The Influence of Menopause on Inflammatory Cytokine and Adipocytokines Profile in Saudi Women
Mohammed H Saiem Al-Dahr*
Department of Medical Laboratory Technology, King Abdulaziz University, Saudi Arabia
Submission: April 04, 2019; Published: May 10, 2019
*Corresponding author:Mohammed H Saiem Al-Dahr, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80324, Jeddah, 21589, Saudi Arabia
How to cite this article: Mohammed H Saiem Al-Dahr. The Influence of Menopause on Inflammatory Cytokine and Adipocytokines Profile in Saudi Women.
002 Adv Res Gastroentero Hepatol. 2019; 13(1): 555851. DOI: 10.19080/ARGH.2019.13.555851.
Background: Menopause is characterized with reduction in serum estrogen level which leads to some physiological changes in addition to high risk of some diseases as cardiovascular disorders.
Objective: This study was designed to measure menopausal-related changes in circulating level of adipocytokines and systemic inflammation cytokines profile among Saudi women. Material and
Methods: Two hundred Saudi women were selected from the out-patient of the Gynecology and Obstetrics Department, King Abdalaziz Teaching Hospital, there were non-smokers and with no hormonal replacement therapy were enrolled for the study. Relative to their hormonal status, the participants were divided in two study groups: group (A) premenopausal women included one hundred women and the mean of their age was 36.53±4.27year, while group (B) included one hundred women and the mean of their age was 54.28±5.63 year.
Results: The mean value of tumor necrosis factor – alpha (TNF-α), Interleukin-6 (IL-6), Interleukin-10 (IL-10), C-reactive protein (CRP) and leptin in were significantly higher in group(A) than group(B). However, there was a statistically significant decrease in serum levels of resistin and adiponectin in group (B) than group (A).
Conclusion: The was an alteration in serum adipocytokines and inflammatory cytokines profile among postmenopausal Saudi women.
Menopause is a commonly used term to refer to the period of climacteric that encompasses the transitional period between the reproductive years up to and beyond the last episode of menstrual bleeding and genetic factors play important role in determining the average age of menopause, whoever, recently women has greater than the third of life after menopause .
Menopause is associated with many physiological changes and risk of many disorders in body systems due to reduced serum level of estrogen . Cytokines play an important role in regulation of many immune system responses , however serum level of some cytokines found to be changed after menopause like increased level of interleukin (IL-6) and interleukin-8 (IL-8) and reduction of tumor necrosis factor-alpha (TNF-α) as well as higher level of macrophage colony-stimulating factor . However, another study reported decrease in serum level of interferon-alpha (IFN- α) and interleukin-4 (IL-4) . Alteration in cytokines found to be associated with high risk of cardiovascular disorders [5-7].
Adipokines, as leptin, adiponectin, visfatin, and resistin, are produced by different fat depots, including subcutaneous, visceral, and mammary adipose tissues [8,9]. The most prominent adipokine, leptin, was first described as a neurohormone whose primary function is to regulate energy balance and food intake in the hypothalamus. Subsequent studies found that leptin can modulate several processes in the peripheral organs, such as immune response, fertility, and hematopoiesis. On a cellular level, leptin has been found to act as a mitogen, metabolic regulator, motogenic, and proangiogenic factor . New evidence suggests that leptin could be involved in tumorigenesis, especially in the
development of breast, colorectal, and prostate cancers .
Adiponectin is another adipocyte-derived peptide hormone
that is inversely associated with adiposity . Adiponectin is a
strong indicator of insulin sensitivity wherein its decline precedes
the onset of obesity and insulin resistance  and may be one
mechanism through which obesity alters breast cancer risk.
Mantzoros et al.  found an inverse association between serum
adiponectin levels and breast cancer risk among postmenopausal
The aim of this study was to examine the examined the influence
of menopausal status on adipocytokines, and inflammatory
cytokines profile in Saudi women.
