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Trans Am Clin Climatol Assoc. 2003;114:233-8; discussion 238-40.
Hormone replacement therapy: dilemmas in 2002.

Moore A.

New York Presbyterian Hospital-Weill Cornell Medical Center, 428 East 72nd Street, Suite 300, New York, New York 10128, USA. almoorail.med.cornell.edu

About 6 million women in the United States are prescribed a combined estrogen-progestin regimen during and after the menopause. The immediate benefits of hormone replacement therapy (HRT) are relief of menopausal symptoms. Doctors and their patients have long presumed that the benefits on cardiovascular disease and osteoporosis outweigh the possible increased risk of breast cancer or venous thrombosis. The Women's Health Initiative, a National Institutes of Health program, is the first study to compare HRT to placebo in healthy women. The July 2002 report of increased cardiovascular events as well as increased breast cancer diagnosis in women on the HRT arm of the study brought widespread media coverage and has led to distress and confusion among women taking HRT. Women with a personal or family history of breast cancer pose a particular challenge to their physicians when they ask for advice about HRT.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12813923&dopt=Abstract

J Gend Specif Med. 2003;6(2):14-21.
Increased estrogen-dependent expression of calcineurin in female SLE T cells is regulated by multiple mechanisms.

Rider V, Keltner S, Abdou NI.

Department of Biology, Pittsburg State University, Pittsburg, KS 66762, USA. vrideittstate.edu

OBJECTIVE: Calcineurin is a key mediator of T cell activation. Previous studies in our laboratory showed a dose-dependent and hormone-specific increase in calcineurin expression in the T cells from females with systemic lupus erythematosus (SLE). This study investigates whether the estrogen-dependent increase in calcineurin expression is due to stabilization of the messenger RNA (mRNA). METHODS: T cells from female patients with SLE and controls were cultured for 18 hours in a serum-free medium with and without estradiol-17 beta (10(-7) M). Some T cells were activated by further culture on anti-CD3-coated plates. Actinomycin D (25 micrograms/mL) was added to some cultures to inhibit new mRNA synthesis. Calcineurin mRNA stability was assessed by reverse-transcription polymerase chain amplification. RESULTS: Resting SLE (n = 9, P = .59) and normal (n = 5, P = .90) T cells showed no significant differences in mRNA stability in response to estradiol. Calcineurin mRNA was not significantly stabilized in activated SLE (n = 10, P = .12) or activated normal (n = 8, P = .09) T cells in response to estradiol. However, the amount of calcineurin mRNA stabilized in activated normal T cells (n = 8) was significantly greater (P = .02) compared with SLE T cells (n = 10) only after culture in medium without estradiol. CONCLUSIONS: These findings highlight the complex gene regulatory mechanisms underlying the differential action of estrogen on SLE T cells. Furthermore, the data indicate that increased calcineurin expression in SLE T cells is not due solely to estrogen-dependent stabilization of the message, and probably involves additional transcriptional regulatory mechanisms.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12813997&dopt=Abstract [PubMed - in process]

Cancer Causes Control. 2003 Apr;14(3):225-33.
Postmenopausal hormone therapy and risk of breast cancer by histologic type (United States).

Newcomer LM, Newcomb PA, Potter JD, Yasui Y, Trentham-Dietz A, Storer BE, Longnecker MP, Baron JA, Daling JR.

Program in Epidemiology, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.

OBJECTIVE: Postmenopausal hormone use and risk of breast cancer by histopathology was examined in a large multi-centered population-based case-control study. METHODS: Women younger than 75 years newly diagnosed with invasive breast cancer between 1988 and 1991 were identified from statewide tumour registries in Wisconsin, Massachusetts, New Hampshire, and Maine. Only postmenopausal women were included in this analysis. Breast cancer cases (lobular (n = 219), ductal, NOS (n = 2172), and specific ductal subtypes (n = 242)) were compared with randomly selected population controls (n = 3179) using adjusted multi-variable polytomous logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for each histology. RESULTS: Lobular carcinoma was associated with recent (within 2 years) estrogen therapy (OR: 1.8, 95% CI: 1.0-3.4) and recent use of combined estrogen-plus-progestin therapy (OR:3.6, 95%CI: 1.8-7.6). Risk of ductal carcinoma was not associated with recent use of either estrogen alone (OR: 0.9, 95% CI: 0.7-1.2) or combined therapy (OR:0.9, 95% CI: 0.6-1.3). No associations were found with ductal subtypes. CONCLUSIONS: The association between postmenopausal hormone use and risk of breast cancer may depend on histopathology. Of particular interest is the association between combined hormone therapy and increased risk of lobular carcinoma. This lesion is increasingly common but, nonetheless, comprises fewer than 10% of invasive breast cancers.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12814201&dopt=Abstract [PubMed - in process]

Cancer Causes Control. 2003 Apr;14(3):285-92.
Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin-like growth factor binding proteins-1 and -2 (USA, Sweden, Italy).

