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11 beta-Hydroxysteroid dehydrogenase type II in the human endometrium: localization and activity during the menstrual cycle.

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) is a potent inactivator of glucocorticoids and is present in high amounts in the placental syncytiotrophoblast and sodium-transporting epithelia. Placental 11 beta HSD2 is thought to protect the fetus from high circulating levels of maternal glucocorticoids, whereas the renal enzyme is important in conferring aldosterone specificity on the mineralocorticoid receptor. An isoform of 11 beta HSD (11 beta HSD1) is also present in a wide range of tissues, but usually acts as an oxoreductase, converting the biologically inactive cortisone to cortisol. In the present study we have used an immunopurified antibody to the carboxy-terminus of human 11 beta HSD2 (HUH23) to demonstrate localization of the enzyme in luminal and glandular epithelia of human endometrium. In some specimens staining was uniformly distributed, but in others there was clear evidence of heterogeneity both between and within epithelia. Although 11 beta HSD2 was found mainly in the cytoplasm, some cells showed evidence of nuclear staining only. Western blot analysis showed a band at 41 kDa in endometrium and myometrium, confirming the presence of 11 beta HSD2. Measurement of activity throughout the menstrual cycle showed that mean levels (+/- SEM) of activity were 156 +/- 17 and 6.1 +/- 1.1 pmol product/min.g homogenate protein for 11 beta HSD2 and 11 beta HSD1, respectively. Patients taking combined estrogen/progesterone contraceptives had significantly lower activities of both enzymes (76 +/- 19 and 1.9 +/- 0.4; both P < 0.01) compared with the control group. 11 beta HSD2 activity was significantly higher in the secretory than in the proliferative phase of the cycle in controls (193 +/- 22 vs. 120 +/- 23; P < 0.05). All groups contained outliers with elevated enzyme activities, with some patients displaying 11 beta HSD2 levels comparable to those observed in human kidney (> 1000 pmol/min.g). Further analysis showed that there was a statistically significant correlation (r = 0.43; P < 0.001) between the levels of 11 beta HSD1 and 11 beta HSD2. There was no detectable mineralocorticoid receptor binding in endometrial cytosols prepared from patients with a range of 11 beta HSD2 activities. It remains to be determined whether elevated or suppressed levels of either isoform are associated with fertility or endometrial pathology.

11-beta-Hydroxysteroid Dehydrogenases↗

Women and coronary artery disease. Gender confers no immunity.

Although women are, in general, at less risk of coronary artery disease (CAD) than men, they have some unique risk factors, especially if they are postmenopausal or diabetic. Cigarette smoking carries increased hazards for women because it is often accompanied by oral contraceptive use, a combination that promotes thrombogenesis. Hypertension, hypercholesterolemia, hypertriglyceridemia, a high waist-hip ratio of body fat distribution, and certain psychosocial factors, while they pose risks for both men and women, have aspects that are unique to women. Clinicians need to identify the gender-related aspects of CAD and intervene aggressively to minimize the special risks to their women patients.

Age Factors↗

Lipid and lipoprotein concentrations in 1604 men and women in working populations in north-west London.

Serum lipid and lipoprotein concentrations in men and women vary with age, and so-called "normal" limits should take account of this. Serum cholesterol, triglyceride, and phospholipid concentrations were measured in 1027 men and 577 women in five working populations in north-west London, and lipoprotein electrophoresis and quantitative analyses of lipoprotein concentrations were also performed. In men the best fit between serum cholesterol, triglycerides, and phospholipids, on the one hand, and age, on the other, was given by a curvilinear relationship expressed as a quadratic regression. In women the best fit was given by a linear regression. White men had higher serum cholesterol and triglyceride concentrations than Black men, and these differences were reflected in the distributions of the lipoproteins. There were no differences between values in White and Black women. Young women on oral contraceptives had lipid concentrations similar to those of older women not on these preparations. These data suggest that the adoption of concentrations of serum cholesterol (275-300 mg/100 ml (7-1-7-8 mmol/l) and triglycerides (175-200 mg/100 ml (2-0--2-3 mmol/l) recommended by a recent report on the prevention of coronary disease as limits above which special attention should be given to the management of hyperlipidaemia could result in as few as 2% of younger men or as many as 31% of older men being selected for treatment.