One hundred Saudi premenopausal women (mean age
36.53±4.27 years, mean body mass index (BMI= 22.83±2.66 kg/
m2) and 100 postmenopausal (mean age 54.28±5.63 years, mean
BMI=23.71±2.25 kg/m2) at the King Abdulaziz Teaching Hospital,
Medical Faculty’s Gynecology and Obstetrics Department were
admitted to the study. Based on menstrual history, we considered
women to be postmenopausal, if they had at least 12 consecutive
months of amenorrhea with no other medical cause. While women
were considered premenopausal, if they had regular periods in
the years preceding their examination. We restricted analyses to
non-pregnant premenopausal women who did not take oral contraceptives.
Exclusion criteria were history of breast or genital tract
malignancy, or hepatic, renal, vascular, or endocrine disease and
acute infection; as well as those reporting tobacco and alcohol use.
All volunteers were asked to read and sign an informed consent
document prior to participation, in addition this study was
approved by the Scientific Ethical Committee, Faculty of Applied
Medical Sciences, King Abdulalziz University
For the biochemical estimations, venous blood samples were
collected between 7:00 A.M. and 9:00 A.M. after fasting overnight
and the samples were allowed to clot. Thereafter, the samples
were centrifuged and divided into aliquots and stored at −70°C
a) Serum adiponectin, leptin, resistin, visfatin measurement:
The levels of adiponectin in human serum were determined
using adiponectin ELISA (Phoenix Pharmaceuticals, Inc.,
Belmont, CA). Serum leptin, resistin, and visfatin levels were
detected using ELISA (Phoenix Pharmaceuticals).
b) Measurement of inflammatory cytokines: Interleukin-6
(IL-6) and interleukin-10 (IL-10) levels were analyzed by
“Immulite 2000” immunassay analyzer (Siemens Healthcare
Diagnostics, Deerfield, USA). However, tumor necrosis
factor-alpha (TNF-α) and C-reactive protein (CRP) levels
were measured by ELISA kits (ELX 50) in addition to ELISA
microplate reader (ELX 808; BioTek Instruments, USA).
The mean values of the investigated parameters obtained
before and after three months in both groups were compared using
paired “t” test. Independent “t” test was used for the comparison
between the two groups (P<0.05).
Table 1 shows the baseline characteristics of the participants
who entered the trial. There was no significant differences in
baseline characteristics related to age, height, body weight, body
mass index and waist hip ratio between the two groups were
found, in addition to significant differences in systolic blood
pressure, diastolic blood pressure, triglyceride, total cholesterol,
low density lipoprotein cholesterol, high density lipoprotein
cholesterol and glucose between both groups.
SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; LDL: Low Density Lipoprotein; HDL: High Density Lipoprotein; (*) indicates a
significant difference between the two groups, P < 0.05.
The serum levels of TNF-α, IL-6, IL-10, CRP and leptin in
women with natural postmenopausal women were significantly
higher than in premenopausal women. However, there was a
statistically significant decrease in serum levels of resistin and
adiponectin in postmenopausal women than premenopausal
women (Table 2).
TNF-α: Tumor Necrosis Factor – alpha; IL-6: Interleukin-6; IL-10: Interleukin-10; CRP: C-Reactive Protein; (*) Indicates a significant difference
between the two groups, P < 0.05.
Menopause is a turning point in every woman’s life, the
final episode of menstrual bleeding associated with cessation
of the activity of ovarian follicle, resulting in the permanent
cessation of menstruation. The onset of menopause is generally
associated with a hormone deficiency, which is a contributory
factor for the increased incidence of osteoporosis, cardiovascular
diseases, vasomotor disturbances and cognitive deterioration. we
examined the influence of menopausal status on adipocytokines,
and inflammatory cytokines profile secretion. Concerning
the inflammatory cytokines profile, the results of the present
study demonstrate that women in post-menopause present, as
compared with their premenopausal counterparts, an alteration
in serum cytokine profile characterized by higher concentrations
of circulating IL-6, TNF-α, IL-10 and CRP were determined to be
elevated in healthy, non-obese postmenopausal women. These
data observed in our study is consistent with the findings from
previous studies on healthy populations [15,16].
