Women With Early Menopause At Higher Risk of Diabetes

MedicalResearch.com Interview with:

Eralda Asllanaj Department of Epidemiology Erasmus University Medical Center Rotterdamthe Netherlands

Eralda Asllanaj

Eralda Asllanaj
Department of Epidemiology
Erasmus University Medical Center
Rotterdamthe Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is known that women with early onset of menopause (age below 45 years) have an increased risk of cardiovascular disease and overall mortality. This increased risk is thought to be due to the adverse effects of menopause on cardiovascular risk factors.

Type 2 diabetes is a major risk factor for cardiovascular disease, but it remains unclear whether age at menopause affects the risk of developing type 2 diabetes. Our study shows that women who experience menopause before the age of 40 were almost 4 times more likely to develop type 2 diabetes than those experiencing menopause after 55 years old. Moreover, those who had menopause between 40 to 44 years were 2.4 times more likely to have diabetes later in life. The risk of having diabetes reduced by 4 % per year older the women experienced menopause. Adjustment for the various confounding factors and differences in genetic predisposition to early menopause did not affect the results.

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Prenatal Acetaminophen Linked To Decreased Masculinization and Testosterone in Male Offspring

MedicalResearch.com Interview with:
David M. Kristensen, PhD
Assistant Professor                                                                                                         Novo Nordisk Foundation Center for Protein Research
Faculty of Health and Medical Sciences, University of Copenhagen,
Blegdamsvej 3A, DK-2200 Copenhagen, Denmark

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have demonstrated that a reduced level of testosterone during fetal life by paracetamol means that male characteristics do not develop as they should. This also affects sex drive. In the trial, mice exposed to paracetamol at the foetal stage were simply unable to copulate in the same way as our control animals. Male programming had not been properly established during their foetal development and this could be seen long afterwards in their adult life. Moreover, the area of the brain that controls sex drive – the sexual dimorphic nucleus – had half as many neurons in the mice that had received paracetamol as the control mice. The inhibition of testosterone seem to have led to less activity in an area of the brain that is significant for male characteristics.

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PCSK9 Inhibitor Praluent Added to Statins Improved Lipid Profile in Diabetes

MedicalResearch.com Interview with:

Dr-Robert-R-Henry.jpg

Dr. Henry

Robert R. Henry, M.D.
Professor of Medicine
Member of the ODYSSEY DM Steering Committee and
Director of the Center for Metabolic Research
VA San Diego Healthcare System

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The ODYSSEY DM-DYSLIPIDEMIA trial was a randomized, open-label, parallel-group study designed to evaluate the superiority of Praluent versus usual care in 413 patients with type 2 diabetes with mixed dyslipidemia at high cardiovascular (CV) risk, not adequately controlled with maximally tolerated dose (MTD) statins. The primary endpoint was percent change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to week 24.

In ODYSSEY DM-DYSLIPIDEMIA, Praluent 75 mg was added to MTD statins, with dose adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose.

Results from the ODYSSEY DM-DYSLIPIDEMIA study found that Praluent added to MTD statins showed significant reduction in non-HDL-C and other lipid parameters compared to those on usual care.

Praluent was superior to usual care in lowering non-HDL-C (37.3 percent and 4.7 percent, for the usual care arm). The mean difference between the two treatment arms was -32.5 percent (p<0.0001).

Praluent in combination with MTD statins reduced LDL-C by 43 percent from baseline compared to a 0.3 percent increase for usual care (p<0.0001). Treatment with Praluent also improved the overall lipid profile.

There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Furthermore, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk.

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Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing’s disease

MedicalResearch.com Interview with:

Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda

Dr. Stratakis

Constantine A. Stratakis, MD, DMSci
Section on Endocrinology and Genetics
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health, Bethesda

MedicalResearch.com: What is the background for this study?

Response: The pituitary and adrenal glands operate on a kind of feedback loop. In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol. Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease.

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Genetic Cause of Cushing’s Disease Detected

MedicalResearch.com Interview with:

Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda

Dr. Stratakis

Constantine A. Stratakis, MD, DMSci
Section on Endocrinology and Genetics
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health, Bethesda 

MedicalResearch.com: What is the background for this study?

Response: The pituitary and adrenal glands operate on a kind of feedback loop.  In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol.  Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease.

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Normalizing Testosterone With Replacement Therapy Reduced Atrial Fibrillation Risk

MedicalResearch.com Interview with:

Rajat S. Barua, MD; PhD; FACC; FSCAI Associate Professor of Medicine (Cardiology), University of Kansas School of Medicine Director, Cardiovascular Research, Dept. of Cardiology, Kansas City VA Medical Center Director, Interventional Cardiology & Cardiac Catheterization Laboratory Kansas City VA Medical Center

Dr. Barua

Rajat S. Barua, MD; PhD; FACC; FSCAI
Associate Professor of Medicine (Cardiology), University of Kansas School of Medicine
Director, Cardiovascular Research, Dept. of Cardiology, Kansas City VA Medical Center
Director, Interventional Cardiology & Cardiac Catheterization Laboratory
Kansas City VA Medical Center

MedicalResearch.com: What is the background for this study?