Adolescent↗

Use of oral contraceptives, alcohol, and risk for invasive breast cancer.

The aim of our study was to examine how the use of oral contraceptives (OCs) interact with alcohol on breast cancer risk within the large prospective follow-up study, Norwegian Women and Cancer Study. Between 1991 and 1997, women aged 30 to 70 years were drawn at random from the central person register and mailed an invitation. Follow-up information was collected throughout 2001 by linkage to national registries. Only women (n = 86,948) with complete information on alcohol consumption and duration of OC use were included in the present analysis. A total of 1,130 invasive breast cancers were diagnosed during 618,638 person-years of follow-up. Consumption of > or =10.0 g/d alcohol was associated with a breast cancer relative risk (95% confidence interval) of 1.69 (1.32-2.15), consistent with a linear relationship (P for trend < 0.0001). Among alcohol consumers, an excess risk of breast cancer was observed for total duration of OC use only among women who consumed <5 g/d alcohol (P for trend = 0.0009). We observed a negative interaction between duration of OC use and alcohol consumption effects (P for interaction = 0.01). After stratification on menopausal status, the association between high alcohol intake and breast cancer was more prominent among postmenopausal women than among premenopausal women (P for heterogeneity = 0.01). No interaction between alcohol and duration of OC use were significant after stratification on menopausal status. Our findings in conjunction with biological data imply that alcohol and OCs have antagonistic effects on breast cancer risk through a common pathway. Whether the interactive effect differs according to menopausal status remains unclear and needs further investigations.

Adult↗

[Effects of oral contraceptive preparations and smoking on lipoprotein repartition].

We studied the effect of oral contraceptives and smoking on the lipid profile of 251 women and 72 men, 20-29-year-old. In women, taking estroprogestatives, cholesterol, triglycerides, apoproteins AI and B were higher than in controls; HDL-cholesterol was not modified. Lipoprotein analyses in polyacrylamide gradient gel exhibited an increase of the HDL3 fraction at the expense of the HDL2 fraction, with a reduced LDL size. Smoking in addition to estroprogestative absorption accentuated these modifications and led to a decreased HDL-cholesterol (HDL2 fraction essentially), with an increased LDL-cholesterol. In men, smoking resulted in higher levels of total cholesterol, apoprotein B and LDL-cholesterol, without any significant change in LDL size, higher levels of triglycerides and lower level of the HDL2 fraction without any change in HDL-cholesterol. In women, smoking led only to an increase in triglycerides. In summary, analysis of the distribution of HDL subclasses and of LDL size showed an evolution towards a supposed more atherogenic lipid profile in women taking oral contraceptives associated or not with smoking, and in male smokers.

Adult↗

Pregnancy intention and pregnancy happiness: are they different?

OBJECTIVES: This study examines the relationship among pregnancy intention and attitudes, inconsistent contraceptive use, and plans for potential pregnancy among 311 women who presented at local health departments to seek a pregnancy test and for whom a pregnancy would be unintended. METHODS: Women were surveyed prior to receiving pregnancy tests. Pregnancy intention was measured using traditional classifications of mistimed and unwanted pregnancies. Frequency distributions and chi-square tests were computed to examine and compare rates of happiness about the pregnancy among women with mistimed or unwanted pregnancy and to compare rates of inconsistent contraceptive use and plans for the pregnancy by intention and level of happiness. RESULTS: Although all of the women selected for our sample stated that their pregnancies would be unintended, almost half (46%) were inconsistent contraceptive users. Further, 48% reported that they would be somewhat or very happy about a pregnancy. The proportion of women who were uncertain about the future of a pregnancy and who considered adoption or abortion was highest among those for whom a potential pregnancy was mistimed and who were unhappy about the pregnancy. CONCLUSIONS: Differentiating between pregnancy intention and happiness has practice implications for family planning and prenatal providers. Additional research should further elaborate these distinctions.

Abortion, Induced↗

[Prediction of the effect of a triphasic contraceptive agent with norgestimate on acne].

