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PubMed1992

Clinical experience and pharmacological effects of an oral contraceptive containing 20 micrograms oestrogen.

The performance of a new low-dose oral contraceptive (Mercilon) containing only 20 micrograms ethinyloestradiol combined with 150 micrograms desogestrel is reviewed. Eight multicentre clinical trials have been completed and provide information on 10,672 women studied over 73,477 cycles. The high efficacy of Mercilon was indicated by the finding that only 10 pregnancies were reported; nine of these occurred in women who omitted to take Mercilon on a number of days and only one in a woman who took all the tablets according to instructions. Cycle control was good; as with all oral contraceptives, the incidence of breakthrough bleeding and spotting was highest in the first treatment cycle and by the sixth treatment cycle the values were usually < 5% and < 7%. More than 80% of women had regular cycles. Side effects were few, the most common being headache, nausea and breast tenderness with incidences in the sixth treatment cycle of less than 2%, 6% and 6%, respectively. There were no significant changes in body weight or blood pressure. Pharmacodynamic investigations showed no adverse effects. Only 1 of 5 studies found an increased response to a glucose tolerance test compared to the pretreatment test. In 8 of 10 studies, serum HDL-C concentrations increased on treatment and this was associated with increases in apoproteins A1 and A2. Serum triglyceride levels also increased but no change occurred in serum cholesterol or LDL-C levels. Haematological factors were assessed in 8 studies and only minor changes were observed. Serum binding protein (SHBG, CBG, caeruloplasmin) concentrations increased and serum androgen levels decreased. Measurements of blood FSH, LH, oestradiol and progesterone indicated adequate inhibition of ovulation. Mercilon is the only oral contraceptive containing 20 micrograms ethinyloestradiol to have high efficacy, to have no adverse pharmacodynamic effects and, importantly, to produce an acceptable bleeding pattern not significantly different from that of oral contraceptives with a higher content of ethinyloestradiol.

Adult↗
PubMed1996

The role of thromboxane A2 in increased whole blood platelet aggregation in oral contraceptive users.

Epidemiological studies have shown that oral contraceptives increase the risk of thromboembolic disease in susceptible women however the mechanisms involved are unclear. We investigated whole blood platelet aggregation in 44 women randomly allocated to 6 cycles of treatment with either gestodene (75ug) or desogestrel (150ug) combined with 30ug ethinyloestradiol (EE). The in vitro effects of aspirin and a thromboxane synthetase inhibitor, dazmegrel (UK38485) were also investigated. Oral contraceptive treatment caused a significant increase in collagen, arachidonic acid (AA) and ADP induced whole blood platelet aggregation. PAF induced aggregation was unchanged. There were no significant differences in the levels of platelet aggregation between the desogestrel/30ugEE and gestodene/30ugEE groups. In vitro incubation of platelets with aspirin and dazmegrel prevented the oral contraceptive induced increase in platelet aggregation. Dazmegrel caused an on treatment decrease in PAF induced aggregation in the desogestrel/30ugEE but not the gestodene/30ugEE group. The results of this study indicate that the use of oral contraceptives is associated with an increase in platelet aggregation that is mediated by changes in thromboxane/prostacyclin ratio(TXA2/PGI2). Although no significant differences were found between the two different progestogen combinations, the effects of dazmegrel on PAF induced aggregation suggest a possible difference in the progestogen modifying effects of desogestrel and gestodene which is unmasked when thromboxane synthetase is inhibited.

Adolescent↗
PubMed1993

Contraceptive choices for behaviorally disordered women.

Women with psychologic disturbances of depression, anxiety, or thought disorganization pose a special management problem when providing a safe and effective means of contraception. The difficulty is compounded by the fact that many mentally disturbed women also abuse drugs. Therefore, providing contraception to the many types of behaviorally disturbed women requires the full range of contraceptive options and protection from sexually transmitted diseases. When compliance can be assured, oral contraceptives are the preferred method. When compliance is questionable, progestin implants or injections may be tried. However, progestin-only preparations are associated with several side effects, including worsening of mood in depressive patients.

Contraception↗
PubMed1994

The response of the pituitary-ovarian axis to pulsatile administration of gonadotropin-releasing hormone in long-term oral contraceptive users.

