PLASMA MAGNESIUM AND CARDIOVASCULAR CHANGES DURING
MENSTRUAL CYCLE IN YOUNG NIGERIAN WOMEN
1Olayaki
L.A., Salman T.M., Ayinla M.T., Soladoye A.O. and 2M.S. Ajao
1Department
of Physiology, 2Department of Anatomy, Faculty of Basic Medical
Sciences, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin
*Correspondence:
Luqman A. Olayaki
Department of Physiology and Biochemistry,
Faculty of Basic Medical Sciences,
College of Health Sciences, University of Ilorin,
P.M.B. 1515, Ilorin, Kwara State,
Nigeria.
Tel.:234-8033814880; e-mail:luqmanolayaki@yahoo.com
ABSTRACT
This study was designed to determine the pattern and magnitude of changes in plasma
magnesium (Mg2+) in relation to Systolic Blood Pressure (SBP), Diastolic Blood Pressure
(DBP), and Heart Rate (HR) during the menstrual cycle.
Plasma Mg2+ was measured in fasting blood samples collected in the morning
three times spread over the three phases of the menstrual cycle: Early Follicular (EF: days
1-3, menstruation), Periovulatory (PO; days 14-15 of the cycle), and mid-luteal (ML;
days 21-23 of the cycle) respectively, in twenty healthy women aged 19-24 years and
with regular menstrual cycle (27-30 days). SBP, DBP, and HR were also determined.
The results obtained showed plasma Mg2+ decreased from 1.85±0.30 mg/dl during
early follicular phase to 1.43±0.37 mg/dl during the periovulatory phase (p<0.05), and
then increased to 1.76±0.32mg/dl during the mid-luteal phase (p<0.05). SBP increased
from 114.35±4.87 mmHg during the early follicular phase to 119.20±4.70 mmHg during
the periovulatory phase (p<0.05), and then fell to 114.10±5.48 mg/dl during the midluteal phase (p<0.05). The DBP increased from 64.45±4.05 mmHg during the early
follicular phase to 68.05±3.41 mmHg during the periovulatory phase (p<0.05) and then
decreased to 64.90±3.09 mmHg during the mid-luteal phase (p<0.05). The HR increased
from 69.30±7.24 beats/minute during the early follicular phase to peak at periovulatory
phase 73.60±7.65 beats/minute. It then fell to 70.35±7.20 beats/minute during the midluteal phase. Though there is no significant difference in HR across the phases of the
menstrual cycle.
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In conclusion, these results indicate that blood Mg2+ levels fluctuate during the
menstrual cycle along with SPB and DPB and could be one of the factors responsible for
changes in cardiovascular parameters during the menstrual cycle.
Key words: Plasma Magnesium, Systolic Blood Pressure, Diastolic Blood Pressure,
Menstrual Cycle.
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INTRODUCTION
Recent studies demonstrated that menstrual cycle is associated with variation in
haemodynamics1,2,3, sympathetic and immune activities4. Dietary Mg2+ has been
inversely associated with blood pressure in populations5,6,7,8, variations in BP9,10, and HR
11,10
.
Variations in blood pressure have been reported across the menstrual cycle, and
Mg2+ deficiency has been linked to the pathogenesis of hypertension12. Mg2+ therapy has
been shown to be useful in the treatment of cardiac dysrythmias13, acute myocardial
infarction14, acute cerebral ischemia15,16, pre-eclampsia and eclampsia17,18. Mg2+ salts
have been shown to lower BP19.
MARERIALS AND METHOD
Twenty young women, who were students of University of Ilorin, participated in the
study. They were aged between 19-24 years with menstrual cycles that were regular and
27-30 days duration. Inclusion criteria for the study were the following: 1) maintaining
regular menstrual cycles of 27-30 days, with the cycle duration not changing by more
than two days for the three prior months, 2) not taking any type of prescribed medication
including oral contraceptives for at least one year prior to study, 3) maintaining a body
weight with a desirable body mass index (18 – 25 kg/m2), 4) not taking alcohol, 5) nonsmoking and non-dieting, 6)no past or ongoing chronic illness, 7) not pregnant or
lactating for one year prior to the study and 8) not exercising for more than 60 minutes a
day or seven hours a week. The subjects were also certified medically fit by the
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university clinic physician. They had no breakfast and abstained from strenuous exercise
before study. Informed consent was obtained from each subject.
