Multicentre cohort study of antihypertensive and lipid-lowering therapy cessation after bariatric surgery.

BACKGROUND: Few studies have assessed changes in antihypertensive and lipid-lowering therapy after bariatric surgery. The aim of this study was to assess the 6-year rates of continuation, discontinuation or initiation of antihypertensive and lipid-lowering therapy after bariatric surgery compared with those in a matched control group of obese patients. METHODS: This nationwide observational population-based cohort study used data extracted from the French national health insurance database. All patients undergoing gastric bypass or sleeve gastrectomy in France in 2009 were matched with control patients. Mixed-effect logistic regression models were used to analyse factors that influenced discontinuation or initiation of treatment over a 6-year interval. RESULTS: In 2009, 8199 patients underwent primary gastric bypass (55·2 per cent) or sleeve gastrectomy (44·8 per cent). After 6 years, the proportion of patients receiving antihypertensive and lipid-lowering therapy had decreased more in the bariatric group than in the control group (antihypertensives: -40·7 versus -11·7 per cent respectively; lipid-lowering therapy: -53·6 versus -20·2 per cent; both P < 0·001). Gastric bypass was the main predictive factor for discontinuation of therapy for hypertension (odds ratio (OR) 9·07, 95 per cent c.i. 7·72 to 10·65) and hyperlipidaemia (OR 11·91, 9·65 to 14·71). The proportion of patients not receiving treatment at baseline who were subsequently started on medication was lower after bariatric surgery than in controls for hypertension (5·6 versus 15·8 per cent respectively; P < 0·001) and hyperlipidaemia (2·2 versus 9·1 per cent; P < 0·001). Gastric bypass was the main protective factor for antihypertensives (OR 0·22, 0·18 to 0·26) and lipid-lowering medication (OR 0·12, 0·09 to 0·15). CONCLUSION: Bariatric surgery is associated with a good discontinuation of antihypertensive and lipid-lowering therapy, with gastric bypass being more effective than sleeve gastrectomy.

Long-term follow-up after bariatric surgery in a national cohort.

BACKGROUND: Lifelong medical follow-up is mandatory after bariatric surgery. The aim of this study was to assess the 5-year follow-up after bariatric surgery in a nationwide cohort of patients. METHODS: All adult obese patients who had undergone primary bariatric surgery in 2009 in France were included. Data were extracted from the French national health insurance database. Medical follow-up (medical visits, micronutrient supplementation and blood tests) during the first 5 years after bariatric surgery was assessed, and compared with national and international guidelines. RESULTS: Some 16 620 patients were included in the study. The percentage of patients with at least one reimbursement for micronutrient supplements decreased between the first and fifth years for iron (from 27.7 to 24.5 per cent; P < 0.001) and calcium (from 14·4 to 7·7 per cent; P < 0·001), but increased for vitamin D (from 33·1 to 34·7 per cent; P < 0·001). The percentage of patients with one or more visits to a surgeon decreased between the first and fifth years, from 87·1 to 29·6 per cent (P < 0·001); similar decreases were observed for visits to a nutritionist/endocrinologist (from 22·8 to 12·4 per cent; P < 0·001) or general practitioner (from 92·6 to 83·4 per cent; P < 0·001). The mean number of visits to a general practitioner was 7·0 and 6·1 in the first and the fifth years respectively. In multivariable analyses, male sex, younger age, absence of type 2 diabetes and poor 1-year follow-up were predictors of poor 5-year follow-up. CONCLUSION: Despite clear national and international guidelines, long-term follow-up after bariatric surgery is poor, especially for young men with poor early follow-up.

Comparison of body composition, basal metabolic rate and metabolic outcomes of adults with Prader Willi syndrome or lesional hypothalamic disease, with primary obesity.