OBJECTIVE: Our purpose was to differentiate between pituitary and hypothalamic feedback effects of oral contraceptives. STUDY DESIGN: Twenty micrograms of gonadotropin-releasing hormone was administered intravenously at 90-minute intervals for 4 days to 14 long-term users of a combined oral contraceptive (30 micrograms of ethinyl estradiol and 150 micrograms of levonorgestrel), starting at different moments in the pill cycle. On the fourth day of administration the pulsatile release of luteinizing hormone was determined by blood sampling every 10 minutes for 6 hours. The sensitivity of the pituitary was determined before, during, and after treatment with gonadotropin-releasing hormone by a 100 micrograms gonadotropin-releasing hormone challenge test. On each sampling day serum estradiol, progesterone, and prolactin levels were measured, and ovarian ultrasonography was performed. RESULTS: After 4 days of pulsatile gonadotropin-releasing hormone administration every exogenous gonadotropin-releasing hormone bolus was followed by an endogenous luteinizing hormone pulse of high amplitude (median 3.30 U/L). Both serum luteinizing hormone and follicle-stimulating hormone levels increased significantly (p < 0.001). The increase in follicle-stimulating hormone levels was accompanied by an increase in serum estradiol (p < 0.01). The luteinizing hormone response to a 100 micrograms bolus of gonadotropin-releasing hormone decreased during gonadotropin-releasing hormone treatment (p < 0.01), whereas the follicle-stimulating hormone response did not change. CONCLUSION: Pituitary sensitivity is not impaired during oral contraceptive use, suggesting that oral contraceptives exert their negative feedback effects predominantly at the hypothalamic level.

Adult↗
PubMed1999

Endometrial histology during use of a low-dose estrogen-desogestrel oral contraceptive with a reduced hormone-free interval.

The object of the study was to determine the effect of a new low-dose ethinyl estradiol-desogestrel oral contraceptive on endometrial histology. The oral contraceptive regimen contained fixed doses of ethinyl estradiol (20 micrograms) and desogestrel (150 micrograms) for days 1-21, placebo on days 22 and 23, and ethinyl estradiol alone (10 micrograms) on days 24-28. Endometrial histology was assessed in tissue samples obtained during treatment cycles 13 and 14. All endometrial samples were sent to a central laboratory for processing and evaluation. No endometrial hyperplasia or metaplasia was found in the endometrial biopsy specimens obtained during cycles 13 and 14 in a subset of 12 women participating in a multicenter efficacy and safety study. These results suggest that this oral contraceptive regimen, which includes 5 days of unopposed ethinyl estradiol, is not associated with endometrial hyperplasia or metaplasia. The endometrial histologic findings observed in this study were similar to those observed during the use of 21-day combination oral contraceptive regimens.

Adult↗
PubMed1978

Comparison of the effects of contraceptive steroid formulations containing two doses of estrogen on pituitary function.

A pituitary stimulation test with gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH) was undertaken to determine (1) whether pituitary responses to GnRH vary in individual women taking oral contraceptive steroids over time, (2) whether a less suppressive pituitary gonadotropin effect is produced by formulations containing less than 50 microgram of estrogen, and (3) to obtain more information concerning prolactin secretion in users of oral contraceptive steroids. The same subjects who had had a suppressed luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response 6 to 9 months previously also had a suppressed response, indicating that this effect persists over time. Contraceptive formulations containing less than 50 microgram of estrogen have a lesser suppressive effect on LH release than do formulations containing 50 microgram of estrogen or more. The basal prolactin (PRL) response as well as the maximal PRL response to TRH were found to be significantly greater in subjects using oral contraceptives than in the control subjects. However, no difference in PRL response was found between the subjects using low or high doses of estrogen fomulations.

Adult↗
PubMed1999

Importance of levonorgestrel dose in oral contraceptives for effects on coagulation.

Combined oral contraceptives show clear differences in effect on the tissue factor-initiated coagulation test of activated protein C resistance, which is dependent on the presence and dosage of levonorgestrel. Multiphasic levonorgestrol oral contraceptives differ from monophasic contraceptives and resemble third-generation contraceptives.

Activated Protein C Resistance↗
PubMed1998

Condom use by Hispanic and African-American adolescent girls who use hormonal contraception.