Height and weight were recorded, and body mass index (BMI, kg/m2), which is
the body weight (in kg) divided by the square of the height (in m), was calculated. Height
was measured without shoes using a standiometer that is a non-stretchable tape attached
to a vertical flat surface (wall), with a right-angle headboard. A beam scale with nondetachable weight was used to measure weight with clothes but no shoes.
During each visit, a total of 5mls of blood was obtained by venepuncture and
collected into lithium heparinised tubes. Blood collections for each subject were
performed at approximately the same time of the day throughout the study period to
reduce variability within each individual. Immediately after the collection, plasma and
erythrocytes were separated by centrifugation. Centrifuged samples were stored at -40C,
until analysis was done.
Plasma Mg2+ was determined by colometric method using xylidyl blue reagent
and glycohetherdiamine tetraacetic acid (GEDTA) as diluting agent.
Table 1: See page 13.
Statistical Analysis
Results are expressed as mean ± SEM, and n denotes the number of subjects. The
values were assessed for statistical significance by one-way analysis of variance
(ANOVA). A probability level of p<0.05 was considered significant.
RESULTS
Table 2: See page 13.
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Changes in plasma Mg2+
In table 2, mean ± SEM of plasma Mg2+, in the three phases of menstrual cycle and
corresponding p-values are presented. Periovulatory phase was associated with lowest
Mg2+ 0.80±0.05 mmol/L. In the early follicular phase, the Mg2+ was 1.10±0.11 mmol/L,
and decreased to 0.80±0.05 mmol/L in the periovulatory phase (p<0.001), (fig.4). The
Mg2+ was increased to 0.98 ± 0.08 mmol/L in the mid-luteal phase (p<0.05), (fig.4).
Changes in blood pressure and Heart Rate
Table 2 shows the mean ± SEM values of SBP and DBP in the three phases of menstrual
cycle. SBP increased from 115.15±5.73 mmHg in the early follicular phase to 119.0±4.70
mmHg (p<0.05, n=20), (fig.1) in the periovulatory phase and reduced to 114.10±5.48
mmHg in the mid-luteal phase (p<0.05, n=20), (fig.1)
DBP increased from 68.50±3.73 mmHg in the early follicular phase to
71.50±4.42 mmHg in the periovulatory phase (p<0.05, n=20), (fig.2), and reduced to
66.50±3.65 mmHg in the mid-luteal phase. However, HR was similar in the phases of the
three phases of the menstrual cycle, (fig.3).
DISCUSSION
The results of this study demonstrated that plasma Mg2+ show distinct variations during
menstrual cycle in healthy young women. Plasma Mg2+ decreased significantly from a
lower level during EF phase to a maximum level during the PO phase, which coincides
with the lowest SBP and DBP. Thereafter, the plasma Mg2+ increased to a higher level
during the ML phase during which SBP and DBP were at their lowest level. Although
variations in plasma Mg2+ concentration were observed across the menstrual cycle, the
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values at each phase were always within the reference range for healthy adults (0.8-1.3
mmol/L).
In most studies negative relationships between urinary Mg2+ excretion and blood
pressure have been established20. Mg2+ is important in activating the Na+-K+ ATPase
pump which in turn, expedites the movement of potassium into the cell and sodium out of
the cell21. Mg2+ is also important in decreasing the entry of Ca2+ into the cell12; hence
Mg2+ deficiency leads to increased intracellular sodium and Ca2+, increased peripheral
resistance and vasospasm.
By regulating smooth muscle tone, Mg2+ may play a role in illnesses such as acute
myocardial infarction, hypertension, acute cerebral ischemia, and asthma exacerbation.
Smooth muscle tone is determined by Ca2+ dependent phosphorylation of myosin light
chain22. Higher levels of intracellular Ca2+ are associated with more smooth muscle
constriction. Mg2+ regulates the intracellular Ca2+ levels and thereby influences smooth
muscle tone22. Mg2+ deficiency is associated with an increase in intracellular Ca2+ and
increased smooth muscle vasoconstriction. Mg2+ salts have been shown to lower blood
pressure19, and it is a naturally occurring antagonist of Ca2+ 23. Mg2+ has also been shown
to affect cardiac contraction, beating rhythm, vasomotor control, and proliferation of
smooth muscle cells in vessels24.
