone and cytokine levels in stable and exacerbation phase COPD patients and control subjects

Stable Exacerbation Controls p* p** p***

Testosterone 4.05 ± 1.53 2.68 ± 1.50 4.80 ± 1.60 0.045 0.000 0.000

DHEAS 98.23 ± 87.76 78.64 ± 73.84 157.85 ± 98.49 0.000 0.000 0.247

LH 8.86 ± 6.63 12.81 ± 10.95 7.03 ± 3.25 0.186 0.050 0.030

FSH 10.10 ± 9.18 12.06 ± 10.70 7.84 ± 5.01 0.095 0.029 0.344

IL-6 68.86 ± 50.42 71.40 ± 130.16 24.77 ± 47.23 0.012 0.019 0.802

TNF-a 11.43 ± 11.91 14.87 ± 36.03 5.99 ± 5.29 0.033 0.034 0.449

*Obtained by the comparison of stable COPD patients and control subjects. **Obtained by the comparison of COPD exacerbation and

control subjects. ***Obtained by the comparison of COPD exacerbation and stable COPD groups. COPD, chronic obstructive pulmonary

disease; Testosterone (ng/ml); DHEAS, dehydroepiandrosteronesulphate (lg/ml); LH, luteinizing hormone (mIU/ml); FSH, follicle stimula-

ting hormone (mIU/ml); IL-6, interleukin-6 (pg/ml); TNF-a, tumour necrosis factor alpha (pg/ml).

Sex hormones in COPD 277


moderate hypoxaemia (PaO2 > 60 mmHg). Testo-

sterone and DHEAS were lower in patients with

hypercapnia (PaCO2 > 45 mmHg) (Table 4).

LH was higher (11.78 ± 9.51 and 8.66 ± 6.67

consecutively; p ¼ 0.013) and DHEAS was lower

(73.60 ± 64.21 and 103.81 ± 92.07 consecutively;

p ¼ 0.020) in COPD patients whose BMI was

lower than normal (< 19) than those with normal

BMI.

During follow-up of COPD exacerbation group,

testosterone was observed to increase in discharge

and recovery measurements, in parallel with the

improvement in arterial blood gases. DHEAS level

decreased further in discharge but increased in recov-

ery measurement; whereas LH decreased progres-

sively and FSH remained stable (Table 5).

Cytokine assaysSerum TNF-a and IL-6 concentrations of COPD

patients and control subjects are shown in Table 2,

together with sex hormones. IL-6 and TNF-a con-

centrations were higher in both stable and exacerba-

tion phase COPD groups than controls.

CorrelationsIn correlation tests of stable COPD group, DHEAS

was inversely related to age (r ¼ )0.348, p ¼ 0.001)

and duration of COPD (r ¼ )0.358, p ¼ 0.001).

Table 3 Sex hormones of moderate (FEV1 ‡ 50) and

severe (FEV1 < 50) stable COPD patients

Moderate

COPD

Severe

COPD p

Testosterone 4.52 ± 1.81 3.48 ± 1.43 0.007

DHEAS 112.26 ± 64.01 87.10 ± 91.98 0.005

LH 8.42 ± 7.09 10.12 ± 8.01 0.213

FSH 8.98 ± 9.63 11.09 ± 9.40 0.066

COPD, chronic obstructive pulmonary disease; FEV1, forced

expiratory volume in 1 s (% predicted); Testosterone (ng/ml);

DHEAS, dehydroepiandrosteronesulphate (lg/ml); LH, luteinizing

hormone (mIU/ml); FSH, follicle stimulating hormone (mIU/ml).

Table 4 Sex hormones of stable COPD patients with moderate (80 > PaO2 ‡ 60 mmHg) and severe hypoxaemia (PaO2

< 60 mmHg) and with (PaCO2 > 45 mmHg) and without (PaCO2 £ 45 mmHg) hypercapnia

PaO2 ‡ 60 PaO2 < 60 p* PaCO2 £ 45 PaCO2 > 45 p**

Testosterone 4.16 ± 1.49 2.92 ± 1.39 0.000 4.20 ± 1.56 2.97 ± 1.41 0.000

DHEAS 107.41 ± 92.70 66.43 ± 60.97 0.004 100.98 ± 84.08 81.69 ± 87.30 0.046

LH 9.14 ± 7.97 10.58 ± 7.44 0.048 9.07 ± 7.77 10.72 ± 7.72 0.119

FSH 9.11 ± 7.34 13.25 ± 12.49 0.088 9.57 ± 8.63 12.22 ± 10.84 0.115

*Obtained by comparison of sex hormones of COPD patients with moderate (80 > PaO2 ‡ 60 mmHg) and severe hypoxaemia (PaO2

< 60 mmHg). **Obtained by comparison of sex hormones of COPD patients with (PaCO2 > 45 mmHg) and without (PaCO2

£ 45 mmHg) hypercapnia. COPD, chronic obstructive pulmonary disease; PO2, oxygen partial pressure (mmHg); PCO2, carbon dioxide

partial pressure (mmHg); Testosterone (ng/ml); DHEAS, dehydroepiandrosteronesulphate (lg/ml); LH, luteinizing hormone (mIU/ml); FSH,

follicle stimulating hormone (mIU/ml).

