CiteULike: omalbam's sideffects

Baseline Characteristics and the Effects of Two Years of Growth Hormone (GH) Replacement Therapy in Adults with GH Deficiency Previously Treated for Acromegaly.

Lise-Lott Norrman — 2008-05-27T16:36:27-00:00

The Journal of clinical endocrinology and metabolism (8 April 2008)

Context: The effects of GH replacement in GH deficient (GHD) adults previously treated for acromegaly are not well known. Objective/Design/Patients: In this single-center, open-labeled, prospective study, 10 consecutive GHD adults with cured acromegaly (A group) and 10 matched GHD adults with previous non-functioning hypopituitary disease (NF group), were included. Comparisons were made at baseline and in the responses in body composition, muscle strength, bone mass, and metabolic indices during 2-year GH replacement. Results: At baseline, upper leg local muscle endurance and serum low density lipoprotein-cholesterol (LDL-C) concentration were more impaired in the A group. The A group contained 3 patients with hypertension, one with diabetes mellitus (DM) type 2, and one with hyperlipidemia. The NF group had only one patient with hypertension. There were no significant between-group differences in the responses to the GH therapy. Body composition and serum lipid pattern improved in both groups without any deterioration of glucose homeostasis. At study end, no difference remained between the two groups in any variable. During the 2-year treatment, one patient had a myocardial infarction and two had cerebral infarctions in the A group whereas no vascular event occurred in the NF group. Conclusions: GHD patients with previous acromegaly have an impaired cardiovascular risk profile and decreased local muscle endurance as compared with other GHD patients. Two-year GH replacement eliminated these differences but vascular events occurred more frequently in the A group. Therefore, GHD patients with cured acromegaly will benefit from GH replacement but careful monitoring of cardiovascular status is needed.

Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials

Robin Christensen — 2008-02-18T04:17:32-00:00

The Lancet, Vol. 370, No. 9600., pp. 1706-1713.

SummaryBackground Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant.Methods We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo.Findings Patients given rimonabant had a 4[middle dot]7 kg (95% CI 4[middle dot]1-5[middle dot]3 kg; p<0[middle dot]0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1[middle dot]4; p=0[middle dot]0007; number needed to harm=25 individuals [95% CI 17-58]), and 1[middle dot]4 times more serious adverse events (OR=1[middle dot]4; p=0[middle dot]03; number needed to harm=59 [27-830]). Patients given rimonabant were 2[middle dot]5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2[middle dot]5; p=0[middle dot]01; number needed to harm=49 [19-316]). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3[middle dot]0; p=0[middle dot]03; number needed to harm=166 [47-3716]).Interpretation Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events--ie, depressed mood disorders and anxiety--despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.

The effects of growth hormone and sex steroid on lean body mass, fat mass, muscle strength, cardiovascular endurance and adverse events in healthy elderly women and men.

SM Harman — 2008-01-31T19:38:03-00:00

Horm Res, Vol. 60, No. Suppl 1. (2003), pp. 121-124.

Decreases in growth hormone (GH) and insulin-like growth factor I occur with age, in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men. These age-related hormonal changes may contribute to reductions in lean body mass, muscle strength and cardiac endurance, which can be partially reversed in elderly people with GH treatment, and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women, respectively. These treatments are, however, thought to have potentially serious adverse effects. We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition, muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people. The results of the study showed that although there were beneficial effects with GH and sex steroid treatment, a high percentage of adverse effects occurred after 26 weeks of treatment, demonstrating a need for more research on the safety of hormonal therapy in the elderly population.

Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men.

BZ Leder — 2008-01-29T20:14:02-00:00

Osteoporos Int, Vol. 16, No. 12. (December 2005), pp. 1487-1494.

Both estrogens and androgens play important roles in skeletal development and maintenance in men. The relative importance of estrogens and androgens in male bone metabolism, however, remains undefined. Anastrozole is an oral aromatase inhibitor that decreases estrogen production and increases androgen production in men. Currently, anastrozole is being investigated as a potential agent for the treatment of hypogonadism in aging men. Because anastrozole lowers estrogen levels and raises androgen levels, its effect on bone metabolism is difficult to predict. To assess the effects of anastrozole on bone turnover, we randomized 37 elderly (ages 62-74) mildly hypogonadal men (serum testosterone <350 ng/dl) to receive either anastrozole 1 mg daily (n=12), anastrozole 1 mg twice weekly (n=11), or daily placebo (n=14) for 12 weeks. Serum gonadal steroid levels, serum and urine biochemical markers of bone turnover, serum osteoprotegerin, and total body bone mineral density were measured at baseline and week 12. Mean serum levels of total and bioavailable testosterone increased substantially in both treated groups. Specifically, mean +/- SD bioavailable testosterone levels increased from 99+/-31 ng/dl to 207+/-65 ng/dl in the group receiving 1 mg of anastrozole daily and from 115+/-37 ng/dl to 178+/-55 ng/dl in the subjects receiving 1 mg of anastrozole twice weekly ( p <0.001 vs placebo for both groups). Serum estradiol levels decreased modestly in both treated groups (from 26+/-8 pg/ml to 17+/-6 pg/ml in the daily treatment group and from 27+/-8 pg/ml to 17+/-5 pg/ml in the twice-weekly treatment group, p <0.001 vs placebo for both groups). Despite these hormonal changes, no increases in biochemical markers of bone resorption were observed. Specifically, mean serum N-telopeptide and urinary deoxypyridinoline concentrations remained stable in both treated groups over the 12-week treatment period. Similarly, serum biochemical markers of bone formation (osteocalcin and amino-terminal propeptide of type 1 collagen), serum osteoprotegerin, and total body bone mineral density did not change. These data demonstrate that although short-term administration of anastrozole decreases serum estradiol levels in elderly men with mild hypogonadism, this intervention does not adversely affect bone metabolism over a 12-week period. This lack of an effect may be due to the concomitant increase in testosterone production, the relative modest effect on estradiol production, or a combination of both factors. These results suggest that anastrozole therapy is unlikely to have an adverse effect on bone metabolism when taken over extended periods and may prove to be a valuable method of normalizing testosterone production in older men.

