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Environmental factors in the etiology of neural tube defects: a negative study.

A case-control study was made on women who had an infant with a neural tube defect and twice as many controls. Cases and controls were selected from a national medical birth registry from which prospectively collected data on previous pregnancy, contraceptive use, and smoking were also retrieved. Women's occupation was either retrieved from that registry or from census information which was partially checked with direct interview. Information on environmental characteristics of the place of living of the women in early pregnancy was given by field workers who were unaware of the status of case or control. Cases and controls showed no statistically significant difference with regard to previous pregnancies and use of contraceptives at or the month before the time of conception. Case women smoked 10 cigarettes or more a day slightly more often than control women did but the difference was not statistically significant. No statistically significant difference in occupation distribution was seen between cases and controls (but cases had slightly more occupations where chemical exposure is likely), and no differences in home environment could be found. It is concluded that the factors studied play no major etiological role for the origin of neural tube defects in Sweden.

Abnormalities, Drug-Induced↗

Female urethral pressure profile; reproducibility, axial variation and effects of low dose oral contraceptives.

The variability of the female urethral pressure profile as determined with the microtransducer technique was studied in a group of healthy nulliparous women according to a standardized methodology. Estimation of the short term reproducibility, as well as investigation of which of several serially recorded urethral pressure profiles can be considered as most representative of the basal condition, was carried out by performing serial urethral pressure profile recordings within the same study session in 12 women. Estimation of the long term reproducibility and investigation of the influence of axial rotation of the transducer membrane on the measurements were carried out in 20 women who were on low dose oral contraceptives. No influence of low dose oral contraceptives on the urethral pressure profile measurements could be detected. When serial recordings were made within the same study session, the lowest values for the urethral closure pressure were generally observed in the 3rd and 4th recordings. The short term and long term reproducibility of urethral pressure profile measurements were generally the same for the measurements in both the supine and the sitting positions. Rotation of the transducer membrane as well as positional changes significantly influenced the urethral pressure profile recordings. The recordings in which the transducer was oriented ventrally generally showed a shorter urethral length and a higher closure pressure than those in which the pressure transducer was oriented laterally or dorsally. These observations as well as the observations made during dynamic testing indicate an asymmetrical distribution of urethral closure forces in healthy nulliparous women.

Adult↗

Protein C activity in healthy volunteers--influence of age, sex, smoking and oral contraceptives.

Interpretation of protein C (PC) levels in a given individual has several limitations. A normal PC activity does not necessarily exclude a genetic deficiency nor can a reduced level confirm it. Measuring PC amidolytic activity in 9,648 healthy blood donors has allowed identification of demographic factors which cause variation in PC activity and further hinder interpretation. PC activity displays a log normal distribution and significant variation with age. This is most marked in young adult males when mean PC activity rises from 0.86 iu/ml (15-19 years) to 1.04 iu/ml (45-49 years; P < 0.0001). Pre-menopausal females, who for most age ranges, have mean PC activity below their male contemporaries, show a less marked rise with age until the menopause when PC activity rises further. The use of hormonal contraceptive preparations is associated with an increase in mean PC activity of 0.05-0.08 iu/ml while smoking habit has no influence on PC activity. In view of these findings we strongly recommend the use of age and sex restricted reference ranges when interpreting PC activity.

Adolescent↗

Long-acting delivery microspheres of levo-norgestrol-poly(3-hydroxybutyrate): their preparation, characterization and contraceptive tests on mice.

The preparative technology for sustained release drug delivery microspheres of levo-norgestrol-poly(3-hydroxybutyrate) was optimized based on the in-liquid-drying method. The formation of the drug microspheres was confirmed with differential thermal analysis. The appearance, particle size and distribution, residual CHCl3, drug content, drug release characteristics in vitro, stability and anticonceptive effect on mice of the microspheres were all examined. The average particle size was 64 microm with over 90% of the microspheres being in the range of 28.7-85.8 microm. The residual CHCl3 was lower than 0.001%. The drug release behaviour in vitro could be described by the Higuchi equation and the drug release t1/2 was prolonged by 1.8 times, compared with the original drug LNG. The microspheres were stable for 3 months and showed significant sustained release and anticonceptive effect in mice, and lower toxicity compared with the original drug.

