Ferrodyn 03 iron gyo

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Gynecological Endocrinology
ISSN: 0951-3590 (Print) 1473-0766 (Online) Journal homepage: http://www.tandfonline.com/loi/igye20
Forty to fifty-five-year-old women and iron
deficiency: clinical considerations and quality of
life
Anne Firquet, Wolf Kirschner & Johannes Bitzer
To cite this article: Anne Firquet, Wolf Kirschner & Johannes Bitzer (2017): Forty to fifty-five-
year-old women and iron deficiency: clinical considerations and quality of life, Gynecological
Endocrinology, DOI: 10.1080/09513590.2017.1306736
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ISSN: 0951-3590 (print), 1473-0766 (electronic)
Gynecol Endocrinol, Early Online: 1–7
! 2017 Informa UK Limited, trading as Taylor & Francis Group. DOI: 10.1080/09513590.2017.1306736
REVIEW ARTICLE
Forty to fifty-five-year-old women and iron deficiency: clinical
considerations and quality of life
Anne Firquet1
, Wolf Kirschner2
, and Johannes Bitzer3
1
Department of Obstetrics and Gynecology, CHR Citadelle, Lie`ge, Belgium, 2
FB + E Forschung, Beratung + Evaluation GmbH c/o Charite´ Frauenklinik
CVK, Berlin, Germany, 3
Basel, Switzerland
Abstract
Between the age of 40 and 55 years, women experience important changes in their lives. This
period, which corresponds to the perimenopause for most women, is associated with the risk of
iron deficiency anemia (IDA). The clinical presentation of anemia can be misleading, and the
underlying cause, particularly bleeding, is frequently treated without concomitant iron
prescription. Iron deficiency (ID) remains a social and economic burden in European countries.
Underdiagnosed and undertreated, this problem has a strong negative impact on women’s
quality of life. The risk factors for ID are well known. The physician’s role is essential in
recognizing the symptoms, identifying the risk factors, detecting IDA by testing hemoglobin,
and evaluating the degree of ID by measuring serum ferritin (SF). Iron therapy treats the anemia
and restores iron stores, thus decreasing symptoms such as fatigue and restoring quality of life.
Among the available forms of iron, evidence is in favor of ferrous sulfate in a slow release
formulation, which is well-tolerated and results in good adherence, a key factor for efficacious
supplementation.
Keywords
Anemia, ferrous sulfate, iron deficiency,
middle-aged women, quality of life
History
Received 8 February 2017
Accepted 11 March 2017
Published online 27 March 2017
Introduction
The period between 40 and 55 years, which covers pre-
menopause, peri-menopause, and for some women, post-meno-
pause, has a great impact on women’s health and quality of life
[1–3]. This natural life stage lasts 4–11 years and is associated
with variations in hormonal levels; menstrual disturbances with
an increased risk of heavy bleeding [4]; an unhealthy life style,
often with restrictive dieting and a lack of exercise; and
subsequent changes in physical and mental well-being, with
fatigue commonly reported [5]. These changes have a negative
impact on quality of life, and many are linked to iron status.
Quality of life is defined by the World Health Organization [6]
as the ‘‘individual’s perception of their position in life, in the
context of the culture and value systems in which they live and in
relation to their goals, expectations, standards and concerns. It is a
broad-ranging concept affected by the person’s health’’.
Worldwide, iron deficiency (ID) is the most prevalent nutri-
tional problem and remains the most common cause of anemia in
both developing and developed countries, including in Western
Europe [7–9]. Anemia affects health and has a strong negative
influence on women’s quality of life [10]. Unfortunately, phys-
icians do not seem to be aware that ID can still be a problem in
women of this age group, as anemia and ID are mainly perceived
as occurring during and after pregnancy. The topic of ID in peri-
menopausal women is rarely addressed in the literature.
The symposium entitled ‘‘Women 40–55 Years Old: Clinical
Considerations and Quality of Life’’, held at the 15th World
Congress of the International Menopause Society in September
2016 in Prague focused on this clinical and public health
problem. This review article reports a summary of the lectures
from the symposium, and is the third in a series on gyneco-
logical care [11,12]. The objectives of the symposium were to
clarify why this transitional period must be carefully monitored
to quantify the level of risk for ID, and to explain how the
treatment of ID can restore the associated impaired quality of
life.
