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The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferases in man using sparteine, caffeine, and paracetamol as probes.

The impact of gender, use of oral contraceptive steroids (OCS), coffee consumption and of smoking on the metabolism of sparteine, caffeine, and paracetamol was studied in 194 randomly selected subjects (98 male and 95 female). Thirty-eight of the male volunteers were cigarette smokers, 40 of the female subjects were smokers and/or users of OCS. The metabolic ratio of sparteine oxidation (MRs) showed a trimodal distribution. 7.7% of the subjects had a MRs > 20 and thus were poor metabolizers (PMs). Within the extensive metabolizer (EM) subjects, a distinct subgroup accounting for 11% was observed with 20 > MRs > 1.2. Six of the 15 phenotypical PMs were heterozygous EMs by genotyping. This indicates the existence of one or several CYP2D6 mutations which cannot be identified by the currently employed genotyping methods. In each subgroup, i.e. smokers/OCS and non-smokers/non-OCS, the cumulative frequency distribution of the heterozygous (wt/B) phenotype caused a shift to higher MRs compared with the wild-type homozygotes (wt/wt). Thus, for the in vivo activity of CYP2D6, genetic determinants prevail over environmental factors. Smoking, use of oral contraceptive steroids, caffeine consumption, or gender had no influence on sparteine metabolism. The distribution of the paracetamol glucuronide/paracetamol metabolic ratio appeared to be unimodal although skewed. Glucuronidation capacity was clearly affected by gender, OCS use and smoking. It was higher in male than in female subjects. Male smokers had the highest, and female non-smokers/non-OCS users the lowest metabolic ratio. CYP1A2 activity, as determined by a caffeine metabolic ratio ((AFMU + 1X + 1U)/1, 7U), was multimodally distributed and was clearly increased in smokers. It was significantly correlated to paracetamol glucoronidation in male heavy smokers (r=0.85), suggesting an element of co-regulation of CYP1A2 and of paracetamol conjugating UDP-glucuronosyltransferase isozymes, including UGTI.6.

Acetaminophen↗

Feminism and regulation collide: the Food and Drug Administration's approval of the cervical cap.

In May 1988, the Prentif Cavity Rim cervical cap, a barrier method of contraception, was approved by the Food and Drug Administration (FDA) for contraceptive purposes in the United States. This paper describes some of the events leading to the approval of the cervical cap as a contraceptive. Of major interest is the unprecedented involvement of the feminist health movement in clinic-based research, policy making, and distribution of the cervical cap. The recall of the Vimule cervical cap, the use of lay health workers in fitting an experimental device, and the feminist providers' response to the FDA's regulation of the cervical cap are detailed.

Contraceptive Devices, Female↗

Preliminary study of sex hormones of medical importance in Bangladeshi plants.

Twenty six different Bangladeshi plants of folkloric contraceptive use were screened for their oil content, percent unsaponifiables and steroids particularly estradiol, and estrogenic steroids. The distribution of these parameters were studied in seeds, roots, leaves, barks and whole plants. The oil content ranged between 0.23 and 6.75% being highest in Jasminium sacbac (family : oleaceae) seeds. The unsaponifiables varied from 0.04 to 7.87% showing highest content in Xanthium stamanium (roots), and least in Litsea sebifera (Leaves). All plants tested showed positive Salkowski test. Of all 26 plants screened, Synedrella Nodiflora (whole plant), Heliotropicum indicum (root), Belva chal (Bark) and Phyllanthus neruri (whole plant), showed high content of estradiol. Amongst these four, Heliotropicum indicum root showed highest concentration of estradiol.

Bangladesh↗

Influences of weight, body fat patterning and nutrition on the management of PCOS.

Polycystic ovary syndrome (PCOS) is a heterogeneous clinical entity that is defined as the association of hyperandrogenism with chronic anovulation in women without specific underlying diseases of the adrenal or pituitary glands. PCOS is also associated with a metabolic disturbance (insulin resistance). The nature of the complex interrelation of obesity, insulin resistance and endocrine abnormalities in PCOS remains unresolved. However, several studies link obesity, body fat distribution and nutritional habitus with the hormonal and metabolic profiles of PCOS. Moreover, intervention studies have suggested that reducing weight and/or hyperinsulinaemia either by diet alone or by a combination of diet and drugs improves hirsutism, fertility and the hormonal and metabolic profiles of PCOS. In fact, the evaluation of nutritional factors in PCOS is helpful for the screening of metabolic abnormalities and the management of women with PCOS. A point of particular interest in the management of PCOS is that the choice of contraception remains difficult in these high cardiovascular risk women. The impact of pills with ethinyl oestradiol on weight, body fat distribution and carbohydrate metabolism in women with PCOS has not been thoroughly evaluated. The lack of prospective studies to evaluate long-term metabolic and cardiovascular tolerance necessitates care and the assessment of other hormonal possibilities.

