Growth of uterine leiomyomata among premenopausal black and white women

Uterine leiomyomata (fibroids) are the leading cause of hysterectomy in the United States. Black women have a greater fibroid burden than whites, yet no study has systematically evaluated the growth of fibroids in blacks and whites. We prospectively tracked growth for 262 fibroids (size range: 1–13 cm in diameter) from 72 premenopausal participants (38 blacks and 34 whites). Fibroid volume was measured by computerized analysis of up to four MRI scans over 12 months. We used mixed effects models to identify factors that are associated with growth, and results were converted to percent change per 6 months for clinical relevance. The median growth rate was 9% (range: −89% to +138%). Seven percent of fibroids regressed (>20% shrinkage). Tumors from the same woman grew at different rates (within-woman component of variation was twice the component among women; both were significant, P < 0.001). Black and white women less than 35 years of age had similar fibroid growth rates. However, growth rates declined with age for whites but not for blacks (P = 0.05). The odds of a tumor growing more than 20% in 6 months also decreased with age for whites but not for blacks (P < 0.01). Growth rates were not influenced by tumor size, location, body mass index, or parity. We conclude that (i) spontaneous regression of fibroids occurs; (ii) fibroids from the same woman grow at different rates, despite a uniform hormonal milieu; (iii) fibroid size does not predict growth rate; and (iv) age-related differences in fibroid growth between blacks and whites may contribute to the higher symptom burden for black women

Differential Expression of Receptor Tyrosine Kinases (RTKs) and IGF-I Pathway Activation in Human Uterine Leiomyomas

Uterine leiomyomas (fibroids) are benign tumors that are prevalent in women of reproductive age. Research suggests that activated receptor tyrosine kinases (RTKs) play an important role in the enhanced proliferation observed in fibroids. In this study, a phospho-RTK array technique was used to detect RTK activity in leiomyomas compared with myometrial tissue. We found that fifteen out of seventeen RTKs evaluated in this study were highly expressed (P < 0.02–0.03) in the leiomyomas, and included the IGF-I/IGF-IR, EGF/EGFR, FGF/FGF-R, HGF/HGF-R, and PDGF/PDGF-R gene families. Due to the higher protein levels of IGF-IR observed in leiomyomas by us in earlier studies, we decided to focus on the activation of the IGF-IR, its downstream effectors, and MAPKp44/42 to confirm our earlier findings; and validate the significance of the increased IGF-IR phosphorylation observed by RTK array analysis in this study. We used immunolocalization, western blot, or immunoprecipitation studies and confirmed that leiomyomas overexpressed IGF-IRβ and phosphorylated IGF-IRβ. Additionally, we showed that the downstream effectors, Shc, Grb2, and MAPKp44/42 (P < 0.02–0.001) were also overexpressed and involved in IGF-IR signaling in these tumors, while IRS-I, PI3K, and AKT were not. In vitro studies showed that IGF-I (100 ng/mL) increased the proliferation of uterine leiomyoma cells (UtLM) (P < 0.0001), and that phosphorylated IGF-IRβ, Shc, and MAPKp44/42 were also overexpressed in IGF-I-treated UtLM cells (P < 0.05), similar to the tissue findings. A neutralizing antibody against the IGF-IRβ blocked these effects. These data indicate that overexpression of RTKs and, in particular, activation of the IGF-IR signaling pathway through Shc/Grb2/MAPK are important in mediating uterine leiomyoma growth. These data may provide new anti-tumor targets for noninvasive treatment of fibroids

Meeting Report: The Role of Beliefs and Perception on Body Size. Proceedings of the 26th Aschauer Soiree, Held at Aschauhof, Altenhof, Germany, May 26th, 2018

Thirty-one scientists met at Aschauhof, Germany to discuss the role of beliefs and self-perception on body size. In view of apparent growth stimulatory effects of dominance within the social group that is observed in social mammals, they discussed various aspects of competitive growth strategies and growth adjustments. Presentations included new data from Indonesia, a cohort-based prospective study from Merida, Yucatan, and evidence from recent meta-analyses and patterns of growth in the socially deprived. The effects of stress experienced during pregnancy and adverse childhood events were discussed, as well as obesity in school children, with emphasis on problems when using z-scores in extremely obese children. Aspects were presented on body image in African-American women, and body perception and the disappointments of menopause in view of feelings of attractiveness in different populations. Secular trends in height were presented, including short views on so called 'racial types' vs bio-plasticity, and historic data on early-life nutritional status and later-life socioeconomic outcomes during the Dutch potato famine. New tools for describing body proportions in patients with variable degrees of phocomelia were presented along with electronic growth charts. Bio-statisticians discussed the influence of randomness, community and network structures, and presented novel tools and methods for analyzing social network data