Topics of Interest in Women With Myeloproliferative Neoplasms

Sex and gender have emerged as central modifiers of disease biology, phenotype, and clinical outcomes in myeloproliferative neoplasms (MPNs). This review will uniquely highlight issues affecting women with MPN and articulate their relevant determinants.

Epidemiology and Diagnosis

A higher overall prevalence of MPN has been established in women. The incidence of essential thrombocythemia (ET) predominates, while, conversely, polycythemia vera (PV) and myelofibrosis (MF) are seen in lower frequencies as compared to men. Diagnostic criteria are dictated by sex‐driven physiological variances in hemoglobin and hematocrit levels in PV, mandating separate diagnostic thresholds, respectively: > 16.0 g/dL and > 48% in women vs. > 16.5 and > 49% in men. Genetic Framework and Phenotype Women with MPN harbor fewer acquired somatic mutations and a lower frequency of high‐risk mutations than their male counterparts; lower JAK2V617F driver variant allele frequency and attenuated allele burden kinetics have also been reported. Women with MPN are younger at diagnosis than men and, contingent on subtype, display more indolent disease features. Importantly, validated symptom burden assessments consistently disclose higher scores in women vs. men.

Women with MPN have a unique thrombotic diathesis with respect to men, more frequently involving the splanchnic venous system in those ultimately diagnosed with PV. Outcomes data depict female sex as a variable associated with more favorable clinical trajectories, including lower rates of MF/leukemic transformation and secondary cancers, as well as improved overall survival rates vis‐à‐vis men. Life‐Cycle Windows, Pregnancy, and Postpartum Potential challenges at each significant life stage will be addressed: puberty, preconception and fertility, and perimenopause; these include issues surrounding oral contraceptives and hormone use. Prospective studies suggest overall favorable maternal and fetal outcomes with pregnancy in women with MPN. Full details on risks and reported outcomes will be discussed, as well as a risk‐adapted approach to management informed by obstetric and thrombosis history. Recommendations include aspirin 81 mg daily in all patients and cytoreduction with interferon‐α in those with antecedent thrombosis, as well as in low‐risk cases with higher‐risk features (e.g., poorly controlled hematocrit and recurrent fetal loss). Antepartum anticoagulation with low molecular weight heparin (LMWH) is recommended in cases with previous venous thromboembolism.

This review highlights female sex and gender as critical drivers of MPN incidence, presentation, and natural history. It further outlines the impact and management of MPN as related to unique female reproductive phases. A sex‐informed lens will be required in order to recalibrate current prognostic tools, a requisite to refining patient counselling and clinical decision‐making in line with precision medicine. Moreover, while several mechanisms underpinning sex‐defined discrepancies have been defined, these mandate further prospective study. Finally, sex and gender‐based differences must be weighted in clinical trials with systematized procedures to correct participation imbalances in favor of sex and gender equity.