Anti-Müllerian hormone is a marker of gonadotoxicity in pre- and postpubertal girls treated for cancer: a prospective study.

CONTEXT: Cytotoxic treatment may accelerate depletion of the primordial follicle pool, leading to impaired fertility and premature menopause. Assessment of ovarian damage in prepubertal girls is not currently possible, but Anti-Müllerian Hormone (AMH) is a useful marker of ovarian reserve in adults. OBJECTIVE: The objective of the study was to prospectively evaluate AMH measurement in children as a marker of ovarian toxicity during cancer treatment. DESIGN AND SETTING: This was a prospective, longitudinal study at a University Hospital. PATIENTS: Twenty-two females (17 prepubertal), median age 4.4 yr (range 0.3-15 yr), were recruited before treatment for cancer. MAIN OUTCOME MEASURES: AMH, inhibin B, and FSH at diagnosis, after each chemotherapy course and during follow-up, were measured. Risk of gonadotoxicity was classified as low/medium (n = 13) or high (n = 9) based on chemotherapy agent, cumulative dose, and radiotherapy involving the ovaries. RESULTS: Pretreatment AMH was detectable across the age range studied. AMH decreased progressively during chemotherapy (P < 0.0001) in both prepubertal and pubertal girls, becoming undetectable in 50% of patients, with recovery in the low/medium risk groups after completion of treatment. In the high-risk group, AMH became undetectable in all patients and showed no recovery. Inhibin B was undetectable in most patients before treatment and, with FSH, showed no clear relationship to treatment. CONCLUSION: AMH is detectable in girls of all ages and falls rapidly during cancer treatment in both prepubertal and pubertal girls. Both the fall during treatment and recovery thereafter varied with risk of gonadotoxicity. AMH is therefore a clinically useful marker of damage to the ovarian reserve in girls receiving treatment for cancer.

Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover.

BACKGROUND: The aim of this exploratory study was to establish whether we could improve skeletal health with a physiological regimen of SSR in young women with premature ovarian failure (POF). PATIENTS AND METHODS: In an open-label randomized controlled crossover trial, 34 women with POF were randomized to 4-week cycles of pSSR (transdermal oestradiol, 100 µg daily for week 1, 150 µg for weeks 2-4; vaginal progesterone, 200 mg twice daily for weeks 3-4) or standard hormone replacement treatment (sHRT) (oral ethinyloestradiol 30 µg and 1·5 mg norethisterone daily for weeks 1-3, week 4 'pill-free') for 12 months. Bone mineral density (BMD) was measured by DEXA at study entry and after each 12-month treatment period. Blood samples for hormones and markers of bone formation (bone alkaline phosphatase, BALP and type I collagen N-terminal propeptide, PINP) and bone resorption (CrossLaps) were collected pre-/postwashout and after 3, 6 and 12 months of each treatment. RESULTS: Eighteen women, mean 27 (range 19-39) years, completed the study. Both regimens caused similar suppression of LH and FSH. Mean baseline lumbar spine BMD z-score was -0·89 (95% CI -1·27 to -0·51) and increased by +0·17 (CI +0·07 to +0·27) in response to pSSR (P = 0·003), compared with +0·07 (CI -0·03 to +0·18) during standard HRT (P = 0·2). During pSSR, the increment in lumbar spine BMD z-score was related positively to oestradiol (r = +0·49, P = 0·04) and inversely to FSH (r = -0·65, P = 0·004). Bone formation markers, BALP and P1NP increased in the pSSR arm (anova P < 0·001) but decreased in the sHRT arm (P < 0·01). Both treatments suppressed the bone resorption marker, CrossLaps (P < 0·001). CONCLUSION: We conclude that pSSR over 12 months has a beneficial affect on bone mass acquisition on the lumbar spine in women with POF, mediated by increased bone formation and decreased bone resorption.

State of the evidence: the connection between breast cancer and the environment.

A substantial body of scientific evidence indicates that exposures to common chemicals and radiation, alone and in combination, are contributing to the increase in breast cancer incidence observed over the past several decades. Key recurring themes in the growing scientific literature on breast cancer and environmental risk factors are: (a) the importance of understanding the effects of mixtures and interactions between various chemicals, radiation and other risk factors for the disease; and (b) the increasing evidence that timing of exposures matters, with exposures during early periods of development being particularly critical to later risk of developing breast cancer. A review of the scientific literature shows several classes of environmental factors have been implicated in an increased risk for breast cancer, including hormones and endocrine-disrupting compounds, organic chemicals and by-products of industrial and vehicular combustion, and both ionizing and non-ionizing radiation.

Policy and research recommendations emerging from the scientific evidence connecting environmental factors and breast cancer.

A substantial body of evidence links environmental exposures to increases in breast cancer incidence over the past decades. State and federal legislative initiatives that could help prevent breast cancer include: federal standards to achieve consistency in radiation-emitting medical and dental equipment; improved state quality assurance standards for radiation-emitting equipment; federal and state exposure limits for electromagnetic radiation; an overhaul of the federal Toxic Substances Control Act to reduce unsafe chemical exposures; strengthened premarket health and safety testing and regulation of pesticides; a federal ban on the manufacture, distribution and sale of consumer products containing bisphenol A and phthalates; and strengthened oversight and regulation of the cosmetics industry. We recommend public and private investment in research on low dose exposures, mixtures, and the timing of chemical exposures, as well as the development of health tracking and biomonitoring programs designed to link data from pollution surveillance systems with disease registries.