Animals↗

[The influence of technical products on sexual activity and gender relations: oral contraceptive, condom, oral treatments of sexual disorders].

Over the past fifty years, sexuality has been marked by an increasing interest in sexual and reproductive health. This progression can be seen in changes in legislation, in social norms, in sexual practices and in gender relations. It is also characterised by the introduction and use of various technical products, which have a direct impact on both sexual activity and its consequences: contraception, methods of sexually transmissible infections prevention and treatment for male impotence. Irrespective of their usefulness or their technical effectiveness, these different products are endowed with a symbolic identity that reflects dominant representations of sexuality and the sexual roles of men and women. An analysis of the way in which these products are used illustrates how they have contributed to the development of scenarios of sexual relations, by distributing specific roles to men and to women. Three models of sexuality associated with each product have been analysed: liberated sexuality, protected sexuality, and functional sexuality.

Condoms↗

Clinical profile of contraceptive progestins.

The term progestogen has been widely utilized to indicate the general class of agents that includes both progesterone and its synthetic analogs, whereas the term progestin refers only to synthetic progestational steroids. The development of progestins has been influenced in a major way by the search for orally active hormonal contraceptives, since it is likely that hormonal contraceptives will continue to utilize a progestin, the only possible alternative being represented by the utilization of antiprogestins. Synthetic progestogens in clinical use today belong to three main chemical families: progesterone derivatives (progesterone, retro-progesterone, 19-norprogesterone and 17alpha-hydroxyprogesterone); gonane and 19-nortestosterone derivatives (norethisterone, levonorgestrel, desogestrel, gestodene, norgestimate); a spironolactone derivative. Biological potency of progestogens varies depending on the end-point measured, usually ovulation inhibition and endometrial transformation; with both these tests, the most active compounds are all gonane derivatives, with a potency over a 100 times that of the natural hormone. When administered in adequate doses, a progestin inhibits fertility by inhibiting ovulation. This action is mainly exerted at the hypothalamic level where, physiologically, progesterone decreases the number of LH pulses. When progestogens are delivered directly to the uterine cavity, their action seems to be purely local. It has been amply proven that--even when administered in doses that do not constantly inhibit ovulation--a progestin can still remain effective as a contraceptive by acting at the level of the cervical mucus and, at least in part, of the endometrium. Progestogens utilized today differ largely in their pharmacokinetics. In general, after intake, these compounds are rapidly absorbed and distributed so that peak serum concentrations are reached between 1 and 4 h. Third-generation progestins (desogestrel, gestodene, norgestimate) have common characteristics: a higher affinity for progesterone receptors than their predecessors, a lower affinity for androgen receptors, a higher selectivity of action, a higher central inhibitory activity, a higher potency at the level of the endometrium, and an overall metabolic neutrality, in terms of effects on lipid and carbohydrate metabolism. In general, progestins can induce two types of adverse effects: changes in lipid metabolism and bleeding irregularities. Whereas the newer compounds seem to have overcome the first of these adverse effects, the second remains untouched: to this day, proper cycle control can only be achieved with combined hormonal contraceptives.

Contraceptive Agents↗

Emergency contraception: knowledge and attitudes of family medicine providers.