OBJECTIVE: Prediction of complexion changes in users of triphasic oral contraceptive containing norgestimate. DESIGN: Analysis of data from a prospective multicentre open study. SETTING: Department of Obstetrics and Gynaecology, Charles University, Prague. METHODS: Acne severity was evaluated in users of a triphasic norgestimate-containing contraceptive within a six month period. Based on subjective evaluation of acne, three subgroups of patients were selected: A) users where acne improved or disappeared; B) users in whom acne deteriorated, C) users who newly developed acne. Differences between group A and the other groups were established in the proportion or distribution of parameters related to the etiology of acne: age, weight, weight changes during the study, presence of hirsutism, presence of a regular menstrual cycle prior to the start of hormonal contraception use, and smoking. RESULTS: The effect of the pill use on acne was assessed in a total of 3,990 women. Out of 1,201 women with acne before the start of the study, improvement or disappearance of acne during the study was reported by 940 users (subgroup A) (78.27%). In 221 women (18.40%), the extent of acne remained unaltered whereas it increased (subgroup B) in only 30 women (2.50%). Acne newly developed during the study in 49 women (subgroup C), i.e., in 1.2% of the whole group. Users showing deterioration of acne (subgroup B) were found to have hirsutism less frequently. The subgroup even showed a decrease in mean weight during the study. Users with newly developed acne were--compared with subgroup A--significantly older, had a lower weight at the start of the study, and showed a higher frequency of regular menstrual cycles prior to starting hormonal contraception. The differences in the incidence of clinical parameters in the subgroups reached only borderline statistical significance and, hence, are not relevant. CONCLUSION: An extensive multicentric study confirmed the beneficial effect of a triphasic norgestimate-containing contraceptive on complexion. The presence of clinical parameters related to the etiology of acne does not allow to predict the individual response of the skin to hormonal therapy.

Acne Vulgaris↗

Metabolism and disposition kinetics of nicotine.

Nicotine is of importance as the addictive chemical in tobacco, pharmacotherapy for smoking cessation, a potential medication for several diseases, and a useful probe drug for phenotyping cytochrome P450 2A6 (CYP2A6). We review current knowledge about the metabolism and disposition kinetics of nicotine, some other naturally occurring tobacco alkaloids, and nicotine analogs that are under development as potential therapeutic agents. The focus is on studies in humans, but animal data are mentioned when relevant to the interpretation of human data. The pathways of nicotine metabolism are described in detail. Absorption, distribution, metabolism, and excretion of nicotine and related compounds are reviewed. Enzymes involved in nicotine metabolism including cytochrome P450 enzymes, aldehyde oxidase, flavin-containing monooxygenase 3, amine N-methyltransferase, and UDP-glucuronosyltransferases are represented, as well as factors affecting metabolism, such as genetic variations in metabolic enzymes, effects of diet, age, gender, pregnancy, liver and kidney diseases, and racial and ethnic differences. Also effects of smoking and various inhibitors and inducers, including oral contraceptives, on nicotine metabolism are discussed. Due to the significance of the CYP2A6 enzyme in nicotine clearance, special emphasis is given to the effects and population distributions of CYP2A6 alleles and the regulation of CYP2A6 enzyme.

Absorption↗

Gender, menstrual cycle, oral contraceptives and red blood cell deformability in healthy adult subjects.

Gender, menstrual cycle and oral contraceptives may have influence on mechanical properties of Red Blood Cell (RBC) and particularly on RBC deformability. So cell transit parameters have been assessed by filtration with the Cell Transit Analyser (CTA) for a large healthy adult population (seventy-nine males and one-hundred-fifteen females). The CTA provides the distribution of cell transit times of 5000 red blood cells, the mean transit time of the population and different percentiles such as p50, p75, p90 and p95. No effect of oral contraceptives was found. Nevertheless, influence of sex and menstrual cycle were demonstrated. A significant increase of the filtration parameters measured in the female population with respect to the male population and during menstruation, preovulation and post-ovulation periods was observed. During ovulation, the CTA parameters are comparable to the same parameters found in males.

Adult↗

Acceptability of Norplant contraceptive subdermal implants in Kenya.