Many studies also reported an increase in pro-inflammatory
serum markers, particularly IL-6 after menopause and suggested
that in addition to age, in postmenopausal women, changes of
the immune system have been attributed to estrogen deprivation
[3,17-19]. It has also been reported that IL-6 concentrations are
usually elevated in postmenopausal women even in absence
of infection or trauma since the regulation of IL-6 synthesis is
impaired with age [20-22]. The increase in concentrations of
proinflammatory cytokines such as IL-6 after menopause may
be associated with the functions of monocytes and macrophages
due to estrogen deficiency. In addition, the change in serum IL-6
concentration has been reported to be correlated with alterations
in serum dehydroepiandrosterone (DHEA) and DHEA-sulfate
levels, the changes in these hormones as well as estrogen may
affect the secretion of cytokines from monocytes and macrophages
. Malutan & colleagues  stated that serum level of IL-1β,
IL-8 and TNF-α in women with natural menopause and in women with surgically induced menopause is significantly higher than in
premenopausal women in the control group.
Vural et al.  stated that postmenopausal women have
increased plasma TNF-α, IL-4, IL-10 and IL-12 concentrations
in comparison with premenopausal individuals. The increase of
anti-inflammatory IL-10, IL-12 and especially IL-4 is probably a
compensatory mechanism, by which these cytokines counteract to
pro-inflammatory TNF-α, and thus balance its osteoclast activating
and oxidative stress inducing effects. Vassalle et al.  stated
that menopausal status is associated with increased systolic and
diastolic pressure (p<0.05), higher IL-6 (p<0.05) and TNF alpha
(p<0.01), and lower antioxidants (p<0.01). In the other hand, Sites
and colleagues proved that the level of TNF-alpha was higher in
postmenopausal compared to premenopausal women (4.81 +/-
1.99 vs. 3.54 +/- 0.85 pg/mL). Interleukin-6 and CRP did not differ
by menopausal status . The difference in these results may be
due to the difference in methods of measurement.
Our results revealed that serum levels of adipocytokines
(included adiponectin, leptin and resistin) were different
according to the menopausal status, serum levels of adiponectin
and leptin were significantly increased, while serum level of
resistin was significantly decreased among postmenopausal
women. Our findings were consistent with Tamakoshi et al. 
proved that adiponectin levels in postmenopausal women were
also significantly higher than those in premenopausal women
[10.3 (9.95, 10.7) vs 9.04 (8.71, 9.39), P = 0.028]. Similarly, Sowers
and colleagues proved that the resistin levels were approximately
two times higher during premenopause compared to peri- or
postmenopause and there were significantly lower adiponectin
and higher ghrelin levels in the perimenopause stage, compared
to either the pre- or postmenopause stage . In the other hand,
Ben et al.  stated that Premenopausal women had significantly
higher leptin and L/A ratio and lower adiponectin levels than
postmenopausal women. In addition, Krentz & colleagues
 found that serum leptin was higher (mean 25.70±15.67 vs 14.94+9.89 ng/mL, P<0.01) and adiponectin lower (mean
11.72±4.80 vs 17.31±7.45μg/mL, P<0.01) in postmenopausal
women with polycystic ovary syndrome versus premenopausal
women with polycystic ovary syndrome. Sherk et al.  concluded
that increases in fat mass, not menopause per se, contributes to
higher leptin levels in older women and age differences in leptin
concentrations were no longer significant after controlling for fat
mass. Lecke & colleagues  suggested that obese individuals
exhibit both leptin resistance and decreased serum adiponectin
levels, where progressive increase in adiposity throughout life
rather than menopausal status seems to influence the relationship
between leptin and adiponectin in women. Douchi & coworkers
 found that serum leptin levels in premenopausal women
8.4+/-4.8 ng/ml, which did not differ from that in postmenopausal
women (9.2+/-7.1 ng/ml) that means that menopausal status
does not have a significant impact on leptin production. The
contradictory results could be due to different selection of patients.
The current study provides evidence that post menopause
present an alteration in serum adipocytokines and inflammatory
cytokines profile. Such changes should be taken into account when
tailoring menopausal therapies to their specific requirements.
This project was funded by the Deanship of Scientific Research
(DSR) at King Abdulaziz University, Jeddah, under grant no. (G-2-
142-39). The authors, therefore, acknowledge with thanks DSR for
technical and financial support.