Matrix delivery transdermal 17beta-estradiol for the prevention of bone loss in postmenopausal women. The International Study Group.

A total of 277 early postmenopausal women were enrolled in this placebo-controlled 2-year study to examine the efficacy of a matrix transdermal 17beta-estradiol system, at three different dosages (25, 50 and 75 mg/day) combined with sequential oral dydrogesterone 20 mg/day, in preventing bone loss. At 2 years, the difference from placebo in percentage change from baseline of L1-4 lumbar spine bone mineral density (BMD) (assessed by dual-energy X-ray absorptiometry) was 4.7% +/- 0.7% with estradiol 25 mg/day, 7.3% +/- 0.7% with estradiol 50 mg/day and 8.7% +/- 0.7% with estradiol 75 mg/day (all values mean +/- SEM). There were also significant increases in femoral neck, trochanter and total hip BMD with all doses of estradiol compared with placebo. Additionally, most patients had a significant gain (increase greater than 2.08%) in lumbar spine bone mass compared with placebo. Patients who received estradiol also experienced clinically significant and dose-related decreases in total serum osteocalcin, serum bone alkaline phosphatase and urinary C-telopeptide, with all three markers of bone turnover returning to premenopausal levels. Estradiol was well tolerated during the 2-year treatment period. Transdermal estradiol is effective and well tolerated at dosages between 25-75 mg/day in the prevention of bone loss in postmenopausal women; 25 mg/day offers an effective option for those women who cannot tolerate higher doses.

A dose-ranging trial of a matrix transdermal 17beta-estradiol for the prevention of bone loss in early postmenopausal women. International Study Group.

This international, randomized, double-blind, placebo-controlled, parallel group, dose-ranging trial was designed to determine the efficacy of 2 years of therapy with a new matrix transdermal 17beta-estradiol (Menorest) in preventing bone loss in early postmenopausal women, and to identify an appropriate dose. Two hundred ninety-two ambulatory women with natural or surgical menopause for 1-6 years were randomized to receive patches delivering 17beta-estradiol 50, 75, or 100 microg/day twice weekly for 25 days per 28 day cycle (with dydrogesterone 10 mg twice daily from days 11 to 24) or placebo, for 24 months. The primary outcome measure was the percentage change from baseline in lumbar spine bone mineral density (BMD) at 2 years. Secondary endpoints were percentage changes from baseline in three sites of proximal femur BMD and total body BMD, and in biochemical bone turnover markers. At 2 years, the difference from placebo in percentage change from baseline of L1-4 spine BMD was 6.2%, 7.6%, and 7.8% in the 50, 75, and 100 microg/day groups, respectively. Lumbar spine bone increased in 65.5%, 76.8%, and 81.0% of patients in the respective active treatment groups, compared with 4.9% on placebo. BMD increased significantly relative to placebo in the femoral neck, trochanter, total hip, and total body. Serum osteocalcin, bone alkaline phosphatase and urinary type I collagen C-telopeptide decreased significantly and dose dependently in 17beta-estradiol patients vs. placebo. For example, at 2 years, the difference between placebo and the 50 microg/day group, expressed in percentage change from baseline, was 3.25% at the femoral neck, 3.92% at the trochanter, 3.52% for total hip, and 2.40% for the total body. Breast pain and skin reactions were more common in the actively treated groups, but tolerability was generally good. Therefore, after 2 years, 17beta-estradiol was well-tolerated and highly effective at doses of between 50 and 100 microg/day in preventing bone loss and reducing bone turnover in early postmenopausal women. The dose of 50 microg/day, the lowest dose tested, is a suitable dose. There was little clinical benefit of increasing the dosage from 75 to 100 microg/day.

Quality of life and insomnia validation study for a specifically designed questionnaire.

A questionnaire was devised to assess changes in the quality of life of insomniac patients when treated by a hypnotic. The questionnaire was validated in two groups of patients (60 non-insomniac and 52 insomniac patients). The results of this study confirmed the relevance of the questionnaire and its power to distinguish between the two groups of patients. A second study carried out simultaneously in 58 insomniac patients receiving treatment showed the internal reliability of the questionnaire and its reproducibility after 3 to 5 days.

Zopiclone in the treatment of insomnia in depressed patients.

During the early treatment of a major depressive episode with amitryptiline, insomnia was treated in 81 patients in a double-blind comparative trial comparing zopiclone and flunitrazepam. The study showed no major differences in the efficacy profile and showed better tolerability for zopiclone than for flunitrazepam.

[Study of vigilance after ingestion of zopiclone in comparison with nitrazepam and placebo (author's transl)]. / Etude de la vigilance après prise de zopiclone en comparaison avec nitrazépam et placebo. Méthodologie de l'étude : questionnaires d'auto-évaluation et tests psychométriques.

Increasing importance is being given to the residual effects of hypnotics on the day following absorption; with zopiclone, a new hypnotic, we have studied vigilance 9, 12 and 15 hours after a single evening dose of 10 mg, on a double-blind basis in comparison with 10 mg of nitrazepam and a placebo. The assessment of vigilance is based on responses to self-rating questionnaires and psychometric tests. Twenty-one healthy subjects forming a homogeneous group as regards age, I.Q., and vigilance were included in this study. Each subject received the three products in random distributed order, with an interval of three months between each trial. The results of these tests reveal modifications which, particularly 9 hours after administration, reflect a modification in vigilance, appearing to be more marked with nitrazepam than with zopiclone. Thus, from the point of view of the residual effects of hypnotics on vigilance, it is possible to position the products tested in the following order: placebo -- zopiclone -- nitrazepam.