Uterine leiomyomas are highly prevalent and symptomatic tumors of women in their reproductive years. The morbidity caused by these tumors is directly related to increasing size. Leiomyoma cells do not rapidly proliferate; instead, the tumors grow primarily due to excessive production of disorganized extracellular matrix (ECM). The aberrant ECM results from excessive production of collagen subtypes and proteoglycans, increased profibrotic cytokines including transforming growth factors beta1 and beta3, and decreased or disrupted matrix metalloproteinases. These alterations result in the development of an ECM that is exceptionally stable. As a result, therapeutic interventions must redirect leiomyoma cells toward extracellular matrix dissolution, rather than solely inhibiting cell proliferation. Gonadotropin-releasing hormone analogues and selective progesterone receptor modulators with demonstrated clinical efficacy provide such a change in abnormal extracellular matrix formation by leiomyoma cells, inhibiting and reversing the fibrotic process. Novel therapies using pathways distinct from gonadal hormones, including antifibrotics, retinoic acid, peroxisome-proliferator-activated receptor gamma ligands, and curcumin, provide promise for a future with improved therapeutic options for women suffering from uterine leiomyomas.
Objective To evaluate ART utilization and outcomes in minority women seeking care at enhanced access, military ART programs. Design Retrospective cohort Setting Federal ART programs Patients 2,050 women undergoing first cycle, fresh, non-donor ART from 2000–2005 Intervention None Main outcome measure(s ): ART utilization rate, clinical pregnancy rate, live birth rate Results African American (AA) women had an almost fourfold increased utilization of ART and Hispanic women had decreased utilization. Clinical pregnancy rates were significantly lower for AA women compared to white women (46.1% vs. 52.6%, RR 0.88, 95% CI 0.78–0.99) as were live birth rates (33.7%. vs. 45.7%, RR 0.74, 95% CI 0.63–0.91). Conclusions Economics appear to influence ART utilization by AA women but not Hispanic women. Despite increased utilization by African American women, outcomes in this group were worse when compared to Caucasian women. Improving access through decreased cost may increase utilization by some, but not all minority groups. Improved access may not translate into improved outcomes in some ethnic groups.
Objective To characterize hyperosmolarity-responsive genes in leiomyoma cells and determine whether gonadotropin-releasing hormone (GnRH) agonist treatment altered their expression. Design Laboratory study. Setting University hospital. Patient(s) None. Intervention(s) Cell culture under hypertonic conditions and with GnRH agonist treatment, RNA isolation, and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Main Outcome Measure(s) Expression of nuclear factor of activated T cells 5 (NFAT5), aldose reductase (AR), and sodium myo-inositol transporter 1 (SMIT) messenger RNA (mRNA) in immortalized leiomyoma and patient-matched myometrial cells. Result(s) Leiomyoma cells had increased basal expression of NFAT5 mRNA (1.7 ± 0.08-fold) compared with myometrial cells. The NFAT5 increased further in leiomyoma cells cultured under hyperosmolar conditions (3.0 ± 0.46-fold at 50 mM NaCl and 3.3 ± 0.48-fold at 100 mM NaCl). The NFAT5-regulated mRNA transcripts for AR and SMIT were increased in untreated leiomyoma cells compared with myometrial cells and further increased in leiomyoma cells exposed to osmotic stress. The NFAT5 transcripts were decreased with low-dose GnRH agonist treatment but increased with supraphysiologic doses. Conclusion(s) Expression of hyperosmolarity genes was increased in leiomyoma cells relative to myometrial cells. Pharmacologic concentrations of GnRH agonist decreased NFAT5 expression, suggesting that water flows out of leiomyoma cells at pharmacologic doses.
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