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Progesterone-releasing vaginal rings for use in postpartum contraception. II. Pharmacokinetic profiles in women.

Vaginal rings releasing progesterone with 3 different initial release rates (5, 8 and 20 mg/day) were used by 11, 10 and 10 women, respectively. The period of insertion was 90 days. The 5 and 8 mg/day rings consisted of a core loaded with progesterone, the 20 mg/day ring contained progesterone homogeneously distributed throughout the mass of the ring. Notwithstanding these differences, the total progesterone levels (areas under curve) were directly related to the release rates. So were the rates of decrease of progesterone levels during the 90 days of insertion of the ring. They were 25, 31 and 47% for the rings releasing 5, 8 and 20 mg/day, respectively.

Administration, Intravaginal↗

Cytokeratins 8, 18 and 19 in endometrial epithelial cells during the normal menstrual cycle and in women receiving Norplant.

Cytokeratins 8, 18 and 19 are members of the cytoskeletal intermediate filament protein family. They are expressed in all simple epithelial tissues, including endometrium, and are recognised as dynamic structures that can be affected by numerous external factors. The Norplant system is a subdermal slow release levonorgestrel implant commonly used as a long-acting progestogen contraceptive. Norplant implants have been shown to have atrophic effects on endometrial epithelial and stromal cells, and cause a range of endometrial bleeding problems among users. The aim of this study is to describe changes in the immunohistochemical expression and distribution of cytokeratins 8, 18 and 19 in endometrial epithelial cells of Norplant implants users and normal menstrual cycle controls. Endometrial biopsies were collected from 65 control normal cycle women and 37 Norplant implants acceptors. The normal menstrual cycle was classified histologically into 9 stages; one menstrual, five proliferative and three secretory. Norplant implants bleeding patterns were categorised into 6 groups according to current World Health Organisation (WHO) definitions; amenorrhoea, frequent bleeding, infrequent bleeding, irregular bleeding, "normal" bleeding, and prolonged bleeding. The tissues were fixed in formalin, embedded in paraffin, and stained immunohistochemically. Semi-quantitative scoring of the staining intensity was performed. Apical versus basal intracellular cytokeratin distribution was also evaluated. The staining intensity was significantly stronger in control endometrial tissue compared to Norplant implants tissue. In control tissues, cytokeratins were predominantly located in the apical region of epithelial cells (52% of biopsies) and in Norplant implants tissues they were predominantly distributed equally between the apical and basal portions of epithelial cells (43% of biopsies). There was no particular cytokeratin distribution pattern associated with the different stages of normal cycle or the different Norplant implants bleeding patterns. It was concluded that long-term exposure to levonorgestrel significantly reduced the cytokeratin expression in endometrial epithelial cells (P < 0.001).

Adult↗

Epidemiology and aetiology of gestational trophoblastic diseases.

Gestational trophoblastic diseases (GTD) consist of a group of neoplastic disorders arising from placental trophoblastic tissue after normal or abnormal fertilisation. The WHO classification of GTD includes hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumour, and miscellaneous and unclassified trophoblastic lesions. GTD have a varying potential for local invasion and metastases and they generally respond to chemotherapy. Broad variations in the distribution of GTD exist worldwide, with higher frequencies in some parts of Asia, the Middle East and Africa, but the extent to which they can be attributed to methodological difficulties in obtaining accurate rates is unclear. Maternal age and a history of GTD have been established as strong risk factors for hydatidiform mole and choriocarcinoma. We review published data on the worldwide distribution of GTD, original data from cancer- registry-based statistics on choriocarcinoma, and major aetiological hypotheses, including parental age, AB0 blood groups, history of GTD, reproductive factors, oral contraceptive use, and other environmental factors.

Choriocarcinoma↗

Prevalence of facial acne vulgaris in late adolescence and in adults.

