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B Lees

Publications and source records attributed to B Lees.

29 records · Page 2Linked to original sources

A randomized comparative study of the metabolic effects of two regimens of gestrinone in the treatment of endometriosis.

OBJECTIVE: To study some of the metabolic effects of oral gestrinone on plasma lipoprotein risk markers for cardiovascular disease and on bone density, a risk marker for osteoporosis. DESIGN: Randomized double-blind study. SETTING: All patients were referred to Gynaecology Clinic of Royal Free Hospital Medical School. PATIENTS: Twenty premenopausal women with laparoscopically confirmed endometriosis. INTERVENTIONS: Subjects were randomized in a double-blind fashion to receive either 1.25 mg or 2.5 mg gestrinone two times per week for 6 months. MAIN OUTCOME MEASURE: Laparoscopy was performed before treatment, and clinical responses were determined by second laparoscopy after 6 months. Plasma lipid and bone density measurements during and after therapy were compared with baseline. RESULT: Median total endometriosis scores decreased from 7.5 to 1.0 in the 1.25-mg group and from 7.0 to 0 in the 2.5-mg group. There were no significant between-group differences in endometriosis scores. At both doses, bone density in the spine and the proximal femur was conserved, but plasma concentrations of low-density lipoproteins rose by 13% and those of high-density lipoproteins fell by 40%. CONCLUSIONS: Reducing the dose of gestrinone to 1.25 mg appeared to maintain the therapeutic effectiveness of this treatment but was still associated with potentially unfavorable effects on lipids and lipoproteins.

Adult↗

Postmenopausal bone loss: does HRT always work?

In a 3-year study comparing oral and transdermal HRT, we measured bone density in the spine and proximal femur by dual-photon absorptiometry. Sixty-six women were randomly allocated to receive either oral conjugated equine oestrogens, 0.625 mg daily, together with cyclical oral dl-norgestrel, 0.15 mg daily, or transdermal 17 beta-oestradiol, 0.05 mg daily, together with cyclical transdermal norethisterone acetate, 0.25 mg daily. We found that only 2% showed significant vertebral bone loss on either treatment, whilst approximately 12% lost from the proximal femur. Compliance was demonstrated by monitoring all used patches and pill packets, recording all side effects and bleeding patterns, and by the demonstration of appropriate changes in levels of gonadal steroids and lipoproteins. Comparing the bone losers with the ten highest gainers, lowers were closer to their menopause but were not different in body mass or life style. Serum oestradiol levels were similar, and both groups showed a similar response in terms of changes in bone biochemical markers and lipoproteins in response to HRT. In thus seems that a small proportion of women do not conserve bone density in the proximal femur with standard doses of HRT. It remains to be determined whether they could be identified by more specific biochemical markers of bone turnover, and whether they would maintain with a higher dose of oestrogen.

Administration, Cutaneous↗

Oral versus transdermal hormone replacement therapy.

Loss of ovarian function at the menopause results in an increased risk for cardiovascular disease and osteoporosis. Hormone replacement therapy (HRT) in postmenopausal women may reduce or remove this increased risk. The high hepatic bolus seen with oral steroid administration, which may produce unwanted metabolic effects, is avoided by transdermal administration. We studied the metabolic effects of transdermal HRT in comparison with oral HRT or no treatment in 96 healthy postmenopausal women over 3 years. Treatment consisted of either continuous oral conjugated equine estrogens, 0.625 mg daily, with sequential oral dl-norgestrel, 0.15 mg daily, for 12 days per month or continuous transdermal estradiol-17 beta, 0.05 mg daily, with sequential transdermal norethindrone acetate, 0.25 mg daily, for 14 days per month. We measured bone biochemistry and density, serum lipids, lipoproteins and apolipoproteins, and glucose, insulin, and C-peptide concentrations following an intravenous glucose bolus. Minimal modelling analyses provided measures of glucose and insulin kinetics. Both HRT regimens were effective in preventing bone loss, and produced generally favourable lipid and lipoprotein changes. Progestin addition prevented increases in HDL2 cholesterol, but lowered triglycerides. Transdermal estrogen lowered triglycerides, whereas oral estrogen increased them. Furthermore, oral HRT resulted in a deterioration in glucose tolerance and an overall increase in insulin secretion. Transdermal HRT appears at least as effective as oral HRT in preventing postmenopausal osteoporosis, and produces as good, if not better, changes in metabolic risk markers for cardiovascular disease.

