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Oral contraceptive use and the incidence of cervical intraepithelial neoplasia.

OBJECTIVE: Our objective was to examine the relationship between oral contraceptive use and the incidence of cervical intraepithelial neoplasia. STUDY DESIGN: In a prospective follow-up study of 6622 women participating in the Second Tromsö Study conducted in 1979 and 1980 in Tromsö, Norway, women aged 20 to 49 years answered a questionnaire regarding their smoking history, dietary habits, alcohol consumption, and oral contraceptive use. They were then followed for 10 years with data from the Pathology Registry of the University Hospital. RESULTS: The age-adjusted incidence rate of cervical intraepithelial neoplasia was 897 per 100,000 person years among noncurrent and 1295 per 100,000 person years among current oral contraceptive users as of 1979. After adjusting for age, marital status, smoking, and frequency of alcohol intoxication the relative rate for current users was 1.5 (95% confidence interval 1.1 to 2.1), and the relative rate for past users was 1.4 (95% confidence interval 1.0 to 1.8), as compared with those who had never used oral contraceptives before 1979. CONCLUSION: These findings support the hypothesis that the occurrence of cervical intraepithelial neoplasia is increased by oral contraceptive use.

Adult↗

Suppression of 24-hour cholecystokinin secretion by oral contraceptives.

Weight gain is a common side effect during oral contraceptive use. The secretion of the satiety hormone cholecystokinin was recorded for 24 hours in women before and during treatment with oral contraceptives. During treatment serum profiles of cholecystokinin were clearly suppressed, which might be related to increased appetite and weight gain.

Adult↗

Effects of monophasic low-dose oral contraceptives on fibrin formation and resolution in young women.

OBJECTIVE: The purpose of this study was to examine key variables in the regulation of coagulation and fibrinolysis during intake of low-dose oral contraceptives containing newly developed progestogens. STUDY DESIGN: Thirty-four healthy young women were allocated to 12 consecutive cycles of treatment with monophasic combinations of 20 micrograms ethinyl estradiol and 150 micrograms desogestrel (n = 15) or 30 micrograms ethinyl estradiol and 75 micrograms gestodene (n = 19). Nonparametric analysis of variance was used for statistical evaluation. RESULTS: In both groups plasma levels of fibrinogen and Factor VIIc increased, and the capacity of coagulation inhibition was affected by increased protein C and decreased protein S levels. Increased fibrinolytic capacity was indicated by elevated activity and reduced antigen levels of tissue plasminogen activator and by reduced activity and concentration of plasminogen activator inhibitor. Thrombin-antithrombin III complexes and fibrin degradation products were unchanged, signifying no effect of hormonal intake on the degree of activation of the coagulation system or the efficacy of fibrinolysis. CONCLUSION: The overall dynamic balance between generation and resolution of fibrin was maintained during treatment with both hormonal compounds. Our findings suggest that the risk of thrombosis in normal women should not be increased.

Adult↗

Association of birth outcome with subsequent fertility.

The association between birth outcome and subsequent fertility was analyzed by using linked Norwegian birth certificates. All births of order 1, 2, and 3 which occurred during 1967 through 1974 were considered index births; there were approximately 207,000 index births of order 1, 165,000 of order 2, and 87,000 of order 3. The mothers' fertility after these index births was summarized with a life-table technique. Fertility was most pronounced if there were no survivors of an index birth, intermediate if there was one survivor, and lowest if both members of a set of twins survived. Advanced maternal age was associated with markedly reduced fertility. The sex of a surviving singleton had little effect on a mother's subsequent fertility. However, there was a sex-related difference if index twins survived; fertility was lower after the birth of unlike-sex twins and higher after the birth of like-sex twins. This probably reflects reproductive limitation rather than a differential fecundity for mothers of dizygotic and monozygotic twins. A comparison of fertility after births of like-sex and unlike-sex twins with one survivor may indicate that mothers of dizygotic twins were more fertile, but the number available for study was small. Reproduction among women who had two index births during 1967 through 1974 was examined separately. Fertility was most marked if neither of the first two infants survived and lowest where three survived (i.e., where one of the index births involved twins). If there were two survivors, the sex composition of the pair influenced fertility; fertility was greater if the two survivors were of the same sex and lower if they were of unlike sex. Since a woman who has an unfavorable outcome in one pregnancy will be at a higher risk of having an unfavorable outcome in a subsequent pregnancy, the higher fertility of such women will, to some degree, inflate the frequency of unfavorable outcomes in a population of births.