A survey of 1066 healthy women and 1089 healthy men aged 18-70 years, performed to determine the prevalence of facial acne, showed that clinical acne was not confined to adolescents. Though it was more prevalent among men than women at 18, beyond the age of 23 clinical acne was more prevalent among women as the prevalence in men gradually declined. At 40-49 years 3% of men and 5% of women still had definite, albeit mild, clinical acne, and at 50-59 years 6% of men and 8% of women had physiological acne. The surprisingly high prevalence of acne in adults may be related to antibiotic treatment or, in women, to the use of oral contraceptives or cosmetics, though this survey did not study their influence. Further studies in different populations are needed to establish the prevalence of acne in the community, and its distribution.

Acne Vulgaris↗

[Evaluation of the gingival status by quantification of the T6 (CD1a) and HLA-DR antigens].

The number/mm2 of sections of Langerhans cells (LC's) expressing antigens T6 and/or HLA-DR was determined in eight human gingival samples which consisting of normal gingivae, contraceptive induced hyperplastic, traumatic, inflammatory and diphenylhydantoin hyperplasic gingivae. All samples, except those from normal gingivae, showed inflammatory and/or hyperplasic histopathological patterns. In the immunostained samples, LC's appeared in variable numbers and were randomly distributed between the keratinocytes. All pathological samples, except the inflammatory gingiva showed HLA-DR+ keratinocytes. Wilcoxon and Mann-Whitney statistical tests suggested the existence of three subpopulations of LC's: T6+/DR+; T6-/DR+ and T6+/DR-. The subpopulation T6+/DR+ was predominant in conditions of normal immune response. The subpopulation T6-/DR+ suggested the presence of newly incorporated LC's from the lamina propia. T6+/DR- subpopulations could indicate the existence of a system to avoid overstimulation. It is concluded that quantitative evaluation of T6 and HLA-DR expression was representative of the gingival conditions and the disease activity.

Adult↗

Human papillomavirus and long-term oral contraceptive use increase the risk of adenocarcinoma in situ of the cervix.

We examined United States Surveillance, Epidemiology, and End Results incidence data and conducted a population-based case-control study to examine the role of human papillomavirus (HPV) and oral contraceptive (OC) use in the etiology of adenocarcinoma in situ of the cervix (ACIS). One hundred and fifty women diagnosed with ACIS and 651 randomly selected control women completed in-person interviews. The presence of HPV DNA in archival ACIS specimens was determined by E6 and L1 consensus PCR. Serum samples from case and control subjects were collected at interview, and antibodies to HPV-16 L1 and HPV-18 L1 were detected by virus-like particle capture assays. The overall prevalence of HPV DNA was 86.6%, with 39.0% positive for HPV-16 DNA, 52.4% positive for HPV-18 DNA, and 13.4% positive for more than one HPV type. The age-adjusted relative risk of ACIS associated with HPV-18 seropositivity was 3.3 (95% confidence interval 2.2-4.9). No increased risk was associated with antibodies to HPV-16 L1. Among women born after 1945, the relative risk increased with duration of OC use, with the highest risk for 12 or more years of use (odds ratio, 5.5; 95% confidence interval, 2.1-14.6) relative to nonusers. The detection of HPV DNA in 86.6% of ACIS and the strong association of ACIS with HPV-18 L1 seropositivity underscore the importance of HPV, particularly HPV-18, in the etiology of ACIS. In addition, long-term OC use may contribute to the pathogenesis of these tumors in some women.

Adenocarcinoma↗

Retrospective vs. prospective coital frequency and menstrual cycle length in a contraceptive effectiveness trial.

PURPOSE: To determine how well information at enrollment would predict coital frequency and menstrual segment length during a prospective contraceptive effectiveness trial. METHODS: We compared retrospective reports of monthly coital frequency and menstrual segment (cycle) length with prospective information for women participating in a contraceptive trial of the Reality((R)) female condom. RESULTS: Participants reported slightly higher mean monthly coital frequency and slightly longer menstrual segments prior to the study than during the study (12.6 acts vs. 12.0 acts per month and 30.8 days vs. 28.4 days). We examined the actual distribution of differences between the retrospective and prospective measures and found considerable variability. Among the 195 participants studied, parous women were less likely to predict accurately menstrual segment length (OR 0.4; 95% CI 0.3--0.9), while older women were more likely to predict accurately coital frequency (OR 1.9; 95% CI 0.9--3.3). CONCLUSIONS: Coital frequency and menstrual segment length vary considerably over time. Hence, prospective data collection is essential to accurately characterize these variations and to properly interpret results from contraceptive trials and other studies concerned with fecundability and hazards of reproduction.

