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Women’s Health Bulletin. 2014 Apr; 1(1): e18962. DOI: 10.17795/whb-18962
Published online 2014 April 1. Research Article
The Effect of Ramadan Fasting on Hypothalamic Pituitary Ovarian (HPO)
Axis in Women with Polycystic Ovary Syndrome
Farideh Zangeneh 1,*; Nasrin Abedinia 2; Mohammad Mehdi Naghizadeh 3; Reza Salman
Yazdi 4; Tahereh Madani 5
1Vali-e-Asr Reproductive Health Research Center, Imam Complex Hospital, Research Institute for Islamic and Complementar y Medicine (RICM), Iran University of Medical Sciences,
Tehran, IR Iran
2Maternal, Fetal-Neonatal Research Center, Tehran University of Medical Sciences, Tehran, IR Iran
3Department of Community Medicine, Medical Faculty, Fasa University of Medical Sciences, Fasa, IR Iran
4Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, IR Iran
5Department of Gynecology and Female Infertility, Royan Institute, Tehran, IR Iran
*Corresponding author: Farideh Zangeneh, Vali-e-Asr Reproductive Health Research Center, Imam Complex Hospital, Research Institute for Islamic and Complementary Medicine
(RICM), Tehran University of Medical Sciences, Tehran, IR Iran. Tel.: +98-2166581616, Fax: +98-2166581658, E-mail: zangeneh14@gmail.com
Received: October 10, 2013; Revised: November 23, 2013; Accepted: January 5, 2014
Background: Ramadan fasting is a religious practice and an exceptional ritual compared to all other religious conventions. The aim of
fasting in Ramadan is to establish a proper religious model of self-control and healthy lifestyle.
Objectives: The purpose of this study was to compare the biochemical neurohormones between women with polycystic ovary syndrome
(PCOS) with and without fasting.
Materials and Methods: This study was conducted during July 2011 at the Infertility Center of Royan Institute, and comprised 40 patients
diagnosed with PCOS, aged from 20-40 years without any special disease. The study group included 20 women with PCOS and fasting
during Ramadan. The control group consisted of 20 non-fasting women with PCOS. The study on the effects of fasting on patients with
polycystic ovary syndrome involved demographic data and biochemical stress hormones including cortisol, adrenaline, noradrenaline,
beta-endorphin and insulin.
Results: In patients with PCOS, mean of cortisol in subjects with and without fasting were 8.2 ± 4.4 and 11.2 ± 4.7, respectively (P = 0.049).
Also the respective median of nor-adrenaline in fasting and non-fasting patients were 1273.5 and 1503.5 (P = 0.047). However, no significant
differences were found in adrenalin (P = 0.151), beta-endorphin (P = 0.543) and insulin (P = 0.818) between PCOS two groups.
Conclusions: This study showed that Ramadan fasting is a well known practice to reduce stress hormones in women with PCOS. So,
Ramadan, beside its spiritual benefit is a blessing from God for improving human lifestyle.
Keywords:Ramadan fasting; Polycystic ovary syndrome; Stress hormones; Beta-endorphine; Insulin; Sex hormones
Implication for health policy/practice/research/medical education:
This study showed that Ramadan fasting can be a good pattern for reducing stress hormones in PCOS women and so sympathetic nervous system may
offer a new therapeutic target for this syndrome.
Copyright © 2014, Health Policy Research Center, Shiraz University of Medical Sciences. This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Background
Islamic fasting is special and novel gift from God Al-
mighty that corrects lifestyle, elevates physical health
and boosts spiritual quality of humans. One month fast-
ing in holy Ramadan is a unique annual practice that is
beneficial to human health, because studies have shown
that brain’s biologic clock needs yearly repair (1). Ac-
cording to the holy Quran and prophet’s tradition, brain
clock must be overhauled in this month, because gates of
mercy are open to the faithful and performing this divine
duty can coordinate physiologic and psychological orga-
nization. Thus fasting adjusts our brain’s biologic clock,
and the resulting energy switches on human's physical
and spiritual lights for eleven months.
