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PubMed1986

Impairment of prednisolone disposition in women taking oral contraceptives or conjugated estrogens.

Companion studies were designed to determine the effects of oral contraceptives and conjugated estrogens on the pharmacokinetics of prednisolone. Twenty-four normal women entered the studies, including six young women taking oral contraceptives and six age-matched control women, and six postmenopausal women receiving conjugated estrogens and six age-matched postmenopausal women. All received 0.53 mg/kg prednisolone phosphate, iv. Significant decreases (P less than 0.05) in the clearance and volume of distribution and significant increases in the half-life were found for both total and unbound prednisolone in the women taking oral contraceptives compared to values in the young control women. A significant decrease in the unbound clearance and increases in the total and unbound half-lives of prednisolone were found in the women receiving conjugated estrogens compared to values in the postmenopausal control women. Total clearance and volume of distribution were unchanged by conjugated estrogen therapy. Administration of prednisolone to women receiving estrogen-containing oral contraceptives or conjugated estrogens results in exposure of these women to increased concentrations of unbound prednisolone for increased periods of time. Increases in the pharmacological and toxic effects of prednisolone might be expected in these women.

Adult↗
PubMed1987

Contraceptive steroid treatment affects steroid binding proteins and the percentage of free 17 beta-estradiol and testosterone in the cynomolgus monkey (Macaca fascicularis).

The levels of steroid binding globulins were characterized in cynomolgus monkeys that were treated with contraceptive steroid preparations delivered either by intravaginal rings (CVR) or orally (OC) in the diet. Levonorgestrel (dNG) was the bioactive progestin and the estrogen was either 17 beta-estradiol (E2) in the CVR treatment or ethinyl estradiol (EE) in the OC treatment. Both contraceptive treatments lowered sex hormone binding globulin (SHBG) levels below those observed in males (P less than 0.05) and normal females (P less than 0.01). Corticosteroid binding globulin (CBG) was elevated (P less than 0.01) in the OC treatment, demonstrating the potency of EE. The distribution of E2 and testosterone (T) between binding to SHBG or albumin and the unbound fraction was calculated after the determination of the percentage of free steroid by centrifugal ultrafiltration. Both contraceptive treatments increased the percentage of free T and E2 (P less than 0.01) in the subset of monkeys that were evaluated, but the percentage bound to SHBG and albumin were different only for the CVR group (P less than 0.05). Decreased total T concentrations in the treatment groups offset any increase in free T concentrations associated with an increase in the percentage of free T. The differences in the distribution of binding to SHBG associated with these contraceptive steroid treatments was influenced more by the reduction in the binding capacity of SHBG than by the displacement of E2 and T from SHBG by dNG.

Administration, Oral↗
PubMed1999

Lipoprotein(a) concentrations in women with a history of severe preeclampsia--a case control study.

A high concentration of lipoprotein(a) is associated with atherosclerotic disease. Atheroma may develop in spiral arteries in both preeclamptic and normal pregnancies, but they are much more common in preeclampsia, particularly in the decidual segments. We hypothesized that a high concentration of lipoprotein(a) is associated with the development of preeclampsia. We studied 40 women with a history of severe preeclampsia, 35 women with a history of preeclampsia and the (H)ELLP syndrome and 67 controls with a normal obstetric history. Lipoprotein(a) levels were measured at least 10 weeks post partum in the second half of a normal menstrual cycle. None of the women in the study or the control group were pregnant or used oral contraceptives. Lipoprotein(a) levels over the 90th percentile of the lipoprotein(a) distribution of our control group (420 mg/l) were defined as abnormal. There was a statistically significant higher prevalence of abnormal levels of lipoprotein(a) in women with a history of severe preeclampsia (33%) in comparison with women with a history of preeclampsia and (H)ELLP syndrome (9%) and with the control group (10%). We found that a history of severe preeclampsia and spontaneous abortion was associated with elevated lipoprotein(a) levels as a post-hoc finding. Whether spontaneous abortion and high levels of lipoprotein(a) are related remains to be demonstrated.

Adult↗
PubMed1988

Haemostasis and oral contraceptives.

