Association of genital talc and douche use in early adolescence or adulthood with uterine fibroids diagnoses

Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO(*)) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain "redox balance" termed also "redox homeostasis". The "two-faced" character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury.

To quantify the incidence of uterine leiomyoma confirmed by hysterectomy, ultrasound, or pelvic examination according to age and race among premenopausal women. From September 1989 through May 1993, 95,061 premenopausal nurses age 25-44 with intact uteri and no history of uterine leiomyoma were followed to determine incidence rates of uterine leiomyoma. The self-reported diagnosis was confirmed in 93% of the medical records obtained for a sample of cases. Using pooled logistic regression, we estimated relative risks (RRs) of uterine leiomyoma according to race and examined whether adjustment for other potential risk factors could explain the variation in the race-specific rates. During 327,065 woman-years, 4181 new cases of uterine leiomyoma were reported. The incidence rates increased with age, and the age-standardized rates of ultrasound- or hysterectomy-confirmed diagnoses per 1000 woman-years were 8.9 among white women and 30.6 among black women. After further adjustment for marital status, body mass index, age at first birth, years since last birth, history of infertility, age at first oral contraceptive use, and current alcohol consumption, the rates among black women were significantly greater for diagnoses confirmed by ultrasound or hysterectomy (RR 3.25; 95% confidence interval [CI] 2.71, 3.88) and by hysterectomy (RR 1.82; 95% CI 1.17, 2.82) compared with rates among white women. We observed similar RRs when the cohort was restricted to participants who reported undergoing a screening physical examination within the 2 years before baseline. A higher prevalence of known risk factors did not explain the excess rate of uterine leiomyoma among premenopausal black women.