PB0877 - Menopause is associated with decreased platelet reactivity among women in the Framingham Heart Study

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Robin E. Pashek

NIH IRTA Post-Baccalaureate Fellow
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States

Co-Author(s)

Melissa V. Chan, PhD

Post-Doctoral Fellow
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States
BN

Bongani B. Nkambule

Associate Professor
University of KwaZulu-Natal
Durban, KwaZulu-Natal, South Africa
Florian Thibord, PhD

Post-Doctoral Fellow
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Jamaica Plain, Massachusetts, United States
AL

Amber Lachapelle

Research Associate
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States
MC

Ming-Huei Chen

Staff Scientist
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, Massachusetts, USA
Framingham, Massachusetts, United States
Andrew D. D. Johnson, PhD (he/him/his)

Professor
Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA.
Framingham, Massachusetts, United States

Background: The influence of low estradiol status on platelet function in postmenopausal women remains unclear. Moreover, menopausal hormone therapy including oral estradiol has been linked to increased incidences of thromboembolic events in women. Whether these events are dependent on platelet function has not been clearly elucidated.

Aims: We aimed to assess platelet reactivity associations in women before and after menopause, as well as in post-menopausal women on hormone replacement therapy (HRT) in a large population cohort.

Methods: Cross-sectional data was obtained from female participants in the Framingham Heart Study (N=1836). Menopause status (premenopausal and postmenopausal) and HRT was assessed by medicine bag intake and standardized medical history questionnaire. We excluded women without natural menopause (n=97) or having menstruation halted for less than 1 year (n=142). Platelet reactivity traits were measured by five bioassays across several agonists in whole-blood and platelet-rich plasma (PRP) samples. Linear mixed effects models adjusted for age, family relatedness, aspirin use, alcohol intake, and serotonin-affecting antidepressant use evaluated associations between platelet reactivity, menopause status, and HRT use.

Results: Compared to women reporting regular menstrual cycles (n=441), post-menopause status for longer than 1-year (n=1065) was associated to lower P-selectin exposure after ADP stimulation in whole-blood (P=1.19E-3) and PRP (P=4.28E-5) and decreased platelet reactivity in nine traits (P < 1.46E-3) among TRAP6 (thrombin PAR1 receptor agonist), ADP, collagen, and arachidonic acid agonists. Only four modest associations were found between postmenopausal women on estrogen-containing HRT (n=60) and decreased platelet function (P < 0.01) relating to primary and secondary wave epinephrine aggregation, but not final aggregation.

Conclusion(s): Counter to expectation, the overall association pattern suggests that platelet reactivity decreases in women in the post-menopausal state, and that estrogen HRT may attenuate this reduction somewhat. Further studies are required to elucidate the precise mechanism by which this may lead to increased thrombosis.