Adolescent↗

Oral contraceptives and insulin receptor binding in normal women and those with previous gestational diabetes.

The effect of a low-dose triphasic oral contraceptive (ethinyl estradiol and levonorgestrel) on glucose tolerance, plasma insulin response to a glucose challenge, and insulin receptor binding to monocytes and erythrocytes was investigated in seven women with previous gestational diabetes and seven nondiabetic control subjects. Investigations were performed in the luteal phase before the hormonal intake and after hormonal treatment for 2 and 6 months. Before treatment, women with previous gestational diabetes had significantly impaired glucose tolerance (p less than 0.05) when compared with the healthy controls, but no differences in insulin receptor binding were observed. Glucose tolerance and the insulin response to oral glucose remained unchanged in both groups during the treatment period. In the control subjects a significant decrease (p less than 0.05) in insulin receptor binding to monocytes was observed after hormonal intake for 6 months whereas the insulin receptor binding remained unchanged in the women with previous gestational diabetes. No correlation was found between the receptor binding data obtained from monocytes and erythrocytes in either group of women. The study demonstrates that in lean nondiabetic women and women with previous gestational diabetes of normal weight without first-degree history of diabetes there is no apparent direct association between glucose tolerance, plasma insulin levels, and insulin binding to erythrocytes and monocytes during intake of low-dose oral contraceptives.

Adolescent↗

Effects of contraceptive steroids on cardiovascular risk factors in women with insulin-dependent diabetes mellitus.

OBJECTIVE: We evaluated established cardiovascular risk factors within lipoprotein metabolism, hemostasis, and endothelial function in women with insulin-dependent diabetes mellitus who were using oral contraceptives. STUDY DESIGN: Twenty-five women with uncomplicated insulin-dependent diabetes mellitus, allocated to treatment with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene (treatment group, n = 12) or with nonhormonal contraception (control group, n = 13), were prospectively followed up for 12 months. Nonparametric methods were used for statistical evaluation. RESULTS: No statistical differences in the biochemical risk markers were noted between the two groups at the start of the study. In the treatment group serum levels of low-density lipoprotein cholesterol decreased, whereas the concentrations of total cholesterol, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglycerides were unchanged. Within the coagulation system factor VII coagulant activity increased, while fibrinogen levels were unchanged. In the fibrinolytic system we found unchanged activities but decreased antigen concentrations of tissue plasminogen activator and plasminogen activator inhibitor. The concentration of von Willebrand factor increased, but no change in albumin excretion rates were found. In the control group no changes in any of the variables were observed. CONCLUSION: Intake of modern oral contraceptives does not deteriorate the cardiovascular risk profile in women with insulin-dependent diabetes mellitus, but our study indicates a risk of disturbances of the endothelial integrity, which needs further investigation.

Adult↗

Omitting the first oral contraceptive pills of the cycle does not automatically lead to ovulation.

OBJECTIVE: Our purpose was to test the hypothesis that omitting the first three pills of the contraceptive cycle leads to ovulation. STUDY DESIGN: Ninety-nine women, randomly assigned to 1 of 3 treatments of combined oral contraceptives, completed the study. Treatments contained ethinyl estradiol and either monophasic gestodene, triphasic gestodene, or monophasic desogestrel. Pituitary-ovarian activity was monitored by ultrasonography of the ovaries and assay of serum concentrations of estradiol, progesterone, and follicle-stimulating hormone over 1 normal cycle (study period 1) and 1 cycle after an extended pill-free interval of 10 days (study period 2). RESULTS: None of the women experienced normal ovulation as evaluated by ultrasonography and serum progesterone concentrations. However, follicle-stimulating hormone reached a maximal serum concentration in most women during the first 7 pill-free days, indicating complete pituitary recovery, and increases in serum estradiol concentrations were seen in each woman although with marked interindividual variation. During study period 2 we found follicles of >18 mm in 24%, 24%, and 40% of the monophasic gestodene, triphasic gestodene, and monophasic desogestrel groups, respectively. CONCLUSIONS: Follicular growth up to preovulatory size is common in women missing the first one to three pills of their contraceptive cycle. Although this creates the prerequisite for ovulation, normal ovulation did not occur when pill omissions were limited to only 3 days.