Adult↗

Does a family history of cancer increase the risk for postmenopausal endometrial carcinoma? A prospective cohort study and a nested case-control family study of older women.

BACKGROUND: As part of the hereditary nonpolyposis colon carcinoma (HNPCC) constellation of neoplasia caused by defects in mismatch repair genes, some endometrial carcinomas are known to have a genetic contribution to etiology. However, most endometrial carcinomas occur in postmenopausal women, presumably without the HNPCC defect. Consequently, the genetic contribution to these cases is unclear. The objective of this study was to determine whether family history of cancer is a risk factor for endometrial carcinoma in older women. METHODS: The authors analyzed incident endometrial carcinoma data, as well as data on family history of various cancers in first-degree relatives, from a cohort of 24,848 postmenopausal Iowa women ages 55-69 years who were cancer free at baseline in 1986. Because a positive family history is dependent on many factors, including the age of the patient, the number of relatives, and the distribution of other risk factors in relatives, the authors also conducted a nested case-control study on family members of 95 patients with endometrial carcinoma diagnosed during 1988-1989 and 91 cancer free controls who were chosen randomly from subjects matched for age (+/-1 year). RESULTS: During 10 years of follow-up of the cohort, 322 incident endometrial carcinoma cases occurred. Women who reported a positive family history of cancer overall or at any specific site (e.g., the endometrium, colon, or breast) were not at increased risk for endometrial carcinoma. Adjustment for potential confounders, such as age, obesity, parity, oral contraceptive use, and estrogen replacement therapy, did not alter these results. Analysis of the family members of the cases and controls produced little evidence to suggest that this lack of association between family history and endometrial carcinoma could be explained by unequal distribution of known risk factors among relatives. Case family members were slightly older than control family members, but no significant differences were found in body mass index (kg/m2), age at menarche, age at menopause, or number of pregnancies. Relation to a case or control was not associated with increased risk of endometrial, ovarian, breast, or colon carcinoma for family members. Controlling for a variety of potential confounders did not alter the results. CONCLUSIONS: No evidence was found that genetics contribute to the risk of postmenopausal endometrial carcinoma for women with no personal cancer history.

Aged↗

A new method for estimating the effectiveness of emergency contraception that accounts for variation in timing of ovulation and previous cycle length.

OBJECTIVE: To develop a new method for estimating the effectiveness of emergency contraception (EC) by using information about previous menstrual cycle length, accounting for the variation in the day of ovulation within the menstrual cycle, and comparing the validity of the new and previous methods. METHOD(S): Secondary analysis of a data set with a biological marker of ovulation and its distribution in the cycle. Based on a sample of cycles with known length and a known biological marker of ovulation, we simulated trials of predetermined EC effectiveness and then calculated estimates of EC effectiveness based on old and new methods. RESULT(S): Under some conditions, all methods produced biased estimates of effectiveness with simulated trials, especially when the actual effectiveness was low. The systematic bias was minimized with the new method. The new method was robust with regard to the distribution of the day of intercourse in women presenting for EC. CONCLUSION(S): Future studies of EC effectiveness should consider both the uncertainty in predicting the day of ovulation and previous cycle length. Our estimates of daily fecundity should be replicated with other data sets.

Contraception, Postcoital↗

[Borderline hypertension].

