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Association between menstrual disturbances and habitual use of caffeine

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Objectives The main objective of this study was to determine whether there is an association between drinking caffeinated beverages and menstruation among Saudi female students. Methods During the 2011 academic year, a cross-sectional study was conducted by administering a questionnaire about menstruation and self-reported habitual use of caffeinated food or drinks to 350 premenopausal women with no known medical disease who were working or studying at the University. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by chi-squared cross-tabulation. All tests were two tailed, and results were considered significant when p < 0.05. Results Irregular periods were reported by 140 women (40%), amenorrhoea by 26%, oligomenorrhoea by 20.9%, heavy periods by 13.4% and prolonged periods by 9.7%. Few women (7.7%) reported a previous diagnosis of polycystic ovary disease. Coffee was a risk factor for both prolonged periods (OR, 2.37; 95% CI, 1.09–5.12; p = 0.03) and oligomenorrhoea (1.95; 1.15–3.30; p = 0.014). Nescafe was a risk factor for heavy periods (2.22; 1.91–4.12; p = 0.011) and menstrual symptoms (1.84; 1.06–3.02; p = 0.039). Chocolate was protective against premenstrual symptoms (0.22; 0.06–0.85; p = 0.049). Conclusions There is a high prevalence of undiagnosed menstrual disturbances among Saudi university women. Habitual use of caffeine should be considered a risk factor for most menstrual abnormalities.
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Student Article
Association between menstrual disturbances and habitual use
of caffeine
Asmaa Zki Bin Mahmoud
*
, Alaa Naeem Makhdoom, Lujain Alaaldeen Mufti,
Rasha Salem Alreheli, Rawan Ghazi Farghal and Sarah Ehab Aljaouni
College of Medicine, Taibah University, Almadinah Almunawwarah, Kingdom of Saudi Arabia
Received 5 February 2014; revised 15 March 2014; accepted 20 March 2014
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Abstract
Objectives: The main objective of this study was to
determine whether there is an association between
drinking caffeinated beverages and menstruation among
Saudi female students.
Methods: During the 2011 academic year, a cross-
sectional study was conducted by administering a ques-
tionnaire about menstruation and self-reported habitual
use of caffeinated food or drinks to 350 premenopausal
women with no known medical disease who were working
or studying at the University. Odds ratios (ORs) and
95% confidence intervals (CIs) were calculated by chi-
squared cross-tabulation. All tests were two tailed, and
results were considered significant when p<0.05.
Results: Irregular periods were reported by 140 women
(40%), amenorrhoea by 26%, oligomenorrhoea by
20.9%, heavy periods by 13.4% and prolonged periods
by 9.7%. Few women (7.7%) reported a previous diag-
nosis of polycystic ovary disease. Coffee was a risk factor
for both prolonged periods (OR, 2.37; 95% CI, 1.09
e5.12; p¼0.03) and oligomenorrhoea (1.95; 1.15e3.30;
p¼0.014). Nescafe was a risk factor for heavy periods
(2.22; 1.91e4.12; p¼0.011) and menstrual symptoms
(1.84; 1.06e3.02; p¼0.039). Chocolate was protective
against premenstrual symptoms (0.22; 0.06e0.85;
p¼0.049).
*Corresponding address: Medical Students at the College of
Medicine, Taibah University, Almadinah Almunawwarah,
Kingdom of Saudi Arabia.
E-mail: asmaazki90@hotmail.com,fullah_zak@hotmail.com
(A.Z. Bin Mahmoud)
Peer review under responsibility of Taibah University.
Production and hosting by Elsevier
Taibah University
Journal of Taibah University Medical Sciences
www.sciencedirect.com
1658-3612 Ó2014 Taibah University. Production and hosting by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jtumed.2014.03.012
Journal of Taibah University Medical Sciences (2014) -(-), 1e4
Please cite this article in press as: Bin Mahmoud AZ, et al., Association between menstrual disturbances and habitual use of caffeine, Journal of Taibah
University Medical Sciences (2014), http://dx.doi.org/10.1016/j.jtumed.2014.03.012
Conclusions: There is a high prevalence of undiagnosed
menstrual disturbances among Saudi university women.
