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Background Thyroid gland dysfunction represents an epidemiologically relevant disease in the female gender, where treatment with oral contraceptives (OCs) is frequently prescribed. Although OCs are able to impact the thyroid gland function, scanty data have been released on this matter so far.AimThe aim of this article was to review how hormonal OCs, including estrogen- or progesterone-only containing medications, interact with the hepatic production of thyroid-binding globulin (TBG) and, consequently, their effects on serum levels of thyroxine (T4) and triiodothyronine (T3). We also reviewed the effect of Levo-T4 (LT4) administration in women taking OCs and how they influence the thyroid function in both euthyroid women and in those receiving LT4.ReviewThe estrogenic component of the pills is capable of increasing various liver proteins, such as TBG, sex hormone-binding protein (SHBG) and coagulation factors. On the other hand, the role of progestogens is to modulate estrogen-dependent effects mainly through their anti-androgenic action. In fact, a reduction in the effects of androgens is useful to keep the thromboembolic and cardiovascular risks low, whereas OCs increase it especially in women with subclinical hypothyroidism or in those treated with LT4. Accordingly, subclinical hypothyroidism is known to be associated with a higher mean platelet volume than normal and this increases cardiovascular risk due to platelet hyperactivity caused by incomplete thrombocytopoietic maturation.
1 23
Journal of Endocrinological
Official Journal of Italian Society of
Endocrinology (SIE)
e-ISSN 1720-8386
J Endocrinol Invest
DOI 10.1007/s40618-020-01230-8
Effects of oral contraceptives on thyroid
function and vice versa
F.Torre, A.E.Calogero,
R.A.Condorelli, R.Cannarella,
A.Aversa & S.La Vignera
1 23
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1 3
Journal of Endocrinological Investigation
Eects oforal contraceptives onthyroid function andviceversa
F.Torre1· A.E.Calogero1· R.A.Condorelli1· R.Cannarella1· A.Aversa2· S.LaVignera1
Received: 2 January 2020 / Accepted: 17 March 2020
© Italian Society of Endocrinology (SIE) 2020
Background Thyroid gland dysfunction represents an epidemiologically relevant disease in the female gender, where treat-
ment with oral contraceptives (OCs) is frequently prescribed. Although OCs are able to impact the thyroid gland function,
scanty data have been released on this matter so far.
Aim The aim of this article was to review how hormonal OCs, including estrogen- or progesterone-only containing medica-
tions, interact with the hepatic production of thyroid-binding globulin (TBG) and, consequently, their effects on serum levels
of thyroxine (T4) and triiodothyronine (T3). We also reviewed the effect of Levo-T4 (LT4) administration in women taking
OCs and how they influence the thyroid function in both euthyroid women and in those receiving LT4.
Review The estrogenic component of the pills is capable of increasing various liver proteins, such as TBG, sex hormone-
binding protein (SHBG) and coagulation factors. On the other hand, the role of progestogens is to modulate estrogen-
dependent effects mainly through their anti-androgenic action. In fact, a reduction in the effects of androgens is useful to
keep the thromboembolic and cardiovascular risks low, whereas OCs increase it especially in women with subclinical hypo-
thyroidism or in those treated with LT4. Accordingly, subclinical hypothyroidism is known to be associated with a higher
mean platelet volume than normal and this increases cardiovascular risk due to platelet hyperactivity caused by incomplete
thrombocytopoietic maturation.
Keyword TBG· Hormonal contraception· Hypothalamic· Pituitary· Thyroid axis
APC Active protein c
CVD Cardiovascular disease
OC Oral contraceptive
DNG Dienogest
EE Ethinyl estradiol
EV Estradiol valerate
FT4 Free thyroxine
FT3 Free triiodothyronine
LNG Levonorgestrel
LT4 Levothyroxine
MI Myocardial infarction
MPV Mean platelet volume
PDW Amplitude of platelet distribution
PLT Platelet count
T3 Triiodothyronine
T4 Thyroxine
TSH Thyroid-stimulating hormone
TRH Thyrotropin-releasing hormone
TBG Thyroxine-binding globulin
TG Triglycerides
TTR Transthyretin
SCH Subclinical hypothyroidism
VTE Venous thromboembolism
The metabolism of body proteins is strictly regulated by thy-
roid hormones, which, in turn, are closely related to the pro-
cesses of development and growth [14]. The thyroid gland
synthesizes and releases thyroxine (T4) and triiodothyronine
(T3), both being iodine-containing hormones. T4 is the main
product of thyroid secretion. Thyroid hormone synthesis is
controlled by thyroid-stimulating hormone (TSH) secreted by
the anterior pituitary in response to hypothalamic thyrotropin-
releasing hormone (TRH). Local deiodination in peripheral
* S. La Vignera
1 Department ofClinical andExperimental Medicine,
University ofCatania, Via S. Sofia 78, 95123Catania, Italy
2 Department ofExperimental andClinical Medicine, “Magna
Graecia” University, Catanzaro, Italy
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tissues produces T3, the biologically active thyroid hormone.
T4 and T3 circulate into the blood stream bound to thyroxin-
binding globulin (TBG), a protein produced by the liver [5].
The fraction of T4 and T3 free from protein binding (FT4 and
FT3, respectively) exert negative feedback on the synthesis and
release of TSH and TRH to maintain the circulating thyroid
hormone levels in the required range [5].
Hyperthyroidism and hypothyroidism represent pathologic
conditions where an excessive or insufficient hormone synthe-
sis occur. In both cases, the hormone imbalance has relevant
consequences on the metabolic environment: hyperthyroidism
causes metabolic hyperactivity, increased energy expenditure
at rest, weight loss, reduced cholesterol levels, increased lipol-
ysis and gluconeogenesis [6, 7]. On the contrary, the decline
in metabolic activity typical of hypothyroidism configures a
lower energy expenditure at rest with consequent weight gain,
hypercholesterolemia and reduced gluconeogenesis [8]. The
hormonal profile of the hypothyroid and/or hyperthyroid male
or female patients have a negative impact also on gonadal hor-
monal profile. Accordingly, alterations are found in the serum
levels of sex hormone-binding globulin, 17β-estradiol, testos-
terone, free-androgen index, progesterone, dehydroepiandros-
terone, luteotropic hormone, follicle-stimulating hormone, etc.
More than 99.8% of the circulating thyroid hormone is
bound to three plasma proteins: TBG, Transthyretin (TTR),
and albumin. TBG is the most quantitatively important and
represents over 70% of the total hormone bound to proteins
(both T4 and T3). About 10–15% of circulating T4 and 10%
of circulating T3 are bound to TTR and almost equal quanti-
ties are bound to albumin. TBG carries most of the hormones,
but all three proteins bind T4 with at least a 10-time grater
affinity than T3, thus the free and unbound concentrations of
T3 and T4 are almost equal. The molecular weight of hor-
mone binding proteins is large enough to not be filtered by the
kidneys; therefore, no thyroid hormone is found in the urine.
