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Endocrine Discovery |
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 Top Endocrine Discovery Endocrine PracticeMilestones in EndocrinologyIn the Journal 25...Endocrinologists |
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An increased risk of atrial fibrillation was associated with serum TSH levels within the normal range, with a multivariate adjusted HR between the lowest and the highest TSH quartiles of 1.94 (95% CI, 1.13-3.34, P=0.02) in an observational cohort study of 1426 healthy elderly subjects over 8 years. (Arch Intern Med [November 10, 2008] 168 (20):2219)
In a 2 year prospective randomized trial of calcium carbonate supplementation in 323 healthy men with a mean age of 57 years, BMD increased significantly at all sites with 1200 mg/d, but not with 600 mg/d, and there were dosage-related decreases in serum parathyroid hormone and alkaline phosphatase. (Arch Intern Med [November 10, 2008] 168 (2):2276)
In a meta analysis, lower rates of pregnancy complications and neonatal adverse outcomes were seen in women who become pregnant after having had bariatric surgery compared with adverse event rates in obese pregnant women. (JAMA [November 19, 2008] 300 (19):2286)
No evidence was found of a reduction of cardiovascular events in a prospective, randomized blinded 4 year trial of low dose aspirin in 2539 patients with type 2 diabetes without a history of atherosclerotic disease. (JAMA [November 12, 2008] 300 (18):2134)
Rosuvastatin decreased the risk of death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P < 0.00001) in a prospective randomized trial of rosuvastin 20 mg/d or placebo in 17,802 healthy men and women with LDL cholesterol levels < 130 mg/dl and high-sensitivity C-reactive protein levels of 2.0 mg/l, causing the trial to be terminated after a median follow up period of 1.9 years. (N Engl J Med [November 20, 2008] 359 (21):2195)
Tesofensine—a presynaptic uptake inhibitor of noradrenaline, dopamine, and serotonin—was found in a randomized, double-blind, placebo-controlled Phase II trial to induce twice the weight loss in obese patients than that of diet and placebo. (Lancet [November 29, 2008] 372 (9653):1906)
Osteoblast activity was shown in vivo and in vitro to be partially regulated by PTH activating β-catenin signaling through the recruitment of low-density lipoprotein-related protein 6 to the PTH/PTH1R receptor complex. (Genes Dev [November 2008] 22:2968)[CrossRef]
A case-control longitudinal study of 1,835 singletons and 998 twins born to mothers with and without gestational diabetes revealed that those born to mothers with this disease were 2 times more at risk of language impairment and were associated with a persistent deficit in expressive language well into middle childhood. (Pediatrics [November 2008] 122 (5):e1073)
A case-control study of 900 male infants with and without cryptorchidism revealed a significant association between bilateral and persistent cryptorchidism and genetic alterations, including mutations in the INSL3 receptor gene (RXFP2) and Klinefelter syndrome. In contrast, genetic alterations were not found in low birth weight or low gestational age infants, both of whom had frequent spontaneous descent of the testes. (JAMA [November 19, 2008] 300 (19):2271)
A 12-year prospective study of 21,919 individuals aged 40-79 years at baseline reported that an energy-dense diet may be linked with increased risk of diabetes development, independent of baseline obesity. (Diabetes Care [November 2008] 31 (11):2120)
Analysis of data from the Diabetes Control and Complications Trial found that longer-term fluctuations in glycemia seem to be independently related to the development of retinopathy and nephropathy in type 1 diabetes, indicating that sole measurement of mean A1C may not be the best predictor of complication risk. (Diabetes Care [November 2008] 31 (11):2198)
An international, randomized controlled trial among 195 very-low-birth-weight infants found that early insulin therapy offered little clinical benefit, providing reduction of hyperglycemia at the expense of increased hypoglycemia. (N Engl J Med [October 30, 2008] 359 (18):1873)
Examination of 359,387 Europeans suggested that both general adiposity and abdominal adiposity are associated with mortality risk and supported the use of waist circumference or waist-to-hip ratio in addition to body mass index to assess mortality risk. (N Engl J Med [November 13, 2008] 359 (20):2105)
A study of 18,831 Swedish and Finnish subjects found that the inclusion of common genetic variants associated with type 2 diabetes very slightly improved the prediction of future type 2 diabetes, as compared with the inclusion of clinical risk factors alone. (N Engl J Med [November 20, 2008] 359 (21):2220)
