Menopausal hormone therapy and coronary heart disease: the roller-coaster history.

In the USA it is estimated that more than one million women become menopausal each year. Coronary heart disease (CHD) is the leading cause of mortality in menopausal woman globally. The majority of perimenopausal to postmenopausal women experience bothersome symptoms including hot flashes, night sweats, mood liability, sleep disturbances, irregular bleeding and sexual dysfunction. While menopausal hormone therapy (HT) effectively treats most of these symptoms, use of HT has become confusing, especially related to CHD risk. Despite years of observational and retrospective studies supporting a CHD benefit and improved survival among HT users, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative (WHI) raised doubts about this long-held premise. The timing hypothesis has since emerged and states that when HT is initiated in younger women, soon after menopause onset, there may be cardiovascular benefit. The following review discusses the roller-coaster history of HT use as it pertains to CHD in postmenopausal women. Studies that highlight HT's CHD benefit are reviewed and provide reassurance that HT utilized in appropriately selected younger postmenopausal women close to the onset of menopause is safe from a cardiovascular perspective, in line with consensus recommendations.

Association between coronary artery vitamin D receptor expression and select systemic risks factors for coronary artery atherosclerosis.

OBJECTIVE: The aim of this study is to analyze the association between coronary artery vitamin D receptor (VDR) expression and systemic coronary artery atherosclerosis (CAA) risk factors. METHODS: Female cynomolgus monkeys (n = 39) consumed atherogenic diets containing the women's equivalent of 1000 IU/day of vitamin D3. After 32 months consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, CAA and VDR expression were quantified in the left anterior descending coronary artery. Plasma 25OHD3, lipid profiles and serum monocyte chemotactic protein-1 (MCP-1) were measured. RESULTS: In postmenopausal monkeys receiving atherogenic diets, serum MCP-1 was significantly elevated compared with baseline (482.2 ± 174.2 pg/ml vs. 349.1 ± 163.2 pg/ml, respectively; p < 0.001; d = 0.79) and at the start of menopause (363.4 ± 117.2 pg/ml; p < 0.001; d = 0.80). Coronary VDR expression was inversely correlated with serum MCP-1 (p = 0.042). Additionally, the change of postmenopausal MCP-1 (from baseline to necropsy) was significantly reduced in the group with higher, compared to below the median, VDR expression (p = 0.038). The combination of plasma 25OHD3 and total plasma cholesterol/high-density lipoprotein cholesterol was subsequently broken into low-risk, moderate-risk and high-risk groups; as the risk increased, the VDR quantity decreased (p = 0.04). CAA was not associated with various atherogenic diets. CONCLUSION: Coronary artery VDR expression was inversely correlated with markers of CAA risk and inflammation, including MCP-1, suggesting that systemic and perhaps local inflammation in the artery may be associated with reduced arterial VDR expression.

A clinical research integration special program (CRISP) for young women with primary ovarian insufficiency.

Large-scale medical sequencing provides a focal point around which to reorganize health care and health care research. Mobile health (mHealth) is also currently undergoing explosive growth and could be another innovation that will change the face of future health care. We are employing primary ovarian insufficiency (POI) as a model rare condition to explore the intersection of these potentials. As both sequencing capabilities and our ability to intepret this information improve, sequencing for medical purposes will play an increasing role in health care beyond basic research: it will help guide the delivery of care to patients. POI is a serious chronic disorder and syndrome characterized by hypergonadotrophic hypogonadism before the age of 40 years and most commonly presents with amenorrhea. It may have adverse health effects that become fully evident years after the initial diagnosis. The condition is most commonly viewed as one of infertility, however, it may also be associated with adverse long-term outcomes related to inadequate bone mineral density, increased risk of cardiovascular disease, adrenal insufficiency, hypothyroidism and, if pregnancy ensues, having a child with Fragile X Syndrome. There may also be adverse outcomes related to increased rates of anxiety and depression. POI is also a rare disease, and accordingly, presents special challenges. Too often advances in research are not effectively integrated into community care at the point of service for those with rare diseases. There is a need to connect community health providers in real time with investigators who have the requisite knowledge and expertise to help manage the rare disease and to conduct ongoing research. Here we review the pathophysiology and management of POI and propose the development of an international Clinical Research Integration Special Program (CRISP) for the condition.

Osteoporosis management in post-menopausal women.

