Influence of estrogen-progestin replacement therapy and exercise on lumbar spine mobility and low back symptoms in a healthy early postmenopausal female population: a 2-year randomized controlled trial.

The purpose of this study was to examine the influence of estrogen-progestin replacement therapy and exercise on the lumbar spine mobility and back symptoms of early postmenopausal women. The population sample consisted of 78 healthy, 49- to 55-year-old women, 0.5-5 years after menopause, who were randomized into three groups, two receiving different protocols of estradiol valerate combined with medroxyprogesterone acetate replacement therapy, and the third group a placebo. These groups were then randomized into exercise and control cases and monitored for 2 years. The mobility of the lumbar spine was measured and symptoms investigated using the Million and Oswestry pain and disability questionnaires and pain drawings at the baseline and after 1 and 2 years. During the follow-up, the mobility of the lumbar spine decreased in all six groups. The decrease was most evident in those who had been the most flexible at baseline (P < 0.0001). The decrease was less notable in the hormone replacement therapy groups than in the control group. When the replacement therapy groups were pooled together, the difference was significant at a P < 0.05 level. No difference was seen between the hormone combinations. The exercise intervention was insufficient to influence lumbar spine mobility. Only sporadic cases of back symptoms appeared and disappeared among the subjects during the follow-up, and no preventive or aggravating effects of hormone replacement therapy or the exercise program on symptoms were detected.

Transdermal oestradiol gel in the treatment of the climacterium: a comparison with oral therapy.

OBJECTIVE: To compare two doses of a transdermal oestradiol gel (Divigel/Sandrena) plus oral sequential medroxyprogesterone acetate (MPA) with oral oestradiol valerate plus oral sequential MPA (Divina/Dilena). DESIGN: Two year, randomised, open-label, comparative study. SETTING: Menopausal outpatient clinic in Helsinki. SUBJECTS: Postmenopausal women with climacteric complaints or already using HRT. INTERVENTIONS: (1) One gram gel containing 1 mg oestradiol for 3 months plus 20 mg oral MPA during the last 14 days; (2) 2 g gel containing 2 mg oestradiol for 21 days plus 10 mg oral MPA during the last 14 days; (3) 2 mg oestradiol valerate tablets for 3 weeks plus 10 mg oral MPA during the last 10 days. In all groups, each treatment period was followed by a 7-day medication-free interval. MAIN OUTCOME MEASURES: Climacteric complaints, bleeding control, bone mineral density, biomarkers of bone metabolism, lipid profile, tolerability and safety. RESULTS: With each preparation, climacteric complaints were significantly reduced and good bleeding control was obtained. In addition, maintenance of bone mineral density as well as a reduction of bone turnover was achieved in all groups. Lipid parameters showed no unfavourable changes. Continuation rates were similar in all groups with overall 74% of patients completing the first year, whereas 94% of patients who elected to continue completed the second year. Tolerability of the gel was good: only 1.7% of patients discontinued treatment due to skin irritation. CONCLUSIONS: Transdermal oestradiol gel and oral oestradiol valerate tablets, used in combination with oral sequential MPA, are effective regimens of HRT in postmenopausal women. Transdermal oestradiol gel is an efficient, well-tolerated form of HRT.

Effects of transdermal oestrogen therapy in postmenopausal women: a comparative study of an oestradiol gel and an oestradiol delivering patch.

OBJECTIVE: To compare the efficacy, safety and tolerability of an oestradiol gel (1.0 mg of oestradiol daily, Divigel/Sandrena) with those of an oestradiol delivering patch (delivering 50 micrograms oestradiol/24 h, Estraderm TTS) in hormone replacement therapy of postmenopausal women. Dydrogesterone tablets (Terolut), 10 mg daily for the first 12 days of every month, were used as the progestogen component of the therapy. MAIN OUTCOME MEASURES: The effect of treatment on clinical symptoms and on endometrium, total body bone mineral density and lipid metabolism as well as the tolerability of the treatments with special emphasis on skin irritation and compliance were evaluated. DESIGN: An open, randomised, controlled, parallel-group trial of 12 months' duration. SETTING: The Medical Clinic of Kalevankatu, Helsinki, Finland. PARTICIPANTS: One hundred twenty postmenopausal women were treated with transdermal oestradiol combined with dydrogesterone. In addition, 25 women without HRT served as a reference group for the bone mineral density measurements. RESULTS: Both treatment regimens were equally effective in alleviating climacteric symptoms, preserving bone mineral density and were equally safe. A trend towards heavier bleeding was detected in patients treated with the oestradiol delivering patch. A statistically nonsignificant decrease of total cholesterol and triglyceride concentrations but no change in high-density lipoprotein cholesterol concentration was observed in both groups. The acceptability of the treatment was higher in the gel group (96.4%) than in the patch group (90.7%). Only two (3.3%) women using the oestradiol gel complained of skin irritation whereas 28 patients (46.7%, P < 0.001) using the oestradiol delivering patch reported this adverse effect. CONCLUSIONS: Both the oestradiol gel and the oestradiol delivering patch are equally effective in hormone replacement therapy but the gel preparation is less irritative to the skin.

HRT and exercise: effects on bone density, muscle strength and lipid metabolism. A placebo controlled 2-year prospective trial on two estrogen-progestin regimens in healthy postmenopausal women.