Habitual use of caffeine should be considered a risk
factor for most menstrual abnormalities.
Ó2014 Taibah University. Production and hosting by
Elsevier Ltd. All rights reserved.
Introduction
Caffeine is one of the most commonly ingested pharma-
cologically active substances. It is present in coffee, tea, soft
drinks, cocoa, solid milk chocolate and many medications.
Caffeine is rapidly absorbed from the digestive tract and
distributed throughout the tissues. The mechanisms of action
of caffeine include inhibition of hydrolysis of cyclic 3ʹ,5ʹ-
adenosine monophosphate and 3ʹ,5ʹ-guanosine mono-
phosphate
1
and antagonism of adenosine.
2
Therefore,
caffeine may alter hormone profiles and thus affect
menstrual function. Menstrual dysfunction, in turn, may be
related to other health outcomes, such as fertility,
osteoporosis and breast cancer.
3
The results of studies of coffee and caffeinated beverage
consumption in relation to fertility are inconsistent. Several
studies have reported deleterious effects,
4e6
while others have
shown either no association,
7
a relation only at very high
levels of intake
8
or even improved fertility.
9
One study
10
concluded that soft drinks may be a risk factor for
infertility, irrespective of their caffeine content. A possible
explanation for this inconsistency is that most of the studies
were retrospective and thus subject to recall and other types
of bias. Although clear pathophysiological mechanisms for
the presumed effects of caffeine on fertility have not been
elucidated, it has been suggested to affect ovulation. In
contrast, caffeine has been linked to greater sensitivity to
insulin,
11
which in turn has been related to improved
ovulatory function in women with polycystic ovary
disease,
12
which is the commonest cause of anovulation in
women of reproductive age and the commonest cause of
infertility due to ovulation disorders.
13e14
No studies have
been performed on Saudi women, who are high consumers
of caffeinated drinks, especially Arabic coffee.
The aim of this study was to investigate whether there is
an association between menstrual abnormalities and caffeine
consumption among premenopausal Saudi women at Taibah
University.
Material and Methods
This cross-sectional study was conducted by third-year
female medical students during the 2011 academic year at
Taibah University, Almadinah Almunawwarah, Kingdom of
Saudi Arabia after approval from the authorities at the
College of Medicine and as part of their research method-
ology course. An online calculation was used to estimate a
sample size of 384 for a confidence interval (CI) of 95% and a
margin of error of 5%. We therefore prepared 384 pre-coded,
well-constructed questionnaires and placed them at the
reception of the infirmary. The receptionists handed the
questionnaire randomly to 384 women aged 17e45 years
who were working or studying at the University and
attending the infirmary for various causes and asked them to
answer the questions carefully, after obtaining their verbal
consent to participate. The questionnaires were collected at
the end of the day by the researchers for revision and data
entry. Of the 384 questionnaires, 34 were excluded because of
incomplete data or exclusion criteria (currently pregnant;
smoker; using oral contraceptives, an intrauterine device or
hormonal medications; taking medications containing
caffeine; history of hysterectomy, hypothyroidism or any
gynaecological disease except polycystic ovarian disease).
The questionnaire elicited information about educational
level, marital status, premenstrual syndrome, amount of
bleeding (average, heavy or scanty) and the regularity and
duration of periods.
Irregular periods were defined as any type of abnormal
bleeding, including late or early period, bleeding between
periods, missed periods, continuous periods or periods
occurring twice in one cycle. Any period that lasted for more
than 8 days was considered to be long, and one that occurred
every 24 days or fewer was considered to be short. Ame-
norrhoea was defined as the absence of menses for 3 months
in a woman with previously normal menstruation or 9
months in a woman with a history of oligomenorrhoea. One
question asked about diagnoses of polycystic ovarian dis-
ease, and others asked about usual daily consumption of the
caffeinated beverages coffee, tea, Nescafe, carbonated soft
drinks, chocolate and hot chocolate, in number of cups or
cans per day.
