Estradiol vs Lysteda in Treatment of Heavy Menstrual Bleeding

BACKGROUND: The acute onset of Heavy Menstrual Bleeding (HMB) during menses results in women
seeking care in the Emergency Department. The current management of HMB among our residents
uses combination oral contraceptives or oral progestins. The residents in the Emergency
Department often send women home without any therapeutic intervention. There is no
Regulatory Agency approved therapy for acute HMB. The etiology of HMB is not well
understood. Two potential causes are changes in endometrial prostaglandins and increased
fibrinolytic activity in the endometrium.

Specific Aim 1 is to investigate and compare the effect of oral estradiol compared to
tranexamic acid in reducing blood loss and the duration of bleeding during an acute episode
HMB.

Specific Aim 2 is to evaluate the effect of estradiol and tranexamic acid on possible causes
of the acute HMB by measuring prostaglandins and Plasminogen activator in menstrual effluent
at the end of treatment.

METHODS: This is a randomized, double-blind, controlled, parallel-group, non-inferiority
trial, with participants between the ages 18 and 45 years, with acute cyclic heavy menstrual
bleeding enrolled during an emergency room visit. Participants are randomized to receive 48
hours' treatment with 1.3 mg oral tranexamic acid or 1.0 mg oral estradiol three times a
day. The primary endpoint is reduction in the amount of menstrual effluent. Sample size was
calculated based on detecting less than 30 ml difference between the mean menstrual blood
loss of the two treatment groups. Amount of blood loss is quantified by alkaline hematin
method on extraction of menstrual pads and tampons. Secondary outcome is the variation of
hemostatic factors in the menstrual effluent in two treatment groups by collecting menstrual
effluent and quantitating prostaglandins, Plasminogen activators, Plasminogen activator
inhibitors, and vascular endothelial growth factor.

ANTICIPATED OUTCOMES: The investigators anticipate a reduction in mean menstrual blood loss
in both treatment groups. Compared with participants treated with estradiol, the group
treated with tranexamic acid will not have statistically significant change in reduction of
menstrual effluent. We also anticipate changes in different local hemostatic factors in
menstrual effluent specific to the treatment arm.

Inclusion Criteria:

- Age: between 18-45 years old

- Hemoglobin concentration: less than or equal to 11.5 g/dL, greater than or equal to
8.0 g/dL

- BMI: less than or equal to 35

- Menstrual cycle: previous menstrual cycle interval between 26 to 34 days with less
than or equal to 10 days of bleeding

- Contraception: at least two months from implant removal, or six months from their
last depo-provera or depo-Lupron injection, or recently(at least 2 months)
discontinued oral, patch or intravaginal ring contraceptives

- On cycle day 1-3 of the current menstrual bleeding episode

Exclusion Criteria:

- NSAID, or aspirin containing medications during the 48 hours preceding the current ER
visit

- Estrogen or progestin treatment during the 30 days preceding the current ER visit

- Using Paraguard

- Pregnant and or lactating

- History of endometrial ablation

- Women with thromboembolic disease, or coagulopathy

- Women with history of myocardial infarction, or cerebrovascular occlusion

- Uncontrolled high blood pressure (blood pressure greater than 150/90)

- Sensitivity to estrogen, or tranexamic acid