Evidence for increased ovarian follicular activity in girls with premature thelarche.

OBJECTIVE: Inhibin B is produced by granulosa cells in small antral follicles, under the influence of FSH, and has a paracrine role in oestradiol synthesis. To test the hypothesis that premature thelarche is associated with increased FSH-driven follicular development, we measured inhibin B and FSH in girls with premature thelarche, girls with central precocious puberty (CPP) and controls matched either for age or breast stage. PATIENTS: Blood samples were collected from 11 girls with premature thelarche (breast stage 2, aged 0.4-5.6 years), 11 prepubertal controls age-matched to the thelarche girls (0.5-5.4 years), 13 girls with CPP (breast stage 2, 3.9-8.2 years) and nine normal pubertal controls (breast stage 2, 9.0-13.2 years). MEASUREMENTS: Dimeric inhibin B was measured in plasma by double-antibody enzyme-linked immunoassay and FSH by immunoradiometric assay. Pelvic ultrasonography was performed on all girls with CPP and 10/11 girls with premature thelarche. RESULTS: Seven of the 13 girls with CPP and three of the eight girls with premature thelarche whose ovaries could be visualized had visibly nonhomogeneous ovarian structure on ultrasonography. Girls with premature thelarche had inhibin B and FSH concentrations higher than those in their age-matched controls (P < 0.01 and P < 0.05, respectively), and similar to those observed in girls with CPP and normal pubertal controls matched for breast stage. In thelarche girls, as in precocious puberty girls and normal pubertal controls, inhibin B and FSH were positively related (rs = 0.54-0.61). CONCLUSIONS: This study provides further evidence that premature thelarche is associated with enhanced follicular development, similar to that which occurs in early puberty, probably under the influence of FSH.

Differences in altruistic roles and HIV risk perception among staff, peer educators, and students in an adolescent peer education program.

This qualitative study examines how adolescent peer educators understand and communicate HIV prevention messages. Semistructured ethnographic interviews were conducted with 21 program participants, including staff, peer educators, and students. Interviews were transcribed and analyzed using concept analysis, a method for identifying shared concepts among interview subjects. We found (a) similar beliefs about HIV transmission and risk reduction across groups; (b) different, but strong, altruistic roles among staff and peer educators; and (c) differences in HIV risk perception across the three groups. Altruistic roles took two forms. Staff acted as life skills mentors, whereas peer educators acted as HIV educators. Students were more passive, receiving counseling but not passing it on to others. Staff contextualized HIV risk, whereas peer educators and students emphasized risk. Although similar HIV knowledge across groups suggests program efficacy, stronger altruistic roles or contextualization of HIV risk may affect how prevention messages are delivered.

Combined false hyperkalemia and hypocalcemia due to specimen contamination during routine phlebotomy.

Combined pseudohyperkalemia and pseudohypocalcemia have not been previously reported in the clinical setting. We report 2 cases in which specimen contamination during routine phlebotomy with ethylenediaminetetraacetic acid (EDTA) caused alteration in serum levels of potassium and calcium. This alteration could be misleading when making clinical decisions and could produce adverse patient outcomes.

New strains of bacteria and exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial. In older studies, the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease. However, these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time. We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease. METHODS: We conducted a prospective study in which clinical information and sputum samples for culture were collected monthly and during exacerbations from 81 outpatients with chronic obstructive pulmonary disease. Molecular typing of sputum isolates of nonencapsulated Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa was performed. RESULTS: Over a period of 56 months, the 81 patients made a total of 1975 clinic visits, 374 of which were made during exacerbations (mean, 2.1 per patient per year). On the basis of molecular typing, an exacerbation was diagnosed at 33.0 percent of the clinic visits that involved isolation of a new strain of a bacterial pathogen, as compared with 15.4 percent of visits at which no new strain was isolated (P<0.001; relative risk of an exacerbation, 2.15; 95 percent confidence interval, 1.83 to 2.53). Isolation of a new strain of H. influenzae, M. catarrhalis, or S. pneumoniae was associated with a significantly increased risk of an exacerbation. CONCLUSIONS: The association between an exacerbation and the isolation of a new strain of a bacterial pathogen supports the causative role of bacteria in exacerbations of chronic obstructive pulmonary disease.

The experiences of lesbian and bisexual women in college residence halls.

SUMMARY In-depth interviews were conducted with ten lesbian and bisexual women university students to learn about their experiences living in college residence halls. Many of the women reported experiencing a hostile environment as a result of direct and indirect harassment and lack of support from roommates, resident assistants, and other residents. Participants also reported supportive factors that helped to make the environment more comfortable. In particular, these students appreciated residence life staff who actively confronted homophobic acts and showed their support by providing information on lesbian, gay, and bisexual topics. Interviewees provided suggestions for improving the climate in residence halls and for training residence hall staff to work more effectively with lesbian, gay, and bisexual students. Implications are offered for addressing homophobia and heterosexism in women's residence halls.