Statistical analysis
All data were managed and analysed with SPSS software
for Windows version 17. Prevalence was calculated as per-
centages (frequency), and odds ratios (ORs) were calculated
with their 95% CIs by chi-squared cross-tabulation. All tests
were two-tailed, and results were considered significant when
p<0.05.
Results
Most women (76%) were aged 17e25 years, had a
bachelor’s degree (82.9%) and were single (63.4%) (Table 1).
Regular menstruation was reported by 60%, an average
duration (3e7 days) by 87.7% and an average volume by
81.7%. The prevalence of premenstrual symptoms (68.6%)
exceeded that of menstrual symptoms (18%). Irregular
periods were reported by 40%, with amenorrhoea in 26%,
oligomenorrhoea in 20.9%, heavy periods in 13.4% and
prolonged periods in 9.7%. Few women reported a
previous diagnosis of polycystic ovarian disease (7.7%)
(Table 2).
The commonest source of caffeine use was chocolate
(66.6%). More than half the women drank coffee (52%),
with 32.9% drinking Arabian coffee; followed by tea
(48.9%), with 36.3% drinking red tea; then carbonated soft
drinks (41.6%), with 31.1% drinking Pepsi Cola; and lastly
Nescafe (34.6%), with 17.4% drinking cappuccino and
11.1% drinking Coffee-Mate
Ò
. Most women did not exceed
two cups of any drink daily (46.6% for coffee, 43.7% for tea,
A.Z. Bin Mahmoud et al.2
Please cite this article in press as: Bin Mahmoud AZ, et al., Association between menstrual disturbances and habitual use of caffeine, Journal of Taibah
University Medical Sciences (2014), http://dx.doi.org/10.1016/j.jtumed.2014.03.012
20.6% for Nescafe, 45.1% for soft drinks and 28% for hot
chocolate). Only a few consumed large amounts (>5 cups or
cans daily) of coffee (9.4%), tea (2.3%), soft drinks (1.7%) or
hot chocolate (0.3%) (Table 3).
Coffee was a risk factor for both prolonged periods (OR,
2.37; 95% CI, 1.09e5.12; p¼0.03) and oligomenorrhoea
(1.95; 1.15e3.30; p¼0.014); and Nescafe was a risk factor
for heavy periods (2.22; 1.91e4.12; p¼0.011) and menstrual
symptoms (1.84; 1.06e3.02; p¼0.039). Chocolate was pro-
tective against premenstrual symptoms (0.22; 0.06e0.85;
p¼0.049) (Table 4). No significant risk seen with drinking
tea or carbonated soft drinks (data not shown).
Discussion
Women who consumed caffeine were more likely to have
menstrual abnormalities, mainly prolonged and heavy
menses, as well as oligomenorrhoea. The association with
prolonged or heavy menstruation is biologically unreason-
able, as caffeine is a known vasoconstrictor
15
and would be
expected to reduce uterine blood flow, which would reduce
menstrual bleeding and shorten the duration of menses.
Research in pregnant animals
16
and humans
17
indicates
that caffeine increases uterine vascular resistance and
reduces uterine blood flow. The mechanism by which
caffeine alters the duration of the menstrual cycle is not
clear, but it could occur via an effect on sex hormones or
hormone receptors. Kitts
18
found that constituents of
coffee are weakly oestrogenic. Caffeine inhibits the action
of adenosine, which in laboratory studies affects luteinizing
hormone and follicle-stimulating hormone,
19,20
which
could in turn affect the length of the menstrual cycle.
Gilbert and Rice
21
found depressed oestrogen levels in
female monkeys at a dose of caffeine associated with
miscarriages, stillbirths and decreased maternal weight
gain. Associations were found between caffeine intake and
oestradiol and/or oestrone levels in some studies
22,23
but
not in others.
24
Cooper et al.
24
found no notable relation
between caffeine intake and cycle length, variability or
menses length. Other researchers
4
found no indication that
caffeine intake is related to an increased risk for anovulation.