CONTEXT: The care of patients with hypothalamic obesity is challenging. OBJECTIVE: To compare body composition, basal metabolic rate (BMR) and metabolic outcomes of adults, with lesional or genetic hypothalamic obesity, with obese patients suffering from primary obesity, once matched for body mass index (BMI). DESIGN AND PATIENTS: Adults with hypothalamic obesity of genetic origin (Prader Willi syndrome (PWS)) or acquired hypothalamic damage (HD), such as craniopharygioma, were compared with obese control candidates awaiting bariatric surgery (C), with a BMI between 35 and 65 kg m(-)(2), and aged between 18 and 50 years. MAIN OUTCOME MEASURES: Body composition measured by whole-body dual-energy X-ray absorptiometry scanning, BMR using indirect calorimetry, hormonal and metabolic assessments. RESULTS: A total of 27 adults with a genetic diagnosis of PWS, 15 obese subjects with HD and 206 obese controls with similar BMI were studied. Compared with the control group, PWS patients had an increased percentage of fat mass (FM), and a decreased percentage of android FM. The BMR of PWS patients was significantly lower than controls and highly correlated with lean body mass in PWS and C patients. Body composition of HD was similar with those of obese patients. A trend toward an increased prevalence of diabetes in HD patients and of cytolysis in PWS was observed in comparison with primary obese patients. CONCLUSION: Genetic and lesional hypothalamic obesities have different consequences for phenotypic features such as body composition or BMR compared with primary obese patients. The mechanisms of adipose tissue development and metabolic complications may be different between genetic and lesional obesities.

A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10.

Obesity, a common multifactorial disorder, is a major risk factor for type 2 diabetes, hypertension and coronary heart disease (CHD). According to the definition of the World Health Organization (WHO), approximately 6-10% of the population in Westernized countries are considered obese. Epidemiological studies have shown that 30-70% of the variation in body weight may be attributable to genetic factors. To date, two genome-wide scans using different obesity-related quantitative traits have provided candidate regions for obesity. We have undertaken a genome-wide scan in affected sibpairs to identify chromosomal regions linked to obesity in a collection of French families. Model-free multipoint linkage analyses revealed evidence for linkage to a region on chromosome 10p (MLS=4.85). Two further loci on chromosomes 5cen-q and 2p showed suggestive evidence for linkage of serum leptin levels in a genome-wide context. The peak on chromosome 2 coincided with the region containing the gene (POMC) encoding pro-opiomelanocortin, a locus previously linked to leptin levels and fat mass in a Mexican-American population and shown to be mutated in obese humans. Our results suggest that there is a major gene on chromosome 10p implicated in the development of human obesity, and the existence of two further loci influencing leptin levels.

Relationship between adiposity, emotional status and eating behaviour in obese women: role of inflammation.

BACKGROUND: Obesity is characterized by chronic low-grade inflammation that may lead to emotional distress and behavioural symptoms. This study assessed the relationship between adiposity, low-grade inflammation, eating behaviour and emotional status in obese women awaiting gastric surgery and investigated the effects of surgery-induced weight loss on this relationship. METHOD: A total of 101 women with severe or morbid obesity awaiting gastric surgery were recruited. Assessments were performed before and at 1 year post-surgery and included the measurement of neuroticism and extraversion using the revised Neuroticism-Extraversion-Openness personality inventory (NEO-PI-R) and eating behaviour using the Three-Factor Eating Questionnaire (TFEQ). Blood samples were collected for the measurement of serum inflammatory markers [interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP)] and adipokines (leptin, adiponectin). RESULTS: At baseline, body mass index (BMI) was positively correlated with inflammatory markers and adipokines. Regression analyses adjusting for age and diabetes revealed that baseline concentrations of IL-6 and hsCRP were associated with the depression and anxiety facets of neuroticism, with higher inflammation predicting higher anxiety and depression. This association remained significant after adjusting for BMI. Gastric surgery induced significant weight loss, which correlated with reduced inflammation. After controlling for BMI variations, decreases in inflammatory markers, notably hsCRP, were associated with reduced anxiety and TFEQ-cognitive restraint scores. CONCLUSIONS: These findings indicate strong associations between adiposity, inflammation and affectivity in obese subjects and show that surgery-induced weight loss is associated concomitantly with reduced inflammation and adipokines and with significant improvement in emotional status and eating behaviour. Inflammatory status appears to represent an important mediator of emotional distress and psychological characteristics of obese individuals.