Body Constitution↗

Clinical experience with triphasic oral contraceptive (Triquilar) in 527 women in China.

From October 1987 to May 1989, a total number of 527 women completed a total of 6,291 treatment cycles in 6 centers in China for the study of a triphasic oral contraceptive - Triquilar. The mean age of subjects was 30.21 +/- 2.84 years. There were 7 pregnancies during the study period. Among them, five were patient failures because of missed pill or incorrect intake; one had taken barbiturates along with Triquilar. Only one woman became pregnant in the 11th treatment cycle without any reason being found. In most cases, menstrual flow decreased and dysmenorrhea improved as treatment continued. Of the total treatment cycles, the incidence of missed withdrawal bleeding was 0.25%, spotting 0.97%, and breakthrough bleeding 0.48%. Nausea and vomiting was the most common side effect and accounted for 6.4% of the total treatment cycles. This was followed by breast tenderness (3.7%), dizziness (2.4%) and headache (1.6%). Most of the side effects occurred during the first few cycles and were alleviated later. By the end of one year, the total dropout was 64 cases. The reasons for discontinuing treatment were: pregnancy 1.33 (per hundred women), menstrual disturbances 0.76, side effects 3.80, other medical reasons 2.09, and personal reasons 4.18. The results confirm that Triquilar is an effective oral contraceptive with good cycle control and low incidence of side effects. No serious reaction has been reported. It has been well accepted by the Chinese women. However, due to the low dosage of steroids, it is of utmost importance to avoid errors in its use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Contraceptive use at first premarital intercourse: United States, 1965-1988.

The proportion of U.S. women who used a contraceptive method at their first premarital intercourse rose from 47 percent in 1975-1979 to 65 percent in 1983-1988. Overall, and among non-Hispanic white women, this change resulted entirely from an increase in the use of condoms by their partners. The proportion of whites who used a condom at first premarital intercourse, for example, increased from 24 percent to 45 percent. Among blacks, condom use at first intercourse increased from 24 percent to 32 percent during that period, and pill use rose from 15 percent to 23 percent. Among all women, the method most often used at first intercourse during every period in the study was the condom, followed by the pill and withdrawal. The proportion of women using a method at first premarital intercourse varies strikingly according to individual characteristics. Among the various demographic subgroups, the proportion who use a method varies from 32 percent of Hispanic women to 68 percent of Jewish women. Whites are more likely to use a method than are blacks, and fundamentalist Prostestants are less likely to use a method than are other Protestants or Catholics. The proportion using a method is higher among women whose mothers completed high school than among those whose mothers did not. In addition, the proportion rises with age at first intercourse. Multiple logistic regression showed that the independent effects of Hispanic origin, Jewish or fundamentalist Protestant religious affiliation and the education of a woman's mother are large and significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Emergency contraception knowledge and prescribing practices: a comparison of primary care residents at a teaching hospital.

STUDY OBJECTIVE: To determine knowledge, opinion, and experience concerning emergency postcoital contraception in primary care physicians who are in training. DESIGN: Cross-sectional survey using a questionnaire survey distributed to primary care specialty housestaff. SETTING: Questionnaire surveys were distributed to all active primary care housestaff in training and Obstetrics and Gynecology attendings at the University of Kentucky. PARTICIPANTS: The study surveyed all primary care specialty housestaff. Specialties included family practice (FP), internal medicine (IM), pediatrics (PD), and obstetrics and gynecology (OG). The attending faculty in Obstetrics and Gynecology (OGA) were also surveyed as a comparison group. MAIN OUTCOME MEASURES: Study variables were compared between specialty of training, year of training, and abortion opinion. ANOVA or Student's t tests were used, with statistical significance defined as P <.05. Each questionnaire was scored 0 to 9 based on knowledge and utilization questions. Overall response rate was 48%, 90 out of 189 surveyed. Response rates per specialty are as follows: FP = 51%, IM = 37%, PD = 48%, OG = 65%, and OGA = 69%. RESULTS: The average score on the survey was significantly different based on specialty of training (P value <. 0001). Scores were not significantly different based on year of training. However, the average attending OG's score was significantly higher than for all the housestaff (P value <.0001). CONCLUSION: Knowledge and utilization of postcoital contraception is dependent on specialty. Unfortunately, this knowledge does not appear to increase with year of training, suggesting that there is a lack of education during the years of training.

Adult↗

Cost-benefit analysis of selective screening criteria for Chlamydia trachomatis infection in women attending Colorado family planning clinics.