Norplant contraceptive implants are a relatively new acquisition onto the Kenyan family planning scene. The method seems highly acceptable to a wide cross-section of Kenyan women in government and non-governmental organisations (NGO) clinics. One thousand, six hundred and fifty four clients were recruited into the programme of the largest family planning NGO between 1991 and 1994. Most of the acceptors were young with an average number of 2.6 living children. Half-yearly acceptance rates have been rising. There were minimal serious side effects reported, but 72.0% of the clients complained of some menstrual disruption. Site infection rates were 0.2%, the same as capsule expulsion rates and benign ovarian cyst. Continuation rates were good at 91.0% over the first year and 80.0% over the second year. Client profile and user characteristics are presented. Norplant seems to be a well accepted contraceptive method by young low-parity Kenyan women seeking long-term, continuous yet reversible contraceptive options.

Adolescent↗

[Detection of progesterone receptors in connective tissue cells of the lower nasal turbinates in women].

BACKGROUND: The syndrome of the Rhinopathia gravidarum has been frequently discussed in the literature, but the etiology is yet unknown. An increase of oestrogen and progesterone concentration is said to contribute to the pathogenesis. The aim of this study was to localize estrogen (ER) and progesterone receptors (PgR) in the nasal mucosa of women and to compare the localization with the distribution of mast cells (MC). The patients' medical history was obtained with special emphasis on nasal symptoms during pregnancy, the menstrual cycle, or with the use of oral contraceptives. METHODS: Immunohistochemistry (IHC) was performed on formalin-fixed paraffin sections (nasal mucosa, inferior turbinate of 40 women) with monoclonal antibodies against ER, PgR, and mast cell tryptase. RESULTS: PgR-positive cells were found in fibroblasts (nuclear staining). The cytoplasmic staining for ER in serous glands and excretory ducts and for PgR in the interstitium of glands is considered nonspecific. The pattern of the receptor distribution was different from the pattern seen in the MC-IHC. No significant statistical results were obtained comparing the patient's medical histories and the immunohistochemical findings. CONCLUSIONS: Our findings possibly indicate a direct influence of progesterone on fibroblasts and therefore on the consistency of the extracellular matrix. Additionally, estrogen and progesterone might cause rhinopathic symptoms indirectly by changing the concentration of neurotransmitters (e.g. substance P, NO) and their receptors.

Adult↗

Relationship of exercise, oral contraceptive use, and body fat to concentrations of plasma lipids and lipoprotein cholesterol in young women.

To investigate the relationship of exercise and oral contraceptive use to plasma lipids and lipoproteins, a cross-sectional study was designed to compare lipid levels in 96 exercising and non-exercising women who used or did not use oral contraceptives. Exercisers had significantly lower plasma triglyceride concentrations and low-density/high-density lipoprotein ratios than non-exercisers after adjustment for differences in pill type distribution between groups. Women using progestin-dominant pills had significantly lower plasma triglyceride and high-density lipoprotein concentrations and significantly higher low-density/high-density lipoprotein ratios compared with women using estrogen/progestin-balanced pills. As body fat was significantly associated with both pill type and physical activity, it is unclear how much of these lipoprotein differences were due to body fat, exercise, or pill use. Regular physical activity together with reduced body fat partially compensated for plasma lipoprotein differences associated with oral contraceptive use.

Adipose Tissue↗

Effects of ABT-761, a novel 5-lipoxygenase inhibitor, on the pharmacokinetics of a single dose of ethinyl estradiol and levonorgestrel in healthy female volunteers.

ABT-761 is a second-generation 5-lipoxygenase inhibitor in clinical development for the treatment of asthma. The effects of ABT-761 on the pharmacokinetics of an oral contraceptive were assessed in 21 female adult volunteers in a phase I, multiple-dose, open-label study. Subjects received a single dose of oral contraceptive (30 microg ethinyl estradiol and 0.15 mg of levonorgestrel) on each of days 1 and 29. Oral doses of 300 mg of ABT-761 were administered once daily beginning on day 15 continuing through day 29. Statistically significant decreases in maximum concentration (Cmax) and area under the concentration-time curve (AUC) of ethinyl estradiol were observed when oral contraceptive was administered concomitantly with ABT-761 compared with administration of oral contraceptive alone. The mean elimination rate constant of ethinyl estradiol increased by 30% (a mean decrease of 3.8 hours in half-life), and the mean apparent volume of distribution during the terminal phase (Vd(beta)/F) of ethinyl estradiol increased by 73% in the presence of ABT-761. Mean Cmax and AUC values for norgestrel decreased by 12% and 10%, respectively, when administered with ABT-761. Mean values for time to Cmax (tmax), terminal rate constant (beta), half-life (t1/2), and Vd(beta)/F of norgestrel were similar when oral contraceptive was administered alone or concomitantly with ABT-761. The mechanism responsible for the effect of ABT-761 on the clearance of ethinyl estradiol remains undefined. Because results of previous multiple-dose studies of ABT-761 do not provide any evidence of autoinduction, the effects of ABT-761 on the pharmacokinetics of ethinyl estradiol are more likely related to absorption of ethinyl estradiol.