The complexity of a common clinical case
Mrs. X is 45 years old. She is booked in for her yearly checkup.
After asking how she feels and giving her some time to explain
her situation, she responds: ‘‘I think I’m getting old. Everything is
changing. I feel so tired; I have no energy but I still try to exercise.
I’m on a very strict diet, I sometimes feel hot and wake up at night
sweating. I was always positive, now I feel depressed, and I’m not
interested in sex anymore. And then I bleed—it’s so embarrassing.
The first few days I’d rather not go out, and it lasts so long, but it’s
become irregular and unexpected. It’s very disturbing.’’ Her
medical examination was unremarkable, apart from mild symp-
toms of irritable bowel syndrome. Ultrasound did not show any
evidence of abnormalities of the uterus or adnexa.
This typical complex picture raises several questions. Do her
symptoms indicate a climacteric syndrome, burn-out, an
unhealthy lifestyle, depression, chronic fatigue syndrome, sexual
dysfunction, or abnormal uterine bleeding? Laboratory tests
revealed a low hemoglobin (Hb) level of 11.0 g/dL and a low
Address for correspondence: Anne Firquet, Department of Obstetrics and
Gynecology, CHR Citadelle, Boulevard du 12e`me de Ligne, 1, 4000
Lie`ge, Belgium. Tel: +32 477955636. E-mail: annefirquet@hotmail.com

3. serum ferritin (SF) concentration, at 15 mg/L, suggesting IDA,
which explains most of Mrs. X’s symptoms [13,14].
Make iron deficiency part of your differential diagnosis
Recognizing the symptoms
Symptoms of ID/IDA are nonspecific and can be wrongly
interpreted as related to other conditions. The typical picture of
ID/IDA includes fatigue, palpitations, irritability, breathlessness,
paleness, cold intolerance, poor concentration, restless leg
syndrome [15] and susceptibility to infection [16–18]. Among
these, fatigue and cognitive impairment are the most confusing.
Fatigue
Fatigue is a syndrome grouping lack of energy, physical and
mental exhaustion and cognitive impairment. It affects 14–33% of
patients seen in general practice and represents a significant
public health problem. It occurs not only in the context of anemia,
but also in cases of ID [19], and can be remedied by iron
supplementation [2,5,20,21].
Cognition
Iron status has an impact on cognitive performance (including
spatial ability, attention, memory, learning, reasoning ability and
executive functioning) in women of reproductive age [22]. Pre-
menopausal women with ID were found to have poorer results on
tests of attention, learning and memory when compared to iron-
sufficient participants [17]. Iron supplementation improves cog-
nitive function regardless of whether the participant suffers from
ID or IDA [23]; a significant improvement in SF was associated
with a five- to seven-fold improvement in cognitive performance
[24].
How can iron deficiency/iron deficiency anemia (IDA)
explain this wide range of symptoms?
Iron is an essential component of many metabolic enzymes. It
plays an important role in essential cellular functions and can be
responsible for mitochondrial dysfunction, abnormal enzyme
activity, abnormal transport, modified structural proteins, altered
neurotransmitter synthesis and apoptosis, all processes that might
explain fatigue, reduced work efficacy, impaired cognitive
performance, increased morbidity and impaired exercise capacity,
as well as the classical physical manifestations such as glossitis,
koilonychia and pica [10,18,25].
The risk of iron deficiency/iron deficiency anemia
Prevalence
Data on the prevalence of ID/IDA in European women aged 40–
55 years are not readily available in the literature. Therefore, an
internet-based data search was performed, collecting publications
or data on the epidemiology, prevalence, risk factors for anemia,
ID or IDA, in women of this age group, excluding data from
developing countries, where the situation differs.
