Phenotypic characteristics associated with insulin resistance in metabolically obese but normal-weight young women.
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Metabolically obese, normal-weight (MONW) individuals are a hypothesized subgroup of the general population. These normal-weight individuals potentially display a cluster of obesity-related features, although this has not been systematically tested in young women. We hypothesized that MONW young women would display higher levels of total and visceral fat and lower levels of physical activity than normal women. In a cohort of 71 healthy nonobese women (21-35 years old), we identified MONW women based on cut points for insulin sensitivity (normal = glucose disposal >8 mg x min(-1) x kg(-1) of fat-free mass [FFM], n = 58; impaired = glucose disposal <8 ml x min(-1) x kg(-1) of FFM, n = 13). Thereafter, we measured body composition (dual energy X-ray absorptiometry) and body fat distribution (computed tomography), cardiorespiratory fitness (VO2max on a treadmill), physical activity energy expenditure (doubly labeled water and indirect calorimetry), glucose tolerance (oral glucose tolerance test), serum lipid profile, and dietary intake. We found a higher body fat percentage (32 +/- 6 vs. 27 +/- 6%, P = 0.01) and higher subcutaneous (213 +/- 61 vs. 160 +/- 78 cm2, P = 0.03) and visceral (44 +/- 16 vs. 35 +/- 14 cm2, P < 0.05) abdominal adiposity in the MONW group versus the normal group. The MONW group showed a lower physical activity energy expenditure (2.66 +/- 0.92 vs. 4.39 +/- 1.50 MJ/day, P = 0.01), but no difference in cardiorespiratory fitness was noted between groups. In conclusion, despite a normal body weight, a subset of young, apparently healthy women displayed a cluster of risky phenotypic characteristics that, if left untreated, may eventually predispose them to type 2 diabetes and cardiovascular disease. (+info)
Regulation of sulphotransferase expression in the endometrium during the menstrual cycle, by oral contraceptives and during early pregnancy.
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The endometrium plays a key role in reproduction, and this function is tightly regulated by endogenous and xenobiotic steroids. Sulphation, catalysed by members of the sulphotransferase (SULT) enzyme family, is a major deactivating mechanism for steroid hormones and we have investigated the expression and regulation in vivo of SULT in the human endometrium. In the normal cycling endometrium, expression of the phenol sulphotransferases SULT1A1 and SULT1A3 and the oestrogen sulphotransferase SULT1E1 were observed, with SULT1A1 and SULT1E1 expression being higher in the luteal phase than in the follicular phase. No expression of the hydroxysteroid sulphotransferase SULT2A1 was detected at any time in the endometrium. In endometrium from women taking the combined oral contraceptive pill (OCP), SULT1E1 expression was virtually absent, and SULT1A1 expression was substantially reduced. Similarly, in early pregnancy (i.e. first trimester) endometrium, SULT1E1 expression was absent, although SULT1A1 and SULT1A3 expression were unaffected. Our results with normal endometrium support in-vitro data showing that SULT1E1 expression is regulated by progesterone. However, the data obtained from OCP and early pregnancy endometrium suggest that factors other than the concentration of circulating progesterone are involved in the regulation of the expression of this important enzyme in the endometrium. (+info)
Hormone and fertility drug use and the risk of neuroblastoma: a report from the Children's Cancer Group and the Pediatric Oncology Group.
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Previous epidemiologic studies have suggested an association between maternal sex hormone use during pregnancy, including infertility medication, and an increased risk of neuroblastoma in the offspring. The authors conducted a case-control interview study from 1992 to 1996 that included 504 children less than 19 years of age whose newly diagnosed neuroblastoma was identified by two national collaborative clinical trials groups in the United States and Canada, the Children's Cancer Group and the Pediatric Oncology Group. Controls, matched to cases on age, were identified by random digit dialing. No association was found for use of oral contraceptives before or during pregnancy (first trimester odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.5, 2.1). The odds ratio was slightly elevated for history of infertility (OR = 1.4, 95% CI: 0.9, 2.1) and ever use of any infertility medication (OR = 1.2, 95% CI: 0.7, 2.2). Specifically, ever use of clomiphene was associated with a 1.6-fold increased risk (95% CI: 0.8, 3.0) but not periconceptionally or during the index pregnancy. A suggestive pattern was found for gender of the offspring, with an increased risk for males but not for females after exposure to oral contraceptives or clomiphene. This study did not find consistent and large increased risks for maternal use of hormones, but the suggestion of an association for male offspring requires further consideration. (+info)
Oral contraceptive use and risk of melanoma in premenopausal women.
