Tumor necrosis factor (TNF) receptor type 2 is an important mediator of TNF alpha function in the mouse ovary.

It is believed that a finite pool of primordial follicles is established during embryonic and neonatal life. At birth, the mouse ovary consists of clusters of interconnected oocytes surrounded by pregranulosa cells. Shortly after birth these structures, termed germ cell cysts or nests (GCN), break down to facilitate primordial follicle formation. Tumor necrosis factor alpha (TNF) is a widely expressed protein with myriad functions. TNF is expressed in the ovary and may regulate GCN breakdown in rats. We investigated whether it participates in GCN breakdown and follicle formation in mice by using an in vitro ovary culture system as well as mutant animal models. We found that TNF and both receptors (TNFRSF1A and TNFRSF1B) are expressed in neonatal mouse ovaries and that TNF promotes oocyte death in neonatal ovaries in vitro. However, deletion of either receptor did not affect follicle endowment, suggesting that TNF does not regulate GCN breakdown in vivo. Tnfrsf1b deletion led to an apparent acceleration of follicular growth and a concomitant expansion of the primordial follicle population. This expansion of the primordial follicle population does not appear to be due to decreased primordial follicle atresia, although this cannot be ruled out completely. This study demonstrates that mouse oocytes express both TNF receptors and are sensitive to TNF-induced death. Additionally, TNFRSF1B is demonstrated to be an important mediator of TNF function in the mouse ovary and an important regulator of folliculogenesis.

Aging may be associated with concentrations of tamoxifen and its metabolites in breast cancer patients.

BACKGROUND: Although tamoxifen (TAM) is the predominant adjuvant therapy for estrogen receptor positive (ER(+)) breast tumors, 50% of breast cancer patients do not respond positively to this therapy, or they experience adverse side effects. This variability in TAM responsiveness may be due to differences in TAM metabolism that stem from differences in race, age, and body mass index (BMI). Thus, the purpose of this study was to test the hypothesis that race, age, and BMI are associated with the metabolism of TAM to two primary metabolites, N-desmethyltamoxifen (N-DMT) and 4-hydroxytamoxifen (4-OHT). METHODS: The study design was cross-sectional, and data were analyzed using independent sample t tests and multiple linear regression models. Breast cancer patients (n = 99) taking TAM for at least 30 days were recruited from a local hospital clinic. Each participant provided informed consent, completed a questionnaire, and donated a blood sample. The questionnaire was used to ascertain race, age, and BMI. The blood samples were used to measure plasma concentrations of TAM, N-DMT, and 4-OHT. RESULTS: Plasma concentrations of TAM, N-DMT, and 4-OHT differed among individual patients. Age, but not race and BMI, was positively associated with plasma concentrations of TAM and N-DMT, even after adjustment for potential confounders (p = 0.02 for TAM and p = 0.03 for N-DMT). CONCLUSIONS: This study suggests that aging may alter the metabolism of TAM. As increased levels of TAM and TAM metabolites may provide a possible explanation for why older women taking TAM are at increased risk for adverse side effects, future studies should determine whether age-related differences in the concentrations of TAM and TAM metabolites are associated with differences in TAM toxicity or responsiveness.

A randomized trial of incentives to improve response rates to a mailed women's health questionnaire.

BACKGROUND: Mailed questionnaires can be a convenient method for collecting data on women's health, although poor response rates are a concern. METHODS: As part of a survey of women's health conducted in Maryland in 2001, a randomized trial was performed to assess the effects of two incentives (US dollars 1.00 or a lottery ticket) as well as precontact with an introductory postcard on response rates. Questionnaires were mailed to 3000 women aged 40-60 who were randomized to one of six incentive/precontact groups: lottery/postcard, money/postcard, postcard only, lottery only, money only, or no incentive/no postcard. RESULTS: The overall response rate was 37.6%. Each incentive/precontact group yielded a higher response rate than the no incentive/no postcard group, although only the response rates for the lottery/postcard group (41.3%) and the money only group (40.0%) were significantly higher than that of the no incentive/no postcard group (33.1%). Money was the only factor that had a significant independent effect on likelihood of response (hazards ratio [HR] compared to no incentive = 1.22, 95% confidence interval [CI] = 1.03, 1.43). Response rates were lower in minority ZIP codes, although the effects of the incentives were generally greater than in the nonminority ZIP codes. CONCLUSIONS: These results indicate that response rates to mailed women's health questionnaires may be improved with modest incentives, particularly cash incentives.

The correlations between estradiol, estrone, estriol, progesterone, and sex hormone-binding globulin and anterior cruciate ligament stiffness in healthy, active females.

BACKGROUND: Injury to the anterior cruciate ligament (ACL) often requires surgery and extensive rehabilitation. Women who participate in collegiate sports and military drills are more likely to injure their ACL than are men participating in similar activities. The influence of the normal fluctuation of sex hormones on the physical properties of the ACL is one potential cause for this disparity. The purpose of this study was to report the correlation between estradiol, estrone, estriol, progesterone, and sex hormone binding globulin (SHBG) and ACL stiffness during three phases of the menstrual cycle in normally cycling, healthy females. METHODS: We tested ACL stiffness and collected blood from 20 female subjects who were not using oral contraception during three phases of their menstrual cycle. Ligament stiffness was tested with the KT-2000 trade mark knee arthrometer (MEDmetric, San Diego, CA). Concentrations of estradiol and SHBG were assessed via radioimmunoassay (RIA). Progesterone, estriol, and estrone concentrations were determined via enzyme-linked immunoassay. RESULTS: Spearman rank correlation analysis indicated a significant correlation between estradiol concentration and ACL stiffness (-0.70, p < 0.001) and estrone concentration and ACL stiffness near ovulation (0.46, p = 0.040). With the effects of the other variables controlled, there was a significant partial correlation between estradiol (-0.80, p < 0.001), estriol (0.70, p = 0.003), and progesterone (0.66, p = 0.005) and ACL stiffness near ovulation. CONCLUSIONS: Our results indicate that there is a significant correlation between estradiol, estriol, and progesterone and ACL stiffness suggesting that fluctuating levels of sex hormones may influence the stiffness of the ACL near ovulation. Future studies that examine the relationship between sex hormones and the physical properties of the ACL should be focused near the ovulation phase of the menstrual cycle.