1.1. The History of Fasting
The research of anthropologists shows that the primi-
tive tribes used to fast before hunting, harvesting, con-
ducting magical ceremonies or carrying out sacrifices to
appease and calm their angry Gods. They usually went on
fasting during the spring season for the purpose of hav-
ing better harvest and fertile soil. The American Indians
used to fast to repel the crop’s pest and believed that fast-
ing would act as a pesticide. The Mexican Indian along
with Peru Incas used fasting as a means of establishing
a communion and cordial relationship with their Gods.
In ancient Egypt; the Egyptians used to fast before their
religious festivals, but it was not compulsory. The Assyr-
ian and Babylonian used to fast for confession of sin and
Zangeneh F et al.
Women’s Health Bulletin. 2014;1(1):e18962
2
God’s forgiveness. Among the supporters of oriental reli-
gions, Hindus, the followers of Confucius and specifically
the Buddhist and people of Tibet observed fasting. In vari-
ous religions the quality, duration and adopted rules or
regulation for fasting was different (2). Based on follower
of the Abrahamic faith; fasting was a compelling need for
all God’s religions, as it was clearly emphasized Baqara
verse 183 of holy Quran. The Christian famous feast is the
day of Easter; Christians do fast in order to cleanse their
spirit and practice strict self-denial. In Judaism; fasting is
the real way to get closer to God, Fasting for Jews means
complete abstaining from food and drink. Traditionally
observant Jews fast six days of the year. Yom Kippur is
considered to be the most important day of the Jewish
year and fasting as a means of repentance is expected of
every Jewish man or woman above the age of bar mitz-
vah and bat mitzvah respectively. It is so important to fast
on this day, that only those such as the ill or frail who are
at risk for mortal danger by fasting are exempt, because
endangering a life is against a core principle of Judaism
(3). Fasting in the history of anthropology indicates the
truth; that even in the past, primitive tribes also sought
the consent of their gods and asked for their help in
times of needs. Ramadan is the holy month for Islamic
World, where, food and fluid consumption is restricted to
the pre-sunrise and post-sunset hours. It is obligatory for
all healthy adult Muslims to abstain from eating, drink-
ing, and smoking each day from dawn to sunset during
this month (4).
1.2. The Historical Aspects of Fasting and its Effect
on PCOS
The sixth year of Hegira marks the first time in Islam
that fasting was recognized and practiced. After the peace
of Hodaybieh, Prophet Mohammad migrated to Medina
city, where he practiced fasting in the holy month of Ra-
madan. In Islam fasting possesses a very special place. In
this context, Quran states: “The faithful does understand
that fasting is a necessity for you all, as it had been before
you” (Baqara/183 verse). According to this verse, it is very
clear that fasting had existed in all religions. God for the
purpose of clarity as stated in Quran, with an example
which reflects on the birth of Christ, and addressed Ma-
donna by saying "if you see others tell them to fast for me.
This holy verse indicates the special Grace of God for fast-
ing to the faithful. In the history of religions before and
after the Islam, fasting in the Islamic nations has been a
necessity. Prophet Mohammad (PBUH) stipulated that ev-
erything humans do is only for their own, except fasting
which is considered for me and rewarded without any
mediators (5). This order of prophet stresses the great
importance of holy month of Ramadan which is God’s
banquet and as Prophet Mohammad had mentioned it is
the God’s holy reception for all Muslims. There are many
reports about the benefits of Ramadan fasting on physi-
cal health, but to our knowledge there is no report on the
effect of Ramadan fasting on polycystic ovarian disease.
Polycystic ovary syndrome (PCOS) is a complex, multi-
faceted, heterogeneous disorder, affecting 4% to 18% of
women in reproductive age and is associated with re-
productive, metabolic and psychological dysfunction
(6). Its prevalence among infertile women is 15% -20% (7).
