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Biomedical subjects

J C Stevenson

Publications and source records attributed to J C Stevenson.

At least 109 records · Page 6Linked to original sources
PubMed1993

Effects of a low-estrogen, desogestrel-containing oral contraceptive on lipid and carbohydrate metabolism.

Fasting serum lipids, lipoproteins and apolipoproteins, and fasting plasma glucose, insulin and C-peptide were measured in 107 non-users and 83 users of an oral contraceptive containing the progestin desogestrel, combined with 20 micrograms ethinyl estradiol. Plasma glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT) were measured in a subgroup of 69 non-users and 39 users. Compared with non-users, users had higher concentrations of total, high density lipoprotein (HDL), HDL subfraction 3 and very low density lipoprotein (VLDL) cholesterol, total triglycerides, VLDL triglycerides, apolipoproteins AI and AII and fasting plasma insulin. There were no differences in HDL subfraction 2, low density lipoprotein cholesterol and apolipoprotein B. OGTT glucose was 60% higher in the users and OGTT insulin response 19% higher. The OGTT C-peptide response did not differ. The effects of 20 micrograms ethinyl estradiol combined with 150 micrograms desogestrel on lipid, lipoprotein, glucose and insulin metabolism are similar to those described previously with a 30 micrograms ethinyl estradiol combination containing the same dose of desogestrel. The relatively favourable metabolic profile associated with the higher estrogen dose desogestrel combination is maintained at the lower dose.

Apolipoprotein A-I↗
PubMed1993

Insulin resistance, secretion, and elimination in postmenopausal women receiving oral or transdermal hormone replacement therapy.

Estrogen/progestin steroid combinations adversely affect glucose tolerance and insulin resistance, but their effects in combined hormone replacement therapy (HRT) have rarely been evaluated. We studied 61 untreated symptomatic postmenopausal women randomized to receive oral (conjugated equine estrogens, 0.625 mg/d continuous + levonorgestrel, 0.075 mg/d for 12 days of each 28-day cycle) or transdermal therapy (estradiol 17 beta, 0.05 mg/d continuous + norethindrone acetate, 0.25 mg/d for 14 days of each 28-day cycle). An untreated control group of 30 postmenopausal women not seeking HRT was also studied. Intravenous glucose tolerance tests (IVGTT) were performed at baseline and 3, 6, and 18 months later. Mathematical modeling analysis of plasma glucose, insulin, and C-peptide concentration profiles provided measures of insulin resistance, secretion, and elimination. There were no changes in glucose or insulin concentrations with transdermal therapy. Oral therapy caused a deterioration of glucose tolerance and an increased overall plasma insulin response, apparently due to a reduction in the immediate plasma insulin response to glucose. This may have resulted from increased hepatic insulin uptake, uncompensated for by an increase in first-phase pancreatic insulin secretion. Neither treatment caused significant insulin resistance compared with baseline, but with the oral treatment insulin resistance was greater during the combined phase compared with the estrogen-only phase. Thus the oral regimen affected both insulin delivery and insulin resistance. The transdermal regimen had relatively few effects on insulin metabolism.

Administration, Cutaneous↗
PubMed1993

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↗
PubMed1993

Alternatives to HRT in prevention and treatment.

Oestrogen hormone replacement therapy remains the first choice for the treatment and prevention of osteoporosis in postmenopausal women, but for patients who are unsuitable for this therapy, which of course includes men, other satisfactory treatments are available. Several placebo-controlled studies have demonstrated that bisphosphonates and calcitonin prevent bone loss or perhaps increase bone density over 2-3-year periods, and reduce the rate of fracture. It is not known whether these treatments will increase bone density over longer periods of time. Cyclical etidronate has recently become licensed in the UK for use in the treatment of osteoporosis, and it is hoped that other bisphosphonates and intranasal calcitonin will soon be added to the available treatments. Fluoride appears to increase bone density but, at doses above a very narrow therapeutic window, it increases the fracture rate, either because of bone redistribution, formation of poor quality bone or a toxic effect on osteoblasts. At present, fluoride remains a treatment to be used only under expert supervision or within the context of controlled clinical trials. Anabolic steroids may be of value in selected elderly patients with osteoporosis. The patient may be able to contribute to the prevention of osteoporotic fracture by exercising, which will improve dexterity and may have a small effect to increase bone density, and by avoiding the factors that predispose to falls, such as icy paths and excess alcohol. Changes in the diet are unlikely to play a major role in the maintenance of bone density in women living in the Western world.

Bone Density↗
PubMed1993

The effects of the menopause on insulin sensitivity, secretion and elimination in non-obese, healthy women.