Promoter adiponectin polymorphisms and waist/hip ratio variation in a prospective French adults study.

BACKGROUND: Adiponectin expression and plasma concentrations are decreased in human and animal models of obesity. Several single nucleotide polymorphisms (SNPs) in the adiponectin gene are known to influence the plasmatic concentration of the encoded protein. Some of these adiponectin polymorphisms have been associated with BMI in cross-sectional studies. OBJECTIVE: The aim of our study was to examine the longitudinal relationships between adiponectin gene polymorphisms and anthropometric indices. DESIGN: Two adiponectin gene (ADIPOQ) SNPs, -11391G>A and -11377C>G, were genotyped in 837 French Caucasian subjects from the SUpplémentation en VItamines et Minéraux Anti-oXydants (SU.VI.MAX) cohort. Anthropometric scores were measured at three clinical examinations over a 7-year period. RESULTS: For -11391G>A as well as for -11377C>G, we detected no association between the variant allele and anthropometric measurements at baseline. Considering longitudinal effects, we detected moderately higher waist-to-hip ratio (WHR) changes for the carriers of the -11391A (P=0.02) and -11377C (P=0.03) allele over the follow-up of the study. -11391G>A and -11377C>G define haplotypes associated also with WHR measurements and their changes over the follow-up of the study. Diploid configurations that combine -11391A and -11377C were associated with significantly higher WHR changes (DeltaCE: P=0.02) compared to other haplotypes. In addition, higher adiponectin levels were observed in AC/AC diplotypes compared to GG/GG carriers (P<0.0001). CONCLUSION: In the SU.VI.MAX study, genetic variations in the adiponectin gene affect abdominal fat gain over life span.

Cathepsin S genotypes are associated with Apo-A1 and HDL-cholesterol in lean and obese French populations.

Cathepsin S (CTSS) is a cysteine protease that has a central role in remodeling the extracellular matrix and, as such, has been implicated in the etiology of cardiovascular disease. This study used five tag single nucleotide polymorphisms (tSNPs) to screen the CTSS gene in healthy lean (n = 1891) and obese French populations (n = 477) for their association with various phenotypes: body mass index, waist-to-hip ratio, glycemia, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1) and apolipoprotein B. Significant associations were identified between rs11576175 tSNP (A/G) and Apo-A1 and HDL-C plasma levels in a sex-specific manner. Lean female subjects homozygous for the minor A-allele had higher levels of circulating Apo-A1 (p = 0.0003), while lean male A/A carriers had higher levels of HDL-C (p = 0.007) compared with the other genotypes. In the obese cohort, associations were found between three tSNPs and Apo-A1 levels in adult female subjects: rs10888390 (G/A), p = 0.01; rs10888394 (T/C), p = 0.03; and rs1136774 (C/T), p = 0.02; however, only rs10888390 remained significant in a combined model (p = 0.03). These results provide the first evidence that CTSS sequence variations are associated with two human metabolic risk factors for cardiovascular diseases: plasma Apo-A1 and HDL-C concentrations.

[Stress urinary incontinence and obesity]. / Incontinence urinaire d'effort et obésité.

In France, the prevalence of urinary incontinence is about 44%. Obesity, defined by a Body Mass Index (BMI) above 30kg/m(2), is well established as a risk factor of stress urinary incontinence. Odds ratio (OR) varies between 1.7 and 2.4. Urge or mixed incontinence also occurs in obesity. Urinary incontinence epidemiology is not well-known in obese women. Weight loss, obtained by a weight reduction diet program or bariatric surgery, improves urinary symptoms of stress, urge or mixed incontinence. Functional outcome of urge incontinence surgery is not influenced by obesity. Typically, functional outcome and morbidity of tension-free vaginal tape are not influenced by BMI variations.

Nutritional deficiency after gastric bypass: diagnosis, prevention and treatment.