Selected hemostasis parameters were assayed in 131 women ingesting different kinds of oral contraceptives and 36 control women. No differences were noted in the plasma levels of fibrinogen, antithrombin III, prekallikrein, alpha 2 antiplasmin, fibrinopeptide A, platelet factor 4 and beta-thromboglobulin. Protein C and plasminogen levels were significantly higher in pill users (p less than 0.001, p less than 0.01) and fibronectin levels were lower (p less than 0.05). Canonical correlation, performed between clinical parameters and hemostasis data, revealed a negative correlation between antithrombin III levels and family history for thromboembolic diseases. A positive correlation was noted between fibrinogen and fibronectin levels in obese OC users. The data suggest that women taking OCs are not in a state of "hypercoagulability."

Adult↗
PubMedDate not supplied

A clinical study on injectable contraceptive Noristerat.

Results of a clinical study involving 382 subjects using the injectable contraceptive Noristerat (norethisterone enanthate) is presented. The maximum number of acceptors were between 21-25 years of age and had been married for 6-10 years. 50% began their 1st injection within 1 year of the last childbirth. Continuation rates were very high and about 75% returned for their 2nd injection. Among the users, weight gain was seen more commonly than weight loss. There was no significant change in blood pressure. 52.2% reported a menstrual pattern which was within the acceptable range of normal, while only 12.7% had amenorrhea. 15% showed other types of menstrual disturbance. Only 1 woman in the series became pregnant. Menstrual abnormality was the most common cause for discontinuation among the 71 subjects available for interview.

Age Distribution↗
PubMed1999

The effects of psychological stress on leukocyte subset distribution in humans: evidence of immune activation.

The aim of the present study was to examine the effects of academic examination stress on leukocyte subset distribution in university students. Thirty-eight university students had repeated blood collections for white blood cell differentiation and flow cytometric assay of lymphocytic subsets a few weeks before and after (i.e. two baseline conditions) as well as the day before a difficult academic examination (i.e. stress condition). Flow cytometry was used to determine the number of peripheral blood mononuclear cells (PBMC). In students, who were reactors to psychological stress (criterion based on changes in the Perceived Stress Scale, PSS), but not in stress non-reactors, a significant increase in the number of neutrophils, monocytes, CD8(+), CD2(+)CD26(+), and CD2(+)HLA-DR+ T cells and CD19(+) B cells, and significant reductions in the CD4(+)/CD8(+) T cell ratio were observed in the stress condition. There were significant and positive relationships between the stress-induced changes in perceived stress (PSS scale) and number of leukocytes, neutrophils, CD2(+), CD2(+)CD26(+) and CD2(+)HLADR+ T cells, and CD19(+) B cells. There were significant and negative relationships between the stress-induced changes in the CD4(+)/CD8(+) ratio and the stress-induced changes in the PSS scale. Female students taking oral contraceptives showed significantly higher stress-induced responses in number of leukocytes, neutrophils and CD19(+) B cells than male and female students without use of oral contraceptives. The results suggest that academic examination stress induces changes in the distribution of PBMC, which indicate immune activation and which are probably orchestrated by a stress-induced production of cytokines.

Adult↗
PubMed2004

Ovarian cancer and polymorphisms in the androgen and progesterone receptor genes: a HuGE review.

Ovarian cancer is the second most common gynecologic cancer among women and the second leading cause of death from gynecologic malignancy worldwide. Androgens, acting through androgen receptors (ARs), have been implicated in the disease, while progestins, acting through progesterone receptors (PGRs), may provide protection against the disease. The PGR gene contains several polymorphisms in the hormone-binding domain, three of which are in linkage disequilibrium (a complex referred to as PROGINS). PROGINS has been associated with increased risk of ovarian cancer. This association has not been found consistently, and it may be limited to women who do not use oral contraceptives. The AR gene contains a trinucleotide CAG repeat, the length of which has been inversely associated with the ability of the AR-ligand complex to transactivate androgen-responsive genes. Data on the association between the AR repeat length and ovarian cancer, both in general and among carriers of mutations in the breast cancer 1 and 2 (BRCA1/2) genes, are inconclusive. There is insufficient evidence that polymorphisms in either the PGR gene or the AR gene may be a risk factor for ovarian cancer, alone or in combination with other factors. The sensitivity, specificity, positive and negative predictive values, and clinical validity of the PROGINS and AR CAG repeat assays are unknown. No recommendations for population-based screening can be made.

