Table 2.
Priority research questions in each focused research domain of the health of people who have or had the potential to menstruate, and their total feasibility-impact-risk score
| Lifespan sex biology | ||
|---|---|---|
| # | Research Question | F-I-R Score |
| 1 | What is the impact of aging in inherited BDs for individuals assigned male at birth versus female, particularly peri- and postmenopausal? | 19 |
| 2 | What are the phenotypic differences of inherited BDs across the lifespan based on sex and gender? | 19 |
| 3 | What effects do hormones, pregnancy, and age have on coagulation factor levels and reference ranges? | 17 |
| 4 | How do the pharmacokinetics and pharmacodynamics of coagulation factor products differ in PPM compared to cisgender men? | 17 |
| 5 | What is the impact of coagulation factor levels on bleeding phenotype with aging in PPM? | 15 |
| 6 | What is the impact of comorbidities on bleeding phenotype, beyond clotting factor levels? (e.g., disability, connective tissue disorder, immunotherapy, COVID-19 infection, rheumatologic disorders) | 11 |
| 7 | How do we assess and define phenotype in PPM with BDs? | 10 |
| 8 | What genes and modifying genes are important in impacting phenotype for PPM with BDs? | 8 |
| Pregnancy and the post-partum context | ||
| # | Research Question | F-I-R Score |
| 1 | What is the optimal timing and dosing of antifibrinolytic agents or coagulation factor for prophylaxis and treatment of primary and secondary PPH? | 22 |
| 2 | What is the best tool to identify clinically relevant PPH, indicating need for inherited BD workup? | 21 |
| 3 | What role does local hemostasis play in pregnancy and PPH compared to systemic hemostasis? | 20 |
| 4 | What are the current barriers to prenatal diagnosis of inherited BDs? | 19 |
| 5 | What is the onset and progression of coagulation factor changes throughout pregnancy and post-partum? | 17 |
| 6 | How can we link inherited BD screening to family planning and obstetric care? | 17 |
| 7 | What is the optimal timing of prophylaxis for first trimester procedures? (e.g., D&C) | 16 |
| 8 | What is the risk of VTE for PPM using hormonal treatments or antifibrinolytic agents in the post-partum or post-surgery setting? | 14 |
| 9 | What role does the placenta play in the development of immune tolerance? | 12 |
| 10 | How can we ensure that pregnancy does not exclude participation in clinical trials? | 10 |
| Uterine physiology and bleeding | ||
| # | Research Question | F-I-R Score |
| 1 | What is the relative safety of intrauterine procedures in the setting of inherited BDs? (e.g., ablation, D&C, IUD placement, biopsy) | 22 |
| 2 | What is the optimal dosing and impact of coagulation factors, antifibrinolytic agents, and desmopressin on HMB? | 18 |
| 3 | What is the impact of androgenic hormone therapy on bleeding symptoms? | 16 |
| 4 | What is the safety and effectiveness of combination therapies for HMB management (antifibrinolytic agents, desmopressin, gonadal steroid hormones)? | 16 |
| 5 | What is the relative effectiveness and optimal dosing of gonadal steroid hormone therapies in inherited BDs in the acute and chronic setting? | 15 |
| 6 | Are there histopathological findings on an endometrial biopsy that could be utilized for diagnosis of inherited BDs? | 15 |
| 7 | What are the impacts of various hormone therapies on bleeding workup? | 15 |
| 8 | How does endometrial physiology contribute to HMB and response to treatment both within and outside of inherited BDs? | 14 |
| 9 | Do defects in primary hemostasis have more of an effect on uterine bleeding compared to defects in secondary hemostasis? | 14 |
| 10 | What is the relative accuracy and feasibility for menstrual blood loss measurements? | 13 |
| 11 | What are the expected bleeding patterns in inherited BDs with gonadal steroid hormone therapies? | 13 |
| 12 | How do hemostasis and the levels of coagulation factors in the blood differ from that in the endometrium? | 12 |
| 13 | What is the relative effectiveness of endometrial drug delivery of NSAIDs, antifibrinolytic agents, or other nonhormonal therapies via IUDs in the treatment of HMB? | 8 |
| Bone and joint health | ||
| # | Research Question | F-I-R Score |
| 1 | What is the prevalence of subclinical joint bleeds among PPM with inherited BDs, and what is the most accurate method of assessment? | 18 |
| 2 | What is the impact on bleeding phenotype of concomitant collagen and inherited BDs? | 15 |
| 3 | What effect do inherited BDs have on bone health and what is the best way to study those effects? What role(s) do hormones play? | 15 |
| 4 | How do the biomechanics of PPM change throughout the lifespan, what is the impact on joint bleeding phenotype and which joints are affected? | 14 |
| Health care delivery | ||
| # | Research Question | F-I-R Score |
| 1 | What do young people with inherited BDs need to be prepared for puberty and menarche? | 22 |
| 2 | What are the most effective interventions to increase primary care awareness (screening, knowledge, referral) about HMB and associated BDs? | 20 |
| 3 | What costs are associated with bleeding symptoms in PPM? | 18 |
| 4 | What are the characteristics of people who are diagnosed with BDs early on versus later? | 18 |
| 5 | What care model is most effective and feasible in caring for PPM with inherited BDs? | 10 |
| Patient-reported outcomes and quality-of-life | ||
| # | Research Question | F-I-R Score |
| 1 | What tools are currently available to assess QoL throughout the lifespan and what is missing? | 21 |
| 2 | How does the presence of an inherited BD or bleeding symptoms affect access to education and educational attainment? | 19 |
| 3 | What is the correlation between QoL scores and other outcomes (e.g., PBAC, ferritin)? | 19 |
| 4 | How does an inherited BD, as well as specific symptoms such as HMB, affect QoL and mental health? | 19 |
| 5 | What costs are associated with bleeding symptoms in PPM? | 18 |
| 6 | What are the QoL outcomes from uterine bleeding in trans-masculine people? | 18 |
| 7 | What are the symptom correlations of HMB in inherited BDs with dysmenorrhea/pelvic pain? | 18 |
| 8 | How does an inherited BD affect intimacy, sexual function, and sexual relationships? | 16 |
BD: bleeding disorder, COVID: coronavirus disease 2019, D&C: dilation and curettage, F-I-R: feasibility-impact-risk, HMB: heavy menstrual bleeding, IUD: intrauterine device, NSAID: nonsteroidal anti-inflammatory drug, PBAC: pictorial blood loss assessment chart, PPH: post-partum hemorrhage, PPM: people who have or had the potential to menstruate, QoL: quality-of-life, VTE: venous thromboembolism