Adult↗

Oral contraceptives and back pain in women in a Swedish community.

BACKGROUND: Female back pain is a clinical problem-especially low back pain with symptoms from the pelvic posterior region-that is often aggravated in connection with pregnancy and childbirth. Hormones have been suggested as an aetiologic factor. This study is aimed to determine whether additional hormone preparations, i.e. oral contraceptives (OC), may contribute to the increased frequency of such pain. METHODS: A register study was conducted to investigate the use of drugs and health care use in a female population with known OC consumption. Specifically, we registered the number of primary health care visits for low back pain, comparing OC users with non-OC using age-matched women with otherwise equal circumstances. RESULTS: OC users recorded a significantly higher incidence of low back symptoms during the study period compared to non-users. Pregnancy was not found to be a confounding factor. CONCLUSIONS: The intriguing association between OC use and a higher incidence of low back pain, does not enable us to conclude that there is a causal connection, but it should lead to further studies.

Adolescent↗

Attitudes and behaviours in smoking cessation among general practitioners in Finland 2001.

OBJECTIVES: To investigate whether smoking by general practitioners (GPs) and gender influence smoking cessation advice. METHODS: A self-administered questionnaire, originally developed by the WHO and modified according to the Finnish health care system was sent by mail to physicians who were members of the Finnish Medical Association (FMA). Participants were restricted to those who were living in Finland and were younger than 65 years. Numbers of participants was 3,057 and the response rate 69%. RESULTS: Smoking male GPs gave less smoking cessation advice only to patients with a stomach ulcer or patients using oral contraceptive pills compared with their non-smoking colleagues. Male GPs gave less smoking cessation advice to pregnant patients or patients using contraceptive pills than female GPs. Female smoking GPs less likely advised patients who were pregnant or who were using oral contraceptive pills to stop smoking than non-smoking female GPs (p <0.001). The percentage of GPs who have never distributed smoking cessation information was lower in men (41%) than in women (45%; p-value: 0.052). CONCLUSION: Minor differences in anti-smoking advice to patients between smoking and non-smoking general practitioners were found. The little involvement of GPs in health promotion activities regarding tobacco control is of concern.

Adult↗

Risk profiles of women with cervical neoplasia.

Risk-factor profiles were compared in M.D. Anderson Cancer Center patients with various uterine cervix histologic diagnoses. Intraepithelial neoplasia (n = 171) and condyloma (n = 82) were associated with significantly lower patient age (mean 23.6 and 25.8 years, respectively). In addition, these two groups were lowest in annual income, age at beginning intercourse and at first pregnancy, and highest in percentages of black and Hispanic patients, number of sexual partners, and history of gonorrhea. Women with squamous carcinoma in situ (n = 47), who were about a decade older, exhibited a similar socioeconomic distribution and sexual history. All three groups also reported high prevalences of current smokers, were most likely to use oral contraceptives, and were least likely to use diaphragms or condoms. Patients with invasive squamous cell carcinoma (n = 77) had a mean age of 46.3 years, a large lowest-income constituency, and the highest mean number of pregnancies; they were least likely to have used oral contraceptives. Adenocarcinoma (n = 21) was epidemiologically distinct: a predominance of white woman characterized by high socioeconomic status, elevated body mass index, and non of the liberal sexual practices of the other groups. Primary and secondary prevention strategies must be tailored to the unique needs and socioeconomic status of the young at-risk populations.

Adult↗