Response Rates of High and Low Dose Estrogen and Their Combination with DDAVP and/or Aminocaproic Acid in Patients with Menorrhagia and Type I Von Willebrand’s Disease.
Authors: Kailasnath Vasundhara , Hertweck S. Paige , Bertolone Salvatore , Ahuja Sanjay P 
Published: October 2019

Abstract
Background: Von Willebrand’s Disease (VWD) is the most common inherited bleeding disorder affecting women and produces significant menorrhagia as its main symptom. Though combined oral contraceptive pills (OCP’s) are the most common treatment modality for menorrhagia, randomized controlled studies to assess their efficacy are lacking. Data on response rates to different doses and combinations of estrogens and progestins in OCP’s, and data on response rates to combined therapy of OCP’s with desmopressin acetate (DDAVP) and/or aminocaproic acid (Amicar) are sparse.
Methods: The patient population consisted of 80 patients aged 9–19 years, who were primary referrals to a combined Hematology/Gynecology clinic for evaluation of menorrhagia. A retrospective chart review was done on these patients following an IRB approval. Collected data included age of menarche, onset of menorrhagia, follow up duration, severity of menorrhagia including PBAC score, co-morbidities, family history of bleeding or clotting disorders, blood group, factor VIII coagulant activity, ristocetin cofactor activity, and VW Ag level. VWD was defined as ristocetin cofactor activity <57 % (57 –149%). Response to treatment modalities as assessed by the gynecologist was subjective (menstrual bleeding lasting less than 7 days and decrease in the number of menstrual products used per day) in most patients and by the PBAC score (Pictorial blood loss assessment chart) in a few.
Results: Of the 80 patients with menorrhagia, 26 patients (32.5%) had ristocetin co factor activity <57 % with normal multimers and were diagnosed with VWD type 1. Mean age in years (±SD) at menarche and at diagnosis of menorrhagia were 11.31±1.54 and 12.65±1.77 respectively. Mean follow up period was 1.73 yrs (range 0.2 – 3 yrs). O blood type was present in 73.1% (19/26) patients. Family history of menorrhagia and easy bruising was present in 34.6% (9/26).
Table 1: Treatment and Response Rate
Treatment* N=26 Response Rate * Patients were on more than one type of OCP prior to achievement of response Low dose Estrogen (20, 25 and 30 mcg) 22 (84.6%) 10 (45.5%) High dose Estrogen (35, 50 mcg) 18 (69%) 15 (83.3%) Progesterone 5 2 (40%) OCP and DDVAP 14 13 (92.9%) OCP and Amicar 6 6 (100%)
During the course of treatment, patients were changed from low to high dose estrogen in 38.5% (10/26), high to low dose estrogen in 7.7% (2/26), estrogen to progesterone in 3.8% (1/26), progesterone to estrogen in 11.5%(3/26). Ten patients (38.5%) remained on the same treatment.
Table 2: Treatment combinations
Treatment Combinations N=26 OCP’s n =9 34.6% OCP + DDVAP n =6 23.1% OCP + Amicar n =2 7.7% OCP + DDVAP+ Amicar n =1 3.8% OCP + DDVAP + Humate P n =3 11.5% OCP + DDVAP+ Amicar + Humate P n =3 11.5% Progesterone only OCP (POCP) n =1 3.8% POCP + DDVAP + Humate P n =1 3.8%
Conclusion: In our retrospective analysis, patients on high dose estrogen had a better response rate compared to patients on low dose estrogen or on progesterone only OCP’s. A third of the patients achieved bleeding control with OCP’s alone whereas the rest required a combination of OCP’s with either DDAVP, Amicar, or both. A prospective study is needed to confirm these findings and to determine standards of treatment in patients with menorrhagia and Von Willebrand’s disease.