BACKGROUND AND OBJECTIVES: Emergency contraception (EC) is an underutilized method of preventing unplanned pregnancy. This study assessed family physicians' and nurse providers' knowledge, attitudes, and beliefs about EC. METHODS: A cross-sectional survey was distributed to faculty, residents, and clinic nurses in a Midwestern department of family medicine. Data were analyzed using Statistical Package for the Social Sciences. Statistical significance was tested by chi-square test, Student's t test, and Mann-Whitney U test where appropriate. RESULTS: Seventy-eight providers participated (response rate 81%). Seventy-four percent of physicians have prescribed EC in the past, with an average of 3.2 (range 0-10) times in the last year. The majority of providers reported that they were familiar with indications (96%) and protocols (78%) for prescribing EC, yet knowledge inaccuracies were identified. Overall attitudes regarding EC were positive. CONCLUSIONS: Although the majority of participating providers were willing to prescribe EC and had generally favorable attitudes toward it, rates of providing this therapy were low. There was a discrepancy between providers' perceived and actual knowledge about EC. Interventions targeting misunderstandings might help reduce missed opportunities to provide EC.

Attitude of Health Personnel↗

Coping with extra Poisson variability in the analysis of factors influencing vaginal ring expulsions.

The vaginal ring is one method of contraception currently under investigation and development by the Human Reproduction Programme of WHO. One factor that reduces its acceptability is that some women experience involuntary expulsions of the ring. WHO have collected prospective data on 1005 women from 19 centres worldwide to investigate various aspects of ring use including factors that might affect expulsions. For each subject the data include number of expulsions, age, parity, ponderal index, number of days of ring use and health care centre. To model the factors influencing expulsion, the number of expulsions was first considered as a Poisson variate with mean directly proportional to the log of the duration of ring use. Such a model gave a poor description of the data and it appeared that the number of expulsions was considerably over-dispersed for an assumed Poisson variate. This paper examines a variety of strategies for coping with the resulting lack of fit of the model. It turns out that a truncated Poisson model gives a better description of the expulsion data and that health care centre and parity influence the rates.

Contraceptive Devices, Female↗

Menstrual cycle patterns and the risk of breast disease.

The relationship between menstrual cycle patterns and the risk of breast disease was evaluated using data from a hospital-based case-control study of 288 women with benign breast disease (203 chronic cystic diseases and 85 benign tumours), 317 with breast cancer and 602 age-matched controls with a spectrum of acute conditions unrelated to any of the established or potential risk factors for breast disease. A lifelong irregular menstrual pattern [defined as frequent occurrence of menstrual-like episodes of bleeding less than 21 or more than 35 days apart) was negatively associated with the risk of benign breast lesions (relative risk, RR = 0.6, with 95% confidence interval = 0.4-1.0) and of breast cancer (RR = 0.4, with 95% confidence interval = 0.3-0.8]. This inverse association could not be explained by any of the identified potential confounding factors, including the major risk factors for breast disease. The findings of this study, showing that a lifelong history of irregular (and hence more likely anovular) cycles was less frequent among women with benign and malignant breast diseases, support the hypothesis that frequent ovular cycles might be more carcinogenic than anovular ones.

Adolescent↗

Metabolism of 36Cl-ornidazole after oral application to the male rat in relation to its antifertility activity.

1. The antimycotic ornidazole (a male antifertility agent in rats) was synthesized incorporating 36Cl in the chloropropyl sidechain and its metabolism was investigated in the male rat after oral ingestion. 2. Blood levels of radioactivity were low over the first 24 h and there was no tissue accumulation of radioactivity over 48 h. 3. Most of the excreted radioactivity (20% of the ingested dose) appeared in the urine within the first 24 h. 4. Three major compounds were detected in 0-24-h urine samples and were characterized as ornidazole (13% of total radioactivity), Cl- (22%) and 3-chlorolactate (30%), the oxidation product of 3-chlorolactaldehyde. 5. No polyuria or glucosuria was observed following the oral administration of ornidazole, suggesting that any (R)-3-chlorolactate produced was insufficient to affect renal metabolism. 6. Conversion of ornidazole initially to (R, S)-alpha-chlorohydrin or ultimately to the glycolytic inhibitor (S)-3-chlorolactaldehyde could explain its antifertility action in the male rat.

Administration, Oral↗

Condom use to prevent incident STDs: the validity of self-reported condom use.