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Melanoma has been increasing in white populations. Incidence rates rise steeply in women until about age 50, suggesting oestrogen as a possible risk factor. Oestrogens can increase melanocyte count and melanin content and cause hyperpigmentation of the skin. We examined prospectively the association between oral contraceptive (OC) use and diagnoses of superficial spreading and nodular melanoma among 183,693 premenopausal white women in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) cohorts. One hundred and forty six cases were confirmed in NHS during follow-up from 1976 to 1994, and 106 cases were confirmed in NHS II from 1989 to 1995. Skin reaction to sun exposure, sunburn history, mole counts, hair colour, family history of melanoma, parity, height and body mass index were also assessed and included in logistic regression models. A significant twofold increase in risk of melanoma (relative risk (RR) = 2.0, 95% confidence interval (CI) 1.2-3.4) was observed among current OC users compared to never users. Risk was further increased among current users with 10 or more years of use (RR = 3.4, 95% CI 1.7-7.0). Risk did not appear elevated among past OC users, even among those with longer durations of use, and risk did not decline linearly with time since last use. In conclusion, risk of premenopausal melanoma may be increased among women who are current OC users, particularly among those with longer durations of use. Further research is needed to determine whether low-dose oestrogen pills in particular are associated with an increase in risk and to describe possible interactions between OC use and sun exposure or other risk factors for melanoma. (+info)
Update on oral contraceptive pills.
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Oral contraceptive pills are widely used and are generally safe and effective for many women. The World Health Organization has developed a risk classification system to help physicians advise patients about the safety of oral contraceptive pills. The choice of pill formulation is influenced by clinical considerations. By choosing appropriately from the available pill formulations, family physicians can minimize negative side effects and maximize noncontraceptive benefits for their patients. Additional monitoring and follow-up are necessary in special populations, such as women over 35 years of age, smokers, perimenopausal women and adolescents. Third-generation progestins are additional options for achieving noncontraceptive benefits, but their use has raised new questions about thrombogenesis. The U.S. Food and Drug Administration has labeled emergency postcoital contraception for use following unprotected coitus. Oral contraceptive pills are associated with few clinically significant drug interactions, although consideration of interactions remains important. (+info)
Benefits and risks of third-generation oral contraceptives.
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OBJECTIVE: To evaluate the risks and benefits of third-generation oral contraceptives. DATA SOURCES: A MEDLINE search was done for English language articles published from 1985 through 1998 relating to the side-effect profile of third-generation oral contraceptives or their association with cardiovascular or thromboembolic disease. All articles containing original data were included. DATA SYNTHESIS: The risk of venous thromboembolism appears to be 1.5- to 2.7-fold greater in users of third-generation, compared with second-generation, oral contraceptives. Compared with nonusers, women who use third-generation oral contraceptives may have a 4.8- to 9.4-fold greater risk of venous thromboembolism. Users of third-generation oral contraceptives do not appear to have an increased risk of myocardial infarction compared with nonusers and may have risk of myocardial infarction of 0.26 to 0.7 compared with second-generation users. Whether third-generation oral contraceptives are associated with a decreased stroke risk is still not clear. CONCLUSIONS: Although third-generation oral contraceptives most likely increase a user's risk of venous thromboembolism, their improved side-effect profile and their possible decreased association with myocardial infarction and stroke may make them a useful new class of oral contraceptives for most women except those at increased risk of venous thrombosis. (+info)
An international study on the acceptability of a once-a-month pill.
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Totals of 450 women attending family planning clinics in Hong Kong, Shanghai and Edinburgh, and 468 in Cape Town, completed a questionnaire designed to seek their views on a contraceptive pill which would be taken only once each month. At least two-thirds of the women in all centres liked the idea of a once-a-month pill. In Hong Kong, Cape Town and Edinburgh, women preferred a pill which inhibited ovulation to one which inhibited implantation, while in all centres a pill which worked after implantation (early menstrual inducer) was considered unacceptable by over half the women. A pill which was taken after a missed menstrual period was considered preferable in all centres, perhaps because it would not be used every month but rather only if pregnancy had occurred. No demographic characteristics, contraceptive experiences or beliefs were consistently correlated with attitudes towards a once-a-month pill, except that women who would not consider having an abortion were more likely to dislike a method that either prevented, or worked after, implantation. A once-a-month pill is now technically possible, although the major drawback is the need to determine when it should be taken. It is reassuring that many women from a variety of different cultures and with widely different experiences, would find this an attractive approach to contraception. (+info)
Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas.
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To assess the hypothesis that oral contraceptives (OCs) increase the risk of cervical adenocarcinomas, we conducted a six-center case-control study of 124 patients with adenocarcinomas, 139 with squamous cell carcinomas, and 307 population controls. Women between the ages of 18 and 69 who were newly diagnosed with cervical adenocarcinomas between 1992 and 1996 were eligible. Healthy female controls and a second case group of incident cervical squamous cell carcinomas were matched to the adenocarcinoma cases. All participants were interviewed regarding OCs, other risk factors for cervical carcinoma, and utilization of cytological screening, and a PCR-based test determined HPV genotype of cervical samples for both case groups and controls. Use of OCs was positively and significantly associated with adenocarcinomas and positively but weakly associated with squamous cell carcinomas. Associations between OCs and invasive adenocarcinomas (n = 91), squamous cell carcinoma in situ (n = 48), and invasive squamous cell carcinomas (n = 91) disappeared after accounting for HPV infection, sexual history, and cytological screening, but a positive association remained between current use of OCs and cervical adenocarcinoma in situ (n = 33). This association persisted after stratification by screening and sexual history and after restriction according to HPV status, but small numbers made it difficult to exclude detection bias, selection bias, or residual confounding by HPV as potential explanations Current OC use was associated with cervical adenocarcinomas in situ, but we saw no other evidence that OCs independently increase the risk of cervical carcinomas. (+info)