In the USA, the Center for Disease Control and Prevention
(CDC) [26] reported an ID prevalence rate of 12% in non-
pregnant women aged 20–49 years and 9% in women aged 50–69,
with the IDA prevalence being 4% and 3%, respectively, in the
year 1999–2000. In Germany, Thefeld and Ellert [27] published
the results of the 1990–1992 German National Health survey
showing that latent ID (SF530 mg/L or transferrin saturation
[TSAT]516%) has a prevalence rate of 10.4% in women aged
40–49 years and 9.8% in women aged 50–54 years. In Europe,
Levi et al. [16] recently reported IDA prevalence rates in women
as being 2.2% in Belgium, 2.9% in Italy, 4% in Germany and 4.5%
in Spain.
In France, a major epidemiological study (the SUVIMAX
trial) found that one menstruating woman in five had depleted
iron stores, while 23% of pre-menopausal women had SF 15 mg/
L, and 4% had anemia (Hb512 g/dL) [28,29]. Approximately 5%
of post-menopausal women presented a total depletion of iron
stores, and 1% had IDA [29].
To calculate the prevalence of ID in German women aged 40–
55 years, the age distribution of natural menopause in Norwegian
women reported by Jacobsen et al. [30] and the prevalence rates
of ID and IDA reported in the SUVIMAX study were used, with
the results indicating that around 1.3 million German women in
this age group are iron-deficient, while 190 000 have IDA. Thus,
ID represents an economic burden that deserves the attention of
physicians.
Risk factors and causes of iron deficiency/iron deficiency
anemia in peri-menopausal women
Several conditions have been identified in the literature as risk
factors for ID in women of this age group [27,29,31–48]: low iron
intake and compromised absorption, chronic blood loss (heavy
menstrual bleeding (HMB), GI lesions) and increased iron
requirements, such as athletic activity (Table 1). Pregnancy is
not included, as only 3% of pregnancies occur over the age of 40
[49,50].
Low iron intake
Fasting. Peri-menopausal women are vulnerable to ID due to low
dietary iron intake resulting from restrictive dieting aimed at
losing weight [9]. In the SUVIMAX study, 93% of menstruating
women had dietary iron intakes lower than the recommended
dietary allowance (RDA) [29], at approximately 12 mg/day
instead of the 18 mg/day recommended [28]. Women of this age
may struggle to manage their weight, which often leads to
restrictive dieting and the elimination of meat [10]. Other
slimming diets also lead to insufficient intake of iron; for
example, in 46 healthy women, two-day food restrictions
(5200 kcal/day) every eight days for a period of 48 days
significantly decreased serum iron concentrations as well as SF
(–28%, p50.001) and Hb (–8%, p50.05) [32].
Vegetarian diets. Vegetarians and vegans have a greater risk of
ID as their heme iron intake is almost nil. Vegetarian diets provide
adequate amounts of non-heme iron if a wide variety of fruit,
cereals and vegetables are consumed [51]; however non-heme
iron is poorly absorbed (1 ± 5%) in comparison to heme iron
(25%), which is only found in foods of animal origin [52]. In the
German Vegan study, 40% of vegan women under the age of 50
were considered iron-deficient [31]. The United States/Canadian
Institute of Medicine recommends that the iron requirements for
vegetarians be 1.8 times that of the regular RDA [53]; to reach
this amount requires complex dietary management.
Increased blood loss
Heavy menstrual bleeding. The prevalence of HMB (formerly
called menorrhagia), defined as menstrual periods lasting more
than seven days and/or involving blood loss greater than 80 ml,
ranges from 11 to 13% in the general population and increases
with age, reaching 25% in women older than 41 years [40,54].
Likewise, in 18 000 women who served in the US Armed Forces
from 1998 to 2002, HMB was diagnosed in 23.1% of women aged
40–49 and 9.2% of women aged 50–55 [55]. HMB is an important
cause of anemia in peri-menopausal women. It is a hidden
condition that is underdetected in women aged 40–55 years for
2 A. Firquet et al. Gynecol Endocrinol, Early Online: 1–7

4. various reasons: a cultural perception that menstruation is an
embarrassing topic that should be concealed [56], the belief that
bleeding is a cleansing process good for health, and the difficulty
of quantifying the losses [57]. Several useful tools have been
developed to quantify menstrual bleeding; for example, the
Matteson questionnaire [58] or a 15-question form developed by a
group of experts (Expert group on Heavy Menstrual Bleeding: I
Fraser, D Mansour, A Kaunitz, J Bitzer; unreferenced). The
causes of HMB have been classified using the PALM-COEIN
acronym [59] and the treatment has been detailed in the recent
update of the National Institute for Care and Health Excellence
(NICE) guidelines [3]. For NICE, HMB has ‘‘a major impact on a
woman’s quality of life’’, and ‘‘any intervention should aim to
improve this rather than focusing on menstrual blood loss.’’ The
guidelines recommend a full blood count on all women with
HMB; however, ferritin testing is not mentioned to help to
identify ID. Peuranpa¨a¨ et al. [1] recommend treating all women
with HMB and IDA/ID with an effective iron preparation at
initiation of HMB therapy.