Osteoporosis is most prevalent in women over the age of 50 as the hormonal influence of estrogen on bone health dissipates with the onset of menopause. The progressive changes in bone structure, quality and density lead to pathological fractures and an increase in morbidity and mortality among menopausal women. This review will examine the 2010 North American Menopause Society (NAMS) position statement and other recent publications to summarize the data and combinations of therapies used to treat women 50 years or older with osteoporosis. To review the latest research and guidelines for osteoporosis management we performed a PubMed search using the parameters Linked to free full text, Humans, Female, Review, English, Middle Age (45-64 years and 45+ years), Age 65+ years, and published in the last five years. Articles were sorted by relevance and hand searching of these articles was done to further increase the yield. While a perfect treatment has yet to be discovered to completely cure this progressive disease, many breakthroughs have been made in order to prevent fractures and improve quality of life. Calcium and vitamin D supplementation are recommended for patients undergoing pharmacological treatment, however, trials looking at their effectiveness have mixed findings. Bisphosphonates are considered the first line therapy in the treatment of osteoporosis and reduce vertebral fractures by 40% to 70% and non-vertebral fractures by 20% to 35%. Calcitonin showed promise during early trials in 2000 with a 33% reduction in fractures but these results have not been replicated and this therapy is now relegated to a second line treatment. Teriparatide is recommended for patients with severe osteoporosis and has been shown to reduce vertebral fractures 65% and non-vertebral fractures 53%. Selective estrogen receptor modulators (SERMs) are another useful therapy resulting in a 55% reduction in vertebral fractures without any documented advantage when looking at non-vertebral fractures. The currently available SERMs for this indication include raloxifene, available in the USA, and bazedoxifene, in Europe. Estrogen is effective, with a 27% reduction in fractures, but often is reserved for concomitant use for other menopausal symptoms or in patients intolerant of other available osteoporosis therapies. The newly approved monoclonal antibody for osteoporosis treatment in postmenopausal women, denosumab, leads to a 68% and 19% reduction of vertebral and non-vertebral fractures, respectively. In conclusion, the 2010 NAMS position statement provides an excellent framework to discuss treatment options with patients. Lifestyle optimization should be the bedrock of any good treatment approach. When pharmacological intervention is warranted, many good therapies are available which have been shown to reduce the risk of fractures in osteoporotic patients. Any treatment plan, however, will be ineffective if the patient is not compliant. Therefore, a detailed discussion regarding each therapeutic intervention should ensue, including its usefulness and side effects.

Meralgia paresthetica: an unusual complication of post-cesarean analgesia.

Intramuscular (IM) injections may be associated with nerve injury, classically the sciatic nerve after intragluteal injection. We describe an unusual injury of the lateral femoral cutaneous nerve following an IM injection of 100 mg meperidine and 25 mg promethazine in the anterolateral right thigh. Although the thigh is advocated as a relatively safe site for IM injection, iatrogenic neuropathy may result. Awareness of the anatomy of the lateral femoral cutaneous nerve and avoiding injections into a partially anesthetized extremity may decrease the likelihood of recurrences.

Pulmonary symptoms associated with gastroesophageal reflux: use of ambulatory pH monitoring to diagnose and to direct therapy.

BACKGROUND: We studied 54 patients with chronic persistent cough or asthma suspected to be due to reflux using distal and proximal pH monitoring. Therapy for reflux was determined by the referring physician and included H2 blockers (51%), omeprazole (36%), surgery (10%), and lifestyle modifications only (3%). On follow-up evaluation, the effect of anti-reflux therapy on pulmonary symptoms (PS) was scored as excellent, good, fair, no change, or worsening symptoms. RESULTS: Forty-two of the 54 patients (78%) had abnormal reflux. Of these, 28 patients (67%) had abnormal proximal acid exposure. Seventy-one percent of reflux patients achieved good to excellent response in PS from anti-reflux therapy. The response was not significantly different between patients with proximal reflux and those with only distal reflux. None of the patients without documented reflux who nevertheless received anti-reflux therapy had a response, even when fair improvement was included as a response. Seventeen percent of patients whose pulmonary symptoms responded to anti-reflux therapy would not have been recognized as having abnormal reflux if proximal pH monitoring had not been done. CONCLUSIONS: The percentage of patients (78%) with pulmonary symptoms having abnormal reflux is consistent with prior studies. Documenting abnormal gastroesophageal reflux helps direct appropriate therapy, and proximal pH monitoring may identify patients with pulmonary symptoms who respond to anti-reflux therapy.

Tennis elbow: a biomechanical and therapeutic approach.

Lateral epicondylitis, one of the most common lesions of the arm, affects some 50% of tennis players. This condition poses a problem in clinical management because treatment is dependent not only on proper medical therapy but also on correction of the improper on-court biomechanics. The most common flaw is a late contact on the backhand groundstroke, forcing the player to extend the wrist with the extensor muscles. This action predisposes to trauma of the tendon fibers at the lateral epicondyle. Understanding the biomechanics will better prepare the physician to advise the patient and to communicate with a tennis teaching professional to facilitate long-term relief.

Pregnancy outcome in mothers with cystic fibrosis: normal neonatal immune responses.

Although pregnancy with cystic fibrosis (CF) has been associated in previous reports with increased maternal and neonatal morbidity, this may not reflect the current outcome with intense perinatal medical support. This report describes the pregnancy and pregnancy outcome in four women with CF. Although one neonate was delivered prematurely to a mother with advanced CF, there were no developmental abnormalities. The one premature infant was appropriately developed for his gestational age. Maternal pulmonary function was not clearly influenced by pregnancy, as confirmed by similar Schwachman scores before conception and after delivery. Finally, in this series of patients the postdelivery Schwachman score could be predicted from the preconception score.