As to blood pressure values between 18.66 kPa and 21.14 kPa systolically and/or 11.99 kPa and 12.52 kPa diastolically according to the WHO-definition is spoken of borderline hypertension. In consequence of high rates of prevalence and incidence also in the borderline hypertension a particular preventive-medical interest is present. Own investigations yielded for 50 to 54-year-old males (n = 281) prevalence rates of 29% and for factory populations (n = 6,646 males and females) on an average 20.7%. Parallel to the results in hypertension in borderline hypertension in all age groups higher mean values of the triglycerides and of cholesterol were observed in normotonics. Under hormonal contraception in certain age groups (30--34, 35--39 and 40--49 years) altogether significantly higher systolic and diastolic values of blood pressure were found then in females without oral anticontraceptives. Within a clinical-ambulatory preventive programme performed for 8 years borderline hypertonics did not show any significant differences to the control group concerning the distribution of frequency of essential organ complications and the mortality. According to the present state of knowledge a permanent treatment of the borderline hypertension with substances reducing blood pressure still cannot be justified immediately.

Adult↗

Determinants of menstrual bleeding patterns among women using natural and hormonal methods of contraception. II. The influence of individual characteristics.

Menstrual diary records were obtained from women using either a natural method of contraception, a combined or progestogen-only oral contraceptive, a vaginal ring, or a long-acting injectable (DMPA). Within each method group, multiple regression analysis was used to examine the relationships between the subjects' bleeding patterns and their age, age at menarche, ponderal index, obstetric and contraceptive history and ethnic origin. The influence of ethnic origin was described in the preceding paper. Among combined pill users, increasing age was associated with more frequent spotting episodes. In both the untreated and combined pill groups, women with a higher ponderal index had less variable bleeding-free intervals; in the vaginal ring and DMPA groups, the more obese women had shorter bleeding/spotting episodes and longer bleeding-free intervals. Among combined oral contraceptive users, the most influential variable was the time since the end of the woman's last pregnancy: subjects who had been more recently pregnant had longer, less predictable episodes and shorter intervals. Previous oral contraceptive use was associated with more predictable bleeding patterns among women currently using either type of oral pill. In the vaginal ring and DMPA groups, subjects whose last pregnancy had ended in abortion had more bleeding/spotting days and episodes than those who had had a live birth. As reported previously, bleeding patterns were more closely related to the woman's geographical region of residence than to any other factor. The associations found with other individual characteristics were often inconsistent or difficult to interpret. A number of variables which could potentially influence menstrual bleeding patterns, such as nutritional status, were not measured and therefore could not be included in the analysis. However, contraceptive method and ethnic origin may be predominant influences, overriding any other factor.

Abortion, Induced↗

Comparison of uterine concentrations of ethinyl estradiol and etonogestrel after use of a contraceptive vaginal ring and an oral contraceptive.

OBJECTIVE: To compare uterine tissue concentrations of ethinyl estradiol (EE) and etonogestrel (ENG) after one cycle of use of a contraceptive vaginal ring (NuvaRing; NV Organon, Oss, The Netherlands) or a combined oral contraceptive (COC). DESIGN: Randomized, open-label, pharmacokinetic study. SETTING: Obstetrics and gynecology unit. PATIENT(S): Eight premenopausal women about to undergo hysterectomy but otherwise healthy. INTERVENTION(S): One cycle (17-21 days) of NuvaRing or COC treatment that ended with surgical hysterectomy. MAIN OUTCOME MEASURE(S): Tissue concentrations of EE and ENG in uterine tissue samples taken from the upper myometrium and mid-myometrium, the cervical region, and the endometrium. RESULT(S): In both groups, concentrations of EE and ENG were similar in uterine tissue taken from the upper myometrium and mid-myometrium and the cervical region. However, compared with the COC group, concentrations of both hormones were markedly lower in tissue samples from the endometrium of women who had been treated with NuvaRing. CONCLUSION(S): Vaginal administration of hormones with NuvaRing did not produce elevated uterine concentrations of EE and ENG, compared with an oral contraceptive.

Administration, Intravaginal↗

Prevalence of hysterectomy in Ireland.