Adolescent↗

Smoking and use of oral contraceptives: impact on thrombotic diseases.

OBJECTIVES: The study was intended to evaluate the effects of oral contraceptives and smoking on the risks of arterial and venous thromboembolic diseases among young women. STUDY DESIGN: The study included a survey of data from published epidemiologic studies and evaluation of registry records of all Danish women discharged from the hospital from 1980 through 1993 after a first thromboembolic event. Questionnaires returned by survivors of such events and by control women during the period from 1994 through 1995 were analyzed. RESULTS: In the 1980-1993 data the absolute risk of thrombotic diseases was seen to increase rapidly with age-exponentially for acute myocardial infarction or cerebral thromboembolic attack, linearly for venous thromboembolism-with risks of arterial diseases exceeding those of venous diseases. In the 1994-1995 data the relative risk of thrombotic diseases was seen to increase among users of oral contraceptives irrespective of age. Risk of venous thromboembolism (but not of acute myocardial infarction or cerebral thromboembolic attack) declined as duration of current oral contraceptive use lengthened, risk of acute myocardial infarction or cerebral thromboembolic attack was significantly decreased as ethinyl estradiol doses were reduced, and the relative risk (compared with nonusers of oral contraceptives) for arterial thromboembolic disease among users of desogestrel or gestodene (in conjunction with midrange or low doses of ethinyl estradiol) was lower than the relative risk among users of second-generation progestogens (in conjunction with midrange doses of ethinyl estradiol). The combination of smoking with oral contraceptive use may have a synergistic effect on risks of acute myocardial infarction and cerebral thromboembolic attack (but not of venous thromboembolism), particularly among users of high-dose (50 micrograms) ethinyl estradiol preparations. CONCLUSION: Among the formulations currently marketed in Denmark, where only the progestins desogestrel and gestodene are available with low-dose (20 micrograms) ethinyl estradiol (and only desogestrel was available in that form at the time of our studies), we prefer these third-generation oral contraceptives for smokers. We might also consider such oral contraceptives for women >35 years old as long as they had no other risk factors for thrombotic arterial diseases.

Adolescent↗

Vaginal epithelial surface appearances in women using vaginal rings for contraception.

Vaginal inspections using colposcopy before insertion of contraceptive vaginal rings and at 2-month intervals during ring use were conducted on 169 users of four different formulations. The rings studied released Nestorone alone (50, 75, 100 g daily over 6 months); ethinyl estradiol: Nestorone (30:100 and 15:150 g daily over 6 months); ethinylestradiol:norethindrone acetate (20:1000 and 15:1000 g daily over 4 months); and ethinyl estradiol:norethindrone acetate (20:1000 g daily over 12 months). A total of 88 altered or atypical conditions of the vaginal surface appearance were recorded in 507 inspections (17.4% of inspections). Many of these atypical appearances were quite subtle. The incidence was significantly higher (p <0.01) than in the single pretreatment examinations (11 in 158 inspections; 7.0%), but closely matched that of a "control group" of sexually active women who were the subject of an earlier study by the same investigators. In that study, the incidence was 18% (57 atypical conditions in 317 inspections). In all, 83% of atypical conditions identified in the vagina during ring use had disappeared by the next scheduled colposcopy despite continued ring use. Findings of potential significance were conservatively defined as all ulcerations, those abrasions and ecchymoses that were >0.5 cm in any direction, and fields of five or more petechiae. Findings fitting those criteria comprised 30% of atypical conditions in ring users, 33% in the control group, and 27% pretreatment. The corresponding incidence as a percentage of inspections were 5.3%, 6. 0%, and 2.5% in the ring users, control groups, and pretreatment groups, respectively. These differences were not statistically significant. The findings suggest that the vaginal rings included in the studies contributed little, if at all, to clinically significant lesions or to total lesion incidence. Further definition would require a larger and longer-term study with matched controls.