BACKGROUND: Studies of sexual behavior and of interventions designed to reduce human immunodeficiency virus risk usually depend on self-report. Validation of self-reported condom use measures has not been previously reported in an urban population at high risk for sexually transmitted diseases and human immunodeficiency virus. METHODS: A prospective cohort study was performed in subjects recruited from sexually transmitted disease clinics in Baltimore. At enrollment, a questionnaire was administered that assessed human immunodeficiency virus risk factors and sexually transmitted disease history, and used a retrospective calendar to assess sexual events and condom use over the previous 30 days. Clinical evaluation was performed for sexually transmitted diseases. At follow-up 3 months later, the same procedures were repeated. Incident sexually transmitted diseases at follow-up were defined as new culture or serologically documented diagnoses of gonorrhea, chlamydia, syphilis, or trichomoniasis. RESULTS: In the 323 male and 275 female (total = 598) subjects who completed a follow-up visit, 21% reported using condoms for every act of sexual intercourse over the previous 30 days, 21% reported occasionally using condoms, and 59% reported not using condoms. At follow-up, 21% of subjects had new incident gonorrhea, chlamydia, syphilis, or trichomoniasis. Fifteen percent of the men who were "always" condom users had incident sexually transmitted diseases compared with 15.3% of "never users;" 23.5% of women who were "always" users had incident sexually transmitted diseases compared with 26.8% of "never" users. CONCLUSIONS: In this high-risk population, self-reported condom use is not associated with lower sexually transmitted disease incidence. This finding suggests that self-reported condom use measures, even in a research setting, may be subject to substantial reporting bias.

Adult↗

[Coronary disease in homozygous twins. Respective roles of heredity and environment].

Two 44 year old female homozygote twins presented with cardiac ischaemia due to coronary atheroma, at 39 years of age and 43 years of age, respectively. The coronary risk factors (hypertension, cigarette smoking, hypercholesterolaemia, obesity, oral contraception) were comparable in both cases. Although presenting at different times, the electrocardiographic changes were in the same territory and coronary angiography showed a similar anatomical and lesional distribution. The literature is reviewed with respect to these cases to try to determine the respective roles of heredity and the environment in the initiation and progression of coronary atheroma.

Adult↗

Effects of long-acting steroid contraceptives on ovarian and uterine histology of rats.

Subcutaneous injection of single doses (5 to 20 mg/kg) of DMPA or NE in virgin female rats caused reduction in number and diameter of CL, and increase in number of atretic and cystic follicles in the ovary. Histological examination of the endometrium of these animals showed low cubiodal cells with sparse distribution of low columnar cells, glands with atrophic changes and compact uterine stroma with or without patches of oedema. The results suggest regressive and atrophic changes in the ovary and endometrium.

Animals↗

Proliferative and secretory activity in human breast during natural and artificial menstrual cycles.

Events of cell proliferation have been assessed by thymidine labeling index (TLI) in morphologically normal breast lobules from women of reproductive age. TLI is higher during the second half of the menstrual cycle both in women with natural menstrual cycles and in those with artificial cycles due to oral contraceptive (OC) use. TLI varies between 0.04% and 5.7% and declines with increasing age. There is no difference in mean TLI between OC users and nonusers if correction is made for the difference in age distribution between these two groups. Immunohistochemical detection of immunoglobulin A (IgA), secretory component (SC), and alpha-lactalbumin shows more frequent positive staining during artificial than natural menstrual cycles, and positive staining tends to be associated with higher TLI values. No significant variation in staining with cycle phase is detected in natural or artificial cycles. These results show that breast tissue does not resemble endometrium in the relationships that exist between proliferation, secretion, and menstrual cycle phase.

Adult↗

A prospective open-label study to evaluate the effects of the oral contraceptive Harmonet (gestodene75/EE20) on body fat.