Women attending family planning clinics in Colorado during 1988 were screened for Chlamydia trachomatis infection by enzyme immunoassay (EIA, Chlamydiazyme, Abbott Laboratories; Abbott Park, IL). Cervical specimens from 11,793 women attending 22 family planning clinics were analyzed. Patient history and physical exams were used to assess risk factors for infection. A total of 913 individuals (7.7%) had positive culture results for C. trachomatis. Multivariate analysis showed that infection was significantly related to endocervical bleeding, cervical mucopurulent discharge, a new sexual partner in the last 3 months or multiple previous sexual partners (greater than 3) in the last year, pregnancy, the use of oral contraceptives, and age. Increased odd ratios were observed for the combination of endocervical bleeding and mucopurulent discharge and sexual history that included partners over the previous year as well as the most recent 3 months. A combination of these criteria was used to selectively screen women attending Colorado family planning clinics on an ongoing basis. A cost-benefit analysis employing a model reported previously showed a significant financial benefit associated with universal screening over either selective screening or no screening for C. trachomatis in this population.

Adolescent↗

Characteristics of respondents and non-respondents from a case-control study of breast cancer in younger women.

BACKGROUND: This study assessed the nature of potential biases by comparing respondents with non-respondents from a case-control study of breast cancer in younger women. METHODS: The case-control study was conducted in three regions in the US: Atlanta GA, Seattle/Puget Sound WA, and central New Jersey. An abbreviated interview or mailed questionnaire was completed by willing non-respondents, most of whom had refused participation in the main study. RESULTS: Respondents and non-respondents appeared similar with respect to age, race, relative weight, smoking, family history of breast cancer, number of births, age at first birth, and several dietary items. Compared to non-respondents, case and control respondents were of shorter stature, and reported less frequent consumption of doughnuts/pastries. Respondent cases, compared with non-respondent cases, were more highly educated and more likely to have consumed alcohol regularly; similar but not statistically significant tendencies were observed for controls. Respondent cases experienced menarche earlier than non-respondents. Respondent controls were more likely to have used oral contraceptives than non-respondents; a similar but not statistically significant tendency was observed in cases. Comparisons of crude and simulated relative risks using available non-respondents' data generally showed a low impact of non-response on relative risks in this study. CONCLUSIONS: Our results suggest that non-response would not greatly affect relative risk estimates in this study, except possibly regarding height. However, we were limited by the numbers of informative non-respondents and the amount of data collected. Collecting similar information in future studies would be useful, especially since varying methods used to encourage participation may lead to differences in respondents' characteristics.

Adult↗

Oral contraceptives and ascorbic acid.

Plasma, leukocyte, and platelet ascorbic acid levels are decreased in women ingesting oral contraceptive steroids. Studies have shown that it is the estrogenic component of the oral contraceptive agents that is associated with the decresased ascorbic acid concentrations. Urinary excretion of ascorbic acid does not appear to be increased by the steroids. Although serum levels of copper are increased by estrogens and oral contraceptives, ascorbic acid catabolism does not appear to be increased (unpublished). Our preliminary data on tissue uptake of ascorbic acid suggest that changes in tissue distribution are one possible answer for the observed effects of the steroids on blood levels of ascorbic acid.

Adrenal Glands↗

Prevention of edema, flight microangiopathy and venous thrombosis in long flights with elastic stockings. A randomized trial: The LONFLIT 4 Concorde Edema-SSL Study.