Adolescent↗

Collagen metabolism markers as a reflection of bone and soft tissue turnover during the menstrual cycle and oral contraceptive use.

Two different groups of women, 23 healthy young adults and 13 women with chronic posterior pelvic pain, were studied before and during use of oral contraceptives (OC). Collagen metabolism markers-here, the amino-terminal propeptide of type I procollagen, the carboxy-terminal telopeptide of type I collagen, and the amino-terminal of procollagen type III-as well as hormones and other endocrine factors indicating the balance between androgen expression/anabolism and catabolism of the subjects (testosterone, sex-hormone binding globulin, and insulin-like growth factor I were measured. Type I procollagen, the carboxy-terminal telopeptide of type I collagen, and the amino-terminal of procollagen type III were all significantly decreased during OC use. These findings implicate OC use-induced changes in collagen type I and III turnover. A shift in the anabolic/catabolic balance was also recorded indicating a less anabolic situation during OC use.

Adolescent↗

Acceptability of a nonsurgical method to terminate very early pregnancy in comparison to vacuum aspiration.

Seventy-seven patients applying for abortion during early pregnancy consented to be treated by prostaglandin vaginal suppositories or vacuum aspiration by Kahrman catheter in a random design. They also consented to participate in an acceptability study of the two procedures. Attitude and preference measures were obtained by interviewing and rating scales on three occasions: before assignment to abortion procedure, immediately after treatment, and two weeks later. The first 30 patients with complete abortion by either procedure participated in the acceptability study. Both treatments were positively evaluated but perceived to have very different characteristics. The preference for the method used for own treatment increased in both groups. Before treatment 1/3 of the patients in each group had a positive attitude to a self-administered method to induce abortion outside clinics. This proportion increased significantly after treatment but only in the group that received prostaglandin by the vaginal route.

Abortion, Induced↗

IUD compared with oral contraception in nulliparae.

172 nulliparae attending a Swedish family planning clinic were studied. Doctors and midwives with various experiences gave the contraceptive method. Continuation rate at 12 months was 58 per cent for IUD and 86 per cent for OC. The expulsion rate in the IUD group was 11 per cent and in 30 per cent of IUD users the device was removed because of adverse effects. 10 per cent of the IUD group and 5 per cent of the OC group discontinued their method without introducing another one, thereby risking an unwanted pregnancy.

Adolescent↗

Two-year rates for Nova T and Copper T in a comparative study.

A random assignment comparative study between Nova T and Copper T 200 after two years of use revealed that the Nova T resulted in a significantly lower pregnancy rate than the Copper T. The study was performed simultaneously in Denmark, Sweden and Finland. The pregnancy rate in Nova T users was lower than in Copper T users in every country and in every age and parity group. There was no clinic effect in the pregnancy rate of Nova T users. The other termination rates of these two devices were not significantly different. The first segment continuation rates at two years of postmenstrual insertions were 64.7 for Nova T and 65.5 for Copper T 200. It seems that Nova T is an improved copper-releasing IUD.

Actuarial Analysis↗

Aspects of thyroid function during use of Norplant implants.

Plasma thyroxin (T4), triiodothyronine (T3), T3-uptake and thyroid stimulating hormone (TSH) were measured in 18 women using Norplant implants or Norplant-2 implants for six months. Free T4-index and free T3-index were also calculated. All women had used non-hormonal contraceptives before insertion of the implants. T4 decreased and T3-uptake increased, indicating a lower level of thyroid binding proteins during treatment. Free T4-index remained unchanged, indicating that the free concentration of thyroxin was unaltered. All women were euthyroid and TSH was unchanged. It is concluded that treatment with Norplant implants does not result in a change in thyroid function.

Adult↗

Termination of early human pregnancy with epostane.