A study in food deprived-mice showed that the more rapid initial steps of fructose metabolism in the central nervous system provoked an immediate drop in the ATP/AMP ratio, unlike glucose metabolism which elevated ATP levels. The fructose increase increased AMP kinase activity, decreased acetyl-CoA carboxylase activity, and lowered malonyl-CoA in the hypothalamus, overall exerting an orexigenic effect. (Proc Natl Acad Sci USA [November 4, 2008] 105 (44):16871)
Treatment of nonobese diabetes (NOD) mice with either the tyrosine kinase inhibitors imatinib (Gleevec) or sunitinib (Sutent) prevented and reversed type 1 diabetes and led to a durable remission of the disease. (Proc Natl Acad Sci USA [December 2, 2008] 105 (48):18895)
Fenretinide positively balanced the metabolic profile in obese and overweight women, as evidenced by improvement in their homeostasis model assessment (HOMA)-based insulin sensitivity scores, whereas tamoxifen worsened insulin sensitivity in these subjects. (Cancer Res [November 15, 2008] 68 (22):9512)
Despite increasing serum IGF-1, the GH secretagogue MK-677 (ibutamoren mesylate) failed to slow the progression of Alzheimer’s disease. (Neurology [November 18, 2008]71:1702)
Examination of genetic polymorphisms in estrogen receptors 
and β (ESR1 and ESR2) in 297 women who were initiating tamoxifen therapy showed that ESR genotype, in addition to menopausal status and prior chemotherapy, may predict which women are most likely to suffer hot flashes during tamoxifen treatment.
(J Clin Oncol [published online November 17, 2008])
A retrospective cohort study of 31,074 women with nonanomalous singleton pregnancies and gestational diabetes mellitus found that women who had gestational weight gain above the IOM guidelines had a higher risk of preterm delivery, macrosomic neonates, and cesarean delivery. Women who gained below the guidelines were more likely to remain on diet control, but have small for gestational age neonates. (Obstet Gynecol [November 2008] 112 (5):1015)
Examination of 20 adolescent girls with and without mild anorexia nervosa found that flat-panel volume computed tomography was effective in evaluating trabecular structure in those with the disease and that their bone structure was abnormal compared to normal-weight control subjects despite normal bone mineral density. (Radiology [December 2008] 249 (3):938)
N-acylphosphatidylethanolamines were found in fat-fed rats to reduce food intake and body weight, suggesting that these plasma lipids may be novel therapeutic targets in treating obesity. (Cell [November 28, 2008] 135 (5):813)
A genome-wide association and meta-analysis study among 82,689 Europeans found melatonin receptor 1B (MTNR1B), a key gene in maintaining the circadian clock, associated with an increase in blood glucose levels and type 2 diabetes. (Nat Genet [published online December 7, 2008])
A meta-analysis of 10 randomized controlled trials involving 13,715 participants and 2 observational studies involving 31,679 participants found that long-term use of rosiglitazone and pioglitazone doubles the risk of fractures in women with type 2 diabetes and has no significant risk in men with type 2 diabetes. (CMAJ [published online December 9, 2008])
Testosterone Patch Proven Effective for Postmenopausal Women with Hypoactive Sexual Desire Disorder
Testosterone patch (300 µg) therapy provides some benefit in the treatment of hypoactive sexual desire disorder (HSDD) in postmenopausal women who are not concurrent users of estrogen or estrogen plus progestin, according to recently published research.
Most postmenopausal women would cite the reasons for why their sex drive is set to park on such typical midlife events such as stress, family demands, medications, depression, relationship problems, and plain old boredom. But some women additionally have what is labeled by the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders as "hypoactive sexual desire disorder" (HSDD)-a decrease or absence of interest in sexual activity that causes emotional distress. Surveys say that this low sex drive afflicts anywhere among 9-43% of women, and 10-15% fulfill the definition of HSDD.
While men with similar issues have been able for the past 10 years to turn to Viagra, "pink" Viagra has remained elusive. Now researchers are focusing on the use of testosterone, often in the form of transdermal patches or gels, and are receiving mixed reviews.
Previous patch studies have been performed in women who have either undergone natural or surgical postmenopause and have been concurrently on estrogens or estrogens and progestins, the logic being that estrogen treatment was required for testosterone to be effective. However, the latest New England Journal of Medicine study, aptly named APHRODITE, found that the patch was equally effective in HSDD postmenopausal women who are not on hormone therapy. In fact, women receiving treatment experienced an additional 2 sexual encounters per month than those on placebo.
"To go from not enjoying sex at all to about half the time or most of the time is a quantum shift in the workings of relationships," declared Susan Davis, M.D., Ph.D., Chair of the Women’s Health Program at Monash University, Prahran, Australia, and lead author in this study.