Although menstrual irregularities in adolescent girls
are often attributed to an immature Hypothalamus-
Pituitary-Gonadal (HPG) axis (8), many adolescents with
persistent menstrual abnormalities may feel apprehen-
sive about PCOS. Women with ovulatory menstrual cycles
have a circadian rhythm superimposed on the menstru-
al-associated rhythm; in turn, menstrual events affect the
circadian rhythm. The investigations into the biological
consequences of circadian disruption in women will of-
fer insight into some menstrual-associated disorders,
including mood changes, as well as reproductive func-
tion and possible links with breast cancer (9). Many of
the common features of PCOS, such as central obesity,
hyperinsulinaemia and obstructive sleep apnoea, are as-
sociated with chronic sympathetic overactivity. This is
suggestive of possible involvement of sympathoexcita-
tion in the pathogenesis of this condition (10). The clini-
cal features include reproductive manifestations such as
reduced frequency of ovulation and irregular menstrual
cycles, reduced fertility, polycystic ovaries on ultrasound,
and high male hormones such as testosterone which
can cause excess facial or body hair growth and acne.
Previous studies have shown that PCOS may cause some
psychological disorders. The relationships between the
psychological health aspects and the clinical characteris-
tics of PCOS are not yet clear. PCOS affects quality of life
and can worsen anxiety and depression either due to
the features of PCOS or due to the diagnosis of a chronic
disease (11). The results confirm Adali΄s and Hirschberg΄s
findings (12), suggesting that treatment of PCOS should
tackle both physical and psychological complaints. This
is because psychological distress reduces amenable mo-
tivation, which is the key to complying with treatment
and dietary management of PCOS (13). Studies in recent
decades show that lifestyle intervention improves body
composition and Ramadan fasting can be a good pattern
for Muslims to improve their morals and habits which
they believe to be beneficial. The purpose of the pres-
ent study was to investigate the possible effect of these
changes on the circadian rhythm of cortisol, cathecola-
mines and sex hormones in PCOS women.
2. Objectives
The purpose of this study was to compare the biochemi-
cal neurohormones between polycystic ovary syndrome
(PCOS) women with and without fasting.
Zangeneh F et al.
3
Women’s Health Bulletin. 2014;1(1):e18962
3. Materials and Methods
This study was performed in Infertility Center of Royan
Institute in July 2011, coinciding with month of Ramadan.
The study comprised 40 patients diagnosed with PCOS ac-
cording to the criteria of the European Society of Human
Reproduction and Embryology and the American Society
of Reproductive Medicine (ESHRE/ASRM) (14).
The study group included 20 women with PCOS who
were fasting during Ramadan, and the control group
consisted of 20 PCOS women without fasting. The effect
of Ramadan fasting was evaluated with respect to stress
neurohormones, serum cortisol, Adrenaline (A), Nor-
adrenalin (NA) and Beta-endorphin (B-end), Insulin as
well as sex hormones such as FSH, LH, Testosterone. The
participants aged 20-40 years and except having PCOS
they lacked no apparent illness. BMI was calculated as
weight (kg)/height 2 (m) and was below 28. This study
was approved by ethics committee of Tehran University
of Medical Sciences. Blood sample was obtained from all
participants before 8 AM. All specimens were kept at -80
C° until used. The samples were measured by relevant
ELISA kits. Clinical data including information about hir-
sutism, acne, menstrual cycle as well as situation of fast-
ing such as nutrition and sleep was gathered by physical
examination and interview. The Elisa kits were used to
measure the serum levels of Adrenaline, Nor-adrenaline
(Oxidized LDL Elisa), Beta-endorphin and estradiol (β-EP
ELISA Kit from China), Cortisol and Insulin (ELISA kit, Di-
ametra from Italy), FSH, LH and testosterone (ELISA kit,
Monobind from USA) at the Laboratory of Pathology of
Royan. Clinical and anthropometric variables, including
body mass index (BMI) calculated as weight kg/height
(m) 2, and demographic social questionnaires were used
for data collection. This questionnaire comprised age,
education, occupation, and duration of illness.