This confirms that plasma proteins also act as a substantial
reservoir of extra thyroid hormone [9]. It is clear that at the
serum level there is a fine balance between the free and bound
to protein fractions that can be altered by oral contraceptives
(OCs) made up of estrogens and/or progestins. These drugs
could influence this ratio either by increasing or decreasing
the concentration of thyroid hormone-binding proteins. There-
fore, the purpose of this review is to answer two fundamental
questions: (a) Does OCs intake affect thyroid function? (b)
Does the intake of LT4 affects the efficacy and safety of oral
hormonal contraception?
Drugs increasing thyroxin‑binding globulin
concentration andinuencing T4 andT3
transport intothebloodstream
The most common causes of increased serum TBG levels are
the raise in estrogen production or administration, either as a
component of an OC or as a replacement therapy [10]. TBG
is a glycoprotein synthesized by the liver. Natural estrogens
causes an increase in the salicylation, which, in turn, decreases
its clearance rate and increases its serum concentration [11].
The usual doses of ethinyl-estradiol (20–35µg per day) and
conjugated estrogens (0.625mg per day) increase serum
TBG concentrations by approximately 30–50% and serum T4
concentrations by 20–35% [12]. The increases begin within
two weeks and a new steady state is reached in 4–8weeks. In
women with hypothyroidism treated with T4 and in pregnant
women, on average, a 45% increase of the dose is required to
maintain normal serum TSH concentrations [13]. Thus, the
increase in total estrogen-induced serum T4 concentrations
occurs as a result of at least a transient increase in T4 secre-
tion (Fig.1).
The addition of progesterone to estrogen therapy does not
alter the estrogen-induced increase in serum TBG concentra-
tions and progesterone alone has no effect. Oral estrogens,
commonly used for replacement therapy rather contraception,
have a first-pass effect on the liver; transdermal administration
of estrogens does not increase serum concentrations of TBG
or T4, although estrogen serum concentrations are comparable
to those measured after oral administration [14]. The second
question to be analyzed, namely whether the intake of levo-T4
(LT4) can affect the efficacy and safety of OCs, is inspired
by an in-vitro and in-vivo study that showed how thyroid
hormones affect the action of estrogen [15]. The binding of
thyroid hormones to their receptors induces a transcriptional
facilitation of estrogen receptor genes. It seems that this fine
gene regulation takes into account seasonal phenomena linked
to reproduction. The treatment with estrogens influences the
hepatic synthesis and/or secretion of different proteins involved
in clinically important pathological processes such as athero-
sclerosis, hypertension, and thrombosis. After performing a
thyroidectomy in female mice, a decreased hepatic expression
of estrogen receptors by 70% was found; the administration
of T3 (1µg/day) normalized both mRNA expression as well
as the receptor protein [6]. This suggests that euthyroidism is
important for the effectiveness of OCs.
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Eects ofcombined oral contraceptive pills
onthyroid function
The use of contraceptive pills exploits pharmacodynamic
properties of the progestin component. Many progestins
have other partial effects (Table1).
Dienogest (DNG) has a higher anti-androgenic profile
than Levonorgestrel (LNG), which has a more andro-
genic profile. The estrogen profile of the DNG is slightly
higher than that of LNG, while the anti-estrogenic action
is scarcer. An important aspect is that there are no differ-
ences from the point of view of the anti-mineralocorticoid
and glucocorticoid action. The use of combined contra-
ceptives should also take into account the pleiotropic
effects of the estro-progestin synergy. For example, in a
state of hyperestrogenism, including pregnancy, there is an
increase in the proportion of sialic acid that decreases its
renal clearance [16]. This results in a decreased TBG real
clearance and, at the same time, leads to a greater capacity
to bind thyroid hormones [9].
Fig. 1 In women with hypothyroidism treated with thyroxin (T4)
and in pregnant women, on average, a 45% increase in the dose is
required to maintain normal serum TSH concentrations. The reduced
renal clearance of thyroxin-binding protein (TBG) due to its hyper
sialylation creates a sequestering effect of T4, which increases TSH
synthesis. A. Excessive stimulation in hypothyroid patients requires
close monitoring of hormonal therapy
Table 1 Effects of progesterone and progestins on thyroid function [57]
N not changed
TSH FT4 FT3 TBG SHBG Reference(s)
Progesterone + ( +) + N – [20]
Dienogest + + – N/N/↑ ↑ – [9, 17]
Drospirenone + + + + N/N[7]
Levonorgestrel + + – N/N/↑ ↑ – [9, 17]
Gestodene + + + + – ––↑ ↑ [58]
MPA + + ( +) – – [19]
Norgestimate + + – – – –-
Norethisterone + + N N – – [59]
Desogestrel + + – – ↑ ↑ [58]
Cyproterone acetate + + + + − N/N– [7]
Chlormadinone acetate + + + – – – [60]
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In a double-blind, controlled, randomized, four-arm clini-
cal trial, the effect of four OCs on thyroid hormones, cortisol,
aldosterone, endothelin-1, and angiotensin II was investi-
gated. Four groups of 25 volunteers each (aged between 18
and 35years) were treated for six cycles with monophasic
combinations containing 21 tablets with 30μg ethinyl estra-
diol (EE) + 2mg DNG (30 EE/DNG), 20μg EE + 2mg of
DNG (20 EE/DNG), 10μg of EE + 2mg of estradiol valerate
(EV) + 2mg of DNG (EE/EV/DNG) or 20μg EE + 100μg
of LNG (EE/LNG). A significant increase of T3 and T4 by
20–40% in all treatment cycles was reported, whereas TSH
significantly increased only with EE/EV/DNG [17].
Treatment with DNG-containing OCs did not cause vari-
ations in FT4 and a transient decrement of FT3 serum lev-
els during the first cycle. EE/LNG administration slightly
increases FT4, whereas FT3 remained stable. This could prob-
ably be related to the slight anti-estrogenic effects of LNG
compared to DNG. In addition, DNG has an anti-estrogenic
action, although bland. Furthermore, DNG has also an anti-
androgenic effect that could explain the serum TBG increase
and the consequent maintenance of FT4 concentrations. These
results suggest that the three low-dose DNG or LNG-contain-
ing OCs may increase T4, T3 and cortisol due to an increased
binding to serum globulins. The amount of free hormones does
not or slightly change. Therefore, these OCs have only minor
effects on thyroid function and adrenal parameters [17].
