Hormone Replacement Therapy Versus the Combined Oral Contraceptive Pill in Premature Ovarian Failure: A Randomized Controlled Trial of the Effects on Bone Mineral Density.

CONTEXT: Women with premature ovarian failure (POF) face many years of estrogen deficiency. One of the major consequences is bone loss. The optimal form of estrogen replacement is unknown and management is not evidence based. The 2 broad options are combined hormone replacement therapy (HRT) or the combined oral contraceptive pill (COCP). OBJECTIVES: To compare the effects of HRT and COCP on bone density and turnover in women with spontaneous POF and to observe the effects of no treatment. DESIGN: Two-year open randomized trial comparing HRT and COCP and nonrandomized observation of women declining treatment using the same protocol. SETTING: London teaching hospital. PARTICIPANTS: A total of 59 women with spontaneous POF aged 18-44, 30 women elected to take treatment and were randomized, and 29 declined treatment. INTERVENTION: Randomization was to HRT (Nuvelle) or COCP (Microgynon 30). MAIN OUTCOME MEASURES: The primary outcome was change in lumbar spine bone mineral density. Changes in total hip and femoral neck bone density and bone turnover markers were also assessed. RESULTS: A total of 36 women (61%) completed the trial (no treatment 52%; HRT 60%; COCP 80%). In comparison with COCP, treatment with HRT increased bone density at the lumbar spine at 2 years (+0.050 g/cm(2); 95% confidence interval 0.007-0.092; P = .025). Bone turnover markers showed similar reductions in the 2 treatment groups. In the no treatment group, bone density dropped at all sites and bone turnover markers remained relatively unchanged. CONCLUSIONS: The results suggest that HRT is superior to COCP in increasing bone density at the lumbar spine in women with spontaneous POF. The limitations of a small sample size and high drop-out rate mean that further research is required to confirm the findings. However, either treatment is clearly superior to no treatment.

Trientine and renin-angiotensin system blockade ameliorate progression of glomerular morphology in hypertensive experimental diabetic nephropathy.

A comparison of the efficacy of the copper chelator, trientine, with combined renin angiotensin system (RAS) blockade on the progression of glomerular pathology in the diabetic (mREN-2)27 rat is reported. Animals were treated for 2 months with trientine, combined RAS blockers, combined trientine plus RAS blockers or none. Treatments began after inducing diabetes with streptozotocin. Physiological data were recorded monthly and light microscopic glomerular features were scored. Plasma allantoin and both plasma and renal protein carbonyls were measured as markers of oxidative stress. Trientine and RAS blockade decreased proteinuria and albuminuria and prevented an increase in creatinine clearance and kidney weight. Both reduced the diabetes-related glomerular features of mesangiolysis and glomerular segmental hypocellularity and trientine prevented severe tuft-to-capsule adhesion and reduced tubularization. Hypertension-related severe mesangial matrix expansion and global hypercellularity were increased by both treatments, which may reflect repair of mesangiolysis. Trientine reduced plasma but not renal protein carbonyls or plasma allantoin. In this model, trientine prevented the development of many diabetes-specific features similarly to RAS blockade. Amelioration of oxidative stress and features commonly observed in human diabetic nephropathy (DN), support a diabetes-related defect in copper (Cu) metabolism. The addition of Cu(II) chelation may improve current DN therapy.

Treatment of premature ovarian failure trial: description of an ongoing clinical trial.

Premature ovarian failure is a relatively common clinical condition, and carries important long-term health consequences. Estrogen replacement is recommended to alleviate unpleasant hypo-estrogenic symptoms and reduce long-term health risks. However, the most suitable form of estrogen replacement, and the exact effects of no treatment, is unknown. Surprisingly, little research has been carried out in this area. We describe the design of an ongoing clinical trial that will address these issues so that we can begin to provide evidence-based care for affected women.

Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial).

We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes gamma-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

Long-term effects of tibolone on mammographic density.

OBJECTIVE: To investigate the long-term effect of tibolone on mammographic density. DESIGN: Open-label, nonrandomized study. SETTING: Academic research environment. PATIENT(S): Postmenopausal women. INTERVENTION(S): Tibolone was administered orally, mammograms were performed annually. MAIN OUTCOME MEASURE(S): Mammographic density according to the Wolfe classification, performed by two independent radiologists, both of whom were blinded to treatment group. RESULT(S): No statistically significant differences were found between the two groups in baseline demographic data. There were no statistically significant differences in mammographic density between the control and active groups at baseline or at 10 years. CONCLUSION(S): This pilot study shows that tibolone does not adversely alter the mammographic density of the breasts over 10 years of treatment.