In recent years, the recourse to obesity surgery to treat morbid obesities has grown. The number of "malabsorptive" interventions, such as the gastric bypass (RYGB: Roux-en-Y gastric bypass) increases each year. The RYGB, which combines two mechanisms promoting weight loss, restriction and malabsorption, has proven its effectiveness in term of weight loss and improvement of obesity-associated co-morbidities. However this intervention involves a profound change in digestive physiology and is the source of nutritional and metabolic complications. The deficits observed most frequently concern proteins, iron, calcium, vitamin B12 and vitamin D. The deficiencies in vitamin B1 are rare but potentially serious. Multidisciplinary follow-up is essential to ensure prevention, diagnosis and treatment of these complications. Based on an analysis of the literature, this article summarizes the various nutritional complications observed after RYGB and the means to diagnose it. It proposes practical recommendations for follow-up, preventive supplementation and treatment of these deficiencies, both generally and in the more specific case of a pregnancy after RYGB.

Increased basal glucose production and utilization in children with recent obesity versus adults with long-term obesity.

To characterize the abnormalities of glucose homeostasis and insulin action early in the course of human obesity, we studied in vivo glucose kinetics in seven children who were recently massively overweight. At time of study they were gaining weight at a rate of 13.5 +/- 1.4 kg/yr. They were compared with six age-matched control subjects. Six adults with long-term obesity and five normal adults were studied in parallel. The obese children and adults were normoglycemic and hyperinsulinemic. We found that glucose production and utilization were remarkably higher in obese children (295 +/- 18 mg/min; 7.6 mg.kg-1 lean body mass.min-1) than in control children (129 +/- 13 mg/min; 4.4 mg.kg-1 lean body mass.min-1, P less than .01) and obese adults (151 +/- 8 mg/min; 3.1 +/- 0.3 mg.kg-1 lean body mass.min-1, P less than .01). Obese adults had normal rates of glucose production and utilization. Insulin- and non-insulin-mediated glucose uptake, estimated with somatostatin-induced suppression of endogenous insulin secretion, contributed almost equally to the excess glucose utilization observed in the obese children. When studied with the euglycemic-hyperinsulinemic clamp, obese children could not increase glucose disposal to the same extent as normal children and were not able to adequately suppress their endogenous glucose production. Recently obese children are therefore characterized by an increased basal glucose turnover rate and an already established insulin resistance of the liver and probably the skeletal muscles.

A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q.

As part of an ongoing search for susceptibility genes in obese families, we performed linkage analyses in 101 French families between qualitative and quantitative traits related to morbid obesity and polymorphisms located in or near 15 candidate genes whose products are involved in body weight regulation. These included cholecystokinin A and B receptors (CCK-AR and CCK-BR), glucagon-like peptide 1 receptor (GLP-1R), the LIM/homeodomain islet-1 gene (Isl-1), the caudal-type homeodomain 3 (CDX-3), the uncoupling protein 1 (UCP-1), the beta3-adrenoceptor (beta3-AR), the fatty acid-binding protein 2 (FABP-2), the hormone-sensitive lipase (HSL), the lipoprotein lipase (LPL), the apoprotein-C2 (apo-C2), the insulin receptor substrate-1 (IRS-1), the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and the liver carnitine palmitoyltransferase-1 (CPT-1). Phenotypes related to obesity such as BMI, adult life body weight gain, fasting leptin, insulin, fasting glycerol, and free fatty acids were used for nonparametric sib-pair analyses. A weak indication for linkage was obtained between the Isl-1 locus and obesity status defined by a z score over one SD of BMI (n = 226 sib pairs, pi = 0.54 +/- 0.02, P = 0.03). Moreover, a suggestive indication for linkage was found between the Isl-1 locus and BMI and leptin values (P = 0.001 and 0.0003, respectively) and leptin adjusted for BMI (P = 0.0001). Multipoint analyses for leptin trait with Isl-1 and two flanking markers (D5S418 and D5S407) showed that the logarithm of odds (LOD) score is 1.73, coinciding with the Isl-1 locus. Although marginally positive indications for linkage in subgroups of families were found with IRS-1, CPT-1, and HSL loci, our data suggested that these genes are not major contributors to obesity. Whether an obesity susceptibility gene (Isl-1 itself or another nearby gene) lies on chromosome 5q should be determined by further analyses.