Intrauterine devices. The use of copper UIDs is also a risk
factor; 28% of women using copper IUDs were found to be iron
depleted [29].
GI bleeding. HMB is not the only culprit responsible for iron
loss. In a population of pre-menopausal women with IDA, 82% of
patients had normal menstrual blood loss, but more than 25%
reported GI symptoms and fecal occult blood was detected in
41%. Only 24% of these anemic patients were treated with iron
supplements [41]. GI bleeding is frequently underdiagnosed and
related ID undertreated [60]. Female patients with IDA not
explained by heavy menses, or those with GI symptoms, should
be evaluated by endoscopy or colonoscopy [41,42]. In post-
menopausal women, gut lesions are the main reason for ID,
predominantly due to cancers and coeliac disease [9]. IDA is also
a known consequence of Helicobacter pylori infection due to
chronic occult blood loss, competition for iron by the bacteria,
reduced ascorbic acid concentration and upregulation of hepcidin
[47,50]. The anemia improves after eradication of the pathogen
[9]. The use of proton pump inhibitors seems to reduce the risk of
upper GI bleeding [43]; however, these medications are known to
inhibit iron absorption [61].
Iatrogenic bleeding. Bleeding associated with anticoagulants/
aspirin/non-steroidal anti-inflammatory drugs (NSAIDs) may
contribute to ID. Aspirin or NSAID use was reported by 35% of
patients with IDA [41]. In patients hospitalized for GI bleeding,
the use of anticoagulants, low-dose aspirin, NSAIDs was linked to
upper and/or lower GI bleeding; the risk was two-fold higher for
anticoagulants [43].
Malabsorption and inflammatory conditions
Celiac disease and inflammatory bowel disease (IBD) affect GI
cells. The villous atrophy of the mucosa impairs iron absorption
[9]. Approximately 80% of anemic patients with celiac disease are
iron-deficient due to impaired iron absorption and blood loss
[25,46]. Anemia is common in celiac disease. According to the
British Society of Gastroenterology guidelines [46], all patients
with IDA should be screened for celiac disease by serological
testing for tissue transglutaminase antibody (tTG-IgA) or
endomysial antibody (EMA-IgA), and/or duodenal biopsy.
Anemia in IBD is multifactorial. IDA, the most common cause,
coexists with anemia due to chronic disease, also known as
anemia of inflammation or functional IDA [25,62]. In the case of
inflammation, cytokines induce the production of hepcidin, which
is responsible for iron sequestration in intracellular ferritin. SF
concentrations increase independently of iron status; however, this
increase may mask a deficiency of iron [46]. It is therefore
essential to detect inflammation by concurrently measuring an
inflammatory marker such as C-reactive protein (CRP) [9], which
is increased during inflammation [36]. Strict inflammatory
anemia is refractory to oral iron therapy because the raised
hepcidin levels result in trapping of iron in the enterocytes [9];
however, in case of concomitant ID, there is little justification for
giving parenteral iron when oral therapy is possible. The
intravenous route is indicated only when the patient is intolerant
or unresponsive, in cases of persistent noncompliance, or when
treated by erythropoiesis stimulating agents [13,25,46].
Obesity, a chronic inflammatory condition with an increasing
prevalence, also has the potential to compromise iron status
[9,45]. Obesity can result in iron being retained in the enterocytes
and macrophages. The higher prevalence of ID in obese people is
possibly due to inadequate iron intake or higher blood volume
[51].
