Uterine fibroids (leiomyomas) are common benign smooth muscle tumors that impose substantial symptom burden and healthcare costs worldwide. Although uterine fibroid (leiomyoma) pathogenesis is multifactorial, hypoxia has emerged as a key feature of the uterine fibroid (leiomyoma) microenvironment, particularly within poorly perfused tumor cores. Hypoxia-inducible factor-1α (HIF-1α) is a central transcriptional regulator of cellular adaptation to low oxygen and coordinates downstream programs that support angiogenesis, metabolic reprogramming, cell survival, and extracellular matrix (ECM) remodeling. In uterine fibroids (leiomyomas), these HIF-1α–dependent processes intersect with steroid hormone signaling, growth factor pathways, inflammatory mediators, and redox imbalance, together promoting tumor persistence and progressive fibrosis. This review synthesizes the molecular regulation of HIF-1α, highlights major HIF-linked effector pathways relevant to uterine fibroid (leiomyoma) biology, and emphasizes mechanistic crosstalk with estrogen- and progesterone-responsive signaling, TGF-β/SMAD-driven fibrosis, NF-κB-mediated inflammation, and metabolic checkpoint pathways including mTOR and AMPK. Finally, we evaluate emerging therapeutic strategies that target HIF-1α directly or indirectly through upstream regulators.

Sickle cell disease is an autosomal recessive hemoglobin disorder affecting about 100,000 people in the United States, predominantly those of African descent. A point mutation in the β-globin gene in red blood cells causes these cells to sickle under hypoxemic conditions, reducing blood flow and oxygen delivery to tissues. This manifests in the form of painful vaso-occlusive episodes, acute chest syndrome, and acute infarction of various organs, including the spleen, bone, and lung. While sickle cell disease complications such as hemolytic anemia, tissue hypoxia, and chronic organ damage are well studied, attention to the unique reproductive challenges faced by patients with sickle cell disease remains underrecognized and underappreciated. This review aims to explore key reproductive health issues in patients with sickle cell disease, including diminished ovarian reserve, infertility, and obstetric and perinatal risk. Secondly, this review aims to identify key counseling and care opportunities for providers to support patients with sickle cell disease in meeting their reproductive goals.