Eects ofestrogen orprogesterone‑only
containing drugs onthyroid function
To date, few data have been published on the effects of drugs
containing only estrogen or progesterone on thyroid func-
tion. A dose–response study in 23 post-menopausal women
assessed the effects of 25, 50, 100 and 200µg of transder-
mal estradiol administered daily on TBG, compared to that of
conjugated estrogens. While treatment with conjugated estro-
gens increased TBG serum levels, transdermal estrogens did
not [18]. In contrast, the use of depot medroxyprogesterone
acetate (DMPA) significantly increased FT4 levels more than
the copper intrauterine device (IUD) did [19]. Accordingly, a
randomized placebo-controlled 12-week trial found that oral
micronized progesterone at the daily dose of 300mg decreased
TSH, increased FT4 and did not have any effect on FT3 serum
levels, compared to placebo [20]. This evidence suggests a
greater role for progestins in influencing thyroid function when
OCs are given.
Contraceptives andthevenous thrombotic
Raps etal. [7] treated 231 women with OCs and evaluated
the following parameters: TBG, FT4, TSH and activated
protein C resistance (APCR). The results showed that TSH
and FT4 did not change significantly. Increases in TBG
levels in patients receiving more thrombogenic molecules,
such as cyproterone acetate, drospirenone, etc. were found.
On the contrary, the administration of less thrombogenic
progestins (e.g. LNG) resulted in lower TBG levels. The
study showed a positive correlation between increases in
TBG and in the thrombogenic protein APCR, thus leading
to a higher thromboembolic risk. The use of combined
OCs is associated with a higher risk of venous thrombo-
embolism (VTE), increased from three to eight times com-
pared to non-use [7]. The thrombotic risk depends on the
dose of estrogen and the type of progestin. The use of OCs
leads to resistance to activated protein C (APC), which can
serve as a marker for the risk of VTE.
As the Practice Committee of the American Society for
Reproductive Medicine (ASRM) reports, the incidence of
VTE has been esteemed to be as high as 16–22 cases per
10,000 women per year [21]. Several epidemiologic stud-
ies confirm the increased thrombotic risk in patients tak-
ing drugs containing only estrogens [21]. The “ET trial”,
carried on patients treated with estrogen-only medica-
tions, reported 30 and 22 thrombotic events per 10,000
women per year in the estrogen-treated group and in the
placebo one, respectively. The risk was high in the first
two years [22]. It was even higher when progesterone was
added to estrogens (1 vs. 2 cases per 1000 women per
year in the estrogen and estrogen plus progesterone groups,
respectively) [22]. A more recent meta-analysis reported
an increased VTE risk among women using oral, but not
transdermal estrogen-only medications [relative risk (RR)
1.48, vs. RR 0.97, respectively] [23]. This suggests that
transdermal estrogens could be preferred in women at
increased VTE risk. Among progestins, the available data
address to medroxyprogesterone acetate a greater safety
compared to other progestins. Based on observational data,
progesterone appears safe with respect to VTE risk [23].
Mean platelet volume andthrombosis
Platelets vary in size. Large platelets are more reactive,
have a greater prothrombotic potential and are more resist-
ant to inhibition with aspirin and clopidogrel (P2Y12).
They are assumed to be immature and their number
increases when there is an increase in the factors affecting
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platelet turnover. Recent studies have shown that the high
MPV is associated with an increased risk of deep VTE and
myocardial infarction (MI) [24]. A meta-analysis of cohort
studies suggests that MPV could be a useful prognostic
marker in patients with cardiovascular disease (CVD).
MPV was significantly higher in patients with acute MI
and/or coronary angioplasty [25]. High MPV has also been
identified as a predictor of VTE [24].
Cardiovascular risk is also influenced by testosterone.
Ajayi etal. [26] have shown that higher testosterone lev-
els increase human platelet thromboxane A2 receptor den-
sity and aggregation responses. This may contribute to
the thrombogenicity of androgenic steroids. Progesterone
administration can increase SHBG binding capacities and
it can control free testosterone level, decreasing the associ-
ated risks [27].
An important study [28] analyzed the correlation between
MPV and the amplitude of platelet distribution (PDW) in
the attempt to establish a clinicopathological relationship
by examining the thrombocyte parameters in cases of SCH.
Indirect evidence points to an effect of estrogen on plate-
let function. Accordingly, the mean platelet count decreases
in post-menopausal women not on OCs, compared to pre-
menopausal levels. On the contrary, no difference in MPV
values was found. The authors also reported a higher per-
centage of reticulated platelet in group of woman after men-
opause, suggesting a more thrombogenic phenotype [29].
Therefore, the available evidence on the impact of OCs on
platelet function suggests that there is no effect [30, 31].
Thyroid hormones can affect platelet function. Accord-
ingly, overt hyperthyroidism is associated with an increased
risk of VTE, due to increased levels of FT4 that cause a
state of hypercoagulability. In greater details, the T4 recep-
tor is able to interact with the platelet integrin αvβ3, thus
initiating the platelet aggregation cascade. In addition, thy-
roid hormones seem able to enhance the interaction between
platelets and endothelial cells involved in thrombus genera-
tion [32]. Hypothyroidism is also able to influence platelets,
mainly acting on MPV, as discussed subsequently. Particu-
larly, while the evidence on the effects of overt hypothyroid-
ism on MPV is contradictory, SCH has been more clearly
associated with increased MPV values.
SCH is defined as TSH elevation and normal serum FT4
levels. There is much evidence showing the relationship
between SCH and CVD. The risk factors that can be identified
in these patients include changes in the lipid profile, low grade
chronic inflammation, oxidative stress, diastolic hypertension,
changes in coagulation parameters and alterations of the car-
diovascular system [3336]. MPV is the most commonly used
measure of thrombocyte size and shows a correlation with
thrombocyte activity. PDW is an index that reflects the het-
erogeneous size of thrombocytes. These indices, in particular
MPV and PDW, are related to the functions of thrombocytes
[37, 38]. Therefore, SCH is a condition with a tendency to
cardiac events. The underlying mechanism is that the larger
thrombocytes are more enzymatically or metabolically active
and, therefore, there is a high potential thrombotic activ-
ity [39]. Since high-volume platelets are more hemostaticly
active, they could be a risk factor for possible coronary throm-
bosis and the development of MI. Current data from the study
on the increase in MPV in patients with SCH suggest that they
may have a specific role in the pre-thrombotic events that could
develop in the future [28].
The study by Kim aimed to find a correlation between
MPV and TSH serum concentrations in a population that
included subjects with unsuspected subclinical hypothyroid-
ism (SCH), but also at evaluating the potential predictive
role of MPV in clinically hypothyroid subjects. It was found
that MPV correlated positively with serum TSH levels and
that MPV could contribute to the pro-thrombotic condition
associated with SCH and perhaps also in putative euthyroid
states in which the TSH level is higher than the normal value
[40]. Demerin and colleagues showed that 95% of the 2290
subjects interviewed had a MPV between 7.2 and 11.7 fL
and that patients with a MPV beyond this range should be
carefully evaluated especially for occlusive arterial diseases.
