Cognitive changes across the menopause transition: A longitudinal evaluation of the impact of age and ovarian status on spatial memory.

Cognitive changes that occur during mid-life and beyond are linked to both aging and the menopause transition. Studies in women suggest that the age at menopause onset can impact cognitive status later in life; yet, little is known about memory changes that occur during the transitional period to the postmenopausal state. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of perimenopausal women.

Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial.

Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects.

Pharmacological blockade of the aromatase enzyme, but not the androgen receptor, reverses androstenedione-induced cognitive impairments in young surgically menopausal rats.

Androstenedione, the main circulating ovarian hormone present after menopause, has been shown to positively correlate with poor spatial memory in an ovary-intact rodent model of follicular depletion, and to impair spatial memory when administered exogenously to surgically menopausal ovariectomized rats. Androstenedione can be converted directly to estrone via the aromatase enzyme, or to testosterone. The current study investigated the hormonal mechanism underlying androstenedione-induced cognitive impairments.

Differential impact of body mass index on absolute and percent breast density: implications regarding their use as breast cancer risk biomarkers.

Percent breast density (PBD), a commonly used biomarker of breast cancer risk (BCR), is confounded by the influence of non-dense breast tissue on its measurement and factors, such as BMI, which have an impact on non-dense tissue. Consequently, BMI, a potent BCR factor, is, paradoxically, negatively correlated with PBD. We propose that absolute breast density (ABD) is a more accurate biomarker of BCR.

Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women.

Background: Recent attention has been given to subclinical hypothyroidism, defined as an elevation of TSH (4.5-10 uIU/L) with T4 and T3 levels still within the normal range. Controversy exists about the proper lower limit of TSH that defines patients in the subclinical hypothyroidism range and about if/when subclinical hypothyroidism should be treated.

Determination of vitamin D in relation to body mass index and race in a defined population of black and white women.

Objective: To examine the contributions of obesity and race to levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) in a defined cohort of black and white women.

Methods: An interventional study was conducted from October 2004 to March 2008, among 219 healthy female volunteers. Serum 25(OH)D and PTH levels were determined in 117 African American women and 102 white women and the results were compared with body mass index (BMI), percentage body fat, serum lipids, and PTH levels.

Continuous estrone treatment impairs spatial memory and does not impact number of basal forebrain cholinergic neurons in the surgically menopausal middle-aged rat.

CEE (conjugated equine estrogens) is the most widely prescribed estrogen-only menopausal hormone therapy in the United States, and is comprised of over 50% estrone (E1) sulfate. Following CEE administration, E1 is the principal circulating estrogen. However, the cognitive and neurobiological effects of E1 in a middle-aged rodent model have not yet been evaluated.

Genetic Ancestry, Skin Reflectance and Pigmentation Genotypes in Association with Serum Vitamin D Metabolite Balance.

Background: Lower serum vitamin D (25(OH)D) among individuals with African ancestry is attributed primarily to skin pigmentation. However, the influence of genetic polymorphisms controlling for skin melanin content has not been investigated. Therefore, we investigated differences in non-summer serum vitamin D metabolites according to self-reported race, genetic ancestry, skin reflectance and key pigmentation genes ( and .

The effects of Tamoxifen and fish oil on mammary carcinogenesis in polyoma middle T transgenic mice.

In these experiments, we tested the hypothesis that inhibition of the estrogen receptor (ER) with Tamoxifen and activation of PPARγ with fish oil (FO) rich in omega-3 (n-3; known PPAR agonists) inhibit the development of hormone-independent breast cancer in view of the known crosstalk between the ER and PPARγ pathways. We selected the polyoma middle T transgenic mouse model, since in this system the development of ER- tumors is preceded by ER positive preneoplastic lesions. Tamoxifen admixed with a 20% corn oil (CO) modified AIN-76A diet delayed mammary carcinogenesis and inhibited tumor multiplicity, volume, and weight in a dose-dependent (1, 10, and 100 ppm) fashion.

Racial influence on the polycystic ovary syndrome phenotype: a black and white case-control study.

Objective: To estimate racial disparities in the polycystic ovary syndrome (PCOS) phenotype between white and black women with PCOS.

Design: Case-control study.

Setting: Two academic medical centers.

Effects of metformin in adolescents with polycystic ovary syndrome undertaking lifestyle therapy: a pilot randomized double-blind study.

Our small study does not support the addition of metformin to the lifestyle of adolescents. Although there are favorable trends toward hyperandrogenism with metformin, these must be balanced against the increased rate of gastrointestinal side effects. However, other treatments were associated with an improved quality of life.

The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study.

Objective: To determine if the combination of lifestyle (caloric restriction and exercise) and metformin (MET) would be superior to lifestyle and placebo (PBO) in improving the polycystic ovary syndrome (PCOS) phenotype.

Design: Double-blind randomized 6-month trial of MET versus PBO.

Setting: Two academic medical centers.

Effects of atorvastatin on vascular function, inflammation, and androgens in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial.