Response: Atrial fibrillation is the most common cardiac arrhythmia worldwide, with significant morbidity, mortality and financial burden. Atrial fibrillation is known to increase with age and is higher in men than in women. Although the underlying mechanisms of this sex difference are still unclear, one preclinical and several small clinical studies have suggested that testosterone deficiency may play a role in the development of atrial fibrillation. To date, no studies have investigated the effect of testosterone-level normalization on incidence of new atrial fibrillation in men after testosterone replacement therapy.

In this study, we investigated the incidence of atrial fibrillation in hypogonadal men with documented low testosterone levels. We compared the incidence of atrial fibrillation among patients who did not receive any testosterone replacement therapy, those who received testosterone replacement therapy that resulted in normalization of total testosterone, and those who received testosterone replacement therapy but that did not result in normal total testosterone levels.

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Late Menopause and Oral Hormone Therapy Linked To High Risk of Hearing Loss

MedicalResearch.com Interview with:

Sharon G. Curhan, MD, ScM Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston, MA 02115

Dr. Curhan

Sharon G. Curhan, MD, ScM
Channing Division of Network Medicine
Department of Medicine
Brigham and Women’s Hospital
Harvard Medical School
Boston, MA 02115

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hearing loss affects approximately 48 million Americans and the number is expected to increase as the population ages. Some previous studies suggested that menopause may increase the risk for hearing loss, presumably due to the reduction in circulating estrogen levels, and that postmenopausal hormone therapy might slow hearing decline by “replacing” estrogen. To evaluate the role of menopause and postmenopausal hormone therapy as risk factors for hearing loss, we examined the independent associations between menopausal status, oral hormone therapy, and risk of self-reported hearing loss in 80,972 women who are participants in the Nurses’ Health Study II, aged 27-44 years at baseline, and were followed from 1991 to 2013.

After more than 1.4 million person-years of follow-up, 18,558 cases of hearing loss were reported (~23% of the women developed hearing loss). We did not observe an overall independent association between menopausal status and risk of hearing loss.

However, the risk among women who underwent natural menopause at an older age was higher. Specifically, the risk among women who underwent natural menopause at age 50 or older was 10% higher than among those who underwent natural menopause before age 50 [multivariable-adjusted relative risk (MVRR): 1.10, 95% CI 1.03, 1.17]. When we conducted an analysis restricted to women who underwent natural menopause and did not use hormone therapy (HT), the multivariable-adjusted relative risk among women who underwent natural menopause at age 50-54 years was 21% higher (MVRR: 1.12, 95% CI: 1.10, 1.34), and among women who underwent natural menopause at age 55+ years was 29% higher (MVRR: 1.29, 95% CI: 1.11, 1.50), compared with women who underwent natural menopause before age 50.

Among postmenopausal women, we also found that use of oral HT was associated with higher risk of hearing loss, and the magnitude of the risk tended to increase with longer duration of use (p-trend < 0.001). Compared with women who never used any type of HT, the MVRR of hearing loss among women who used oral HT for 5-9.9 years was 15% higher (MVRR: 1.15, 95% CI: 1.06, 1.24), and for 10+ years was 21% higher (MVRR: 1.21, 95% CI: 1.07, 1.37). When specific types of oral HT were examined, longer duration of use of either oral estrogen-only or of combined estrogen plus progestogen HT were each associated with higher risk. Fewer women reported use of progestogen-only oral HT, yet among these women a higher risk was suggested, but not significant (MVRR: 1.15, 95% CI: 0.98, 1.35). Transdermal HT use was less common, but the associations observed were similar to those with oral hormone therapy. When examined separately by type of menopause, the results for HT use were similar.

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Thyroid Function Associated With Atherosclerotic Cardiovascular Morbidity and Mortality

MedicalResearch.com Interview with:
Arjola Bano, MD, DSc

PhD candidate
Departments of Internal Medicine and Epidemiology
Erasmus Medical Center, Rotterdam, The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Atherosclerosis is a chronic condition, characterized by the accumulation of lipids and fibrous elements in the arterial walls. It can progress insidiously from an asymptomatic narrowing of the arterial lumen (subclinical phase) to the clinical onset of vascular events (as coronary heart disease or stroke) and death. Despite advances in prevention and treatment, atherosclerotic diseases remain a leading cause of mortality worldwide. Therefore, identifying additional modifiable risk factors for atherosclerosis is of major importance.