OBJECTIVES: To evaluate the effect of 1- or 3-monthly sequential combinations of estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) on menopausal symptoms, bone density, muscle strength and lipid metabolism in postmenopausal women. METHODS: Changes in bone mineral density (BMD), isometric muscle strength, serum lipids and climacteric symptoms were evaluated in 78 women, 49-55 years of age, with a spontaneous menopause 0.5-3 years earlier. Treatment group I received 2 mg E2V tablets for 11 days, followed by 2 mg E2V + 10 mg MPA for 10 days and placebo for an additional 7 days; treatment group II received 2 mg E2V for 70 days, 2 mg E2V + 20 mg MPA for 14 days, and placebo for 7 days. The placebo group received placebo continuously for 24 months. Each group was further randomised to exercise and non-exercise subgroups. RESULTS: Both hormone regimens significantly reduced menopausal symptoms, and prevented equally well the decrease of BMD both in the lumbar spine and proximal femur. A positive effect of exercise on BMD was observed in the placebo group. No synergistic effect of exercise and estrogen on BMD could be shown. Both hormone regimens increased the isometric strength of back extensor muscles. Serum total and LDL cholesterol decreased during the first year with both estrogen regimens. CONCLUSIONS: Estrogen-progestin regimens were equally effective in the control of menopausal symptoms and preventing bone loss, increasing muscle strength and lowering serum cholesterol.

Twice daily dosing of erythromycin acistrate in the treatment of acute bronchitis and pneumonia.

Erythromycin acistrate (Erasis, CAS 96128-89-1) is a 2'-acetyl ester prodrug of erythromycin. Due to prolonged half-life it is more suitable for twice daily dosing than the conventional erythromycin preparations. In the present double-blind trial, totally 297 ambulatory patients with respiratory tract infections were treated either with erythromycin acistrate 800 mg daily or doxycycline 100 mg daily. 243 of the included patients had bronchitis, 15 patients bronchitis and other respiratory tract symptoms, 25 patients pneumonia and 14 other respiratory tract infections. The duration of treatment varied from 7 to 14 days depending on the severity of infection. The efficacy of both treatments was very good. 96.6% of the patients treated with erythromycin acistrate and 97.2% of the patients treated with doxycycline improved. The efficacy of erythromycin acistrate in the treatment of bronchitis and pneumonia was 96.7 and 100%, respectively. Only 5 of the totally 148 patients failed. Side effects (mainly gastrointestinal symptoms) were seen in 12.1% of the patients (20 patients in the erythromycin acistrate group and 16 patients in the doxycycline group). The results show that erythromycin acistrate dosed twice daily is as effective as doxycycline and well tolerated in the treatment of lower respiratory tract infections.

Serum levels and urinary excretion of mequitazine after a single oral dose.

Pharmacokinetics of mequitazine, a recently introduced peripheral H1-histamine receptor antagonist of phenothiazine type, was followed up to 72 h after the single oral dose of 5 mg of the drug to eight fasted healthy volunteers. Each subject was treated thrice with a dosing interval of 15 days or more. Thus all the results were triplicated. Serum mequitazine was measured by mass fragmentography using a gas-liquid chromatograph/mass spectrometer set in the electron impact mode. Urine phenothiazines were determined fluorometrically before and after cleaving phenothiazines from their glucuronide conjugates. Peak concentration of mequitazine in serum was 3.19 +/- 1.70 (s.d.) ng.ml-1, time to peak concentration 5.67 +/- 1.68 h, elimination half-life 45 +/- 26 h, and elimination rate constant 0.018 +/- 0.007 h-1. Only 10.9 +/- 3.3% of the dose appeared in urine in unconjugated plus the glucuronidated form during the first 72 h. About 46% of the urinary phenothiazines were glucuronide conjugates. The results suggested that after the oral administration only low mequitazine concentrations appeared in serum, most of the drug seemed to be deactivated by the extrarenal route, and the kinetic properties of the drug resembled those of several phenothiazines used for psychiatric therapy.

A controlled, double-blind, cross-over study of terodiline in motor urge incontinence.

In a placebo-controlled, randomized, double-blind, cross-over study, terodiline (50 mg/d) was compared with emepronium (600 mg/d) in 20 patients with motor urge incontinence. Evaluation of clinical efficacy was based on changes in micturition pattern, flow measurements, residual urine, cystometry and patient preferences, and safety on adverse reactions, blood chemistry, urine examinations and ECG. The number of voluntary micturitions decreased from a mean of 21.5 per 48 h on placebo by 1.6 on terodiline and 2.8 on emepronium. Involuntary micturitions decreased from 3.6 per 48 h by 1.3 on both treatments (p less than 0.05). The maximal flow rate decreased from a mean of 24.5 ml/sec to 19.6 ml/sec on emepronium and increased to 25.4 ml/sec on terodiline. Residual urine decreased from a mean of 54 ml to 49 ml on terodiline and increased to 60 ml on emepronium. Volume at first desire to void in the supine position increased on emepronium by 44 ml (p less than 0.05) and on terodiline by 3 ml, on the upright position by 11 ml and 18 ml, respectively. Bladder capacity increased in the supine position on emepronium by 32 ml and decreased on terodiline by 8 ml, in the upright position increased by 9 ml and 5 ml, respectively. The bladder pressure at first desire to void in the supine position increased on emepronium by 2 cmH2O, and decreased on terodiline by 2 cmH2O. The intravesical pressure at strong desire to void decreased on emepronium by 6 cmH2O and on terodiline by 7 cmH2O, in the upright position by 2 cmH2O and 1 cmH2O, respectively. 39% of the patients preferred terodiline, 39% emepronium and 22% placebo.(ABSTRACT TRUNCATED AT 250 WORDS)