Adult↗
PubMed1999

Use of oral contraceptives and endometrial cancer risk (Sweden).

OBJECTIVES: To estimate the magnitude and persistence of the protective effect of use of combined oral contraceptives (COCs) and endometrial cancer risk. METHODS: We performed a nation-wide, population-based case-control study among postmenopausal women aged 50-74 years in Sweden, which included 709 subjects with incident, histopathologically verified endometrial cancer, and 3,368 controls with an intact uterus. We used unconditional logistic regression to calculate odds ratios as estimates of relative risks. RESULTS: Use of any sort of oral contraceptive decreased risk for endometrial cancer by 30%, while progestin-only pills reduced risk more markedly. For COCs the reduction in risk was noticeable following 3 or more years of use (OR 0.5, 95% CI 0.3-0.7), and increased with duration of intake, reaching 80% lower risk after 10 years of use. The protective effect of COC use was similar for all degrees of tumor differentiation and invasiveness, and remained for at least 20 years after cessation of use. Subsequent use of hormone replacement did not modify these protective effects. CONCLUSIONS: We conclude that COC use confers a long-lasting protection against endometrial cancer risk which is particularly marked for long-term users.

Age Distribution↗
PubMed2000

Acceptability and performance of the levonorgestrel-releasing intrauterine system (Mirena) in Campinas, Brazil.

The objectives of this study were to evaluate the acceptability of the LNG-IUS Mirena(R), when offered as an additional option in a free choice context, and to evaluate the possibility of using this method in women with increased bleeding wanting an IUD and in copper IUD users requesting removal of the device for bleeding problems. A total of 256 women chose Mirena and were accepted into the study during the enrollment period. This represents 23.3% of all new acceptors of contraceptive methods in the clinic during the same period. Discontinuations were fairly evenly distributed among expulsion, bleeding changes, pain, and personal reasons. Bleeding changes were decreased bleeding, oligomenorrhea or amenorrhea. Comparing the performance in the group of women who chose the LNG-IUS as a first option with those having heavy bleeding, the only difference found was a higher expulsion rate in the group with bleeding problems. No pregnancies occurred and continuation rate was slightly over 75% in the total sample and in both groups. The characteristics of the LNG-IUS (Mirena) allow predicting that this method can effectively contribute to the increase in contraceptive options when introduced to family planning programs in Brazil.

Brazil↗
PubMed1993

Trends in breast cancer incidence in Sweden 1958-1988 by time period and birth cohort.

Statistics from the Swedish National Cancer Registry based on all 110,658 cases of invasive breast cancer during the 31-year period 1958-1988 were analysed. Age-specific incidence rates increased over successive calendar periods. The average annual increase in the age-standardised incidence rate was 1.3%, with the greatest percentage changes among the youngest age groups. During the latter half of the study period, the rates of increase tended to diminish in the youngest age groups and even reversed significantly among women from 75 years of age. In analyses using age-period-cohort models, the best fit of the cancer incidence data was found for the full model which simultaneously considered the effects of age, period and cohort. Cohort effects were found to be more important than period effects, in terms of model fit. These effects emerged as a seemingly consistent, and in a logarithmic scale, fairly linear increase in the relative risk of breast cancer incidence with a 3-fold elevation in women born in the 1950's relative to those born in the 1880's. It is concluded that the rising breast cancer incidence in Sweden is explained chiefly by birth cohort effects, which indicate persistent secular changes in largely unknown risk factors associated with life style. We could not in the present data see any clear evidence for an adverse effect of contraceptive or replacement sex steroids on breast cancer incidence.

Adult↗
PubMed1982

Two oral contraceptives, efficacy, serum proteins, and lipid metabolism. A comparative multicentre study on a triphasic and a fixed dose combination.