Increased iron requirements
Some women, concerned about their weight, begin an obsessive
exercise program. Female athletes, and especially long distance
runners, suffer ID due to insufficient iron intake, menstruation or
increased blood losses due to exercise (sweating, hemolysis,
hematuria or GI bleeding) [48]. In endurance athletes, the RDA for
iron should be increased by 70% [48]. ID can be corrected with
Table 1. Risk factors for iron deficiency and iron deficiency anemia in women aged 40–55 years.
Risk factors for ID/IDA OR/RR Source
Low iron intake, low absorption
Vegetarian, vegan diet, poor diet 1.76 Thefeld and Ellert [27], Waldmann et al. [31]
Fasting N/A Wojciak [32]
Low BMI 1.7–2.97 Contreras-Manzano et al. [33]
Low vitamin C intake 2 Ramakrishnan et al. [34], Peneau et al. [35]
Malabsorption N/A Qamar et al. [36]
High consumption of coffee/tea N/A Fairweather-Tait [37]
Increased blood loss
Use of intrauterine devices (not . . .) 2 Galan [29]
High menstrual blood loss 2.6 Kirschner et al. [38], Milman et al. [39], Janssen et al. [40]
Intestinal bleeding N/A Green and Rockey [41], Bull-Henry and Al-Kawas [42]
Use of NSAIDs, aspirin, anticoagulants 2–4.2 Green and Rockey [41], Lanas et al. [43]
Repeated blood donations 5 Milman et al. [44]
Inflammatory chronic diseases/obesity 2 Aigner et al. [45]
Helicobacter pylori infection 1.38–2.8 Goddard et al. [46], Hudak et al. [47]
Increased needs
Competitive sports 2 Alaunyte et al. [48]
N/A: ratio not available.
DOI: 10.1080/09513590.2017.1306736 ID in women aged 40–50 3

5. iron supplementation [63], and a recent Cochrane review [20]
concluded ‘‘Daily iron supplementation effectively reduces the
prevalence of anemia and ID, raises Hb and iron stores, improves
exercise performance and reduces symptomatic fatigue.’’
Treat iron deficiency/iron deficiency anemia effectively
to restore quality of life
Iron therapy produces a rapid improvement of symptoms
‘‘Anemia control produces an immediate increase in physical
work output, higher productivity outside the workplace, improved
quality of leisure time, increased learning capacity, and a greater
sense of well-being’’ [13].
Quality of life
Patterson et al. confirmed a link between ID and decreased well-
being that was improved by iron treatment [2]. In Finland, 236
women referred for HMB were randomized to two groups: one
treated by hysterectomy and one with a levonorgestrel IUD, and
followed up for five years [1]. At baseline, 27% of women were
found to be anemic, 60% were severely iron-deficient (fer-
ritin515 g/L), with only 8% of the anemic women taking an iron
supplement. Anemia was corrected in the first year after treatment
of HMB in most women, and was associated with an improvement
of health-related quality of life as measured with the RAND 36
questionnaire; however, it took several years to replenish the iron
stores with dietary iron. After five years, the mean ferritin value
was 49.31 g/L (range 7–237) in the initially anemic group and
67.51 g/L (range 5–464 mg/L) in the initially non-anemic group
(p ¼ 0.03), showing that despite reassuring mean values, some of
the women in both groups were still iron-deficient. Surprisingly,
iron supplementation was rare, which probably explains the
persistence of deep ID in some women. A possible explanation is
that clinicians focus on the treatment of HMB itself, and may not
consider the possibility of ID. Many doctors expect that anemia
and ID will spontaneously resolve once HMB is treated.
Choosing the right iron supply
Diet or oral supplementation?
Although theoretically useful, dietary advice is difficult to follow.
It is recommended to avoid inhibitors of iron absorption (e.g.
tannins and phytates in tea or coffee; calcium), to favor efficient
iron absorption [9,64], and to eat iron-rich foods (meat, blood
sausages, lentils, herrings, etc.) [65]. This advice rarely matches
the patient’s dietary choices and is often rapidly abandoned,
despite initial goodwill. If an iron-rich diet is elected as the sole
measure, Hb and SF should be regularly monitored to control the
normalization of iron stores.