Fifty-six healthy women, with a gestational length of less than 49 days from the last menstrual period, who requested termination of pregnancy were treated with Epostane, a progesterone synthesis inhibitor. Epostane, which competitively inhibits the 3 beta-hydroxy steroid dehydrogenase enzyme system, was given in the dose 200 mg X 4 for seven days. Physical examination, routine laboratory screening and determination of hCG, progesterone, estradiol and cortisol was performed on days 0, 7 and 14. The treatment resulted in 84% complete abortions (90% among women completing therapy). Two women experienced vaginal bleeding only, while 7 were non-responders. Among subjective side effects nausea dominated totally and was also the reason for discontinuation in 4 cases. The average length of bleeding among women with complete abortions was 10.7 days and the decrease in hemoglobin and hematocrit was very slight. Routine laboratory values remained within the normal range. Cortisol levels were elevated on day 7 compared to days 0 and 14, but all single values were within the normal limits.

Abdomen↗

Clinical performance of a levonorgestrel-releasing intracervical contraceptive device during the first two years of use.

One-hundred-and-ninety-eight women used a levonorgestrel-releasing intracervical contraceptive device (LNG-ICD) designed to release 20 micrograms levonorgestrel/day. Clinical performance during the first two years of LNG-ICD use was evaluated. A total of seven pregnancies occurred during the study period, all of them during the first year. Six pregnancies were after unnoticed expulsion of the device. One pregnancy occurred in an epileptic women using carbamazepine, with the LNG-ICD remaining in situ. Eighteen spontaneous expulsions occurred, 16 during the first year and 2 during the second year. Three pelvic infections were observed, all of them during the first year. Bleeding problems, hormonal side effects and other medical reasons were the most common side effects resulting in removal of the device. The continuation rate was 72.6 per cent after one year and 57.1 per cent after two years.

Female↗

Plasma levonorgestrel levels and ovarian function during the use of a levonorgestrel-releasing intracervical contraceptive device.

Levonorgestrel, estradiol and progesterone plasma concentrations were measured over four years of use of a 20 micrograms/day levonorgestrel-releasing intracervical device (LNG-ICD). The mean levonorgestrel concentration showed a slight decline, being 142 + 46 (SD) pg/ml in the third month and 81 +/- 22 pg/ml in the 48th month of LNG-ICD use. However, considerable interindividual variation in levonorgestrel plasma levels between study subjects was observed. In 77% of the monitored cycles, ovulation or a luteinized follicle was observed when judged by a plasma progesterone elevation of over 5 ng/ml. Some follicular function was also noted in anovulatory cycles. Inhibition of ovulatory ovarian function is not the mode of contraceptive action of the LNG-ICD.

Adult↗

Decline in cerebral thromboembolism among young women after introduction of low-dose oral contraceptives: an incidence study for the period 1980-1993.

The aim of this study was to analyze age-specific incidence rates (IRs) of cerebral thromboembolic attacks (CTA) among women and men 15-44 years of age in Denmark from 1980 through 1993 and to quantify possible influences from oral contraceptives (OC) on the incidence figures. The discharge diagnoses ICD 432-436 from all Danish neurological, neurosurgical and medical departments during the period 1980-1993 were identified in a central diagnosis register. The use of OC was achieved from complete sale statistics during the study period and cross-sectional studies assessing the type-specific use of OC at different ages. During the 14-year study period, 2,100 female and 2,552 male attacks were registered. Men had an exponentially increasing IR with increasing age. Compared with men in the period 1980-86, women had more attacks in the 20-35-year age group and fewer attacks above the age of 35. After 1987 the sex differences below the age of 35 were not significant. From the first half (1980-86) to the last half (1987-1993) of the study period, women below 30 years had a significantly falling CTA IR of -20.4%, compared with a non-significant fall of -9.5% among men below 30 years. In the age group above 30 years, women experienced a not significant increase of 4.2%, men a significant increase of 11.4%. Assuming that use of OC implied an average relative risk of CTA 111115 and pregnancy a relative risk of 4, a correction was made for the contribution of incident cases among women. (ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