1.3. Statistical Analysis
Data are presented as Mean ± Standard Deviation and
Median. Comparison of symptoms between study groups
was done using Chi square test. Kolmogorov-Smirnov
test was used to check normality of distribution. FSH, LH,
Testosterone, Insulin and Cortisol had normal distribu-
tion and were compared between two groups by t test.
Mann-Whitney test was used for comparing the other
hormones that did not follow normal distribution. Spear-
man rank correlation coefficient was used to assess rela-
tionship between the hormones. Statistical analysis was
done using SPSS 18 (SPSS Inc, Chicago, Ill), and p value less
than 0.05 were considered significant.
4. Results
This study included 40 women with PCOS of which 20
were in fasting (case) and 20 in non-fasting groups (con-
trol). Mean age of fasting group was 29.4 ± 4.60 and in
non-fasting group it was 28.8 ± 3.67 years (P = 0.658). The
mean weight in fasting group was 63.9 ± 5.78 Kg and in
non-fasting was 66.3 ± 6.42kg (P = 0.221). Acne was found
in 6 (30%) women in fasting and 5 (25%) in non-fasting
women. Acne (P = 0.723), hirsutism (P = 0.451), and irreg-
ular menstrual period (P = 0.231) were the same in both
groups. Demographic and symptoms in participants are
presented in Table 1.
The results of biochemical tests measuring FSH (P =
0.542), LH (P = 0.827) and testosterone (P = 0.683) were
not significantly different between the two groups (Table
2). The mean cortisol hormone significantly decreased in
fasting group (8.2 ± 6.7, P = 0.049) as compared to 11.2 ± 9.3
in non-fasting women.
Nor-adrenaline decreased in fasting group (1176 ± 439,
P = 0.047), compared to 1430 ± 404 in non-fasting sub-
jects. There was no significant changes in adrenalin
level between fasting and non-fasting groups (P = 0.151.
There were no significant differences in beta-endorphin
(P = 0.543) and insulin (P = 0.818) levels between the two
groups (Table 3). Spearman rank correlation coefficient
showed an inverse correlation between insulin and nor-
adrenalin (r = -0.328, P = 0.039). However, no significant
inverse correlation was observed between beta endor-
phin, adrenalin (P = 0.256). Also there was no significant
direct correlation (P = 0.224) between adrenalin (P =
0.464), and noradrenalin (Table 4).
Table 1. Demographic Information and Symptoms of Women with PCOS
Variables, Mean ± SD Not Fasting, (N = 20) Fasting, (N = 20) P Value
Age, year 28.80 ± 3.86 29.40 ± 4.60 0.65
Age at marriage time, year 21.00 ± 3.09 21.15 ± 3.91 0.89
Infertility duration, year 7.55 ± 4.05 6.60 ± 3.73 0.44
Weight, kg 66.30 ± 6.42 63.90 ± 5.78 0.22
Variables, No. (%) Count (%) Count (%)
Acne 5 (25) 6 (30) 0.72
Hirsutism 17 (85) 14 (70) 0.45
Irregular menstrual cycle 20 (100) 17 (85) 0.23
Zangeneh F et al.