PURPOSE: The purpose of the present study was to examine condom use by teens who use hormonal contraceptives [i.e., Depo-Provera, Norplant, or oral contraceptives (OCs)]. METHODS: This is a cross-sectional study of 578 Hispanic and African-American female adolescents between the ages of 12 and 21 years who came to a reproductive health care clinic. A paper-and-pencil questionnaire which addressed sexual behaviors, sexual history, and communication about sexuality was distributed to adolescent girls attending the clinic. Several important analyses included only those who had been sexually active in the last 4 weeks (n = 452). RESULTS: Adolescents who used OCs [odds ratio (OR) 1.7], long-acting agents (i.e., Depo-Provera or Norplant) (OR 1.6), were less likely to have used a condom in the last 4 weeks than teens whose only method of birth control was condoms. Only those teens who had previously been diagnosed with a sexually transmitted disease (STD) were more likely to have used a condom (OR .67 for not using a condom). Overall, condom use by teens in this sample was low, with only 19% reporting that they "always" use a condom, and 47% of the teens who had been sexually active in the last 4 weeks reporting that they had not used a condom at least once during that time. CONCLUSIONS: This study provides data which suggest that adolescent girls who use hormonal contraceptives are less likely to use condoms than other sexually active teens. Therefore, when prescribing hormonal contraception to prevent pregnancy, clinicians must provide appropriate counseling to mitigate against the potential to increase the risk of STDs.

Adolescent↗
PubMed1999

Patterns of contraception in UK women with Type 1 diabetes mellitus: a GP database study.

AIM: To establish the patterns of contraceptive prescribing for women aged 15-49 with Type 1 diabetes mellitus (DM) and compare them with the patterns in women without diabetes. METHODS: This was a cross-sectional study using a UK primary care database. RESULTS: Nine hundred and thirty-eight women with a diagnosis of Type 1 DM were identified. A comparison group of women aged 15-49 without diabetes (n = 10000) were randomly selected from the database. Twenty-five per cent of the women with diabetes and 32% without diabetes were prescribed a hormonal contraceptive in 1994. Women with Type 1 DM were more likely to be prescribed a combined oral contraceptive than a progestogen only pill (POP) but were 2.12 (95% CI 1.65-2.72) times more likely to be prescribed a POP than women without diabetes and were less likely to be prescribed a combined pill - odds ratio 0.53 (95% CI 0.44-0.64). The pregnancy rate in women with Type 1 DM over the age of 25 years was lower than for women without diabetes. Women under 25 years with Type 1 DM seemed more likely to record a pregnancy. CONCLUSIONS: Differences between women with Type 1 DM and those without diabetes highlight the variation in the way that GPs and patients evaluate the risks and benefits when deciding on contraception.

Adolescent↗
PubMed1998

Contraceptive use in a rural general practice.

All women aged 20-49 in a general practice were sent a questionnaire about their reproductive health, and 72% responded. 78% of respondents were using a method of fertility control. More than a quarter of women were obtaining their contraceptive supplies (condoms especially) from non-medical outlets. Knowledge of the existence of emergency contraception was high (83%). The general practitioner (GP) was the most popular source of contraceptive supplies for those aged under 40 years and more than four-fifths of women said that they would rather turn to their GP than to other sources for future contraceptive advice.

Adult↗
PubMed1992

Hormone levels and anogenital swelling of female chimpanzees as a function of estrogen dosage in a combined oral contraceptive.

A combined oral contraceptive consisting of ethinyl estradiol (EE2) in three dosages (50, 100, and 400 micrograms) and norethindrone (0.5 mg) was given to female chimpanzees to determine the effect on endogenous sex hormone levels and anogenital swelling. Serum levels of EE2 increased with increasing dosages of EE2, estradiol decreased, and luteinizing hormone, progesterone and testosterone were maintained at approximately midfollicular phase levels. Urinary levels of EE2 glucuronide increased with the increasing dosages of EE2, whereas estrone and pregnanediol glucuronide were essentially undetectable. The cyclic increase in female anogenital swelling was abolished when the norethindrone was combined with 50 micrograms of EE2 and relatively constant and low levels of swelling were recorded. Relatively constant but successively higher levels of swelling were recorded when the norethindrone was combined with the higher dosages of EE2. These effects of oral contraceptives on female genital tissues are relevant to our laboratory studies of sexual behavior in chimpanzees given oral contraceptives and could also have implications for women taking oral contraceptives.