Soluble leptin receptor in serum of subjects with complete resistance to leptin: relation to fat mass.

Leptin resistance and obesity have been related to mutations of the leptin receptor gene in rodents and, recently, in a consanguineous family. The latter mutation results in a receptor lacking transmembrane and intracellular domains. Homozygous and heterozygous individuals with this mutation had serum leptin levels higher than expected, given their BMIs: 600, 670, and 526 ng/ml and 145, 362, 294, 240, and 212 ng/ml, respectively. Their serum leptin was fractionated by gel filtration: >80% was present as a high-molecular size complex vs. 7.5% in the nonmutated sister. Western blot analysis showed a band at 146 kDa reacting specifically with an antibody directed against the leptin receptor ectodomain. In 10 obese control subjects, as in the mutated patients, free leptin levels correlated with BMI (r = 0.70, P = 0.0011) and reflected fat mass, regardless of leptin receptor functioning. In the patients, bound leptin levels correlated with BMI (r = 0.99, P = 0.0002) and were related to the number of mutated alleles. These data demonstrate that the truncated receptor is secreted into blood and binds the majority of serum leptin, markedly increasing bound and total leptin. Free serum leptin was similarly correlated with BMI in the mutated and nonmutated obese individuals, providing evidence that the relationship between BMI and circulating free leptin is preserved in this family. This finding suggests that the leptin receptor itself may not be specifically involved in the control of leptin secretion, and it supports the concept of relative resistance to leptin in common obesity.

Genetic studies of the sulfonylurea receptor gene locus in NIDDM and in morbid obesity among French Caucasians.

The sulfonylurea receptor (SUR) is a key component in glucose-stimulated insulin secretion. Obesity and NIDDM are frequently associated and share some metabolic abnormalities, suggesting that they might also share some susceptibility genes. Thus, the SUR encoding gene is a plausible candidate for a primary pancreatic beta-cell defect and thus for hyperglycemia and weight gain. Through association and linkage studies, we have investigated the potential role of the SUR gene in families with NIDDM and in two independent sets of morbidly obese families. The exon 22 T-allele at codon 761 was more common in patients with NIDDM (7.7%) and morbid obesity (7.8%) than in control subjects (1.8%, P = 0.030 and P = 0.023, respectively). This variant was associated with morbid obesity (odds ratio 3.71, P = 0.017) and NIDDM (odds ratio 2.20, P = 0.04; association dependent on BMI). Although the frequencies for intron 24 variant were similar in all groups, morbidly obese patients homozygous for the c-allele had a more deleterious form of obesity. Sib-pair linkage studies with NIDDM in French Caucasian families gave no evidence for linkage to the SUR locus. However, in one set of the obese families, we found an indication for linkage with a SUR-linked microsatellite marker (D11S419, P = 0.0032). We conclude that in Caucasians, the SUR locus may contribute to the genetic susceptibility to NIDDM and obesity.

Indication for linkage of the human OB gene region with extreme obesity.

Obesity is one of the most significant risk factors for hypertension, coronary heart disease, and NIDDM (Frayn KN, Coppack SW: Insulin resistance, adipose tissue and coronary heart disease. Clin Sci 82:1-8, 1992; Kaplan NM: The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 149:1514-1520, 1989). While family segregation, adoption, and twin studies have indicated that degree of adiposity has a significant genetic component (Stunkard AJ, Harris JR, Pedersen NL, McClearn GE: The body-mass index of twins who have been reared apart. N Engl J Med 322:1483-1487, 1990; Bouchard C, Despres J-P, Mauriege P: Genetic and nongenetic determinants of regional fat distribution. Endocr Rev 14:72-93, 1993), the genes and predisposing mutations remain poorly understood. This is in contrast to several well-defined genetic models for obesity in rodents, particularly the mouse obese (ob) gene, in which loss-of-function mutations cause severe obesity. Recent studies have demonstrated a substantial reduction in body fat when recombinant ob protein (leptin) is administered to mice. To test the relevance of these observations to human obesity, the location of the human homologue (OB) was established by radiation hybrid mapping and eight microsatellite markers spanning the OB gene region (7q3l.3) were genotyped in 101 obese French families. Affected-sib-pair analyses for extreme obesity, defined by BMI >35 kg/m2, revealed suggestive evidence for linkage to three markers located within 2 cM of the OB gene (D7S514, D7S680, and D7S530). The OB gene is therefore a candidate for genetic predisposition to extreme obesity in a subset of these families.