A triphasic, combined oral contraceptive containing 30 - 40 - 30 micrograms ethinyloestradiol (EE), and 50 - 75 - 125 micrograms levonorgestrel was compared with a fixed dose combination containing 30 micrograms EE and 150 micrograms desogestrel in a randomized multicentre trial in 193/199 women and 1 063/1 073 cycles, respectively. The duration of the trial was six months. Eleven centres in Denmark, Sweden, and Norway participated. Contraceptive reliability, bleeding control and side effects were evaluated. Influence on serum sex hormone binding globulin (SHBG) and transcortin was assayed as well as lipid metabolism. Three pregnancies occurred in the group using the triphasic regimen but none in the fixed dose regimen. Two of the three pregnancies were considered drug failures and the third a possible interaction. Possible reasons for the triphasic contraceptive failure are discussed with special reference to a British report on eight pregnancies. Bleeding control appeared to be equally good for the two preparations. However, the number of cycles with spotting, breakthrough bleeding and missed withdrawal bleeding were above the levels reported earlier on the triphasic regimen. About 80 per cent of the women completed the planned six months on either combination. Side effects were generally mild and in accordance with earlier reports on low dose oral contraceptives. Metabolically the triphasic levonorgestrel combination increased SHBG 100 per cent versus 200 per cent for the fixed desogestrel combination. Transcortin rose about 98 and 110 per cent, respectively. Both preparations induced similar changes in the levels of lipids and lipoproteins with the exception of a significant increase in the arachidonic content of cholesterol during treatment with the desogestrel-containing preparation.

Adolescent↗
PubMed2000

Determinants of thyroid volume in healthy French adults participating in the SU.VI.MAX cohort.

OBJECTIVE: To study the relative importance of determinants of thyroid volume. DESIGN: Cross-sectional study on a sample of subjects issued from the SU.VI.MAX cohort. SUBJECTS: 2987 French subjects (1713 women aged 35-60 years and 1274 men aged 45-60 years). None of them had previous or present thyroid disease. MEASUREMENTS: Thyroid volume was determined by ultrasound. Serum TSH and free thyroxine (fT4) were measured in duplicate. Urinary iodine and urinary thiocyanate were assayed in random morning urine samples. RESULTS: For both sexes, thyroid volume (ml) was positively correlated with weight, height, body mass index and body surface area (P = 0.0001) and negatively with age for females (P = 0.0009). When the urinary iodine concentration was adjusted for urinary thiocyanate concentration and their interaction, the thyroid volume was negatively correlated with urinary iodine (males P = 0.02, females P = 0.006) and positively correlated with urinary thiocyanate (males P = 0.0001, females P = 0.004). Mean thyroid volume was greater among active smokers than non-smokers (males P < 0.0001, females P = 0.0004) and was greater among former smokers than among non-smokers (males P = 0.0001, females = 0.004). Free T4 and thyroid volume were positively correlated for both sexes (P = 0. 0001). TSH was negatively correlated with thyroid volume for both groups (P = 0.0001). Female users of oral contraception (aged 35-45 years) had a smaller thyroid volume than non-users (P = 0.0009). CONCLUSIONS: The state of borderline iodine deficiency observed in France, in association with a slightly goitrogenic environment, may result in sustained stimulation of the thyroid, independently of TSH level, and is of paramount importance in the formation of goitre. Smoking may affect the thyroid, inducing marked long-lasting thyroid enlargement.

Adult↗
PubMed1995

An Italian survey on how information campaigns about AIDS have changed contraception in young couples. A sectional study and a comparison with the literature.

The purpose of the present investigation was to ascertain whether adolescent had been sensitized by the campaign against AIDS and if their behaviour regarding the use of contraception had changed accordingly. To this end 2,000 questionnaires (of which 1,554 were returned) were distributed to a population aged 13-20 years, recruited from high schools or sporting centers. The results of our survey, which started in 1992 and lasted 15 months, indicate that after the informative campaigns of 1986, contraceptive habits have changed, and at present, the method predominantly used by teenagers (60.6%) at their first sexual intercourse is the condom. The results of the present study have been compared with those of the literature regarding the years previous to our study. In our investigation, only 18.9% of the interviewed used oral contraception vs. 43.3% and 34.50% of those reported in 1980-85 and 1986-89, respectively. Particularly significant is the fact that 11.6% of teenagers used the condom in addition to oral contraception at their first sexual intercourse. In conclusion, we can assert that AIDS campaigns conducted in Italy, starting from 1986, has resulted in an increase of the use of condoms with respect to other methods of contraception.

Acquired Immunodeficiency Syndrome↗