Skeletal consequences of thiazolidinedione therapy

A Grey — 2008-01-22T20:41:12-00:00

Osteoporosis International, Vol. 19, No. 2. (4 February 2008), pp. 129-137.

Abstract Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator-activated receptor gamma (PPARγ) nuclear transcription factor. Two members of this drug class, rosiglitazone and pioglitazone, are commonly used in the management of type II diabetes mellitus, and play emerging roles in the treatment of other clinical conditions characterized by insulin resistance. Over the past decade, a consistent body of in vitro and animal studies has demonstrated that PPARγ signaling regulates the fate of pluripotent mesenchymal cells, favoring adipogenesis over osteoblastogenesis. Treatment of rodents with TZDs decreases bone formation and bone mass. Until recently, there were no bone-related data available from studies of TZDs in humans. In the past year, however, several clinical studies have reported adverse skeletal actions of TZDs in humans. Collectively, these investigations have demonstrated that the TZDs currently in clinical use decrease bone formation and accelerate bone loss in healthy and insulin-resistant individuals, and increase the risk of fractures in the appendicular skeleton in women with type II diabetes mellitus. These observations should prompt clinicians to evaluate fracture risk in patients for whom TZD therapy is being considered, and initiate skeletal protection in at-risk individuals.

Approach to the Prostate Cancer Patient with Bone Disease

Susan Greenspan — 2008-01-10T22:51:41-00:00

J Clin Endocrinol Metab, Vol. 93, No. 1. (1 January 2008), pp. 2-7.

Prostate cancer is the most common visceral malignancy in men. Androgen deprivation therapy (ADT) is commonly used in patients with nonmetastatic prostate cancer and is associated with significant bone loss and fractures. The greatest bone loss occurs during initiation of ADT. Men should have assessment of skeletal integrity with bone mineral density examination by dual x-ray absorptiometry of the hip and spine. Men with fragility fractures or osteoporosis by bone density should be considered for bisphosphonate therapy. Men with low bone mass may need antiresorptive therapy, depending on other risk factors. Men with a normal bone mineral density should be followed up closely with bone densitometry while on ADT. All men should receive preventive measures with calcium (1200 mg daily in divided doses), vitamin D (8001000 IU/d), and weight-bearing exercise. Men should be evaluated for additional secondary causes of bone loss including vitamin D insufficiency. Guidelines are needed for androgen-induced bone loss screening and treatment. 10.1210/jc.2007-1402

Effects of torcetrapib in patients at high risk for coronary events.

PJ Barter — 2008-01-09T04:07:55-00:00

N Engl J Med, Vol. 357, No. 21. (22 November 2007), pp. 2109-2122.

BACKGROUND: Inhibition of cholesteryl ester transfer protein (CETP) has been shown to have a substantial effect on plasma lipoprotein levels. We investigated whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib. METHODS: We conducted a randomized, double-blind study involving 15,067 patients at high cardiovascular risk. The patients received either torcetrapib plus atorvastatin or atorvastatin alone. The primary outcome was the time to the first major cardiovascular event, which was defined as death from coronary heart disease, nonfatal myocardial infarction, stroke, or hospitalization for unstable angina. RESULTS: At 12 months in patients who received torcetrapib, there was an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, as compared with baseline (P<0.001 for both comparisons), in addition to an increase of 5.4 mm Hg in systolic blood pressure, a decrease in serum potassium, and increases in serum sodium, bicarbonate, and aldosterone (P<0.001 for all comparisons). There was also an increased risk of cardiovascular events (hazard ratio, 1.25; 95% confidence interval [CI], 1.09 to 1.44; P=0.001) and death from any cause (hazard ratio, 1.58; 95% CI, 1.14 to 2.19; P=0.006). Post hoc analyses showed an increased risk of death in patients treated with torcetrapib whose reduction in potassium or increase in bicarbonate was greater than the median change. CONCLUSIONS: Torcetrapib therapy resulted in an increased risk of mortality and morbidity of unknown mechanism. Although there was evidence of an off-target effect of torcetrapib, we cannot rule out adverse effects related to CETP inhibition. (ClinicalTrials.gov number, NCT00134264 [ClinicalTrials.gov].).