To determine the effects of statins on vascular function, inflammation, and androgen levels in women with polycystic ovary syndrome (PCOS), we randomized 20 women with PCOS who had low-density lipoprotein cholesterol levels >100 mg/dL to atorvastatin (40 mg/day) or placebo for 6 weeks and found that atorvastatin reduced androgen levels, biomarkers of inflammation, and blood pressure; increased insulin levels and brachial artery conductance during reactive hyperemia; and failed to improve brachial artery flow-mediated dilation. We conclude that until additional studies demonstrate a clear risk-to-benefit ratio favoring statin therapy in PCOS, statins should only be used in women with PCOS who meet current indications for statin treatment.

Brachial artery conductance during reactive hyperemia is increased in women with polycystic ovary syndrome.

Objective: To examine changes in brachial artery conductance (BAC) during reactive hyperemia in women with polycystic ovary syndrome (PCOS) compared to controls.

Study Design: This is a pilot case-control study performed at a single academic medical center. Changes in BAC during reactive hyperemia were evaluated in 31 women with PCOS and 11 healthy control women.

Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer.

BACKGROUND: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival. OBJECTIVE: Opioid growth factor (OGF; [Met(5)]-enkephalin) is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice.

A variant in the fibrillin-3 gene is associated with TGF-β and inhibin B levels in women with polycystic ovary syndrome.

In an attempt to evaluate the association between allele 8 (A8) of D19S884 in the fibrillin-3 gene and circulating transforming growth factor (TGF) β and inhibin levels in women with polycystic ovary syndrome (PCOS), we studied 120 similarly aged women from families with PCOS and compared 40 women with PCOS who did not have A8 (A8- PCOS) with 40 women with PCOS who had A8 (A8+ PCOS) and 40 normally menstruating women who did not have either PCOS or A8 (A8- Non-PCOS). A8- PCOS is associated with higher levels of TGF-β1 compared with A8+ PCOS or A8- Non-PCOS, similar levels of TGF-β2 compared with A8+ PCOS but lower levels of TGF-β2 compared with A8- Non-PCOS, and lower levels of inhibin B and aldosterone compared with A8+ PCOS.

Androgen deficiency in women; role of accurate testosterone measurements.

Androgen deficiency in women has been recognized as a distinct clinical syndrome that affects thousands of women particularly women in the postmenopausal period of their life. This syndrome has been described by several names including female androgen deficiency syndrome as well as hypoactive, sexual desire disorder. A recent large survey concerning sexual problems in women also adds personal distress as a potential contributor to the low sexual desire found in some women with sexual dysfunction.

Premarin improves memory, prevents scopolamine-induced amnesia and increases number of basal forebrain choline acetyltransferase positive cells in middle-aged surgically menopausal rats.

Conjugated equine estrogen (CEE) is the most commonly prescribed estrogen therapy, and is the estrogen used in the Women's Health Initiative study. While in-vitro studies suggest that CEE is neuroprotective, no study has evaluated CEE's effects on a cognitive battery and brain immunohistochemistry in an animal model. The current experiment tested whether CEE impacted: I) spatial learning, reference memory, working memory and long-term retention, as well as ability to handle mnemonic delay and interference challenges; and, II) the cholinergic system, via pharmacological challenge during memory testing and ChAT-immunoreactive cell counts in the basal forebrain.

Testosterone and estradiol assays: current and future trends.

Sex steroid measurements for the investigation of endocrine disorders have been fraught with accuracy and imprecision problems since the advent of high throughput, direct assays almost 10 years ago on automated analyzers. Results from testosterone and estradiol measurements at the low end of detectability have suffered the most and there are few automated systems that can accurately measure these steroids in women, children and hypogonadal males on a routine basis. With the advent of mass spectrometry coupled to either gas chromatography or liquid chromatography, an improved approach to the measurement of these steroids has developed that shows promise for accurately and precisely measuring testosterone and estradiol in all patient populations including women and children.

Urine markers do not predict biopsy findings or presence of bladder ulcers in interstitial cystitis/painful bladder syndrome.

Purpose: We tested for associations between urine markers, bladder biopsy features and bladder ulcers in interstitial cystitis/painful bladder syndrome.

Materials And Methods: Subjects were 72 patients with interstitial cystitis/painful bladder syndrome undergoing bladder distention and biopsy. Urine was collected before the procedure.

Comparison of hormonal and metabolic markers after a high-fat, Western meal versus a low-fat, high-fiber meal in women with polycystic ovary syndrome.

Objective: To determine the effect of meal composition on postprandial T levels in women with polycystic ovary syndrome (PCOS).

Design: Randomized, crossover design.

Setting: Academic research center.

Diminished paternity and gonadal function with increasing obesity in men.

Objective: To examine the relationship of male obesity and reproductive function.

Design: Observational study.

Setting: Academic medical center.

Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study.

Objective: Hyperandrogenia and insulin resistance are heritable family traits, likely to cluster in children of polycystic ovary syndrome (PCOS) mothers.

Design: We performed a case control study of PCOS children (n = 32) compared with children from control women (n = 38) for reproductive and metabolic abnormalities, stratifying results by three Tanner stage groupings. The children underwent history and physical examinations, a 3-h timed urine collection, a 2-h oral glucose tolerance test, and abdominal ultrasound examination (females only).