Gender Clinical Trial
Official title:
Haemostasis Evaluation Related to Sexual Hormones: Gender Perspective
Atherothrombotic disorders account for 25% of all deaths among women and for substantial
morbidity and resource use in health care. Nonetheless, gender-related differences in the
epidemiology of cardiovascular disease (CVD) remain largely unexplained. Among mechanisms
that could account for such differences, the biology of platelets, which exert a pivotal
pathogenetic role in atherothrombosis, and of coagulation system are on investigation.
Thus, differences in platelet reactivity between women and men have been described using
several methods and in response to varying stimuli. Indeed, sex steroid hormones could be
involved in a different response of platelet to physiological response to agonists. The
finding that estrogen receptors are expressed in platelets makes these cells an excellent
model for studying the non-genomic effects of steroid hormones. Also coagulation cascade has
been reported to be influenced by sexual endogenous as well as exogeneous hormones (i.e
contraceptives) In particular, the impact of endogenous estrogens (menstrual cycle) on
platelet activity and on response to antiplatelets drugs in fertile women has never been
evaluated.
Accordingly, the goal of this proposal is to investigate relationship between platelet
function (assessed by aggregometry tests and markers of platelet activation in vivo such as
thromboxane production, CD40L and P- selectin levels) and sex hormones during physiological
regular menstrual cycles (28-30 days) in healthy pre-menopausal women aged from 18 to 40
years. Moreover, in a subgroup of healthy women free from antiplatelet drugs, will be
planned a proof of concept study to investigate if there will be variations, during a short
term (1 month) low dose aspirin, in platelet reactivity according to the different phases of
menstrual cycle in 10 healthy premenopausal women aged from 18 to 40 years. Moreover, it
will be investigate effect of steroid hormonal pattern on residual platelet activity
response on treatment
Atherothrombotic disorders account for 25% of all deaths among women and for substantial
morbidity and resource use in health care. Nonetheless, gender-related differences in the
epidemiology of cardiovascular disease (CVD) remain largely unexplained. Thus, the
application of sex-gender medicine is strongly recommended by WHO and other international
organization. In fact, it is emerging that although men and women are subject to the same
cardiovascular diseases (CVD), however, they have different risk factors, disease
progression and response to drug treatment.
In the last decades emerging scientific knowledge about platelet role in the
atherothrombotic diseases physiopathology provides clues and asks questions about the
possibility that a different platelet function modulation could influence the women
population cardiovascular disease clinical course, especially considering that, compared to
men population, the women one recognizes a worst cardiovascular outcome.
It is widely acknowledged that platelet reactivity plays a pivotal role in thrombus
formation and atherosclerosis. Differences in platelet reactivity between women and men have
been described using several methods and in response to varying stimuli. In particular,
platelets from women without vascular diseases are more reactive than those of men in
response to standard concentrations of agonists such as adenosine diphosphate (ADP) and
thrombin receptor agonist protein. Mechanisms that could account for such differences are on
investigation. Indeed, sex steroid hormones could be involved as they exert multiple direct
and indirect effects on cardiovascular physiology. The pleiotropic effects of estradiol-17
(E2) and estrogen receptors (ERs), a part of thei pivotal role in sexual development and
reproduction,are a consequence of both the widespread expression of ER in many cell
populations within the body as well as possibly reflecting the ancestral status of ER in the
steroid receptor family.
Epidemiologic and experimental studies now support an atheroprotective effect of both
endogenous and exogenous estrogens. The Women's Health Initiative study did not show a
coronary protective effect of estrogen in postmenopausal women, but subsequent studies have
shown that this was because of both inappropriate timing (ie, administering the hormone
therapy too late) and the identity of the associated progestin.
Physiologic differences between men and women affect also drug activity, including
pharmacokinetics and pharmacodynamics. Women are underrepresented in cardiovascular studies,
even as their preponderance in the aging population steadily increases. A better
understanding of the factors contributing to the observed sex-related differences in
platelet biology is warranted. In particular concerns have been raised about the role of
specific hormones in mediating platelet activation and function and the differential benefit
of antiplatelet medications for women.