The difference between our results and those of others
could be due to the presence of confounding factors, as
66.6% of our participants habitually used non-caffeinated
beverages. Methodological differences might also explain
the differences in results. In most other studies, data was not
collected on all drinks, food and drugs containing caffeine,
while we had information on all foods and excluded all
medications containing caffeine in order to minimize their
contribution to total caffeine intake. Still, potential exposure
Table 2: Characteristics of menstrual periods of participants.
Variable No. (%)
Regularity
Regular 210 (60%)
Irregular 140 (40 %)
Duration (days)
<3 7 (2.0%)
3e7 307 (87.7%)
>7 34 (9.7%)
Volume
Moderate 286 (81.7%)
Heavy 47 (13.4%)
Light 17 (4.9%)
Symptoms 63 (18%)
Premenstrual syndrome 240 (68.6%)
Amenorrhoea 91 (26.0%)
Oligomenorrhoea 73 (20.9%)
History of polycystic ovary disease 27 (7.7%)
Table 3: Use of caffeine-containing beverages by participating
women.
Caffeinated food
or drink
No. (%) Amount: No. (%)
Coffee 182 (52%) 1e2 cups: 163 (46.6%)
3e5 cups: 44 (12.6%)
>5 cups: 33 (9.4%)
Nescafe 121 (34.6%) 1e2 cups: 72 (20.6%)
3e5 cups: 2 (0.5%)
>5 cups: 0%
Tea 171 (48.9%) 1e2 cups: 153 (43.7 %)
3e5 cups: 44 (12.6%)
>5 cups: 8 (2.3%)
Carbonated
soft drink
146 (41.6%) 1e2 cans: 123 (35.1%)
3e5 cans: 17 (4.9%)
>5 cans: 6 (1.7%)
Chocolate 233 (66.6%) One piece: 109 (31.1)%
Whole bar: 67 (19.1%)
>bar: 29 (8.3%)
Hot chocolate 105 (30%) 1e2 cups: 98 (28%)
3e5 cups: 6 (1.7%)
>5 cups: 1 (0.3%)
Table 4: Significant odds ratios (ORs) for menstrual abnor-
malities associated with use of caffeine-containing products.
Product Abnormality or symptoms OR 95% CI p
Coffee Prolonged periods 2.37 1.09e5.12 0.03
Oligomenorrhoea 1.95 1.15e3.30 0.014
Nescafe Heavy periods 2.22 1.91e4.12 0.011
Menstrual symptoms 1.84 1.06e3.02 0.039
Chocolate Premenstrual symptoms 0.2 0.05e0.90 0.021
Table 1: Characteristics of participants.
Characteristic No. (%)
Age (years)
17e25 266 (76%)
25e35 52 (14.9%)
35e45 30 (8.6%)
Education
None 0.3%
Primary school 0%
Secondary school 8.9%
Bachelor degree 82.9%
Other 6.6%
Marital status
Single 63.4%
Married 19.7%
Divorced 1.4%
Widowed 13.4%
Separated 1.1%
Association between menstrual disturbances and caffeine intake 3
Please cite this article in press as: Bin Mahmoud AZ, et al., Association between menstrual disturbances and habitual use of caffeine, Journal of Taibah
University Medical Sciences (2014), http://dx.doi.org/10.1016/j.jtumed.2014.03.012
misclassification might have affected our estimates of
caffeine intake. We estimated caffeine dose from a self-
administered questionnaire, and there may be substantial
variation in caffeine content according to serving size, brand,
ingredients, method of beverage preparation and brewing
time.
25,26
Another limitation of our study is its cross-
sectional design, which provides limited capacity to estab-
lish causal relations.
Conclusions
Our study shows that caffeine consumption is related to
prolonged, heavy menses and oligomenorrhoea. Non-
caffeinated drinks, soft drinks and chocolate were not asso-
ciated with abnormal menstruation, and chocolate was
associated with fewer premenstrual symptoms. These find-
ings could have implications for women’s long-term health.
We also found a high prevalence of undiagnosed men-
strual disturbances among Saudi university women.
Habitual use of caffeine-containing products, apart from
chocolate, should be considered a risk factor for most men-
strual abnormalities. Clinical trials should be performed to
confirm these findings and to examine subsequent health
outcomes in women.