Table 5 Admission, discharge and recovery serum sex hormone levels and blood gas analyses of COPD exacerbation

patients

Admission Discharge Recovery p

Testosterone 2.68 ± 1.50 3.23 ± 1.98 5.09 ± 1.58 0.000

DHEAS 78.63 ± 73.84 55.97 ± 36.06 88.42 ± 46.62 0.001

LH 12.81 ± 10.95 10.91 ± 10.70 9.20 ± 5.61 0.047

FSH 12.06 ± 10.70 12.54 ± 11.58 11.59 ± 8.12 0.705

pH 7.40 ± 0.04 7.39 ± 0.05 7.41 ± 0.02 0.188

PaO2 70.35 ± 13.23 72.36 ± 7.57 76.81 ± 7.15 0.036

PaCO2 43.37 ± 8.99 45.27 ± 10.31 39.60 ± 5.11 0.000

COPD, chronic obstructive pulmonary disease; Testosterone (ng/ml); DHEAS, dehydroepiandrosteronesulphate (lg/ml); LH, luteinizing

hormone (mIU/ml); FSH, follicle stimulating hormone (mIU/ml); PO2, oxygen partial pressure (mmHg); PCO2, carbon dioxide partial

pressure (mmHg).



There was positive correlation between testosterone

and FEV1 (r ¼ 0.226, p ¼ 0.040); negative correla-

tion between FSH and O2 sat. (r ¼ 0.233, p ¼0.034); LH and FVC (r ¼ 0.256, p ¼ 0.020). There

was no correlation between sex hormones and smo-

king (pack-years). There was no correlation between

sex hormones and either TNF-a or IL-6.

In COPD exacerbation group, testosterone was

positively correlated to PaO2 (r ¼ 0.530, p ¼ 0.016).

DHEAS was positively related to FEV1/FVC (r ¼0.549, p ¼ 0.012).

Discussion

The anabolic hormone DHEAS is the sulphated

metabolite of DHEA, produced by adrenal glands.

DHEAS may act directly at the tissue level, or after

conversion to androstenodione or androstenodiol,

and finally to testosterone. In males, testosterone is

secreted mainly by the gonads. Testosterone synthesis

in Leydig cells is controlled by LH secreted from

hypophysis. FSH can also stimulate testosterone

secretion by inducing Leydig-cell maturation.

Several chronic wasting diseases were reported to be

associated with decreased anabolic hormone levels.

Accumulating data indicate that anabolic hormone

levels are low in COPD, although the underlying

mechanisms are unclear (3). One of the suggested

underlying factors for hypogonadism is hypoxaemia,

which is present in a proportion of COPD patients.

Gosney observed decrease in testis volume and Leydig-

cell number in male albino rats exposed to hypobaric

hypoxia (25). The same investigator found smaller tes-

tis volume and Leydig-cell atrophy in necropsy of

COPD patients, and suggested that this atrophy may

be a consequence of hypoxic inhibition of pituitary

synthesis or release of LH (26).

Semple et al. (9) found low testosterone levels in

acutely ill, hospitalised COPD patients with hypoxae-

mia and reported that the degree of testosterone

suppression was correlated to severity of arterial

hypoxaemia and hypercapnia. Again Semple et al.

detected lower testosterone levels in 16 male COPD

patients compared with controls. Circulating DHEA

was lower in hypercapnic COPD compared with

normocapnic patients (11). They performed com-

bined anterior pituitary function test to COPD

patients to investigate the effect of hypoxia on hy-

pothalamic-pituitary function. Baseline testosterone,

LH and FSH levels of COPD group were lower than

controls. After GnRH (gonadotrophin releasing hor-

mone) injection, LH response was normal whereas

FSH response was decreased. They suggested that

hypoxia produce abnormalities of hypothalamic-

pituitary-testicular function, rather than primary tes-

ticular dysfunction (13). They concluded that these

hypoxaemia-induced changes were reversible as tes-

tosterone and DHEA concentrations increased signi-

ficantly in men recovering from a severe

exacerbation of COPD, as in the present study (12).

The findings of Aasebo et al. supported these data.

They showed that long-term oxygen treatment

increased sexual function and testosterone levels

(27).