Lukanova A, Lundin E, Micheli A, Akhmedkhanov A, Rinaldi S, Muti P, Lenner P, Biessy C, Krogh V, Riboli E, Hallmans G, Berrino F, Zeleniuch-Jacquotte A, Toniolo P, Kaaks R.

International Agency for Research on Cancer, Lyon, France.

OBJECTIVE: To investigate the association of prediagnostic circulating levels of C-peptide, as a marker of pancreatic insulin secretion, and IGF binding proteins -1 and -2, as indicators of the biologically active IGF-I concentration, with risk of developing ovarian cancer. METHODS: The study was nested within three prospective cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Case subjects were 132 women with primary invasive epithelial ovarian cancer diagnosed at least one year after blood donation. For each case, two control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. RESULTS: Odds ratios and their 95% confidence intervals for risk of developing ovarian cancer over quartiles of peptides concentrations after adjustment for BMI and fasting were: 1.00, 0.66 (0.35-1.23), 0.96 (0.51-1.82) and 0.89 (0.44-1.81) for C-peptide; 1.00, 1.10 (0.58-2.09), 1.07 (0.55-2.04) and 0.79 (0.38-1.62) for IGFBP-1; and 1.00, 1.01 (0.54-1.89), 0.98 (0.51-1.88) and 0.87 (0.45-1.68) for IGFBP-2. In women who had ovarian cancer diagnosis before age 55 the ORs for the top tertiles of IGFBP-1 and IGFBP-2 were 0.51 (0.18-1.49) and 0.53 (0.18-1.54), respectively. CONCLUSIONS: This study does not support an independent direct etiological role of C-peptide in ovarian cancer pathogenesis, but suggests a possible protective effect of circulating IGFBP-1 and -2 in women who develop ovarian cancer before age 55.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12814208&dopt=Abstract [PubMed - in process]

Reproduction. 2003 Jul;126(1):61-71.
Effect of different nutritional regimens before ovulation on plasma concentrations of metabolic and reproductive hormones and oocyte maturation in gilts.

Ferguson EM, Ashworth CJ, Edwards SA, Hawkins N, Hepburn N, Hunter MG.

SAC, Animal Biology Division, Bucksburn, Aberdeen AB21 9YA, UK. e.fergusobdn.ac.uk

This study examined the effect of feeding either a maintenance (1.35 kg day(-1)) or high (3.5 kg day(-1)) plane of nutrition for 19 days after oestrus on oocyte maturity and both reproductive and metabolic hormone concentrations in gilts. Blood samples were collected each day from oestrus until slaughter on day 19 and during two pulse bleeds (15 min samples for 8 h) conducted on day 12 and day 18. After slaughter, oocytes were recovered from the presumed ovulatory population of follicles, matured in vitro for 46+/-2 h with 10% of their own follicular fluid, and then fixed and stained to determine the stage of nuclear maturation of the oocyte. Gilts fed the high diet had a higher proportion of oocytes that reached metaphase II than gilts fed the maintenance diet (88.3+/-2.71% versus 68.2+/-6.48%; P=0.013). Circulating concentrations of insulin-like growth hormone I (IGF-I) and the number of LH pulses were lower (P<0.05) in gilts fed the maintenance diet compared with gilts fed the high diet on day 12 and day 18. Mean oestradiol and progesterone concentrations were higher (P<0.05) for gilts fed the maintenance diet compared with gilts fed the high diet. Leptin concentrations were also higher on day 19 in gilts fed the high diet (2.16+/-0.26 ng ml(-1) (n=9) versus 3.20+/-0.32 (n=11), P=0.025). The results of this study indicate that improved oocyte quality (increased proportion of oocytes that reached metaphase II) is associated with a number of changes in reproductive and metabolic hormones. Further studies are required to indicate which hormonal mechanism may, in turn, lead to increased embryo survival and eventual litter size.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12814348&dopt=Abstract [PubMed - in process]

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