At this point, it is useful to evaluate the association between
platelet count, MPV, and VTE [41]. A meta-analysis of 18
studies was conducted in accordance with the guidelines for
preferred reporting for systematic reviews and meta-analysis
(PRISMA) with primary endpoint aimed at analyzing the
onset of VTE and, as secondary endpoints, platelet count
and MPV assessment. The results showed that patients with
deep VTE were very likely to have a significantly higher
MPV value than the control group [42]. Changes in MPV
also occur under different pathological conditions. An
increased MPV has been observed in cardiovascular dis-
eases, stroke, respiratory diseases, chronic renal failure,
intestinal diseases, rheumatoid diseases, diabetes mellitus,
and various cancers, while a decrease in MPV was observed
in tuberculosis during exacerbation of the disease, ulcerative
colitis, systemic lupus erythematosus in adults and various
neoplastic diseases [43].
In conclusion, while it is accepted that MPV and PDW
increase is a risk factor for CVD, further studies are
needed to confirm the increase in platelet activation and
the increased risk of cardiovascular complications in SCH
Thyroid dysfunction: inuence onarterial
function andlipid prole
Previous studies have suggested that SCH is associated
with harmful effects on the cardiovascular system [44].
Studies have also suggested an association between SCH
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and hypertension, which was later confirmed by some, but
not all, large cross-sectional and case–control studies [44].
Over the past 5years, six large cross-sectional studies on this
topic have produced mixed results [4550]. Three studies
concluded that patients with SCH had a significantly higher
systolic blood pressure than euthyroid subjects (adjusted for
age, gender and body mass index) [45, 49, 50].
In the studies by Kuusi and colleagues [51] and O’Brien
[52], hypothyroidism was found to be associated with an
altered lipid profile [17, 26]. However, the relationship
between SCH and abnormal lipid profile is not yet clear.
Higher serum triglycerides (TG) levels were found in
patients with hypothyroidism compared to euthyroid par-
ticipants in their study. No convincing results were reported
on the association between hypothyroidism and serum TG,
as well as credible mechanisms. Previous studies have found
that LT4 therapy could decrease serum total cholesterol (TC)
or LDL-cholesterol levels, but in those studies serum TG
levels did not change after LT4 administration [53, 54]. This
result indicated that T4 may have limited effects on TG.
Hence, the association between hypothyroidism and TG is
not yet clear. In the meta-analysis by Xiao-Li Liu and col-
leagues [55], patients with SCH showed significantly higher
total cholesterol, TG and LDL-cholesterol values than euthy-
roid subjects.
In the review by La Vignera and his colleagues [56], it
is evident that a thyroid dysfunction due to SCH can cause
long-term alterations in lipid profile and MPV. All of this
can increase the risk of cardiovascular events. This may be
due to endothelial dysfunction; traditional effects can be
added to risk factors that promote atherosclerosis and non-
traditional effects on vascularization. In particular, TSH is
associated with an increase in LDL cholesterol, diastolic
pressure and markers of chronic inflammation (C-reactive
protein) and simultaneously reduces the bioavailability
of nitric oxide to blood vessels and increases angiotensin
receptor expression. Furthermore, LT4 replacement therapy
appears to improve all these aspects.
Finally, OCs prescription needs a careful evaluation of
the thyroid function, taking into account the impact of OCs
and of thyroid dysfunctions on the cardiovascular system
and lipid profile.
From the evidence above reviewed, it can be concluded that
significant changes in T4 and TSH levels are present after
the use of combined OCs. This means that there is a real
effect of OC pills on serum concentrations of thyroid hor-
mones. The increase in T4 and T3 appears to be related to
the increase in TBG level following OCs. FT4 and FT3 are
increased, but the lower TBG clearance and consequently
the increase in thyroid hormone synthesis, could be a
problem especially in patients with overt hypothyroidism
or SCH. In this regard, the prescription of OCs should be
associated with a monitoring of thyroid function (i.e.: serum
TSH levels). Hypothyroidism also requires attention to car-
diovascular risk since the increase in serum TBG correlates
positively with APCR, whose increase, in turn, indicates
both a state of hyper-coagulation and also a pro-aggregating
state. Accordingly, a positive correlation between MPV and
high TBG values in patients with hypothyroidism has been
reported. Since hypothyroidism may lead to lipid altera-
tions (e.g. hypercholesterolemia or hypertriglyceridemia)
and also to systolic/diastolic pressure alterations, both pro-
moting endothelial shear stress and, therefore, deep VTE, it
comes to light the importance to evaluate thyroid function
in patients on OC therapy.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
Ethical approval This article does not contain any studies with human
participants performed by any of the authors.
Informed consent No informed consent.
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... However, GnRHa in depot formulation has been associated with alteration of thyroid function, both with hyper and hypothyroidism [4,10,11,13]. e data about this International Journal of Endocrinology 3 correlation are scanty and exact pathophysiological mechanisms are not known yet and both hormonal and immune factors might be involved [11,[15][16][17]. Rapid changes of sex hormone globulin levels seem to play a role in thyroid function, especially when thyroid autoimmunity is present [11]. ...
... Estrogen deprivation seems not a reasonable mechanism of thyroid dysfunction because enrolled women received estradiol valerate for endometrial preparation. High estradiol levels administered could also be responsible for a decreased clearance of TGB with a subsequent greater capability of binding thyroid hormones and increased TSH [15]. Also, women in the control group received estradiol therapy. ...
... e usual doses of oestrogens in OCPs (20-35 μg ethinyl-estradiol per day) increase serum thyroxine-binding globulin concentrations by approximately 30-50% and serum thyroxine concentrations by 20-35% [18], and these increases usually begin within two weeks [19]. However, the pharmacodynamic properties of the progestin component of OCP modify the effects of OCP itself [15]. In particular, the different progestins have different roles on thyroid function, and DNG has a bland antiestrogenic effect and an antiandrogenic action [20]. ...
Full-text available
GnRH agonists (GnRHa) are a useful tool for pretreatment before artificial endometrial preparation for frozen-thawed embryo-transfer (FET). Their prolonged administration has been associated with thyroid dysfunction, both hyper and hypothyroidism. The aim of this study is to investigate the impact of GnRHa administration on thyroid function in women undergoing artificial endometrial preparation. Seventy-eight euthyroid women undergoing endometrial preparation with hormone replacement for FET were retrospectively reviewed. They were divided into two groups according to pretreatment with GnRHa (group A, 42 women) or with an oral contraceptive (group B, 36 women). Group A was subsequently divided into two subgroups according to thyroid autoimmunity presence. Thyroid function has been evaluated and compared among groups and subgroups. Our results did not show any statistically significant differences in age, body mass index, and basal thyroid stimulating hormone (TSH). Total estradiol dosage, duration of treatment, and endometrial thickness were comparable among groups. When TSH was measured 14 days after embryo transfer, no significant differences between the two groups were reported. Among women of group A, TSH was significantly higher only in women with thyroid autoimmunity. GnRHa seems to be associated with thyroid dysfunction in women with thyroid autoimmunity undergoing hormone replacement therapy for FET.