Anal Canal↗
PubMedDate not supplied

Fertility and contraceptive adoption and discontinuation in rural Kenya.

After a long period of slow progress, the recent uptake of contraceptive use in Kenya has been dramatic. This report describes adoption of a method and method switching and discontinuation among a cohort of married women aged 25-34 in two contrasting rural areas. A retrospective "fertility diary" completed by each woman provided information on spousal separation, reproductive status, and contraceptive use over a period of 46-48 months. Contraceptive prevalence rose rapidly over the period in both areas, with significant net adoption of injectables in both areas and of IUDs in one only. Method discontinuation was concentrated among users of pills, barrier methods, and "natural" methods, and only one-third of all discontinuations were voluntary. The wide differences between the two rural areas in contraceptive prevalence were not totally reflected in recent fertility levels, and the contribution of other proximate determinants of fertility, particularly postpartum amenorrhea and spousal separation, are discussed.

Adult↗
PubMed1992

Serum bile acids and the bile acid tolerance test under oral contraception.

Oral contraceptives (OC) have lithogenic properties as shown by a rise in biliary cholesterol secretion and cholesterol saturation index. Since we noted not only a rise in saturation index, but also a reduction in chenodeoxycholate (CDC) pool size and an increase in cholate (C) pool size during oral contraception (30 micrograms ethinylestradiol + 150 micrograms desogestrel), we investigated the endogenous bile acid tolerance test as a potential predictor of this effect on bile acid pool sizes using a cholecystokinin infusion of 55 min duration (1.2 U.kg-1.hr-1) as stimulus of the enterohepatic bile acid circulation in 12 healthy females before and during oral contraception for 3-5 months. Serum C and CDC conjugates were measured at 5-10 min intervals over a period of 150 min and analysed by two specific RIA's. Although no significant correlations between the serum CDC and C measurements and CDC and C pool sizes were found, a significant reduction of nearly 40% for both serum peak levels and the integrated area under the serum curve of CDC conjugates during oral contraception, but not of C conjugates was found. The reduction in serum levels of CDC conjugates during OC using the present model is best explained by both a reduction in CDC pool size and more efficient hepatic uptake of CDC conjugates (consisting of considerably more taurine conjugates during OC use), as well as by an intestinal effect on bile acid absorption under OC.

Adult↗
PubMed1979

[Primary malignant tumour of the liver associated with the ingestion of oral contraceptives (author's transl)].

A 42-year-old woman, who had been taking oral contraceptives for 10 years, developed a primary carcinoma of the liver. The diagnosis was made by biopsy under laparoscopic control. Twenty one cases have already been reported in the literature. The aetiological role of contraceptives in the development of generally benign (approximately 200 published cases) and sometime malignant hepatic lesions, has not been definitely proven. The regression of certain benign tumours when contraceptives are stopped is the essential argument. In some patients, the association of benign lesions and of hepatic carcinoma suggests a single pathogenesis. The early recognition of such lesions justifies their being sought routinely in patients taking oral contraceptives (palpation of the liver, questioning concerning pain in the hepatic region). A national register will be required in order to determine their exact prevalence.

Adult↗
PubMed1979

[Oral contraception with an associated therapeutic action using a progestational method at two levels (author's transl)].

The authors, basing their work on their experience over many years with a large number of cases, are proposing that synthetic progestational agents can be used at two levels of dosage, to serve as contraception and as a treatment when a progestational agent is used and is followed by micro-dosages of another progestational substance. So they prescribe at the end a of cycle following different dosages for different lengths of time, the same (or a different) progestational agent to treat breast troubles or menstrual troubles which are often intricate, particularly near the menopause. The authors in this way can compare by trials the effects of this method as compared with those of a progestational contraceptive administered in high doses and prescribed in an interrupted way and the prescription of micro-dosages of progestational agents that are taken "non-stop" which is now a classical method of treatment. This new method of contraception using progestational agents at two levels of dosage is particularly useful in patients who cannot take oestrogens because of metabolic upsets or because of tumours and who have reacted badly to the two other methods mentioned. If the dose, which can be calculated thanks to our knowledge of the hormonal background of the patient, is altered good therapeutic results and a relatively sure method of contraception is evolved without metabolic risks for the patient. This association of two progestational levels of dosage seems to be indicated particularly in women of over 40 years of age.