Authors’ contributions
All the authors, in association with Zainab Ahmed, con-
structed, distributed and collected the questionnaires and
analysed the data. They wrote the manuscript under the su-
pervision of Dr Intesar Sultan.
Conflict of interest
The authors have no conflict of interest to declare.
Acknowledgements
We thank Zainab Ahmed Dumiati, a fifth-year medical
student at Taibah University for her participation in con-
structing the study, collecting data and writing up the results.
We also thank Dr Intessar Sultan, Professor of Medicine at
the College of Medicine, for her time and help in reviewing
the findings.
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A.Z. Bin Mahmoud et al.4
Please cite this article in press as: Bin Mahmoud AZ, et al., Association between menstrual disturbances and habitual use of caffeine, Journal of Taibah
University Medical Sciences (2014), http://dx.doi.org/10.1016/j.jtumed.2014.03.012
... Seven studies [16,29,38,44,48,52,55] did not find any significant association between caffeine intake and dysmenorrhea, but Faramarzi and Salmalian [49], Pejčić and Jankovic [57], and Hailemeskel et al. [56] found significant associations between caffeine consumption and higher intensity of menstrual pain. Drinking tea did not have a significant association with dysmenorrhea in 4 studies [28,43,45,60], but Wang et al. [37] reported more tea consumption among women with dysmenorrhea. The association between coffee and menstrual pain was reported in 3 studies [28,43,60] indicating a positive association, but 7 studies [45] reported that coffee consumption had no association with dysmenorrhea. ...
... Drinking tea did not have a significant association with dysmenorrhea in 4 studies [28,43,45,60], but Wang et al. [37] reported more tea consumption among women with dysmenorrhea. The association between coffee and menstrual pain was reported in 3 studies [28,43,60] indicating a positive association, but 7 studies [45] reported that coffee consumption had no association with dysmenorrhea. ...
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Pregnancy requires a variety of physiological adaptations to create an environment for the optimal development of the fetus. The widespread consumption of the methylxanthines especially caffeine and to a lesser extent theophylline by pregnant women suggests that it is important to determine whether these methylxanthines may influence maternal physiology during pregnancy. Forty female monkeys (Macaca fascicularis), randomly divided into three groups, were exposed to caffeine in their drinking water (0, 0.15, or 0.35 mg/ml) before, during, and after pregnancy. This exposure resulted in a dose-related increase in reproductive failure in the form of stillbirths, miscarriages, and decreased maternal weight gain. Blood and 24-hr urine samples were collected every 2 weeks for clinical chemistry analysis. There were a number of both pregnancy-related changes and treatment-related effects on the clinical chemistry measures. As expected, serum cholesterol and triglyceride levels declined during pregnancy for all dose groups but there were no treatment-related effects. Serum and urine creatinine levels were increased in both treated groups. Serum glucose levels, which usually decline during pregnancy, remained elevated in the high-dose group. Serum estrogen levels in the high-dose groups were depressed compared to those of the other two groups. These changes indicate that elevated serum levels of caffeine and its metabolites, particularly theophylline, may influence maternal physiology during pregnancy in the monkey.
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Many studies have examined whether caffeine, alcohol, or specific beverages containing these substances affect fertility in women. However, most of these studies have retrospectively collected information on alcohol and caffeine intake, making the results susceptible to biases. We followed 18,555 married women without a history of infertility for 8 years as they attempted to become (or became) pregnant. Diet was measured twice during this period and prospectively related to the incidence of ovulatory disorder infertility. There were 438 incident report of ovulatory disorder infertility during follow-up. Intakes of alcohol and caffeine were unrelated to the risk of ovulatory disorder infertility. Comparing the highest to lowest categories of intake, the multivariate-adjusted relative risk, was 1.11 (95% confidence interval = 0.76-1.64; P for trend 0.78) for alcohol and 0.86 (0.61-1.20; 0.44) for total caffeine. However, intake of caffeinated soft drinks was positively related to ovulatory disorder infertility. Comparing the highest to lowest categories of caffeinated soft drink consumption, the RR was 1.47 (1.09-1.98; 0.01). Similar associations were observed for noncaffeinated, sugared, diet, and total soft drinks. Our findings do not support the hypothesis that alcohol and caffeine impair ovulation to the point of decreasing fertility. The association between soft drinks and ovulatory disorder infertility seems not to be attributable to their caffeine or sugar content, and deserves further investigation.
