Long-term, low-dose lead exposure alters the gonadotropin-releasing hormone system in the male rat.

Lead is a male reproductive toxicant. Data suggest that rats dosed with relatively high levels of lead acetate for short periods of time induced changes in the hypothalamic gonadotropin-releasing hormone (GnRH) at the molecular level, but these changes were attenuated with increased concentration of exposure. The current study evaluated whether exposure to low levels of lead acetate over longer periods of time would produce a similar pattern of adaptation to toxicity at the molecular and biologic levels. Adult 100-day-old Sprague-Dawley male rats were dosed with 0, 0.025, 0.05, 0.1, and 0.3% lead acetate in water. Animals were killed after 1, 4, 8, and 16 weeks of treatment. Luteinzing hormone (LH) and GnRH levels were measured in serum, and lead levels were quantified in whole blood. Hypothalamic GnRH mRNA levels were also quantified. We found no significant differences in serum LH and GnRH among the groups of animals treated within each time period. A significant dose-related increase of GnRH mRNA concentrations with lead dosing occurred in animals treated for 1 week. Animals treated for more than 1 week also exhibited a significant increase in GnRH mRNA, but with an attenuation of the increase at the higher concentrations of lead with increased duration of exposure. We conclude that the signals within and between the hypothalamus and pituitary gland appear to be disrupted by long-term, low-dose lead exposure

Estrogenic activity, race/ethnicity, and Indigenous American ancestry among San Francisco Bay Area women.

Estrogens play a significant role in breast cancer development and are not only produced endogenously, but are also mimicked by estrogen-like compounds from environmental exposures. We evaluated associations between estrogenic (E) activity, demographic factors and breast cancer risk factors in Non-Latina Black (NLB), Non-Latina White (NLW), and Latina women. We examined the association between E activity and Indigenous American (IA) ancestry in Latina women. Total E activity was measured with a bioassay in plasma samples of 503 women who served as controls in the San Francisco Bay Area Breast Cancer Study. In the univariate model that included all women with race/ethnicity as the independent predictor, Latinas had 13% lower E activity (p = 0.239) and NLBs had 35% higher activity (p = 0.04) compared to NLWs. In the multivariable model that adjusted for demographic factors, Latinas continued to show lower E activity levels (26%, p = 0.026), but the difference between NLBs and NLWs was no longer statistically significant (p = 0.431). An inverse association was observed between E activity and IA ancestry among Latina women (50% lower in 0% vs. 100% European ancestry, p = 0.027) consistent with our previously reported association between IA ancestry and breast cancer risk. These findings suggest that endogenous estrogens and exogenous estrogen-like compounds that act on the estrogen receptor and modulate E activity may partially explain racial/ethnic differences in breast cancer risk

Antimullerian hormone and obesity: insights in oral contraceptive users

The study was conducted to examine the impact of oral contraceptives (OCs) on serum antimullerian hormone (AMH) levels by obesity status in reproductive-age women

Оплата труда и стимулирование трудовой деятельности в организации ООО "ТСМ Ковчег"

Объект исследования в выпускной квалификационной работе – оплата труда и стимулирование трудовой деятельности ООО "ТСМ Ковчег". Цель выпускной квалификационной работы заключается в разработке рекомендаций по совершенствованию системы оплаты труда и стимулирования трудовой деятельности в организации. В целях решения поставленных в выпускной квалификационной работе задач, применялись методы познания: аналитический, структурный, системный и метод экономического анализа. При проведении прикладного анализа выявилась возможность представить рекомендации по совершенствованию системы оплаты труда и стимулирования трудовой деятельности в организации ООО "ТСМ Ковчег".The object of research in the final qualifying work is payment for labor and stimulation of labor activity of LLC "TSM Kovcheg". The purpose of the final qualifying work is to develop recommendations for improving the system of labor remuneration and stimulating work in the organization. In order to solve the tasks set in the final qualifying work, methods of cognition were used: analytical, structural, system and method of economic analysis. When carrying out applied analysis, it became possible to provide recommendations on improving the system of labor remuneration and stimulating work in the organization of LLC "TSM Kovcheg.

Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians

Background: Estradiol, testosterone (T), and sex hormone binding globulin (SHBG) levels are associated with lipid subfractions in men and women. Our objective was to determine if associations are independent from adipose tissue area among Asian Indians. Methods: We used data from 42 women and 57 Asian Indian men who did not use exogenous steroids or lipid-lowering medications. Lipoprotein subfractions including low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), and intermediate density lipoprotein (IDL) were assessed by ion mobility spectrometry. Intra-abdominal adiposity was assessed by computed tomography. Multivariable regression models estimated the association between sex hormones with lipoprotein subfractions before and after adjustment for adiposity. Results: Among women, lower logSHBG levels were associated with smaller logLDL particle size and higher logtriglycerides, logVLDL, and logIDL, although these associations were attenuated with adjustment for visceral adiposity in particular. Among women, lower logSHBG levels was significantly associated with lower logmedium LDL and logsmall LDL concentrations even after consideration of visceral and hepatic adiposity and insulin resistance as represented by the homeostasis model assessment of insulin resistance (HOMA-IR). Among men, lower logSHBG was also associated with smaller logLDL peak diameter size and higher logtriglycerides and logVLDL, even after adjustment for HOMA-IR and adiposity. Relationships between sex steroids and lipid subfractions were not significant among women. Among men, higher total testosterone was associated with higher logHDL and logLDL particle size, and lower logtriglycerides and logVLDL, but these associations were partially attenuated with adjustment for adiposity and HOMA-IR. Conclusions: Among Asian Indians, SHBG is associated with more favorable lipid subfraction concentrations, independent of hepatic and visceral fat.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140166/1/met.2015.0063.pd

Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age

Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential or “fertility tests.

Antimüllerian Hormone as a Predictor of Natural Fecundability in Women Aged 30–42 Years

To generate estimates of the association between markers of ovarian aging and natural fertility in a community sample at risk for ovarian aging

Effect of Protease Inhibitors on Steady-State Pharmacokinetics of Oral Norethindrone Contraception in HIV-Infected Women

OBJECTIVE: Pharmacokinetic interactions exist between combined oral contraceptives and protease inhibitors (PI). However, such information is lacking for progestin-only oral contraception. We sought to define the steady-state pharmacokinetic interaction between norethindrone (NET) and PI in HIV-infected women. METHODS AND DESIGN: We conducted an open-label, prospective, nonrandomized trial to characterize the steady-state pharmacokinetics of serum NET in HIV-infected women receiving PI compared with a control group of HIV-infected women receiving other noninteracting drugs. After 21 days of 0.35 mg of NET ingestion once daily, serial serum samples were obtained at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours. The area under the curve between 0 and 72 hours after ingestion was calculated by trapezoidal approximation. RESULTS: Thirty-five women were enrolled, 2 withdrew. Sixteen women in the PI group and 17 controls completed the study. NET half-life and maximum concentration were not significantly different between the 2 groups. Minimum concentration of NET was significantly higher in the PI group (P = 0.01). The ratio of the geometric mean NET area under the curve in the PI group compared with controls was 1.5 (90% confidence interval: 1.21 to 1.86). NET serum concentrations were significantly higher in HIV-infected women taking a PI compared with controls (P = 0.004). CONCLUSIONS: Coadministration of PI inhibits NET metabolism as shown by higher serum NET area under the curve levels, a surrogate marker for therapeutic contraceptive efficacy. This study supports the increased utilization of progestin-only pills in HIV-infected women receiving certain PI regimens.Keywords: norethindrone, HIV, efficacy, hormonal contraception, drug interactions, pharmacokinetics, progestin only pills, protease inhibitor, contraceptio

Anti-Mullerian Hormone Concentrations in Premenopausal Women and Breast Cancer Risk

Laboratory models support an inverse association between anti-Müllerian hormone (AMH) and breast tumor development. Human studies are lacking; one study (N=105 cases, 204 controls) with prospectively-collected serum reported the opposite—an approximate 10-fold increase in breast cancer risk comparing 4th to 1st quartile AMH levels. We investigated the relation between serum AMH levels and breast cancer risk in a case-control (N=452 cases, 902 controls) study nested within the prospective Sister Study cohort of 50,884 women. At enrollment, participants were ages 35-54, premenopausal, and completed questionnaires on medical and family history, lifestyle factors, and demographics. AMH (ng/ml) was measured by ultrasensitive ELISA in serum collected at enrollment and log-transformed for analysis. Multivariate conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) to account for matching on age and enrollment year. Mean age at enrollment was 46.8 years with an average 2.9 years from blood draw to breast cancer diagnosis (SD=1.9). AMH concentrations were below the limit of detection (0.003 ng/ml) for ~25% of samples. Compared with samples below the LOD, women with AMH >2.84 ng/ml (90th percentile among controls) had a two-fold increase in breast cancer odds (OR=2.25; 95% CI: 1.26-4.02). For each 1-unit increase in lnAMH, overall breast cancer odds increased by 8% (OR=1.08; 95% CI: 1.02-1.15) and odds of ER-positive, invasive disease increased by 15% (OR=1.15; 95% CI: 1.05-1.25). Our findings demonstrate an overall positive relation between AMH and breast cancer