Recommendations regarding obesity surgery.

In France, 1,000 obese persons per month undergo a bariatric operation. Obesity surgery requires coordination and monitoring of aftercare. The French public health-care insurer asked the medical associations involved in obesity management to provide guidelines for obesity surgery. The recommendations were developed by the national associations of Obesity, Nutrition and Diabetes: the Association Française d'Etudes et de Recherches sur l'Obésité (AFERO), member of the EASO and IASO; the Association de Langue Française pour l'Etude du Diabète et des Maladies Métaboliques (ALFEDIAM); the Société Française de Nutrition (SFN); and the Société Française de Chirurgie de l'Obésité (SOFCO). This article presents the short version of the guidelines.

Type 2 diabetes mellitus in France in 2012: results from the ObEpi survey.

AIM: This analysis estimates the prevalence of type 2 diabetes mellitus (T2DM) in French adults participating in the ObEpi (obesity epidemiology) 2012 survey and also proposes a description of that population, according to comorbidities, treatments and sociodemographic factors related to the disease. METHODS: A self-administered questionnaire was posted to 20,000 households from the Kantar Health panel. In total, 25,714 adults aged≥18 years and representative of the French population completed the survey between January and March 2012. RESULTS: The prevalence of T2DM was 5.5±0.3% (95% CI) in this representative sample of the adult French population. Average age of patients was 65.9 years; 55% were men. Mean body mass index was 29.9kg/m(2) (men: 29.4kg/m(2), women: 30.6 kg/m(2); P<0.01); the prevalence of obesity was 43.1% (men: 39.9%, women: 47.1%; P<0.01). Patient-reported treatments for comorbidities were frequent: high blood pressure, 59.1%; dyslipidaemia, 59.9%; myocardial infarction/angina pectoris, 9.7%; revascularization, 7.8%; heart failure, 7.4%; sleep apnoea, 8.3%; and osteoarthritis, 10.7%. With regards to known treatments, 81.4% of patients were taking oral antidiabetic drugs (OADs), and 15.3% were using insulin therapy. Also, 18.8% of diabetic respondents reported financial hardship. CONCLUSION: T2DM remains a disease of major concern: compared with the non-diabetic population, all parameters surveyed showed unfavourable ratings, particularly for women.

[Pregnancy and bariatric surgery: Critical points]. / Grossesse et chirurgie bariatrique: points critiques.

More than 200,000 people underwent obesity surgery in France. Most of them are women. Pregnancy after bariatric surgery is becoming a common situation. This surgery results in major nutritional and gastro-intestinal tract modifications that may influence or be influenced by pregnancy, and yields benefits as well as complications. A multidisciplinary management including a nutritionist, an obstetrician, an anesthesiologist, and a bariatric surgeon is required. The aim of this review is to analyze the impact of bariatric surgery on pregnancy and vice versa, and to identify the key points of this management.

Contraception in hypertensive women using a vaginal ring delivering estradiol and levonorgestrel.

Contraception with a vaginal ring (CVR) that delivers estradiol and levonorgestrel was used during a mean of 15.6 menstrual cycles in 12 hypertensive women. Blood pressure (BP) was measured 5 times on each visit during 2 pretreatment control cycles; during the 1st, 2nd, 4th, 6th, and from the 9th to 12th cycles of CVR use; and again after a 1-month recovery period. No significant change in BP occurred during CVR use in any of the subjects. Plasma renin substrate and antithrombin III activity did not vary significantly, which suggests the utility of administering natural estradiol via the vagina, thus avoiding the first pass effect that occurs with oral contraceptives. Significant decreases in plasma sex hormone-binding globulin, cholesterol, high density lipoprotein cholesterol, phospholipids, and triglycerides occurred, indicating an androgenic effect of levonorgestrel. We conclude that the CVR is a method of contraception that does not elevate BP in hypertensive women.