Her team looked at 814 naturally or surgically postmenopausal women from 65 international centers. For 52 weeks, the researchers gave these women either a patch delivering 150 or 300 µg of testosterone per day or placebo and recorded their 4-week frequency of satisfying sexual episodes.
Compared to the placebo group, those on the 300 µg patch reported significant increases in desire and decreases in distress—and an increase of 2.1 satisfying sexual episodes vs. 0.7. Their pleasure however came at a slight cost: 30% of women on this dose experienced unwanted hair growth. Additionally, breast cancer was diagnosed in four women who received testosterone therapy but none in the placebo group.
Dr. Davis characterized the breast cancer data as "messy" in that 2 of these women had the cancer before enrollment and two respectively developed it one and two years into the study.
Her co-author, Glenn Braunstein, M.D., a medical professor at Cedars-Sinai Medical Center in Los Angeles, California, concurred. "This may well be a chance occurrence. On the other hand, it does say that future studies will have to look very carefully at the potential risk," he said.
Yet others are not as dismissive of these risks.
"It’s unlikely that breast cancer sprung de novo over such a short-term trial, but the fact that new breast cancer cases were seen only in the treatment group raises concern about longer term use," declared Nanette Santoro, M.D., director of the division of Reproductive Endocrinology at Albert Einstein College of Medicine in Bronx, New York. Regarding the excess hair growth witnessed, she said, "That’s a lot of hair. I don’t know if it’s worth two more satisfying sexual encounters a month. I think every woman would have to do that math herself."
In 2006, The Endocrine Society issued a guideline on androgen therapy in women, concluding that not enough long-term data was known about the use of testosterone in HSDD women and that one couldn’t optimally diagnose androgen insufficiency in women because most testosterone assays could not accurately or precisely detect the low levels of testosterone seen in normal postmenopausal women.
"The effect of high physiological doses of testosterone appears to be consistent among the different groups of women recruited to studies of the testosterone patch—premenopausal, surgical or natural menopausal women on estrogen, and now testosterone alone to postmenopausal women, which is surprising to most endocrinologists. It was thought naturally premenopausal women would respond differently than surgically postmenopausal women," said Margaret E. Wierman, M.D., Chief of Endocrinology at the University of Colorado Denver and former head of the 2006 androgen therapy guideline task force. "At this point we don’t have great insight into the optimal therapeutic window and who will respond and who won’t."
She added, "Since HSDD is a chronic problem any therapeutic intervention must have a high safety to risk profile for long-term use. Further research is needed." (New Engl J Med [November 6, 2008]359 (19):2005)
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Endocrine Practice |
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TopEndocrine DiscoveryEndocrine PracticeMilestones in EndocrinologyIn the Journal 25...Endocrinologists |
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The National Osteoporosis Foundation has updated its recommendations for daily adequate calcium and vitamin D intake. Adults under age 50 need 1,000 mg of calcium and 400-800 IU of vitamin D daily while adults age 50 and over need 1,200 mg of calcium and 800-1000 IU of vitamin D daily. (For more information go to: http://www.nof.org/prevention/calcium_and_VitaminD.htm).
A U.S. Centers for Disease Control and Prevention study published in the November 7, 2008 Morbidity and Mortality Weekly Report found that although at least one fourth of U.S. adults are known to have prediabetes, only an estimated 4% have been told they have this condition. In addition, only 24% of U.S. adults with prediabetes did not participate in risk-reduction activities such as diet and exercise. (The report can be seen at: www.cdc.gov/mmwr/preview/mmwrhtml/mm5744a3.htm).
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Milestones in Endocrinology |
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TopEndocrine DiscoveryEndocrine PracticeMilestones in EndocrinologyIn the Journal 25...Endocrinologists |
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In the Journal 25 Years Ago |
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TopEndocrine DiscoveryEndocrine PracticeMilestones in EndocrinologyIn the Journal 25...Endocrinologists |
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"These observations suggest that the abnormal patterns of pulsatile gonadotropin secretion, and by inference GnRH secretion, are important factors in the etiology of amenorrhea associated with hyperprolactinemia."
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Endocrinologists |
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TopEndocrine DiscoveryEndocrine PracticeMilestones in EndocrinologyIn the Journal 25...Endocrinologists |
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"To go from not enjoying sex at all to about half the time or most of the time is a quantum shift in the workings of relationships," declared Susan Davis, M.D., Ph.D., about her latest study on the testosterone patch in postmenopausal women with hypoactive sexual desire disorder.
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