We have carried out intravenous glucose tolerance tests with measurement of plasma glucose, insulin and C-peptide concentrations on 66 premenopausal and 92 postmenopausal non-obese caucasian women. After adjustment for the effects of a number of possible confounding variables, including age and body mass index, there was little difference between pre and postmenopausal women in glucose and insulin concentrations either fasting or in response to intravenous glucose. Mathematical modelling analysis of the resultant plasma concentration profiles was used to obtain measures of insulin sensitivity, secretion and elimination, and non-insulin dependent glucose disposal. We found reciprocal differences in mean insulin sensitivity (increased by 50%) and non-insulin dependent glucose disposal (decreased by 30%). Plasma C-peptide response and pancreatic insulin secretion were markedly lower in the postmenopausal group (-35% and -51% respectively). However, the rate constant for insulin elimination was also lower in these women. As a result, intravenous glucose tolerance test plasma insulin concentrations were not significantly different between the two groups. We conclude that, despite the occurrence of little or no variation in plasma glucose and insulin concentrations, the menopause is associated with significant changes in insulin metabolism.

Adult↗
PubMed1993

Effects of tibolone on serum concentrations of lipoprotein(a) in postmenopausal women.

OBJECTIVE: To evaluate the effects of tibolone (Org OD14), a synthetic steroid used for the relief of postmenopausal symptoms, on serum concentrations of lipoprotein(a) (Lp(a)), an independent risk marker for coronary heart disease. DESIGN: Subset of women participating in a non-randomized prospective trial of tibolone therapy. Twenty-seven women requesting relief of menopausal symptoms were treated with tibolone 2.5 mg/day for six months; 27 women who did not request treatment acted as controls. RESULTS: Tibolone induced a substantial fall (p < 0.001) in serum Lp(a) levels (median change -48%, range -100% to +3%). CONCLUSIONS: In terms of cardiovascular risk, the ability of tibolone to lower serum concentrations of Lp(a) may be advantageous in view of the unwanted reduction in high density lipoprotein concentrations which has previously been demonstrated in users of this steroid.

Anabolic Agents↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipoproteins.

OBJECTIVE: We attempted to ascertain whether transdermal postmenopausal estrogen-progestin therapy has the typical effects of oral therapy on serum lipoprotein risk markers for cardiovascular disease. STUDY DESIGN: Sixty-one postmenopausal women were randomized to receive either transdermal continuous 17 beta-estradiol, 0.05 mg/day, with transdermal cyclic norethindrone acetate, 0.25 mg/day, or oral continuous conjugated equine estrogens, 0.625 mg/day, with oral cyclic dl-norgestrel, 0.15 mg/day. Twenty-nine untreated subjects served as controls. Lipoprotein profiles at 3 and 6 months were compared with baseline values by means of analysis of variance. RESULTS: In the estrogen-alone phase both therapies reduced serum levels of total and low-density lipoprotein cholesterol; high-density lipoproteins were largely unchanged. Oral therapy increased triglycerides whereas this lipid fell with transdermal therapy. In the combined phase of the cycle both therapies reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. CONCLUSION: Transdermal and oral therapies had similar effects on lipoprotein cholesterol but different effects on triglycerides.

Administration, Cutaneous↗
PubMed1992

Lipoprotein Lp(a) levels are reduced by danazol, an anabolic steroid.

Serum levels of lipids, lipoproteins and apolipoproteins were measured in 26 premenopausal women with endometriosis both before and after six months therapy with the anabolic steroid danazol (600 mg/day) and in 15 untreated women who acted as controls. No changes were seen in the control group over six months. In women treated with danazol, mean levels of low density lipoprotein (LDL) cholesterol increased by 36% while those of high density lipoprotein (HDL) cholesterol decreased by 46%, changes characteristic of androgenic steroids. In contrast to this potentially detrimental lipoprotein profile, lipoprotein(a) [Lp(a)] levels were reduced by 78.6% +/- 24.0% (mean +/- S.D.) in women taking danazol. These dramatic changes in Lp(a) levels correlated with baseline Lp(a) levels but not with changes in LDL or HDL. Anabolic steroids such as danazol appear to be powerful modulators of serum Lp(a) concentrations. This could be due to direct effects on Lp(a) metabolism, or secondary to the effects of these steroids on insulin metabolism or on the coagulation and fibrinolysis system.

Adolescent↗
PubMed1992

Ageing and the response of plasma insulin, glucose and C-peptide concentrations to intravenous glucose in postmenopausal women.

1. Eighty-six apparently healthy postmenopausal women not receiving hormone replacement therapy were given an intravenous glucose tolerance test. Plasma glucose, insulin and C-peptide concentrations were determined in fasting and post-glucose challenge samples. 2. Using a multivariate regression model, with predictor variables of chronological age, menopausal age and body mass index, neither chronological age nor menopausal age correlated with fasting or post-challenge plasma glucose or C-peptide concentrations. In contrast, menopausal age was positively associated with fasting plasma insulin concentration (P = 0.038, model r2 = 0.107), insulin area (P = 0.01, model r2 = 0.236) and incremental insulin area (P = 0.024, model r2 = 0.243). This relationship could not be explained by differences in lifestyle variables of alcohol consumption, physical activity, previous duration of oral contraceptive usage, history of cigarette smoking or body mass index. 3. Our findings suggest that loss of ovarian function is associated with hyperinsulinaemia, possibly via alterations in the clearance of circulating insulin from the plasma. The hyperinsulinaemia observed may contribute to the increased risk of cardiovascular disease seen in postmenopausal women.

Adult↗
PubMed1992

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↗