Administration, Cutaneous↗

An evaluation of dual-energy X-ray absorptiometry and comparison with dual-photon absorptiometry.

Dual-photon absorptiometry (DPA) is a well-established procedure for measuring bone mineral density (BMD). Recently, dual-energy X-ray absorptiometry (DXA) has become available, which has the ability to measure BMD both regionally and in the total body (TB). We have evaluated the in vivo and in vitro precision of a DXA instrument and compared it with a DPA instrument with similar software characteristics. The short-term precision of BMD measurements using DXA was assessed in 65 postmenopausal women who had duplicate scans performed, with repositioning between scans. Precision was 0.9% in the lumbar spine and 1.4% in the femoral neck. The midterm precision of DXA was compared with DPA by scanning 10 volunteers a mean of four times over 24 weeks, on both instruments. The precision of the bone mineral content (BMC) and area measurements was significantly better (P less than 0.05) with DXA than with DPA. Long-term in vitro precision was assessed by scanning an aluminium spine phantom over 42 weeks, and a cadaveric sample over 52 weeks, on both instruments. Precision was similar using the aluminium phantom, but was significantly improved (P less than 0.001) when using DXA for scanning the cadaveric sample. Highly significant correlations (all P less than 0.001) of BMD, BMC and area measurements were observed when 70 volunteers were scanned on both instruments. However, there was a systematic difference in BMD values between the instruments. The precision of TB composition measurements assessed in 16 volunteers, over a 16-week period, were TB BMD 0.65%, TB lean tissue 1.47%, and TB fat tissue 2.73%.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Sex- and menopause-associated changes in body-fat distribution.

We investigated sex- and menopause-related differences in body composition and regional fat distribution, using dual-energy X-ray absorptiometry (DEXA) in nonobese healthy volunteers. Men (n = 103) had a 50% greater lean tissue mass (P less than 0.001) but a 13% lower fat mass (P less than 0.001) than the women (n = 131). Postmenopausal (n = 70) women had a 20% greater fat mass (P less than 0.001) than premenopausal (n = 61) women. The proportion of android (upper body) fat was greatest in men (48.6%, P less than 0.001) but was significantly lower in premenopausal (38.3%) than in postmenopausal (42.1%) women (P less than 0.001). The reverse was found for gynoid (lower body) fat (P less than 0.001). DEXA measurements thus clearly demonstrated that sex differences in total fat mass were opposite those of android fat, and that marked menopausal changes in fat mass and its distribution existed. Body mass indices did not demonstrate that men had less total fat than women whereas postmenopausal women had more total fat than did premenopausal women. Our findings suggest that DEXA measurements of fat distribution may be useful for studies related to obesity-associated disease risk.

Absorptiometry, Photon↗

Changes in body composition with danazol therapy.

Whole body lean and fat mass measurements by dual energy x-ray absorptiometry were performed in 14 premenopausal women undergoing danazol treatment for endometriosis. After 6 months, there was a significant increase in lean tissue mass. Body fat decreased but this was significantly less in the android (upper body segment) region than in the gynoid (lower body segment) region. Danazol thus has both anabolic and androgenic effects on body composition. Dual energy x-ray absorptiometry provides a new, noninvasive, and rapid means of studying body composition.

Adipose Tissue↗

The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism.