The mechanisms for the observed cyclic changes in Mg2+ parameters during the
menstrual cycle are uncertain. Estradiol may be a physiological modulator, regulating
Mg2+ concentration directly or indirectly. It has been suggested that oestrogen plays a
protective role against cardiovascular disease, partly by decreasing the likelihood of low-
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density lipoprotein perioxidation25,26. Our results suggest that effects of oestrogen may
also be responsible for modulation of CVS parameters.
In the present study, the increased in SBP observed during the PF coincided with
a decrease in the plasma Mg2+during the PF. It is possible that the change in plasma Mg2+
could be responsible for the increase in SBP and DBP.
Oestrogen is known to enhance Mg2+ utilization and uptake by soft tissues and
bones27, and this may be one of the mechanisms by which oestrogen contribute to
resistance of young women to heart diseases, as well as increased prevalence of these
diseases when oestrogen secretion ceases. It has been observed that patterns of 17-βestradiol concentration observed over four points during menstrual cycle fluctuated
significantly over the menstrual cycle with lowest concentration during the early
follicular phase and highest during the periovulatory phase and decreased by about 50%
during the mid-luteal phase28.
Mg2+ might even have a stronger effect on the cyclic nature of cardiovascular
parameters during the menstrual cycle. It could be seen that the lowest concentration of
plasma Mg2+ is associated with the highest levels of systolic and diastolic blood pressure.
It was at the period of expected highest plasma oestrogen concentration.
These results indicate that the phase of the menstrual cycle should be considered
when Mg2+ status is assessed in women of reproductive age. In the current study, plasma
Mg2+ concentrations decreased by approximately 9% during the periovulatory phase.
Marginal Mg2+ status therefore, could be misinterpreted as inadequate if blood sampling
occurred during this phase.
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The results of this study also suggested that plasma Mg2+ characteristics and
fluctuations should be considered when establishing cardiovascular parameters in
premenopausal women. It is likely that a decreased in plasma Mg2+ may be accompanied
by an increased in systolic and diastolic blood pressure.
Because of the significant increase in SBP and DBP during the periovulatory
phase when there was highest concentration of plasma oestrogen and lowest
concentration of plasma Mg2+, plasma Mg2+ might be one of the factors influencing the
cyclical changes in blood pressure across the phases of menstrual cycle in young women.
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Table 1. Age, Anthropometric Data, and Estimated Menstrual Cycle Length for Subjects
at Enrollment to the Study (mean±SEM, n=20).
Characteristics
Values
Age (years)
21.6±0.2
Weight (kg)
53.7±2.3
Height (m)
1.64±0.12
BMI (kg/m2)
19.97
Cycle length (d)
28.4±0.3
Table 2. Change in estimates (mean±SEM) of Systolic and Diastolic blood pressures
(SBP and DBP), Heart Rate, and Plasma Magnesium concentration (Mg2+) during the
early Follicular (EF), Periovulatory (PO), and Mid-Luteal (ML) phases of menstrual
cycle (n=20)
GROUP SBP(mmHg)
DBP(mmHg)
HR(beats/min) Mg2+ (mmol/L)
EF
115.15±1.28a 68.50±0.83a
69.30±1.62a
1.10±0.11a
PO
119.20±1.05b 71.50±0.99b
73.60±1.71b
0.80±0.05b
ML
114.10±1.23a 66.50±0.82a
70.25±1.59a
0.98±0.08a
NB: Different superscript along the column indicates p<0.05
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122
b
SBP(mmHg)
120
118
116
114
a
a
112
110
108
EF
PO
ML
Menstrual Phases
Fig 1. Systolic Blood Pressure
Changes During Menstrual
Cycle(between a and b,p<0.05)
DBP (mmHg)
74
b
72
70
a
68
a
66
64
62
EF
PO
ML
Menstrual Phases
Fig. 2 Diastolic Blood Pressure
Changes During Menstrual
Cycle(between a and b,p<0.05)
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HR (beats/min)
76
a
74
72
a
a
70
68
66
64
EF
PO
ML
Menstrual phases
Plasma Mg (mmol/L)
Fig 3. Heart Rate Changes During
Menstrual Cycle(a indicates no
statistical difference)
1.4
1.2
a
a
1
b
0.8
0.6
0.4
0.2
0
EF
PO
ML
Menstrual Phases
Fig 4. Plasma Magnesium Changes
During Menstrual Cycle(between a and
b,p<0.05)
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