... Furthermore, whether the ovarian hormones regulate skeletal muscle protein content or activity of transamination and branched-chain amino acid oxidation enzymes remains to be determined. Alternatively, some suggest P4 upregulation and E2 downregulation of thyroid function and availability of free triiodothyronine (T3) (Ben-Rafael et al. 1987;Torre et al. 2020) is causative of the greater protein catabolism in the luteal phase (Lariviere et al. 1994). Resting plasma free T3 concentration was found to be higher coincident to a greater leucine oxidation rate in the ML versus EF phase in one study (Lariviere et al. 1994). ...
... Resting plasma free T3 concentration was found to be higher coincident to a greater leucine oxidation rate in the ML versus EF phase in one study (Lariviere et al. 1994). P4 binds PR within the thyroid gland to promote T3/thyroxine (T4) secretion and reduce its binding to the plasma protein, thyroid-binding globulin to maximize free T3 availability (Torre et al. 2020;Kaminski et al. 2021) thereby accounting for the higher resting metabolic rate (Benton et al. 2020) and thus possibly protein catabolism reported in the luteal phase compared with follicular phase. ...
Full-text available
Research should equitably reflect responses in men and women. Including women in research, however, necessitates an understanding of the ovarian hormones and menstrual phase variations in both cellular and systems physiology. This review outlines recent advances in the multiplicity of ovarian hormone molecular signaling that elucidates the mechanisms for menstrual phase variability in exercise metabolism. The prominent endogenous estrogen, 17-β-estradiol (E2), molecular structure is bioactive in stabilizing plasma membranes and quenching free radicals and both E2 and progesterone (P4) promote the expression of antioxidant enzymes attenuating exercise-induced muscle damage in the late follicular (LF) and mid-luteal (ML) phases. E2 and P4 bind nuclear hormone receptors and membrane-bound receptors to regulate gene expression directly or indirectly, which importantly includes cross-regulated expression of their own receptors. Activation of membrane-bound receptors also regulates kinases causing rapid cellular responses. Careful analysis of these signaling pathways explains menstrual phase-specific differences. Namely, E2-promoted plasma glucose uptake during exercise, via GLUT4 expression and kinases, is nullified by E2-dominant suppression of gluconeogenic gene expression in LF and ML phases, ameliorated by carbohydrate ingestion. E2 signaling maximizes fat oxidation capacity in LF and ML phases, pending low-moderate exercise intensities, restricted nutrient availability, and high E2:P4 ratios. P4 increases protein catabolism during the luteal phase by indeterminate mechanisms. Satellite cell function supported by E2-targeted gene expression is countered by P4, explaining greater muscle strengthening from follicular phase-based training. In totality, this integrative review provides causative effects, supported by meta-analyses for quantitative actuality, highlighting research opportunities and evidence-based relevance for female athletes.
... Inductively coupled plasma mass spectrometry (ICP-MS) was used to assess the levels of trace elements in biological samples, and the levels of lead, Cd, and mercury in whole blood were determined [26]. Values below the limit of detection (LOD) for heavy metal concentrations were handled by dividing the LOD by the square root of 2 [27]. ...
Full-text available
Background The association between exposure to environmental metals and chronic obstructive pulmonary disease (COPD) is preventing chronic lung diseases. However, little is currently known about the interaction between heavy metals and flavonoids in relation to the risk of COPD. This study aims to bridge this knowledge gap by leveraging The National Health and Nutrition Examination Survey (NHANES) database to evaluate thecorrelation between blood levels of heavy metals (cadmium, lead, mercury) and the intake of various flavonoid compounds (isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols, total flavonoids). Additionally, appropriate dietary recommendations are provided based on the study findings. Materials and methods Cross-sectional analysis was conducted using the 2007–2010 and 2017–2018 NHANES data. Specialized weighted complex survey design analysis software was used for data analysis. Multivariate logistic regression models and restricted cubic splines (RCS) were used to evaluate the relationship between blood heavy metal levels, flavonoids intake, and COPD incidence in all participants, and to explore the effect of different levels of flavonoids intake on COPD caused by heavy metal exposure. Results A total of 7,265 adults aged ≥ 40 years were analyzed. Higher levels of blood cadmium (Cd), blood lead and Anthocyanidin (AC) intake were independently associated with an increased risk of COPD (Cd highest quantile vs. lowest: OR = 1.73, 95% CI, 1.25–2.3; Lead highest quantile vs. lowest quantile: OR = 1.44, 95% CI, 1.11–1.86; AC highest quantile vs. lowest: OR = 0.73, 95% CI, 0.54–0.99). When AC intake exceeded 11.56 mg/d, the effect of Cd exposure on COPD incidence decreased by 27%, and this finding was more significant in smokers. Conclusion Higher levels of Cd (≥ 0.45ug/L) and lead (≥ 0.172 ug/L) were positively correlated with the risk of COPD among participants aged 40 years and above, while AC intake (≥ 11.56 mg/d) could reduce the risk related to blood Cd.
... OC may potentially influence thyroid function by enhancing liver SHBG synthesis and modulating tissue estrogen action (194). Long-term OC use was associated with a~4 times higher risk of hypothyroidism. ...
Full-text available
Background Published data on the relationship between polycystic ovary syndrome (PCOS) and thyroid dysfunction are sparse and confusing. Objective To comprehensively review data available in the literature regarding the relationship between PCOS and the thyroid function, and its abnormalities. Methods Nine main areas of interest were identified and analyzed according to the available evidence: 1) Evaluation of thyroid function for PCOS diagnosis; 2) Epidemiology data on thyroid function/disorders in patients with PCOS, and vice versa; 3) Experimental data supporting the relationship between thyroid function/disorders and PCOS; 4) Effects of thyroid function/disorders on PCOS features, and vice versa; 5) Effect of thyroid alterations on the cardiometabolic risk in women with PCOS; 6) Effect of thyroid abnormalities on reproductive outcomes in women with PCOS; 7) Relationship between thyroid function/abnormalities in patients with PCOS who are undergoing fertility treatment; 8) Effect of treatments for thyroid diseases on PCOS; and 9) Effect of treatments for PCOS on thyroid function. An extensive literature search for specific keywords was performed for articles published from 1970 to March 2023 using PubMed and Web of Science. Data were reported in a narrative fashion. Results PCOS is a diagnosis of exclusion for which diagnosis is possible only after excluding disorders that mimic the PCOS phenotype, including thyroid dysfunctions. However, the tests and the cutoff values used for this are not specified. Many experimental and clinical data suggest a relationship between perturbations of the thyroid function and PCOS. Direct and unequivocal evidence on the effects of thyroid function/disorders on PCOS features are lacking. High thyroid-stimulating hormone levels and subclinical hypothyroidism may be associated with significant worsening of several intermediate endpoints of cardiometabolic risk in women with PCOS. Thyroid abnormalities may worsen reproductive outcomes, especially in patients undergoing fertility treatment. To date, there are no data demonstrating the efficacy of thyroid medications on fertility and cardiometabolic risk in women with PCOS. Lifestyle modification changes, metformin, and vitamin D seem to improve thyroid function in the general population. Conclusion PCOS and thyroid disorders are closely related, and their coexistence may identify patients with a higher reproductive and metabolic risk. Regular screening for thyroid function and thyroid-specific autoantibodies in women with PCOS, particularly before and during pregnancy, is highly recommended.