It has been reported that many of sex gender differences associated with CVD in women could
depend by estrogen. The finding that estrogen receptors are expressed in platelets renders
these cells an excellent model for studying the non-genomic effects of these hormones.
In conclusion, the impact of estrogens endogenous (menstrual cycle) and/or exogenous (oral
contraceptives therapy) on platelet activity and response to antiplatelets drugs in women
has not been extensively evaluated.
To fill this gap in evidence and to find a support to optimize cardiovascular therapy by
gender-oriented approach, the investigators planned to study the effect of endogenous
estrogens (menstrual cycle) on platelet function and on antiplatelet therapy response in
pre-menopausal healthy women.
Phase 1 Evaluation of platelet function in different menstrual cycle phases. Phase 2: "Proof
of concept study" A short treatment period with aspirin (100 mg daily) was also planned.
Patients involved in the first phase study will be asked to participate in the
interventional study. The investigators plan to enroll in the study 10 women and to follow
them for 1 month.
Blood samples will be obtained at baselines and at four time points during treatment to
verify the effect of aspirin on platelets' function related to menstrual cycle hormonal
fluctuations.
;
Observational Model: Cohort, Time Perspective: Prospective
Status | Clinical Trial | Phase | |
---|---|---|---|
Not yet recruiting |
NCT06441942 -
Prospective Multicenter Registry of Gender, Diversity and Inclusion (GEDI) of Women With Acute Coronary Syndrome
|
||
Recruiting |
NCT05593692 -
Gender Differences and Age Related Differences in Emergency Department Admission
|
||
Active, not recruiting |
NCT06345573 -
Heart-brain-axis and Psychosocial Stress
|
||
Completed |
NCT01571128 -
Gender-Specific Combination HIV Prevention for Youth in High Burden Settings (MP3-Youth)
|
N/A | |
Completed |
NCT06138119 -
The Impact of Gender Stereotypes on Fiberoptic Intubation Performance
|
N/A | |
Active, not recruiting |
NCT03884608 -
Analysis of Both Sex and Device Specific Factors on Outcomes in Patients With Non-Ischemic Cardiomyopathy
|
||
Recruiting |
NCT05789667 -
Gender-based Impact on Safety and Efficacy of Lenvatinib in Patients With Differentiated Thyroid Cancer
|
||
Not yet recruiting |
NCT06018623 -
Dosage of Propofol Based on Lean Body Weight
|
||
Completed |
NCT03534375 -
Gender Differences of Neuroanatomical and Neurophysiological Correlates of Risk-proneness in Early Adolescents
|
||
Completed |
NCT02651233 -
Factors That Influence Adipose Derived Regenerative Cells' Yield and Viability
|
N/A | |
Completed |
NCT04077151 -
Transgender Youth and PrEP: PK, Safety, Uptake & Adherence - Demonstration Project
|
N/A | |
Not yet recruiting |
NCT05686187 -
Establishing and Evaluating the Effectiveness of an Augmented Reality Technology in Gender Empowerment System
|
N/A | |
Active, not recruiting |
NCT03890237 -
GAGE Act With Her-Ethiopia Evaluation
|
N/A | |
Completed |
NCT06357325 -
2023 Problems Faced by Women Earthquake Survivors in Kahramanmaraş
|
||
Completed |
NCT02532725 -
Work-Related Effects of Heat, Activity, and Fat in Middle Aged Men
|
N/A | |
Completed |
NCT03652623 -
Transgender Youth and PrEP: PK, Safety, Uptake & Adherence - PK Study
|
Phase 1/Phase 2 | |
Completed |
NCT04452539 -
Gender Influence on Morbi-mortality in Pediatric Cardiac Surgery.
|
||
Completed |
NCT06391060 -
Gender Differences in Robotic Surgery for Rectal Cancer: a Retrospective Study
|
||
Recruiting |
NCT04440761 -
Barts-MINOCA Registry
|
||
Completed |
NCT03281213 -
Acute Postthoracotomy Pain - Impact of Gender
|
N/A |