Article
Caffeine constitutes the active drug principle in a number of commonly consumed beverages. Among North American adults, it holds the distinction as being probably the most widely utilized psychotropic drug. The compound is most often consumed in the form of coffee, which is derived from the bean of the tropical tree Coffea arabica or Coffea robusta. The unique pharmacologic and physiologic properties of caffeine have led to extensive research efforts, especially in the area of mutagenically and teratogenically mediated effects. In this regard, investigators have often overlooked the alterations in catecholamine, free fatty acid and cyclic nucleotide levels that the the presence of caffeine brings about. Such alterations are discussed in light of their effect on reproduction, and an attempt has been made to clarify the effects that the associated habits of alcohol and smoking have on the reproductive system.
Article
Tea, coffee, carbonated and chocolate beverages were analyzed for caffeine, and results compared in terms of usual serving sizes. Significant differences in caffeine levels were found to result from the preparation method of coffee or brewing time of tea. It is possible for a cup of tea, instant coffee, or can of cola beverage to have similar caffeine content (55 to 65 mg.); however, the mean values per cup of black tea (28 to 46 mg.) are considerably lower than for brewed coffee (107 to 151 mg.). Caffeine is readily absorbed and can have pharmacologic effects on adults or on children who consume quantities of cola beverages or chocolate. Both preparation method and quantity of beverage consumed should be considered in taking dietary histories or estimating caffeine intake.
Article
Total estrogen (TE), estradiol (E2), estriol (E3), and human placental lactogen (hPL) levels were determined by radioimmunoassay in the blood of 141 pregnant women during their 26th and 31st weeks of pregnancy and the results were studied in relation to coffee and alcohol intake. After controlling for maternal age, maternal weight at the corresponding week of pregnancy, parity, and tobacco smoking, as well as for mutual confounding effects, coffee intake, ascertained at the 26th week, was found to be negatively related to pregnancy E2 levels (P = 0.04 during the 26th week, and P = .16 during the 31st week), whereas alcohol intake, also ascertained at the 26th week, was found to be positively related to pregnancy TE levels (P = .04 during the 26th week, and P = .18 during the 31st week). The negative relation between coffee consumption on the one hand and E2 (and possibly TE) levels on the other may be responsible for the inverse association between maternal coffee intake and birth weight; the latter association has been repeatedly confirmed in the literature, although it was neither strong nor statistically significant in the present study. The relations of maternal coffee and alcohol consumption with pregnancy estrogen levels, if confirmed, could be utilized in studies exploring the role of prenatal exposure to these hormones in the etiology of gonadal germ-cell tumors and possibly other diseases.
Article
High caffeine consumption has been proposed as a risk factor for osteoporotic fracture, but the evidence associating high caffeine intake with low bone density is inconsistent. We therefore examined the influence of caffeine consumption on bone mineral at six skeletal sites in an age-stratified random sample of white women residing in Rochester, Minnesota. After age adjustment, there was no association between overall caffeine consumption and bone mineral at five of the six sites. In the femoral shaft, however, there was a statistically significant interaction between age and caffeine consumption so that high caffeine intake was associated with slight reductions in bone mineral among elderly subjects but with modestly increased bone mineral at younger ages. When caffeine intake was categorized by source, no consistent influence of coffee, tea, or other caffeinated beverage consumption could be detected on bone mineral. Caffeine intake was, however, positively associated with cigarette smoking and alcohol consumption. After adjusting for age, caffeine consumption was not correlated with biochemical indices of bone turnover, circulating concentrations of estradiol and estrone, or other dietary and musculoskeletal variables. These data suggest that caffeine intake in the range consumed by a representative sample of white women is not an important risk factor for osteoporosis. Among elderly women, however, in whom calcium balance performance is impaired, high caffeine intake may predispose to cortical bone loss from the proximal femur.