... The regulation of the reproductive status by thyroid hormones (TH) in mammals is quite complex [1]. TH can affect sex steroids in several ways: by acting directly on the gonads, through their interaction with estradiol (E2), progesterone (P4), testosterone (T), FSH, LH and prolactin (PRL), or on the production of GnRH-releasing hormone in the hypothalamus pituitary-gonadal axis (HPG) [2,3]. ...
The aim of our research work was to study the level of sex steroids in blood, the tumor and the perifocal zone in rats of both sexes with Guerin’s carcinoma against the background of hypothyroidism. Materials and methods. The experiment was performed in 110 outbred rats of both sexes. Hypothyroidism was induced in animals for 30 days with Mercazolil medication, and then Guerin’s carcinoma was transplanted (the main group). The reference groups included animals with an independent growth of Guerin’s carcinoma and with independent hypothyroidism, as well as intact animals (the norm). On the 18th day of the tumor growth, the animals were sacrificed, and, using standard RIA kits, in the serum, the tumor homogenates and the perifocal zone, the levels of estradiol (E2), testosterone (T) and progesterone (P4) were determined. Results. In comparison with intact animals, hypothyroidism caused an increase in the blood content of E2 in animals of both sexes by 2.2-2.4 times and T by 1.4-16 times, and P4 by 1.7 times only in females, but recorded was a decrease therein in males by 2.4 times. The growth of Guerin’s carcinoma resulted in a 2.5-5.5-fold decrease in E2 in blood of the animals of both sexes, an increase in T by 2.1 times and P4 by 3 times in the females, but a decrease in T by 2.6 times without changing P4 in the males. In the main group, in the animals of both sexes, similarly to the processes in hypothyroidism, the level of E2 and P4 increased by 1.4-1.6 times, and in females also T by 4.4 times, compared with the intact animals. Conclusion. Hypothyroidism and the growth of Guerin’s carcinoma changed E2 in different directions in animals of both sexes the level of sex hormones in blood and shifted the steroid balance in the tumor and its perifocal zone. In the females of the main group, the saturation of the tumor with estrogens, androgens and progesterone decreased, while in the males, on the contrary, the concentration of steroids increased.
... The relationship between the two glands is mutual [3,4]. Thyroid hormone increase the synthesis of sex hormone binding globulin (SHBG), testosterone, and androstenedione, reducing the clearance of estradiol and androgens while increasing the conversion of androgens to estrone [5]. The main role of estrogens in thyroid physiology is related to the increase in serum concentrations of thyroxine binding globulin (TBG) [6]. ...
Full-text available
Background To evaluate the endocrine hormone and metabolic indices in postmenopausal women with euthyroid and mild subclinical hypothyroidism after menopause hormone therapy (MHT). Methods A retrospective study of 587 postmenopausal women receiving MHT was conducted. Median (25–75th percentile) age was 52 (49–54) years. According to thyroid stimulating hormone (TSH) levels at initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After a continuous oral MHT regimen using the same estradiol potency for 6–18 month cycles, serum endocrine hormone and metabolic indices were reassessed. Results Compared with baseline, serum TSH levels in groups I and II significantly changed but all values were within the normal range. No significant difference was observed in serum TSH levels in group III. After treatment, all serum free tri-iodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index had significantly decreased in group I. There were no significant differences in all observed lipid and glucose parameters in group III, before and after treatment. Conclusion MHT did not affect thyroid function in postmenopausal women with euthyroid and mild subclinical hypothyroidism. MHT led to an improvement in lipid and glucose indicators in euthyroid women with low normal TSH range.
... The relationship between the two glands is mutual [3] [4]. Thyroid hormone increase the synthesis of sex hormone binding globulin (SHBG), testosterone and androstenedione, reduce the clearance of estradiol and androgens and increase the conversion of androgens to estrone [5]. The main role of estrogens in thyroid physiology is related to the increase of the serum concentrations of thyroxine binding globulin (TBG) [6]. ...
Full-text available
Objective To evaluate the endocrine hormone and metabolic indexes in euthyroid and mild subclinical hypothyroidism postmenopausal women after menopause hormone therapy (MHT). Methods A retrospective study was conducted including 587 postmenopausal women received MHT, whose median (25-75th percentile) age was 52.00 (49.00–54.00) years. According to the state of thyroid stimulating hormone (TSH) level at the initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After continuous oral MHT regimen used same potency of estradiol for 6–18 month cycles, serum endocrine hormone and metabolic indexes were reassessed. Results Compared with baseline, serum TSH level in group I and II changed with significant difference, but all values were within the normal range, no significant difference was found of serum TSH level in group III. After treatment, all serum free triiodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index were decreased in group I with significant differences. All lipid and glucose parameters were found no significant differences in group III before and after treatment. Conclusions MHT did not affect thyroid function in euthyroid and mild subclinical hypothyroidism women. MHT led to an improvement of lipid and glucose indicators in euthyroid women with low normal TSH range.