Most of the previous studies do not have an age-

matched control group. In the present study, we

compared circulating levels of gonadal hormones of

COPD patients and age-matched control subjects

and found significant differences. Testosterone and

DHEAS levels of COPD group were lower than that

of controls; besides, they were further decreased in

patients with severe hypoxaemia and hypercapnia.

Makarevich et al. (10) assessed relation of sex hor-

mone status and the stage of COPD. They concluded

that the intensity of sex hormone changes were cor-

related with the stage of COPD. As the severity of

disease increased, testosterone decreased and LH,

FSH increased compensatively. Likewise, we com-

pared moderate and severe COPD patients and

observed that testosterone and DHEAS were lower in

severe COPD patients who had FEV1 < 50%. Besides,

we detected a positive correlation between testoster-

one and FEV1.

An inverse relationship was found between circula-

ting levels of testosterone and acute-phase C-reactive

protein (28). Although insufficient data is yet avail-

able on the involvement of systemic inflammatory

response in testosterone metabolism, experimental

data in healthy males showed that TNF-a application

increases LH and decreases testosterone (20).

Together with experiments on rats showing testicular

atrophy as a result of TNF-a injection, these data

suggest that TNF-a affects hypothalamo-pituitary-

gonadal axis at multiple levels and might be involved

in hypogonadism in systemic disease (19,20). There-

fore we also investigated the association of augmen-

ted systemic inflammation and alterations in

hormonal status.

However, a significant relationship between sex

hormones and TNF-a has not been shown in clinical

studies. Van Vliet et al. (28) assessed the relation of

hormonal changes and systemic markers of inflam-

mation in COPD patients. They found that low and-

rogen status was not related to increased circulating

levels of IL-8 or soluble receptors of TNF-a. A weak

inverse relationship between circulating levels of IL-6

and bioavailable testosterone has been reported in

men with COPD (15). In the present study, although

circulating IL-6 and TNF-a concentrations were

higher in both stable and exacerbation phase COPD



groups than controls, we did not find a correlation

between sex hormones and inflammatory markers.

However, our approach is limited by intrinsic circa-

dian variability of the measured parameters and fluc-

tuation of circulating cytokines.

In the present study, we also studied the altera-

tions in hormonal status during an acute exacerba-

tion of COPD and reversibility of these changes

during follow-up. In addition to decreased testoster-

one and DHEAS, LH and FSH levels were increased

during exacerbation. In COPD exacerbation group,

testosterone was positively correlated to PaO2. In fol-

low-up measurements, testosterone and DHEAS

increased and LH decreased, in parallel with the

improvement in arterial blood gases. Lower serum

values of androgens compared to stable phase, com-

pensatory increase in LH and FSH during exacerba-

tion when hypoxaemia is more significant, and

subsequent regression of these alterations when dis-

ease is stabilised indicates that hypoxaemia affects

hypothalamo-pituitary-gonadal axis, prominently at

the testicular level.

Hypogonadism in chronic diseases is related to

BMI. Systemic inflammation and oxidative stress in

COPD leads to muscle wasting and malnutrition

(14,17,29,30). Likewise, in the present study, IL-6

and TNF-a concentrations were higher in both stable

and exacerbation phase COPD groups than controls.

Probably as a result of systemic inflammation, BMI

of COPD patients in our study were lower than that

of control group. Besides, further decreased DHEAS

in a subgroup of our stable COPD patients with

low-than-normal BMI suggests that hormonal chan-

ges are also related to malnutrition.

We did not detect correlation between hormone

levels and smoking (pack-years). The results of the

studies on the effect of smoking on hormone status

are contradictory. Lower serum testosterone was

reported previously in heavy smokers (31). However,

English et al. (32) found higher testosterone levels in

healthy smokers compared to age- and height-

matched non-smokers but the bioavailability was

similar in both groups. Their findings indicate that

smoking does not have a significant effect on biolo-

gically active testosterone.

In conclusion, there are alterations in sex hormone

levels of male COPD patients which seem to be

caused by a combination of factors. In the present

study, the hormonal alterations are particularly rela-

ted to FEV1, hypoxaemia and hypercapnia. There are

significant differences in hormone levels during sta-

ble and exacerbation phases of COPD. Further

decrease in androgens and compensatory increase in

gonadotrophins during exacerbation phase when

hypoxaemia is more significant, and subsequent

regression of these alterations when disease is stabi-

lised may be accepted as a compensatory reaction of

hypothalamo-pituitary-gonadal axis against suppres-

sion of testicular function in COPD.

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Paper received February 2007, accepted June 2007



sex hormone alterations and systemic inflammation in chronic obstructive pulmonary disease

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