Adult↗
PubMed1984

Oral contraception for the adolescent.

Sexual activity among unmarried women aged 15-19 living in metropolitan areas rose 66% in the 1970s. Additionally, teenage pregnancies average 1.2 million yearly. However, based largely upon a 25% increase in contraceptive use, the pregnancy rate among teenagers declined 15% between 1973 and 1978. The data on the use of various contraceptive methods by women aged 15-19 show the Pill to be the first choice (1,539,000). Oral contraceptives are safest for young women, with rare risks of serious cardiovascular complications and no deaths reported from cardiovascular disease for women under 18. In contrast, the mortality risk associated with childbirth for this age group is 11.1 deaths per 100,000 live births. Noncontraceptive health benefits associated with oral contraceptive use, such as a 50% decrease in the risk of developing pelvic inflammatory disease, resulting in a protective effect on future fertility, is an excellent rationale for prescribing the Pill for young women who are sexually active. The pill of choice should be one with low doses of both estrogen and progestin yet doses high enough to minimize break-through bleeding, for such bleeding is the most frequent cause of discontinuation. Adolescents require careful screening for contraindications to Pill use prior to initial prescription plus frequent follow-up and monitoring so as to minimize side effects and maximize compliance and continuation of use.

Adolescent↗
PubMed1980

[Spontaneous mesenteric venous thrombosis, a rare complication of oral contraceptives (author's transl)].

Spontaneous mesenteric venous thrombosis without recognizable aetiology is a rare condition. Only 10 cases have been described in world literature as a complication of oral contraceptives. The case report is presented of a 51 year-old married woman who had been taking oral contraceptives for 7 years. After abdominal pain for weeks segmental mesenteric venous thrombosis with a gangrenous small bowel loop was diagnosed. The gangrenous small bowel loop was treated by resection. Subsequently after discontinuance of contraceptive medication she was symptom free. The problems of diagnosis are pointed out and it is suggested that immediate discontinuance of oral contraceptives in women with unexplained abdominal pain might prevent gangrene of small bowel.

Contraceptives, Oral↗
PubMed1999

Risk of venous thrombosis with use of current low-dose oral contraceptives is not explained by diagnostic suspicion and referral bias.

BACKGROUND: The magnitude of the relative risk of venous thrombosis caused by low-dose oral contraceptive use is still debated because previous studies might have been affected by diagnostic suspicion and referral bias. METHODS: We conducted a case-control study in which the effect of diagnostic suspicion and referral bias was excluded. The study was performed in 2 diagnostic centers to which patients with clinically suspected deep vein thrombosis of the leg were referred. History of oral contraceptive use was obtained before objective testing for thrombosis. Young females with an objective diagnosis of deep vein thrombosis were considered case patients, and those who were referred with the same clinical suspicion but who had no thrombosis served as control subjects. Participants were seen between September 1, 1982, and October 18, 1995: 185 consecutive patients and 591 controls aged 15 to 49 years with a first episode of venous thrombosis and without malignant neoplasms, pregnancy, or known inherited clotting defects. RESULTS: The overall odds ratio for oral contraceptive use was 3.2 (95% confidence interval [CI], 2.3-4.5); after adjustment for age, family history of venous thrombosis, calendar time, and center, the odds ratio was 3.9 (95% CI, 2.6-5.7). In the idiopathic group (120 patients and 413 controls, excluding recent surgery, trauma, or immobilization), the odds ratio for oral contraceptive use was 3.8 (95% CI, 2.5-5.9); after adjustment, the odds ratio was 5.0 (95% CI, 3.1-8.2). CONCLUSIONS: In this study, in which patients and controls were subj ect to the same referral and diagnostic procedures, we found similar relative risk estimates for oral contraceptive use as in previous studies. We conclude that diagnostic suspicion and referral bias did not play an important role in previous studies and that the risk of venous thrombosis with use of current brands of oral contraceptives still exists.

Adolescent↗