Iron supplements are not all the same
From a practical point of view, the oral route is the first choice to
treat IDA and rebuild iron stores. Ferrous sulfate is preferred, as
the bioavailability of ferric iron is 3–4 times lower because of its
poor solubility and the fact that it must be transformed into ferrous
iron before it can be absorbed [66]. Moreover, ID upregulates iron
absorption from ferrous sulfate better than from ferric iron [67].
Iron preparations vary in their bioavailability, efficacy and side
effects. Good tolerability is key, as it guarantees good compliance,
essential for efficacy. The major reason for iron therapy failure is
noncompliance due to side effects. Patients may take the
supplement for a few days and cope with the associated
discomfort, but stop the treatment as soon as they experience an
improvement from the rise in their Hb levels. Unfortunately, this
occurs long before Hb has reached a normal level [13]. To avoid
high amounts of iron being in contact with the GI mucosa, slow
release preparations have been proposed as they improve absorp-
tion and GI tolerance [13].
Slow release ferrous sulfate
Bioavailability and kinetics. Ferrous sulfate in a polymeric
complex (FSPC), TardyferonÕ
(Pierre Fabre Pharma Laboratory,
Castres, France) was tested in non-pregnant women with IDA (Hb
85–105 g/L, SF515 mg/L) taking a single dose of two tablets of
80 mg [68]. Iron was released slowly, with the median time to
reach the peak concentration around 4 h. At 12 post-dose, the
mean iron concentration was six-fold higher than at baseline. All
patients displayed similar curves of iron concentration, with
elevated iron concentrations maintained up for to 12 h.
Efficacy. In the PEARL study [69], women with symptomatic
fibroids, excessive uterine bleeding, and anemia (Hb 10.2 g/dL)
were randomized to receive oral ulipristal acetate, a selective
progesterone receptor modulator [70], at a dose of 5 mg or 10 mg/
day or placebo for 13 weeks. All patients were supplemented with
80 mg of FSPC once daily during the study. At 13 weeks, uterine
bleeding was contained in more than 90% of the women receiving
ulipristal acetate and in 19% of those receiving placebo
(p50.001). The percentage of patients with normal Hb (412 g/
dL) increased over time in all groups and anemia was corrected in
most patients in the placebo group. Hb levels reached at least
13.50 g/dL ± 1.32 in the ulipristal group and 12.61 g/dL ± 1.30 in
the placebo group, showing that FSPC efficiently restored Hb
levels, despite ongoing bleeding.
A group of 144 women with unexplained fatigue received
either FSPC or placebo for four weeks. Half of them had SF
levels 20 mg/L. After one month of treatment with FSPC, the
level of fatigue, measured with a visual analog scale, decreased by
29% in the iron group and decreased by 13% in the placebo group
(p ¼ 0.004) [5].
Zaim et al. [71] demonstrated that the ability of the FSPC
80 mg prolonged-release formulation to restore Hb levels in
women with IDA was not inferior to that of a different dosage
(105 mg) of a reference ferrous sulfate formulation when admin-
istered for 12 weeks. This can be explained by better iron
absorption from the prolonged-release formulation.
Tolerability. A systematic review [72] analyzed the tolerability
of oral iron supplements in 111 studies including over 1000
patients. FSPC showed the lowest rate of GI adverse effects
(3.7%), compared to other FS (30.2%), ferrous fumarate (43.4%)
and preparations containing ferric iron (7%) (Figure 1).
This evidence on bioavailability, efficacy and tolerability of
FSPC was confirmed in Fadeenko et al.’s study [73], where
patient adherence, an important parameter for treatment efficacy
and tolerability, was considered excellent since more than 95% of
patients took their treatment until the end of the study.
Discussion
Risk factors for middle-aged women have been identified
Risk factors specific for the 40–55 year age group are well known
(Table 1) and should trigger further evaluation. Fatigue or
impaired exercise capacity by itself is associated with a risk of ID/
IDA and should prompt a biological assessment for anemia (Hb)
and iron status (SF, TSAT) [25]. ID is deleterious by itself and can
aggravate concomitant pathological conditions such as cardiovas-
cular diseases, recovery from surgery, or cancers [74,75].
