Faculty Bibliography

Morphofunctional changes in hypothalamic neurons are highly energy dependent and rely on mitochondrial metabolism. Therefore, mitochondrial adenosine triphosphate production plays a permissive role in hypothalamic regulatory events. Here, we demonstrated that in the female rat hypothalamus, mitochondrial metabolism and tissue oxygenation show an asymmetric lateralization during the estrous cycle. This asymmetry was not detected in males. The observed sidedness suggests that estrous cycle-linked hypothalamic functions in females are based on hemispheric distinction. The novel concept of hypothalamic asymmetry necessitates the revision of hypothalamic neural circuits, synaptic reorganization, and the role of hypothalamic sides in the regulation of integrated homeostatic functions.

Abstract Unintended pregnancy is an important public health problem worldwide. Unwanted pregnancies may end in induced abortion (legal or illegal, safe or unsafe) or in childbirth. In many parts of the world both can be life threatening. Even where both are safe, abortion is distressing for all concerned while unwanted births often lead to poor health and social outcomes for both the mother and her child.

BACKGROUND: Whether menopausal hormone therapy (MHT) protects against cardiovascular disease (CVD) remains unclear. OBJECTIVE: To assess atherosclerosis progression and CVD risk factors after MHT initiated in early menopause. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT00154180). SETTING: Nine U.S. academic centers. PARTICIPANTS: Healthy menopausal women aged 42 to 58 years between 6 and 36 months from last menses without prior CVD events who had a coronary artery calcium (CAC) score less than 50 Agatston units and had not received estrogen or lipid-lowering therapy for at least 90 days. INTERVENTION: Oral conjugated equine estrogens (o-CEE), 0.45 mg/d, or transdermal 17beta-estradiol (t-E2), 50 mcg/d, each with 200 mg of oral progesterone for 12 days per month, or placebo for 48 months. MEASUREMENTS: Primary end point was annual change in carotid artery intima-media thickness (CIMT). Secondary end points included changes in markers of CVD risk. RESULTS: Of 727 randomly assigned women, 89.3% had at least 1 follow-up CIMT and 79.8% had CIMT at 48 months. Mean CIMT increases of 0.007 mm/y were similar across groups. The percentages of participants in whom CAC score increased did not differ significantly across groups. No changes in blood pressure were observed with o-CEE or t-E2. Low- and high-density lipoprotein cholesterol levels improved and levels of C-reactive protein and sex hormone-binding globulin but not interleukin-6 increased with o-CEE. Insulin resistance decreased with t-E2. Serious adverse events did not differ by treatment. LIMITATION: Power to compare clinical events was insufficient. CONCLUSION: Four years of early MHT did not affect progression of atherosclerosis despite improving some markers of CVD risk. PRIMARY FUNDING SOURCE: Aurora Foundation.

INTRODUCTION: Carbon monoxide poisoning is a very common cause of death in accidental, suicidal, or homicidal cases throughout the world. Fingernail bed manifestation is reported in survivors of carbon monoxide poisoning. CASE PRESENTATION: A 40-year-old Caucasian woman was exposed to carbon monoxide when she was sleeping alone in her one-bedroom apartment; fortunately, the beeps from her First Alert combination smoke and carbon monoxide detector woke her and she was saved from any extensive health issues. The most indicative symptoms experienced were a severe headache, blurred vision, agitation, and confusion. Following contact with the Emergency Responses Services, she was promptly transferred to the hospital via ambulance and was treated with high-flow oxygen on the way. She was discharged from the emergency department on the same day, but carbon monoxide exposure had already had adverse effects on her fingernail beds. The fingernail tips were altered and appeared as if a bite had been taken out of their distal borders. The changes in the tips of her fingernails were significant, but they completely disappeared eight weeks later without any additional treatment. CONCLUSIONS: Worldwide, carbon monoxide poisoning is a potentially lethal condition that is preventable with educational programs and installation of carbon monoxide detectors in the home setting. Exposure to carbon monoxide frequently goes unrecognized until it is too late and causes silent death. To the best of the authors' knowledge, this is the first report in the literature of fingernail bed manifestations in a survivor of carbon monoxide poisoning.

The Women's Health Initiative (WHI) assessed the long-term effects of hormone therapy (HT) in postmenopausal women. The WHI started HT treatment on women aged 50-79 years in order to ascertain these effects. The study was ended early, due to findings of increased risk of coronary heart disease, breast cancer, stroke, and thromboembolic complications in women receiving estrogen plus progestin, compared to placebo. An increased risk of thromboembolic complications was also demonstrated in the estrogen only component of the WHI. The WHI results were initially reported for all subjects, and showed little difference when data were not analyzed by age. New WHI sub-analyses stratifying results by age, and an extended follow-up of the WHI offer a more complete picture of the effects of HT, revealing that starting HT in postmenopausal women less than ten years from last menstrual period appears to have less risk. In addition, hysterectomized women treated with estrogen only in the WHI have showed less risk of adverse outcomes than women in the estrogen plus progestin group. In this paper, we review data supporting the use of HT administered to postmenopausal women, showing it to have more benefit than risk for symptom control, prevention of bone mineral loss and fracture, and improvement of the metabolic profile in women who began HT when they were less than 60 years of age and had their last menstrual period less than ten years previous. In hysterectomized women treated with estrogen only, a reduction in breast cancer risk was noted in all age groups. The WHI raised many important questions. Ten years later, some have been answered, including confirmation that HT for most newly menopausal women is safe and effective. The treatment of the aging woman, including hormone treatment after menopause, should remain one of our highest research priorities. This article is part of a Special Issue entitled 'Menopause'.