Full-text available
Latar Belakang. Hipertiroid dapat mengakibatkan percepatan detak jantung, penurunan berat badan, peningkatan nafsu makan, dan kecemasan. Hipertiroidisme lebih sering terjadi pada wanita. Pajanan asap rokok, stres psikologi, penggunaan kontrasepsi hormonal, umur, periode melahirkan, dan konsumsi iodium pada tahap tertentu dapat memicu hipertiroid. Tujuan. Penelitian ini mencari hubungan antara status merokok, tingkat stres, penggunaan kontrasepsi hormonal, umur, dan penggunaan garam beriodium rumah tangga dengan kejadian hipertiroid pada wanita usia subur (WUS). Metode. Penelitian ini adalah penelitian observasional dengan desain kasus-kontrol pada pasien baru WUS berusia 15–49 tahun di Klinik GAKI Magelang tahun 2013–2014. Populasi penelitian terdiri atas kelompok kasus yaitu 51 pasien WUS didiagnosis hipertiroid. Kelompok kontrol yaitu 102 WUS yang didiagnosis sehat dan tidak mengalami gangguan fungsi tiroid (eutiroid/normal). Data dikumpulkan melalui wawancara responden disertai uji cepat kandungan iodium garam rumah tangga. Uji Chi-square dilakukan untuk mendapatkan hubungan bivariat antara variabel independen dan kejadian hipertiroid pada responden. Analisis uji regresi logistik dilakukan untuk mendapatkan hubungan variabel dependen secara bersamaan terhadap kejadian hipertiroid. Hasil. Wanita usia subur dengan stres berat mempunyai risiko hipertiroid 2,4 kali daripada WUS dengan stres ringan (OR=2,435; 95% CI=1,031–5,755; p=0,043; p<0,05). Wanita usia subur bukan pengguna kontrasepsi hormonal memiliki risiko hipertiroid 3,5 kali dibandingkan dengan WUS pengguna kontrasepsi hormonal (OR=0,284; 95% CI=0,114–0,709; p=0,007; p<0,05). Kesimpulan. Stres berat berhubungan dengan risiko hipertiroid pada WUS. Wanita usia subur (WUS) hendaknya melakukan manajemen stres sebagai salah satu upaya pencegahan terhadap hipertiroid dan juga pencegahan kekambuhan hipertiroid.
Thyroid dysfunction is a common endocrine disorder among reproductive-aged women, the groups of women who most commonly use effective hormonal contraceptives (HCs) for both spacing and limiting births. However, HCs including either combined estrogen-progestin or progestin-only contraceptives and thyroid hormones have profound interactions to each other. Although women with no thyroid disease adapt quickly to thyroid hormonal alterations induced by those agents, those small alterations may be clinically important for women who suffer from thyroid disorders. Similarly, there are limited studies suggesting that thyroid hormones may affect the action of estrogen and subsequently can affect the efficacy and safety of HCs. This chapter focuses on the various aspects of interaction between thyroid hormones and HCs in order to present the clinical guide for daily practice.
This study aimed to investigate the impact of short-time hypothyroidism on the expression of aromatase, estrogen receptors (ERα, β), and GPR30 in the pancreas of female rabbits. The formation of new islets and the expression of insulin, GLUT4, and lactate dehydrogenase (LDH) were also analyzed. This purpose is based on actions that thyroid hormones and estrogens have on β-cells differentiation, acinar cell function, and insulin secretion. Twelve Chinchilla-breed adult virgin female rabbits were divided into control (n=6) and hypothyroid (n=6; methimazole 10 mg/kg for 30 days) groups. In the complete pancreas, expressions of aromatase and estrogen receptors, as well as proinsulin, GLUT4, and LDH were determined by western blot. Characteristics of islets were measured in slices of the pancreas with immunohistochemistry for insulin. Islet and acinar cells express aromatase, ERα, ERβ, and GPR30. Hypothyroidism increased the expression of ERα and diminished that for aromatase, ERβ, and GPR30 in the pancreas. It also promoted a high number of extra small islets (new islets) and increased the expression of proinsulin and GLUT4 in the pancreas. Our results show that actions of thyroid hormones and estrogens on β-cells neogenesis, acinar cell function, and synthesis and secretion of insulin are linked. Thus, the effects of hypothyroidism on the pancreas could include summatory actions of thyroid hormones plus estrogens. Our findings indicate the importance of monitoring estrogen levels and actions on the pancreas of hypothyroid women, particularly when serum estrogen concentrations are affected such as menopausal, pregnant, and those with contraceptive use.
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Platelet size has been demonstrated to reflect platelet activity and seems to be a useful predictive and prognostic biomarker of cardiovascular events. It is associated with a variety of prothrombotic and proinflammatory diseases. The aim is a review of literature reports concerning changes in the mean platelet volume (MPV) and its possible role as a biomarker in inflammatory processes and neoplastic diseases. PubMed database was searched for sources using the following keywords: platelet activation, platelet count, mean platelet volume and: inflammation, cancer/tumor, cardiovascular diseases, myocardial infarction, diabetes, lupus disease, rheumatoid arthritis, tuberculosis, ulcerative colitis, renal disease, pulmonary disease, influencing factors, age, gender, genetic factors, oral contraceptives, smoking, lifestyle, methods, standardization, and hematological analyzer. Preference was given to the sources which were published within the past 20 years. Increased MPV was observed in cardiovascular diseases, cerebral stroke, respiratory diseases, chronic renal failure, intestine diseases, rheumatoid diseases, diabetes, and various cancers. Decreased MPV was noted in tuberculosis during disease exacerbation, ulcerative colitis, SLE in adult, and different neoplastic diseases. The study of MPV can provide important information on the course and prognosis in many inflammatory conditions. Therefore, from the clinical point of view, it would be interesting to establish an MPV cut-off value indicating the intensity of inflammatory process, presence of the disease, increased risk of disease development, increased risk of thrombotic complications, increased risk of death, and patient’s response on applied treatment. Nevertheless, this aspect of MPV evaluation allowing its use in clinical practice is limited and requires further studies.
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Purpose: The aim of the study was to evaluate thyroid function profile as a possible factor influencing weight and body composition variation in new users of depot medroxyprogesterone acetate (DMPA). Materials and methods: A prospective, non-randomised, comparative study was conducted at the University of Campinas, Brazil. Women aged 18–40 years with a body mass index (BMI) less than 30 kg/m², normal oral glucose tolerance test, no known diseases, and using no medication, who opted to use DMPA were paired by age (±1 year) and BMI (±1 kg/m²) with women initiating copper intrauterine device (IUD) use. The main outcome measures were thyroid function profile, weight, and body composition, as measured by dual-energy X-ray absorptiometry. We used repeated measures ANOVA to perform comparisons between times and groups. Results: We evaluated 28 DMPA users and 24 IUD users who completed the 12-month follow-up. We observed that FT4 levels were higher at 12 months (compared to baseline) in the DMPA group (p < .0001) and that FT4/FT3 ratio had increased in both groups. Additionally, at 12 months, total body mass had increased around 2 kg and lean mass increased in the DMPA group compared to the IUD group; there was also an increase in weight, BMI, total body mass, and fat mass when compared to baseline. Conclusions: No changes in thyroid function occurred that could explain the weight increase observed in DMPA users.