So far, the role of thyroid hormone on atherosclerosis remains unclear. Moreover, a comprehensive investigation exploring the link of thyroid function with the wide spectrum of atherosclerosis, including subclinical atherosclerosis, clinical atherosclerosis and atherosclerotic mortality, within the same population is lacking.

Therefore, in a prospective study of 9231 middle-aged and elderly people, we explored the association of thyroid function with subclinical atherosclerosis (coronary artery calcification), atherosclerotic events (fatal and nonfatal coronary heart disease or stroke) and atherosclerotic mortality (death from coronary heart disease, cerebrovascular or other atherosclerotic disease). Higher free thyroxine (FT4) levels were associated with higher risk of subclinical atherosclerosis, atherosclerotic events and atherosclerotic mortality, independently of cardiovascular risk factors.

The risk of atherosclerotic mortality increased with higher FT4 levels (HR; CI: 2.35; 1.61-3.41 per 1 ng/dl) and lower thyroid-stimulating hormone (TSH) levels (HR; CI: 0.92; 0.84-1.00 per 1 logTSH), with stronger estimates among participants with a history of atherosclerotic disease (HR; CI: 5.76; 2.79-11.89 for FT4 and 0.81; 0.69-0.95 for TSH).

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Thyroid Hormone Medication Should Not Be Taken With Cow’s Milk

MedicalResearch.com Interview with:
Deborah Chon MD
Endocrinology fellow
UCLA David Geffen School of Medicine 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our study shows that drinking cow’s milk concurrently with oral levothyroxine significantly reduces the absorption of the medication.

Levothyroxine is used for the physiologic replacement of thyroid hormone in patients with hypothyroidism and for serum TSH suppression in patients with thyroid cancer. It is the mostly commonly prescribed medication in the United States as of 2014. Frequent dose adjustments of levothyroxine have been shown to be a costly burden to the national healthcare system.

Previous studies have shown that certain foods and medication, such as calcium supplements, can interfere with levothyroxine absorption. However, this is the first study to demonstrate that ingesting cow?s milk, a common breakfast staple, affects oral levothyroxine absorption.

To determine the possible effect of cow’s milk ingestion, we measured levothyroxine absorption in humans with and without concurrent milk consumption. Pharmacokinetic studies were conducted in healthy adults without allergies to milk or levothyroxine, and who were not pregnant nor using oral contraceptives. All subjects had no history of known thyroid disease and normal thyroid hormone function at baseline. Following an overnight fast, serum total thyroxine T4 (TT4) concentrations were measured at baseline and at 1, 2, 4, and 6 hours after ingestion of 1,000 ?g of oral levothyroxine alone or when co-administered with 12 oz. of milk (2% fat). There was a four-week washout period between the two study visits.

Ten subjects (mean age 33.7?10.2 years, 60% male) completed the study. The serum total T4 absorption over six hours, calculated as area under the curve (AUC), was significantly lower when taking cow?s milk concurrently with levothyroxine compared levothyroxine alone (mean?SD: 67.26?12.13 vs. 73.48?16.96; p = 0.02). Also, peak serum TT4 concentrations were significantly lower in those who ingested levothyroxine concurrently with milk, compared to taking levothyroxine alone (p=0.04).
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Exposure to BPA Substitute, BPS, Multiplies Breast Cancer Cells

Sumi Dinda

Dr. Sumi Dinda

MedicalResearch.com Interview with:
Sumi Dinda, PhD, NRP, IC.

Associate Professor
Biomedical Diagnostic and Therapeutic Sciences,
School of Health Sciences and
Adjunct Associate Professor
Department of Biological Sciences
School of Health Sciences
Oakland University
Rochester, MI 48309.


MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Bisphenol-S (BPS), a substitute for bisphenol-A (BPA), has been suggested to be an endocrine disrupting compound interfering with normal hormonal activity. This bisphenol analogue is found in plastic substitutes, paper currency, and most products marked “BPA free.” Endocrine disrupting compounds interfere with the normal hormonal activity in the body.

Bisphenols, specifically, disrupt the proper functioning of estrogen receptors, such as ERα causing interference with the normal activity of the hormone estrogen. Studies suggest BPS induces ERα pathways via its estrogen-mimicking properties in the body causing increased cell proliferation resulting in increased breast cancer risk. Despite the hope of a safer substitute, studies have shown that BPS exhibits similar estrogenic activity compared to its analogue BPA, due to their structural commonalities.

BRCA1 is a commonly mutated gene in breast cancer; therefore, it is also important to study the effects of BPS on the expression of this protein. The potency of the endocrine disrupting abilities of BPS compared to BPA could show whether BPS is a suitable alternative to BPA in many everyday products.

The results of this study may contribute to the understanding of the relationship between ERα, BRCA1 expression and Bisphenol-S in breast cancer treatment and prevention.

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