Concerns pertaining to the risk of estrogen exposure through HT have prompted an increase in the use of natural alternatives. Phytoestrogens may provide postmenopausal women with a practical alternative and many women have already begun to utilize phytoestrogen supplements. However, research regarding the efficacy of phytoestrogens as a hormone therapy alternative has been previously pessimistic or questionable at best. This review scrutinizes the most current research regarding the efficacy of three types of phytoestrogens, isoflavones, lignans and coumestans, and their specific effect on the reduction of climacteric symptoms, specifically vasomotor symptoms, vaginal atrophy, insomnia and osteoporosis. A discussion of the research pertaining to the relative safety of each phytoestrogen in terms of breast and endometrial health is also included. Overall, current research demonstrates that phytoestrogens are effective in reducing the intensity of hot flushes, and some phytoestrogen combinations result in a decreased frequency. Certain phytoestrogens have also been shown to decrease vaginal atrophy, improve sleep and cognition, and positively affect bone health. Even though initial research was generally unconvincing, the more recent evidence reviewed here is rather positive. In terms of safety and reports of adverse reactions, trials have not shown an increase in breast cancer risk or increase in endometrial hyperplasia following phytoestrogen use, but trials explicitly designed to find neoplasia have not been reported. Moreover, unlike hormone therapy, lignans may not increase clotting risk in postmenopausal women, thus supplements may serve as a treatment option for patients who have contraindications to hormone therapy. Phytoestrogens may provide a safe and partially effective alternative to HT. However, because research regarding phytoestrogens is relatively new, pharmaco-vigilence is still required, as these products are not yet FDA-approved. This article is part of a Special Issue entitled 'Phytoestrogens'.

Midlife vascular risk factors influence later cognitive decline and Alzheimer's disease (AD). The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk, such as high blood pressure (BP), which independently contributes to cognitive dysfunction and AD. We describe the extent to which vascular risk factors relate to cognition in healthy, middle-aged, recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS-Cog) at baseline. KEEPS-Cog is a double-blind, randomized, placebo-controlled, parallel group, clinical trial, investigating the efficacy of low-dose, transdermal 17beta-estradiol and oral conjugated equine estrogen on cognition. All results are cross-sectional and represent baseline data only. Analyses confirm that the KEEPS-Cog cohort (n = 571) was middle aged (mean 52.7 years, range 42-59 years), healthy, and free of cognitive dysfunction. Higher systolic BP was weakly related to poorer performance in auditory working memory and attention (p = 0.004; adjusted for multiple comparisons p = 0.10). This relationship was not associated with endogenous hormone levels, and systolic BP was not related to any other cognitive domain. BP levels may be more sensitive than other vascular risk factors in detecting subtle differences in cognitive task performance in healthy, recently menopausal women. Lower BP early in menopause may affect cognitive domains known to be associated with AD.

In industrialized societies the progression of natural selection has been determined and in many cases superseded by social evolution. In the case of reproduction, there has been a decline and delay of childbearing without diminished sexual activity. While this has value for these societies, there are penalties associated with barren cycles. These include increases in endometriosis and breast and genital cancer. There also are associated issues regarding population movements that fill the "vacuums" left by underpopulation. These matters are of more than passing interest as we cope with unintended consequences of Man's dominance over the environment and other life forms.

Practice-based research networks (PBRNs) can function as a platform for delivery of patient-centered care consistent with the Patient Protection and Affordable Care Act. Patient-centered (centric) clinical studies encourage the patient to be an integral part of study design and outcome. The patient's electronic health record contributes to the shared national health care data set. PBRNs integrate health care data in real time at the point of care and reflect the full context of the person's health. PBRNs designed under the principles of good clinical practice (GCP) validate studies related to comparative effectiveness research and drug development. PBRNs can generate large amounts of data from known patient histories so that side effects can be assessed in their totality. The larger and more diverse number of patients recruited suggests that point-of-care-data, where both provider and patient participate in the treatment, may be more robust in that side effects, drug-drug interactions and number of concomitant medications used may be identified earlier in the development process. The GCP PBRN concept affords continuous patient information for both care and research purposes. These all contribute to an ethical approach for the pharmaceutical industry to generate clinical research data for regulatory submission and to contribute to a HIPAA-compliant national database that could contribute to improved health care delivery and pharmacovigilance.