PAI-1, tPA, TFPI and HEECs in Uterine Hemostasis

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to learn more about the role of blood clotting factor proteins and cells in menstrual (period) bleeding. The investigators are hoping to identify differences in these proteins and cells in the menstrual blood of individuals with heavy periods compared to menstruating individuals who do not have heavy periods.

Detailed Description
-----------------
The purpose of this study is to learn if human endometrial endothelial cells (HEECs) regulate human uterine hemostasis through the up and down-regulation of pro- and anti-coagulant factors in menstrual blood including PAI-1, factor XI (FXI)-PAI-1 complex, tPA, and TFPI. This study will enroll participants with heavy menstrual bleeding (HMB) and participants without HMB. Coagulation factors will be measured in menstrual blood and mRNA for these factors will be quantified from cultured HEECS from endometrial biopsies and compared between groups.

Official Title
-----------------
The Role of Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), Tissue Factor Pathway Inhibitor (TFPI), and Endometrial Endothelial Cells in Uterine Hemostasis in Humans

Conditions
-----------------
Menstrual Bleeding, Heavy

Intervention / Treatment
-----------------
* Procedure: Sample Collection and Endometrial Biopsy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Regularly menstruating participants between 18-45 years of age Exclusion Criteria: Pregnancy within 3 months of enrollment Lactating at the time of enrollment Hormonal contraceptive use or use of the copper intrauterine device (IUD) Antifibrinolytic use Inherited or acquired bleeding disorder or anticoagulant use Known structural cause of HMB Inability to complete PBACs Unwilling to refrain from sexual intercourse for the two weeks prior to endometrial biopsy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Heavy Menstrual Bleeding<br>Participants with heavy menstrual bleeding will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture. | Procedure: Sample Collection and Endometrial Biopsy<br>* Participants will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture.<br>|
| Active Comparator: Regular Mensural Bleeding<br>Participants with normal menstrual bleeding will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture. | Procedure: Sample Collection and Endometrial Biopsy<br>* Participants will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of mRNA copies from HEEC culture of tPA | The total number of mRNA copies of tPA in HEEC cultures from enrollment to 60 days. | Enrollment to 60 days | 
| Total number of mRNA copies from HEEC culture of PAI-1 | The total number of mRNA copies of PAI-1 in HEEC cultures from enrollment to 60 days. | Enrollment to 60 days | 
| Total number of mRNA copies from HEEC culture of TFPI | The total number of mRNA copies of TFPI in HEEC cultures from enrollment to 60 days. | Enrollment to 60 days | 
| Change in the numerical score of Pictorial Blood Loss Assessment | The change in the Pictorial Blood Loss Assessment Charts (PBACs) from baseline to 60 days. Participants will be asked to tally the number of pads and tampons, the level of saturation of menstrual blood on the pads or tampons, and the number of clots. Scores greater than 100 are considered diagnostic of heavy menstrual bleeding. | Enrollment to 60 days |