Iron deficiency is not limited to developing countries
Even though ID is less prevalent than in developing countries,
where iron supplementation is recommended for adult women
4 A. Firquet et al. Gynecol Endocrinol, Early Online: 1–7

6. where the prevalence of IDA is 40% [50], ID remains a public
health concern in Western Europe as it affects large numbers of
women [8,13]. IDA-related signs and symptoms are nonspecific
and are often underestimated or overlooked by patients, who
therefore may not report them to their general practitioner or
gynecologist. A checklist (Table 2) in the form of an acronym has
been proposed for screening the main risk factors and deciding
whether in addition to Hb testing determining the ferritin level
would be useful to confirm the ‘‘deficit’’.
In addition to anemia correction, iron stores should be
restored to normal levels
In cases of IDA/ID, iron supplementation should be implemented
and combined with the treatment of the underlying condition. As
recommended by different guidelines [7,13,14,19,46], prescribing
oral ferrous sulfate at a dose of 60–120 mg/day for three months to
treat anemia, and for an additional three months to replenish the
iron stores, is a common approach [50]. Therefore, there is a need
to maintain the patient’s motivation for those who do not perceive
themselves to be ill.
What is the contribution of ferritin testing in the
management of iron deficiency anemia/iron deficiency?
Hb testing only detects anemia, which is a late-stage indicator of
ID. A higher Hb threshold has been proposed to optimize ID
screening [76]. Ferritin values, which represent the iron stores,
seem a better candidate for screening [77]. The British Columbia
Guidelines [19] consider that in adults, SF515 mg/L denotes ID,
at between 15 and 50 mg/L ID is probable, between 50 and 100 mg/
L ID is possible, and if SF4100 mg/L ID is unlikely. If SF is
persistently more than 1000 mg/L, the risk of iron overload should
be considered. Nevertheless, IDA may coexist with anemia due to
chronic disease, and the distinction between these forms of
anemia is sometimes difficult [16]. In case of CRP45 mg/L,
Kirschner et al. [38] recommend the assessment of Soluble
Transferrin Receptor (sTfR) instead of ferritin, and some authors
[46,78,79] have suggested raising the SF threshold to 50 mg/L or
even higher.
With the natural cessation of menstruation and the associated
decrease in iron loss, ferritin is expected to increase. At
menopause, the ferritin curve crosses the estradiol curve, which
is declining [80,81]. Some authors have even signaled a risk of
iron overload [79]. However, this represents the mean value and
does not take into account any extreme values [1]. A low ferritin
value confirms ID. An overly high ferritin value evokes either an
associated inflammatory process (with elevated CRP and
decreased TSAT suggestive of iron sequestration [62]) or
unmonitored high iron intake, such as by self-medication with
over-the-counter supplements containing iron, or a real iron
overload possibly related to genetic factors.
Considering the economic impact of ID and the large range of
ferritin values observed, all health care authorities should
recommend this additional marker as a screening test in middle-
aged women at risk of ID.
The essential role of physicians
Physicians are in a position to recognize the possible clinical
presentations of ID/IDA, and have a responsibility to search for
possible causes, explain the negative effects of excessive bleeding
and the consequences of ID. Considering that it is not realistic to
rely on dietary advice for the correction of ID/IDA, iron
supplementation represents a medical issue and should be
proposed to the patients until their iron status is restored to
normal [12].
Conclusions
Women between the ages of 40–55 years are at risk of ID/IDA and
merit attention as the symptoms of ID can be misinterpreted or
overlooked. The assessment of Hb to detect anemia, and at least
SF to confirm ID, should guide therapy initiation and follow-up.
The use of a slow release form of ferrous sulfate, such as FSPC,
with proven efficacy and tolerability, will help to ensure patient
compliance with treatment and seems to be a valuable choice to
treat ID/IDA and to restore quality of life.
Declaration of interest
All authors report receiving fees from Pierre Fabre Medicament
for preparing and presenting the information included in this
review, which they presented at the symposium entitled ‘‘Women
40–55 Years Old: Clinical Considerations and Quality of Life’’,
held at the 15th World Congress of the International Menopause
Society in September 2016 in Prague. Funding for editorial
support was provided by Pierre Fabre Medicament.
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