UNLABELLED: The LONFLIT1/2 studies have established that in high-risk subjects after long (> 10 hours) flights the incidence of deep venous thrombosis (DVT) is between 4% and 6%. The LONFLIT4 study has been planned to evaluate the control of edema and DVT in low-medium-risk subjects. The aim of this study was to evaluate edema and its control with specific flight stockings, in long-haul flights. In the first part of the study 400 subjects at low-medium risk for DVT were contacted; 28 were excluded for several nonmedical problems; 372 were randomized into 2 groups to evaluate prophylaxis with stockings in 7-8-hour flights; the control group had no prophylaxis. Below-knee, Scholl, Flight Socks, producing 14-17 mm Hg of pressure at the ankle, were used in the treatment group. The occurrence of DVT was evaluated with high-resolution ultrasound scanning (femoral, popliteal, and tibial veins). Edema was assessed with a composite score based on parametric and nonparametric measurements. Part II: In this part of the study 285 subjects at low-medium risk for DVT were included and randomized into 2 groups to evaluate edema prophylaxis in 11-12-hour flights; the controls had no prophylaxis while the prevention group had below-knee, Scholl, Flight Socks (comparable to part I). RESULTS: Part 1: DVT evaluation. Of the 184 included subjects in the stockings group and 188 in the control group, 358 (96.2%) completed the study. Dropouts were due to compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 179 subjects (mean age 49; SD 7; M:F = 101:78), none had DVT or superficial thromboses. CONTROL GROUP: of 179 subjects (mean age 48.4; SD 7.3; M:F = 98:81), 4 (2.2%) had a DVT. There were also 2 superficial thromboses. In total, 3.35% (6) subjects had a thrombotic event. The difference (p<0.002) is significant. Intention-to-treat analysis detects 15 failures in the control group (9 lost + 6 thromboses) out of 188 subjects (7.9%) versus 5 subjects (2.7%) in the stockings group (p <0.05). All thrombotic events were observed in passengers sitting in nonaisle seats. The tolerability of the stockings was very good and there were no complaints or side effects. Thrombotic events were asymptomatic. No difference was observed in the distribution of events between men and women. The 3 women who had a thrombotic event were taking low-dose, oral contraceptives. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 6.7 (3.1) in controls; in the stockings group the score was 2.9 times lower (p<0.05). The control of edema with stockings was clear considering both parametric (circumference, volume) and nonparametric (analogue scale lines) data. Part II: DVT evaluation. Of the 285 included subjects, 271 (95%) completed the study. Dropouts were due to low compliance or connection problems. Age/sex distributions were comparable in the groups. Stockings Group: of 142 subjects (mean age 48; SD 8; M:F = 89:53), none had DVT or superficial thromboses. CONTROL GROUP: of 143 subjects (mean age 47; SD 8; M:F = 87:56), 3 had a popliteal DVT and 3 a superficial thrombosis. In total, 4.2% (6) subjects had a thrombotic event. The difference (p<0.02) between groups is significant. Intention-to-treat analysis detects 14 failures in the control group (8 lost + 6 thromboses = 9.7%) versus 6 (all lost = 4.2% in the stockings group) (p<0.05). Four of 6 events (3 DVT + 1 SVT) were observed in non-aisle seats. The tolerability of the stockings was very good. No difference was observed in the distribution of events between men and women. Edema evaluation: The level of edema at inclusion was comparable in the 2 groups. After the flight there was a score of 8.08 (2.9) in controls while in the stockings group the score was 2.56 (1.5) (p < 0.005). In conclusion. Scholl Flight Socks are very effective in controlling edema. Also this type of compression is effective in significantly reducing the incidence of DVT and thrombotic events in low-medium-risk subjects, in long-haul flights. CONCLUSIONS: Considering these observations, Flight Socks are effective in controlling edema and in reducing the incidence of DVT in low-medium-risk subjects, in long-haul flights (7-11 hours).

Aerospace Medicine↗

Serum distribution of the major metabolites of norgestimate in relation to its pharmacological properties.

Norelgestromin (NGMN) and levonorgestrel (LNG) are the main active metabolites of norgestimate (NGM), but their relative contributions to the pharmacological effects of NGM are unclear. We have therefore determined the serum distribution of these NGM metabolites and assessed their steady-state concentrations in women following >or=3 cycles of oral contraceptive (OC) use. The administration of 250 microg NGM/35 microg ethinyl estradiol (EE) resulted in significantly higher sex hormone-binding globulin (SHBG) levels (p = 0.002), and 30% lower serum non-protein-bound (NPB) levels of testosterone, when compared to treatment with 150 microg LNG/30 microg EE. We also confirmed that NGMN does not bind to SHBG, and found that 97.2% of this metabolite is bound to albumin while only 2.8% is in the NPB fraction. In contrast, most of the LNG was bound to SHBG (92.5% and 87.2% after NGM/EE and LNG/EE treatment, respectively), and the NPB fraction of LNG (0.7%) during NGM/EE treatment was lower (p < 0.001) than during LNG/EE treatment (1.4%). Combining these serum distributions with the C(max) and AUC(0-24h) data obtained after NGM/EE treatment gave NPB and albumin-bound values of NGMN that were much greater than the corresponding LNG values. Furthermore, the C(max) and AUC(0-24h) values for NPB LNG during NGM/EE treatment were estimated to be lower than during LNG/EE treatment. Since LNG is primarily bound by SHBG, its access to target tissues is restricted. Moreover, because SHBG does not bind NGMN, it appears to be quantitatively the more important NGM metabolite available to target tissues, and probably accounts for a substantial proportion of the progestogenic activity of NGM/EE OCs. However, it is also possible that simultaneous exposure of NGMN and LNG after treatment with NGM/EE may provide clinical benefits not seen with LNG/EE combinations.

Adolescent↗

The effects of recent oral contraceptive use on the outcome of pregnancy.

Of 10479 singleton pregnancies in South Glamorgan between January 1974 and June 1976, 27.3% occurred in women who had used oral contraceptives in the 3 months prior to their last menstrual period (users) and 72.7% occurred in women who had not used oral contraception during the same period (non-users). Significantly more users gained weight excessively. Oral contraceptive use increased the likelihood of uncertain dates and post-maturity. The incidence of neural tube defects was higher among children born to users, although the overall perinatal outcome was not adversely affected. The sex distribution of the offspring was the same in both groups.

Abnormalities, Drug-Induced↗