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Substantial clinical evidence indicates hyperthyroidism enhances coagulation and increases the risk of thrombosis. In vitro and clinical evidence implicate multiple mechanisms for this risk. Genomic actions of thyroid hormone as 3,5,3′-triiodo-L-thyronine (T3) via a nuclear thyroid hormone receptor have been implicated, but recent evidence shows that nongenomic mechanisms initiated at the receptor for L-thyroxine (T4) on platelet integrin αvβ3 are prothrombotic. The T4-initiated mechanisms involve platelet activation and, in addition, cellular production of cytokines and chemokines such as CX3CL1 with procoagulatory activities. These procoagulant actions of T4 are particulary of note because within cells T4 is not seen to be functional, but to be only a prohormone for T3. Finally, it is also possible that thyroid hormone stimulates platelet-endothelial cell interaction involved in local thrombus generation. In this brief review, we survey mechanisms by which thyroid hormone is involved in coagulation and platelet functions. It is suggested that the threshold should be lowered for considering the possibility that clinically significant clotting may complicate hyperthyroidism. The value of routine measurement of partial thromboplastin time or circulating D-dimer in patients with hyperthyroid or in patients treated with thyrotropin-suppressing dosage of T4 requires clinical testing.
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The purpose of this study was to evaluate the association between platelet (PLT) count and mean platelet volume (MPV) and venous thromboembolism (VTE). Thus, this study reviewed and performed a quantitative synthesis on data from the literature. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 18 studies were included in this paper. A random-effect meta-analysis was conducted for the assessment of heterogeneity using thrombosis place, type of analyzer, type of anticoagulant and incubation time of samples as covariates. A mixed-effect meta-regression was performed based on the subgroup for the whole samples using thrombosis place and method of measurement as moderators for MPV and PLT, respectively. The cumulative estimates and 95% confidence interval (95%CI) of specificity, sensitivity, area under the receiver operator characteristic curve (AUC) and diagnostic odds ratio (DOR) for MPV were calculated using a random effect model. The quality assessments were evaluated according to the quality assessment and diagnostic accuracy tool-2 (QUADAS-2). The primary outcome was the occurrence of VTE. Secondary outcomes included PLT and MPV. Patient with deep vein thrombosis is likely to have a higher value of MPV than control group (P < 0.001). The presence of pulmonary embolism (PE) had no significant effect on the standardized mean difference of MPV between patients and controls. Patients are likely to have less PLT than the control group regarding all studies. However, subgroup analysis demonstrated that this effect was significant for patients with PE (P < 0.05). The summary receiver operating characteristic (SROC) curve indicated that AUC was 0.745 (95% CI: 0.672–0.834). The DOR for MPV was 4.76 (95%CI: 2.3–9.85), with diagnostic accuracy of 0.66.
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Haemostasis and thrombosis are complex, multifactorial processes. There is an evolving understanding of the mechanisms influencing vascular occlusion and the role of inflammation and immunity. Despite major advances in elucidating the mechanistic pathways mediating platelet function and thrombosis, challenges in the treatment of vascular occlusive diseases persist. Pharmacological advances have greatly affected thrombotic outcomes, but this has led to the unwanted side effect of bleeding. Detailed assessment of the impact of nonthrombotic diseases on haemostasis and thrombosis is necessary to better evaluate thrombotic risk and establish optimal treatment. This review will focus on recent advances in understanding the contribution of evolving risk factors to thrombosis.
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Background: Decreased platelet (PLT) count is one of the independent risk factors for mortality in intensive care unit (ICU) patients. This study was to investigate the relationship between PLT indices and illness severity and their performances in predicting hospital mortality. Methods: Adult patients who admitted to ICU of Changzheng Hospital from January 2011 to September 2012 and met inclusion criteria were included in this study. Univariate analysis was used to identify potential independent risk factors for mortality. Multiple logistic regression analysis was used to calculate adjusted odds ratio for mortality in patients with normal or abnormal PLT indices. The relationship between PLT indices and illness severity were assessed by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores or sequential organ failure assessment (SOFA) scores in patients with normal and abnormal PLT indices. The performances of PLT indices in predicting mortality were assessed by receiver operating curves and diagnostic parameters. The survival curves between patients with normal and abnormal PLT indices were compared using Kaplan-Meier method. Results: From January 2011 to September 2012, 261 of 361 patients (204 survivors and 57 nonsurvivors) met the inclusion criteria. After adjustment for clinical variables, PLT count <100 × 10 12 /L (P = 0.011), plateletcrit (PCT) <0.108 (P = 0.002), mean platelet volume (MPV) >11.3 fL (P = 0.023) and platelet distribution width (PDW) percentage >17% (P = 0.009) were identified as independent risk factors for mortality. The APACHE II and SOFA scores were 14.0 (9.0-20.0) and 7.0 (5.0-10.5) in the "low PLT" tertile, 13.0 (8.0-16.0) and 7.0 (4.0-11.0) in the "low PCT" tertile, 14.0 (9.3-19.0) and 7.0 (4.0-9.8) in the "high MPV" tertile, 14.0 (10.5-20.0) and 7.0 (5.0-11.0) in the "high PDW" tertile, all of which were higher than those in patients with normal indices. Patients with decreased PLT and PCT values (all P < 0.001), or increased MPV and PDW values (P = 0.007 and 0.003, respectively) had shortened length of survival than those with normal PLT indices. Conclusions: Patients with abnormally low PLT count, high MPV value, and high PDW value were associated with more severe illness and had higher risk of death as compared to patients with normal PLT indices.
Postmenopausal hormone therapy (HT) is a modifiable risk factor for venous thromboembolism (VTE). While the route of estrogen administration is now well recognized as an important determinant of VTE risk, there is also increasing evidence that progestogens may modulate the estrogen-related VTE risk. This review updates previous meta-analyses of VTE risk in HT users, focusing on the route of estrogen administration, hormonal regimen and progestogen type. Among women using estrogen-only preparations, oral but not transdermal preparations increased VTE risk (relative risk (RR) 1.48, 95% confidence interval (CI) 1.39–1.58; RR 0.97, 95% CI 0.87–1.09, respectively). In women using opposed estrogen, results were highly heterogeneous due to important differences between the molecules of progestogen. In transdermal estrogen users, there was no change in VTE risk in women using micronized progesterone (RR 0.93, 95% CI 0.65–1.33), whereas norpregnane derivatives were associated with increased VTE risk (RR 2.42, 95% CI 1.84–3.18). Among women using opposed oral estrogen, there was higher VTE risk in women using medroxyprogesterone acetate (RR 2.77, 95% CI 2.33–3.30) than in those using other progestins. These clinical findings, together with consistent biological data, emphasize the safety advantage of transdermal estrogen combined with progesterone and support the current evidence-based recommendations on HT, especially in women at high VTE risk.
Hypothyroidism is a commonly encountered clinical condition with variable prevalence. It has profound effects on cardiac function that can impact cardiac contractility, vascular resistance, blood pressure, and heart rhythm. With this review, we aim to describe the effects of hypothyroidism and subclinical hypothyroidism on the heart. Additionally, we attempt to briefly describe how hypothyroid treatment affects cardiovascular parameters.