OBJECTIVES: To assess factors influencing the prevalence of hysterectomy in Ireland. METHODS: Analysis of results of a questionnaire completed by a population-based cohort of 17735 women aged 50-65 years attending for breast screening. RESULTS: Prevalence of hysterectomy was 22.2%, was increased in proportion to parity and was higher in younger women, those who had previously used oral contraception and those who had private health insurance; peak age at operation was 45-49 years. CONCLUSION: The relatively high prevalence parity reflects contraceptive practices and utilization of health service resources.

Adult↗

Glycodelin: a reproduction-related lipocalin.

Glycodelin, a human lipocalin, is a major endometrial protein with at least two differentially glycosylated isoforms. Glycodelin-A (GdA) is purified from human mid-trimester amniotic fluid, where it is secreted from the decidualized endometrium. Glycodelin-S (GdS) is synthesized in the male reproductive tract, mainly in the seminal vesicles, and secreted into seminal plasma. These two glycodelin isoforms, glycosylated in a completely different manner, serve as a good model for studying the effects of glycosylation on protein function and physicochemical properties. We have reviewed here the structure, expression and biological functions of glycodelin.

Cell Differentiation↗

Adolescent sexuality and the HIV epidemic in Yaoundé, Cameroon.

Adolescents are the focus of many interventions that aim to prevent HIV transmission. In order for these interventions to be effective, it is essential to understand adolescents' sexual behaviour. Using data collected in Yaoundé, Cameroon, in 1997, the study analysed risk exposure and HIV prevalence among 426 men and 510 women aged 15-24. Although risky behaviours seem to be more prevalent among young men, their HIV prevalence remains under 1%. In contrast, HIV prevalence is high among young women (7.5%), even those who report having had few sexual partners. Mixing patterns among sexual partners, and especially the age difference between men and women, do not seem to be sufficient to explain the large male-female discrepancy in HIV prevalence that is evident in these data. The results are therefore probably due to a greater susceptibility to infection of young women than men. This study highlights the necessity of reinforcing prevention campaigns among youth and fighting the obstacles that continue to impede the use of condoms in this population.

Adolescent↗

The efficiency of male-to-female and female-to-male sexual transmission of the human immunodeficiency virus: a study of 730 stable couples. Italian Study Group on HIV Heterosexual Transmission.

To compare the efficiency of male-to-female and female-to-male sexual transmission of human immunodeficiency virus (HIV), we studied 524 female partners of HIV-infected men and 206 male partners of HIV-infected women in 16 Italian clinical centers. All of the partners had had a sexual relationship with the index case lasting for at least 6 months and presented no other risk factor than sexual exposure to the HIV-infected partner. Among the 730 couples, 24% of the female partners were HIV positive, in comparison with 10% of the male partners. Using logistic regression analysis, including gender and controlling for condom use, frequency of intercourse, anal sex, partner's CD4+ cell count and clinical stage, sexually transmitted diseases, genital infections, and contraceptive use, we found that the efficiency of male-to-female transmission was 2.3 (95% confidence interval = 1.1-4.8) times greater than that of female-to-male transmission. Between-gender differences in the contact surfaces and the intensity of exposure to HIV during sexual intercourse are possible reasons for the difference in efficiency of transmission.

Acquired Immunodeficiency Syndrome↗

Two-level proportional hazards models.

We extend the proportional hazards model to a two-level model with a random intercept term and random coefficients. The parameters in the multilevel model are estimated by a combination of EM and Newton-Raphson algorithms. Even for samples of 50 groups, this method produces estimators of the fixed effects coefficients that are approximately unbiased and normally distributed. Two different methods, observed information and profile likelihood information, will be used to estimate the standard errors. This work is motivated by the goal of understanding the determinants of contraceptive use among Nepalese women in the Chitwan Valley Family Study (Axinn, Barber, and Ghimire, 1997). We utilize a two-level hazard model to examine how education and access to education for children covary with the initiation of permanent contraceptive use.

Adolescent↗