PIP: Contraception with a vaginal ring (CVR) that delivers estradiol and levonorgestrel was used during a mean of 15.6 menstrual cycles in 12 hypertensive women. Blood pressure (BP) was measured 5 times on each visit during 2 pretreatment control cycles; during the 1st, 2nd, 4th, 6th, and from cycles 9-12 of CVR use; and again after a 1-month recovery period. No significant change in BP occurred during CVR use in any of the subjects. Plasma renin substrate and antithrombin III activity did not vary significantly, which suggests the utility of administering natural estradiol via the vagina, thus avoiding the 1st pass effect that occurs with oral contraceptives. Significant decreases in plasma sex hormone-binding globulin, cholesterol, high density lipoprotein cholesterol, phospholipids, and triglycerides occurred, indicating an androgenic effect of levonorgestrel. The authors conclude that the CVR is a method of contraception which does not elevate BP in hypertensive women.

Biological effects of estradiol-17 beta in postmenopausal women: oral versus percutaneous administration.

To determine whether the route of administration or the type of estrogen used in estrogen replacement therapy (ERT) is more important in avoiding effects on hepatic function, 24 postmenopausal women were studied before and at the end of 2 months of oral or percutaneous administration of the same estrogen, estradiol-17 beta (E2). The treatments studied were oral micronized E2, 2 mg/day (9 women); oral E2 valerate, 2 mg/day (5 women), and percutaneous E2, 3 mg/day (10 women). Specific plasma biological and biochemical markers of estrogenic action were evaluated, namely, E2, estrone (E1), LH, FSH, sex steroid binding protein (SBP), renin substrate, antithrombin activity, and lipoproteins (high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein triglycerides). Both oral and percutaneous administration of E2 increased plasma E2 levels up to midfollicular values and decreased LH and FSH levels into the same range. Oral administration of E2 led to substantial increases in plasma E1, SBP, renin substrate, and VLDL levels, whereas AT decreased significantly. Percutaneous administration of E2 led to a physiological plasma E1/E2 ratio and did not induce any change in hepatic proteins. These data suggest that the route of administration of E2 determines the biochemical response to ERT in postmenopausal women. SBP is the most sensitive marker of the liver action of estrogen, and triglycerides also are simple and useful markers for this effect. Percutaneous E2 therapy is an effective method of ERT, and has no measurable effects on hepatic markers of estrogen action.

Nutritional induction of adipose tissue lipoprotein lipase in obese subjects.

Other workers have reported increased adipose tissue lipoprotein lipase after a weight loss in obese subjects and have suspected that this enzyme is a primary factor of pathophysiological significance. In order to determine whether this effect was the consequence of refeeding rather than weight loss, six obese females were included in a controlled study. Adipose tissue lipoprotein lipase was measured before weight loss, at the end of 30 days on a diet of 800 kcal/day (mean weight loss 8.7%), and four times during the 8 days after the initiation of refeeding a 1500 kcal/day mixed diet to insure weight stability. Adipose tissue lipoprotein lipase decreased by 77% by the end of the weight loss, and an average 2-fold increase (24.2 +/- 2.7 mean +/- sem versus/11.1 +/- 2.3 mU/10(6) cells, p less than 0.01) was shown as early as 2 days after refeeding. Peak values after refeeding did not surpass predieting values. Changes during restriction and peak postrefeeding values were both positively correlated to baseline values. It can be concluded that the previously shown increase in lipoprotein lipase during weight stability after a weight loss is likely to be a secondary effect of partial refeeding; the individual sensitivity of adipose tissue lipoprotein lipase to nutritional induction could be of critical importance.