Women’s Health Bulletin. 2014;1(1):e18962
4
Table 2. Biochemical Tests of PCOS Women in Ramadan Fasting
Control, (N = 20) Ramadan Fasting, (N = 20) P Value
Mean ± SD Median Mean ± SD Median
FSH (mIU/ml) 5.60 ± 1.96 5.55 5.24 ± 1.72 5.40 0.54
LH (mIU/ml) 8.08 ± 6.77 5.45 8.51 ± 5.46 7.10 0.83
Testosterone (ng/ml) 1.73 ± 1.18 1.45 1.94 ± 1.97 1.20 0.68
Cortisol (µg/dL) 11.2 ± 4.7 9.3 8.2 ± 4.4 6.7 0.04
Table 3. Hormonal Tests of PCOS Women in Ramadan Fasting
Hormones Control, (N = 20) Ramadan Fasting, (N = 20) P Value
Mean ± SD Median Mean ± SD Median
Adrenaline, (pg/ml) 135.49 ± 97.90 110.00 98.83 ± 82.96 84.00 0.15
Nor-adrenaline, (pg/ml) 1430.30 ± 404.46 1503.50 1176.15 ± 439.16 1273.50 0.04
Beta endorphin, (ng/Lit) 233.2 ± 494.6 47.7 360.2 ± 759.2 55.6 0.54
Insulin, (mIU/Lit) 19.2 ± 18.2 11.5 19.7 ± 20.8 11.5 0.82
Table 4. Spearman's Correlation Coefficient between Hormones in PCOS Women in Ramadan Fasting
Cortisol Adrenaline Nor-adrenaline Beta endorphin Insulin
Cortisol
Correlation 0.043 0.170 -0.030 -0.140
P Value 0.793 0.294 0.856 0.390
Adrenaline
Correlation 0.043 0.197 -0.184 -0.057
P Value 0.793 0.224 0.256 0.726
Nor-adrenaline
Correlation 0.170 0.197 -0.119 -0.328
P Value 0.294 0.224 0.464 0.039
Beta-endorphin
Correlation -0.030 -0.184 -0.119 0.142
P Value 0.856 0.256 0.464 0.384
Insulin
Correlation -0.140 -0.057 -0.328 0.142
P Value 0.390 0.726 0.039 0.384
5. Discussion
Polycystic ovary syndrome (PCOS) is a common endo-
crine condition associated with long-term health risks,
including type 2 diabetes and vascular dysfunction in
addition to reproductive sequelae. Many of the common
features of PCOS, such as central obesity, hyperinsulinae-
mia and obstructive sleep apnea (OSA), are associated
with chronic sympathetic overactivity, suggesting that
sympathoexcitation may be involved in the pathogen-
esis of this condition. The aim of this study was to inves-
tigate the effect of Ramadan fasting on the sympathetic
nervous system activity expressed as stress hormones in
women with PCOS. The recent studies on patients with
PCOS showed evidence of increased muscle sympathetic
nerve activity (MSNA). This affected heart rate variability
and delayed post exercise heart rate recovery, compared
with age and BMI-matched controls, suggesting a gen-
eralized increase in sympathetic nerve activity (10). The
increased secretion of noradrenalin hormone, a stress-
related chemical, occurs in response to excessive levels
of insulin, and under conditions of emotional upset and
glucocorticoids such as cortisol is also a stress-associated
chemical in women. The female reproductive system is
regulated by the hypothalamic-pituitary-adrenal (HPA)
and the hypothalamic-pituitary-ovarian (HPO) axes. The
Zangeneh F et al.
5
Women’s Health Bulletin. 2014;1(1):e18962
principal regulators of HPO axis are HPA and gonadotro-
pin-releasing hormone (GnRH) that stimulates FSH and
LH secretion with subsequent release of estradiol
andprogesterone by the ovary (15). Hypothalamic tar-
get neurons of estrogen include neurosecretory neurons
(GnRH), dopamine neurons, and local circuitry neurons
like proopiomelanocortin (POMC) and γ-aminobutyric
acid (GABA) neurons. These and other hypothalamic neu-
rons are involved in regulating numerous homeostatic
functions comprising reproduction, thermoregulation,
stress responses, and feeding and motivated behaviors
(16). The HPA axis, when activated by stress, exerts an in-
hibitory effect on the female reproductive system, cortico-
tropine releasing hormone (CRH) and CRH-induced proo-
piomelanocortin peptides, such as β-endorphin, inhibit
hypothalamic GnRH secretion (17). In addition, glucocorti-
coids suppress gonadal axis function at the hypothalamic,
pituitary and uterine level (18). Glucocorticoid administra-
tion significantly reduces the peak luteinizing hormone
response to intravenous GnRH, suggesting an inhibitory
effect of glucocorticoids on the pituitary gonadotroph
(19). The locus coeruleus (LC) provides the sole source of
noradrenaline (NA) and increasing tonic discharge of LC
neurons elevates extracellular levels of NA in the cortex
and thalamus. The LC-NA system has been shown to be ac-
tivated by a myriad of stressors and opioids are important
mediators of the LC-NA system during stress (20). The LC
is densely innervated by processes exhibiting endogenous
opioid peptides (Figure 1) (21). Endogenous opioids have
modulating role on cathecolamine secretion, and stud-
ies of these effect show that, opioids inhibit the release of
cathecolamine during stress (21, 22). These studies show
that there is interaction between sympathetic and opioid
systems in HPO, in modeling of PCOS in rat, as reported by
Zangeneh et al., in 2011 (23).