BACKGROUND: Oral contraceptives can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low-density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, we examined whether modification of the type or dose of progestin in oral-contraceptive preparations diminishes these changes. METHODS: We measured plasma lipoprotein levels and performed oral glucose-tolerance tests in a cross section of 1060 women who took one of nine types of oral contraceptives for at least three months and 418 women who took none. Seven of the contraceptive formulations contained various doses and types of progestin: levonorgestrel in low (150 micrograms), high (250 micrograms), and triphasic (50 to 125 micrograms) doses; norethindrone in low (500 micrograms), high (1000 micrograms), and triphasic (500 to 1000 micrograms) doses; and a new progestin, desogestrel, in one dose (150 micrograms). All seven contained 30 to 40 micrograms of ethinyl estradiol. Two additional formulations contained progestin alone. RESULTS: As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13 to 75 percent in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14 percent in women taking the combination containing desogestrel and by 12 percent in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5 percent and 16 percent by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29 percent and 43 percent, respectively, in the levels of HDL subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10 percent. The desogestrel combination increased HDL cholesterol levels by 12 percent. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose-tolerance test that were 43 to 61 percent higher than in controls, insulin responses 12 to 40 percent higher, and C-peptide responses 18 to 45 percent higher. Progestin-only formulations had only minor metabolic effects. CONCLUSIONS: The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles.

Adolescent↗

Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women.

66 early postmenopausal women were randomised to 28-day cycles of either transdermal hormone replacement therapy--continuous oestradiol 17-beta 0.05 mg daily, with norethisterone acetate 0.25 mg daily for 14 of each 28 days--or oral therapy--continuous conjugated equine oestrogens 0.625 mg daily, with dl-norgestrel 0.15 mg daily for 12 of each 28 days. An untreated reference group of 30 women were studied concurrently. Bone density was measured in the lumbar spine and proximal femur by dual photon absorptiometry at 6-month intervals for 18 months. Skeletal turnover was assessed by serum measurements of calcium, phosphate, and alkaline phosphatase, and by urine estimations of hydroxyproline/creatinine and calcium/creatinine excretion. In both treatment groups by comparison with the untreated groups by comparison with the untreated group, bone density increased in the vertebrae and proximal femur and biochemical measurements indicated a significant reduction in bone turnover.

Absorptiometry, Photon↗

Determinants of bone density in normal women: risk factors for future osteoporosis?

Postmenopausal osteoporosis is an important public health problem in developed countries. Preventive treatment might effect a large reduction in the incidence, but this needs to be applied selectively to those women at increased risk. Loss of bone density results in an increased risk of fractures in the classical sites of vertebrae and proximal femur. A cross sectional study of bone density measurements was carried out in these sites in British women with a modern, precise densitometric technique. Possible predictors and risk factors for bone density were assessed in these women. Bone density was measured by dual photon absorptiometry in 284 apparently healthy women volunteers aged 21 to 68. The values obtained were similar to those obtained from equivalent studies performed in women in the United States. Peak adult bone density had been attained soon after the end of linear skeletal growth. Thereafter there was some decline with age in the proximal femur, but the major fall in bone density in all sites was related to the menopause. Other factors decreasing bone density, and hence increasing risk for osteoporosis, such as low body weight, alcohol and cigarette consumption, nulliparity, lack of previous use of oral contraceptives, and lack of regular exercise, seemed to be important. None, however, could predict satisfactorily women at future risk for osteoporosis. Direct measurements of bone density in the clinically relevant sites are necessary to determine which women should received preventive treatment for postmenopausal osteoporosis. This would help make such treatment more cost effective.

Adult↗

A comparison of the skeletal effects of goserelin and danazol in premenopausal women with endometriosis.

The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 premenopausal women have been studied. Eleven women received goserelin 3.6 mg monthly by subcutaneous implant and 12 women received danazol 600 mg daily, orally, both for 6 months. Goserelin causes a small decline in spinal bone density, but a greater loss of density in the proximal femur. Preliminary results show no evidence that bone loss is reversible after stopping therapy. Danazol treatment is not associated with loss of bone. Prolonged or repeated courses of treatment with goserelin alone could lead to a clinically significant adverse effect on the skeleton.

Adult↗