Prevalence of Heavy Menstrual Bleeding and Use of Hormonal Therapy Among Women Type 1 Von Willebrand Disease from the Zimmerman Program

Background: Women with von Willebrand disease (VWD) experience substantial reproductive tract bleeding, including heavy menstrual bleeding (HMB). Over 80% of women with VWD experience HMB resulting in morbidity from decreased quality of life, lost productivity, and iron deficiency. Hormonal birth control is a standard treatment and can elevate VW activity (RCo/GPB1M) and antigen (Ag) levels. Little is known about the impact of such therapy on bleeding assessment tools (BATs). We hypothesized that women on hormonal therapy (HT) would have lower ISTH-BAT scores and higher VWD levels than those not on HT. Women who participated in the Zimmerman Program (PPG) for the Molecular and Clinical Biology of VWD, a natural history study (NHLBI HL081588), had demographic, medication history, and laboratory samples collected. We sought to identify differences in patient, disease-specific factors, and BATs between type 1 VWD women on HT and those not on HT.

Methods: Women with type 1 VWD and reported menstrual history were selected from the PPG. Women were split into those taking HT (OCPs, injectable progestins, hormone replacement therapy, intravaginal devices, and IUDs) vs. those who were not. Women >50 years of age were excluded from the group analysis due to their assumed postmenopausal status. Descriptive statistics were calculated to characterize the demographics, VWD testing (VWF:Ag, VWF:RCo, GPIbM), and ISTH-BATs (total, HBM, and PPH) of the two groups. Continuous variables were compared between groups using two sample t-test and categorical variables by Fischer's exact test. A two-sided p-value of< 0.05 was considered statistically significant.

Results: In the full cohort, 269 women answered yes to experiencing menstrual cycles. The group was predominantly pediatric/young adult with a mean age of 25.3 years (range 11-76). Whites comprise 86% of subjects. Women were further defined by disease laboratory testing with 186 women (69.1%) diagnosed as VWF:Ag 0.3-0.5 IU/mL, 57 women (21.2%) VWF:Ag <0.3 IU/mL, and 26 women (9.7%) clearance type VWD (genetic result). The mean VWF:Ag for the entire cohort was 0.37 IU/mL (Standard Deviation 0.14 IU/mL). The mean VWF: RCo was 0.36 IU/mL (SD 0.15 IU/mL). The ISTH-BAT scores ranged from 0-29, with a mean of 7.6 (SD 5.1). An evaluation of the HMB domain of the ISTH-BAT demonstrated that 94% (253) of women reported HMB with >1 point (on a 4-point scale) overall, 47% (119) of whom reported severe HMB with 3 or 4 points. Of the 269 women, 108 were taking HT at enrollment. The types of HT included OCPs (71), medroxyprogesterone acetate (11), levonorgestrel IUD (11), contraceptive implant (3), and etonogestrel/ethinyl estradiol vaginal ring (1).

After excluding women with presumed postmenopausal status, we identified 105 women on hormonal therapy and 143 who were not. Graph 1 provides an overlay of the ISTH-BAT scores by hormone treatment status. Table 1 demonstrates the demographic and disease features of the two groups. On average, women on HT were younger, 20.7 years vs. 24.5 years (p= 0.003), than those who were not. Other disease characteristics, including disease subtype, VWF laboratories (VWF:Ag, VWF: RCOF, VWF GPIbM), and ISTH-BAT HMB and PPH specific domains were not significantly different between the groups. Higher total ISTH-BAT scores were observed for women not on HT (7.4± 5.1) compared to those who were (6.8± 4.2); however, the difference was not statistically significant.

Conclusions: For women with type 1 VWD, HMB is widespread, affecting 94% of the subjects enrolled in the PPG. Hormone therapy was common, with 47% receiving treatment. Apart from age, there were no significant differences in the disease characteristics or BATs between women with type 1 VWD who are and are not receiving hormone therapy in this cohort.

Machin:Takeda: Honoraria. Ragni:BioMarin: Honoraria; Takeda: Honoraria, Other: Provided study (rVWF) drug for trial.