This open-label study evaluated the effects on body fat of the use of a low-dose oral contraceptive (gestodene75/EE20) in a group of 61 women (OC-U group) as compared to a nonuser group (OC-N group) of 51 women who did not receive an oral contraceptive. Weight, body mass index (BMI), waist-over-hip ratio and body composition data, obtained by bioelectrical impedance [percentages of body fat (%FAT), water (%TBW) and lean mass (%FFM)], were assessed before and after six treatment cycles. Baseline OC-U group weight, BMI, %FAT, %TBW and %FFM did not differ from the OC-N group, either at baseline or at the end of the study, and did not significantly change within each group during the study. Also, there was no modification of fat distribution in either group. Among women in the OC-U group, there was a slight increase in total cholesterol levels and a trend towards higher triglycerides levels. No changes were detected in blood pressure. In conclusion, this low-dose oral contraceptive did not affect weight or body composition. Thus, our data suggest that gestodene75/EE20 represents an appropriate OC choice and may enhance compliance of women who mistakenly believe that the use of oral contraceptives always leads to weight gain.

Adolescent↗

Caffeine as a probe for CYP1A2 activity: potential influence of renal factors on urinary phenotypic trait measurements.

Two established caffeine-based urinary methods for measuring CYP1A2 activity were compared with each other, and also with the systemic clearance of caffeine which served as a standard of reference for such activity. Following a standardized dose, caffeine (137X) and its metabolites were measured in urine and plasma of 39 healthy subjects. The measurements allowed determinations of: (1) systemic caffeine clearance (CL(caff)); (2) the caffeine metabolite ratio (AFMU + 1X + 1U)/17U determined in an overnight-urine specimen and referred to as CMR, and (3) the ratio (17X + 17U)/137X measured in urine collected between 4 and 5 h after caffeine intake and referred to as PCUR for 'paraxanthine-caffeine urinary ratio'. The PCUR showed a bimodal distribution and a relatively wide variation, CL(caff) and CMR were both normally distributed. The correlation between CL(caff) and CMR was r = 0.77 (p < 0.001), between CLcaff and PCUR r = 0.46 (p < 0.01), and between CMR and PCUR r = 0.40 (p < 0.02). The difference between the correlation coefficients 0.77 and 0.46 was statistically significant (z-test; p < 0.05). The well established decrease of caffeine metabolism by oral contraceptive use was observed with both CL(caff) and CMR but not with PCUR. Examination of possible explanations for the differences between PCUR and CMR led to the finding of a correlation between PCUR and the renal clearance of caffeine (CLr) with r = -0.47 (p < 0.01). Further scrutiny demonstrated that a bimodal or non-normal frequency distribution as shown by PCUR was also shown by CLr and by urine flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Births to teenagers in the United States, 1940-2000.

OBJECTIVES: This report presents trends in national birth rates for teenagers, with particular focus on the decade of the 1990s. The percent change in rates for 1991-2000 is presented for the United States, and the change for 1991-99 is presented for States. METHODS: Tabular and graphical descriptions of the trends in teenage birth rates for the Nation and each State, by age group, race, and Hispanic origin, are discussed. RESULTS: Birth rates for teenagers 15-19 years generally declined in the United States since the late 1950s, except for a brief, but steep, upward climb in the late 1980s until 1991. The 2000 rate (49 births per 1,000) is about half the peak rate recorded in 1957 (96 per 1,000). Still the U.S. rate is considerably higher than rates for other developed countries. During the 1990s rate declines were especially large for black teenagers. State-specific rates fell significantly in all States for ages 15-19 and 15-17 years, and in all but three States for ages 18-19 years. Overall the range of decline in State rates for ages 15-19 years was 11 to 36 percent. For teenagers 15-17 years, the range of decline by State was 13 to 43 percent. Reductions by State were largest for black teenagers 15-19 years, with rates falling 40 percent or more in seven States. The factors accounting for these declines include decreased sexual activity reflecting changing attitudes towards premarital sex, increases in condom use, and adoption of newly available hormonal contraception, implants, and injectables.

Adolescent↗