Figure 1. Heuristic representation of the interplay among the hypothalam-
ic-pituitary-adrenal axis, the locus ceruleus/norepinephrine (LC/NE) sym-
pathetic system and the hypothalamic-pituitary-gonadal axis. The dotted
lines represent inhibition while the solid lines represent stimulation (24).
Peripherally, the analyzed relationship between sym-
pathetic and opioid system in pathogenesis of stress
demonstrates a protective role by the peripheral mu-
opioid receptors associated with decrease in activity
of sympathico-adrenal system. This phenomena in the
heart leads to an increase in stress-related heart damage
via increasing sympathical influence on the myocardium
(25) and now the question is, how does this pathogenetic
process affects reproductive system?
In this study, our data showed that Ramadan fasting
reduces the level of serum cortisol and noradrenaline
(stress hormones) in study group (PCOS). But adrena-
line decreasing and beta-endorphin increasing were not
significant. Endogenous opioids have a tonic inhibitory
effect on sympathetic tone, (26) and the subsequent in-
crease in beta-endorphin reduces the amount of catheco-
lamines in women with PCOS. According to our study, re-
duced noradrenaline in both subjects indicated reduced
stress in patients in Ramadan and unchanged levels of
sex hormones. Marshal’s study in 2001 showed catechol-
amines stimulate GnRH release, whereas endogenous
opioid peptides and prolactin inhibit GnRH secretion
(27). Thus, the unaltered levels of sex hormones observed
in our study could be due to reduced noradrenaline and
increased beta-endorphin. Lack of change in serum insu-
lin levels could also represent reduction in noradrena-
line. The general action of sympathetic nervous system
is to mobilize the body's nervous system fight-or-flight
response, a command issued by the hypothalamus. This
system in brain serves globally as an alarm system that
decreases neurovegetative functions, such as eating and
sleeping, and contributes to accompanying increases
in autonomic and neuroendocrine responses to stress,
including HPA axis activation (28). Reciprocal connec-
tions exist between the CRH and LC/NE system neurons
of the central stress system, with mutual stimulation
of CRH and norepinephrine, the latter being primarily
through noradrenergic receptors (28, 29). These results
indicate that chronic sympathetic overactivity in PCOS
can be reduced by fasting. Fasting can reduce stress neu-
rohormone levels and to insure the physical and men-
tal health. On the other hand, the sympathetic nervous
system may thus offer a new therapeutic target in PCOS.
However, more extensive and longer-term studies are
needed before these treatments can be applied to clini-
cal practice. Finally, it should be noted that the time limit
during Ramadan is the main reason for low sample size
in this study therefore; more samples are needed for a sig-
nificant response. This study showed that Ramadan fast-
ing can be a good pattern for reducing stress hormones
in PCOS women and so sympathetic nervous system may
offer a new therapeutic target for this syndrome.
Acknowledgements
This study was conducted in the Infertility Center of
Zangeneh F et al.
Women’s Health Bulletin. 2014;1(1):e18962
6
Royan Institute. We thank Royan’s Research Council and
Mrs. Rastegar helped us in carrying out this study.
Financial Disclosure
The authors would like to thank the Iran University of
Medical Science for funding this study.
Funding/Support
This work was supported by the Research Institute for
Islamic and Complementary Medicine (RICM), Iran Uni-
versity of Medical Sciences, Tehran, Iran.
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