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Oral contraceptives and panic disorder.

BACKGROUND: There are no published reports of an association between triphasic oral contraceptives and the development of panic disorder. METHOD: The authors describe two cases in which the use of triphasic oral contraceptives in women appear to have precipitated panic disorder. Treatment with the triphasic oral contraceptives was stopped and the patients were followed for 2 years. RESULTS: Both subjects had rapid and total resolution of their panic disorder symptoms following cessation of triphasic oral contraceptive medications. CONCLUSION: Triphasic oral contraceptives in some predisposed women may lead to precipitation of panic disorder.

Adult↗

Conception delay after oral contraceptive use: the effect of estrogen dose.

A significant delay was observed in conception among 248 former oral contraceptive (OC) users compared with women discontinuing other methods of contraception (n = 1,365). The mean time to conception was 5.88 cycles (95% confidence interval [CI] 5.38, 6.38) for former OC users and 3.64 cycles (95% CI 3.49, 3.79) after other contraceptives. Women discontinuing OCs with higher doses of estrogen (greater than or equal to 50 micrograms) had greater conception delays than those on lower estrogen doses who, in turn, had longer delays than other method users. Oral contraceptive use was associated with significant reductions in conception for each of the first six cycles after discontinuation. This study provides further evidence for a direct effect of oral contraception on delayed conception, suggests that the delay lasts longer than previously thought, and finds that the probability of conception after OC discontinuation depends on the estrogen dose of the OC.

Adolescent↗

[Residual function in the ovary during low-dose oral contraceptive treatment].

Development in oral contraceptives during the past 20 years has involved continued reduction in the total quantity of hormone and alterations in the oestrogen/gestagen ratio and in the steroid structure for the gestagens employed. These changes have been undertaken primarily to counteract metabolic side effects and influence on the haemostatic system. Inhibition of the mechanism of ovulation is, however, also dependent on the steroid dosage and in cases where low-dosage oral contraception is employed, ultrasound investigations have demonstrated a risk of continued ripening of follicles during treatment. Correspondingly, hormone measurements during the pill-free week have demonstrated increase in the follicle-stimulating hormone, luteinizing hormone and the oestrogen concentration. The permissible margin of error in employing oral contraception has therefore diminished and is more dependent on the dosage and potency, particularly of gestagens. As the critical phase for failure of treatment is the first week of intake of oral contraceptives, it is important that treatment is commenced at the correct time not only at the commencement of treatment but also after the pill-free periods. If a pill is forgotten during the preovulatory oestrogen level and two pills are then taken, this may be interpreted by the organism as a positive oestrogen feed-back and, theoretically, this may result in increased gonadotropin production and thus further increase the risk of ovulation. In cases with the risk of malabsorption on account of gastro-intestinal disease and in cases with interaction with other medicaments, employment of alternative forms of contraception is recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraceptives, Oral, Combined↗

Contraceptive practices of patients referred for colposcopy with an abnormal cervical smear.

This study examined the contraceptive practices of 100 patients referred for colposcopy because of an abnormal cervical smear. At presentation 49% were using oral contraception but 94% had taken the pill at some time. Eight of the 10 patients using barrier methods were relying on condoms: in at least seven of the eight cases an abnormal cervical smear preceded condom usage. Thus, the method of contraception used when cervical neoplasia develops may differ from the method used when the patient presents for colposcopy. Although consistent with previous studies suggesting that the incidence of cervical neoplasia is increased in women using oral contraception, the risk of neoplasia is more likely to be explained by the degree of exposure of the cervix to an infectious carcinogen or to the immunosuppressive effects of seminal plasma. We suggest that future studies of the epidemiology and natural history of cervical neoplasia should include a detailed contraceptive history.

Adolescent↗

Contraceptive use and fertility in Paraguay, 1987.

In 1987, 38 percent of married Paraguayan women aged 15-44 were practicing contraception, with oral contraceptives being the most prevalent method. Fertility rates for the population were at corresponding levels, with an overall fertility rate of 5.4 births per woman. Fertility has not changed substantially for the nation as a whole since 1979, and contraceptive use has increased by only 6 percentage points. Findings from the present study are consistent with the lack of a public sector family planning program in the country. Pharmacies are the principal source of contraceptives in the country. Twenty-two percent of all women and one-third of married women are at risk of having an unplanned pregnancy. The greatest impact on contraceptive use can be made if new and continued program efforts focus n the interior of the Oriental region of the country.

Adolescent↗

Evaluation of contraceptive history data in the Republic of Korea.

The consistency of retrospective and current status data on contraceptive use from a series of national fertility surveys carried out during the 1970s in Korea is investigated. Aggregate consistency is examined among random samples from the same cohort or cohorts of women interviewed in each survey. The results indicate that estimates of trends in contraceptive use from a retrospective history in one survey, or from cross-sectional estimates in a series of surveys, can each yield misleading findings. Data from the 1974 Korean National Fertility Survey (KNFS) appear to be more reliable than those from other surveys, possibly because an interval-by-interval contraceptive history was used, explicit definitions of contraceptive methods were given prior to taking the contraceptive history, and the KNFS involved longer interviewer training and, perhaps, less time pressure during interviews.

Adolescent↗

Clinical and metabolic considerations of long-term oral contraceptive use.

Newer lower dose formulations are associated with an improved cardiovascular disease risk marker profile, which supports their use for longer periods and among older women. Epidemiologic studies of the newer formulations are limited. Without clinical information, an evaluation of the effects of more recent formulations on metabolic risk markers for cardiovascular disease is useful. In a large cross-sectional study, a reduction in the progestin dose and use of alternative progestins substantially reduced the proportion of oral contraceptive users with values associated with an increased risk of cardiovascular disease. No progression in metabolic changes was found by analyzing the effect of the duration of oral contraceptive use. The user's age interacted positively with the oral contraceptive--induced increase in serum triglyceride levels, but there was no interaction of age with the oral contraceptive's effect on oral glucose tolerance, glucose and insulin responses, low-density lipoprotein cholesterol, or high-density lipoprotein subfraction 2 cholesterol levels.

Age Factors↗

A randomized, double-blind study of two combined and two progestogen-only oral contraceptives.

A randomized double-blind study of two combined oral contraceptives and two progestogen-only oral contraceptives was conducted using the same protocol at WHO Collaborating Centres for Clinical Research in Human Reproduction in Bombay and Ljubljana of the 518 women admitted to the trial, 123 received mestranol 50 micrograms + norethisterone 1mg (MES 50 + NET 1); 137 received ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms (EE 30 + LNG 150); 130 received norethisterone 350 micrograms/NET 350); and 128 received levonorgestrel 30 micrograms (LNG 30). At one year, between 52.6 and 61.0 percent of those recruited had discontinued oral contraceptive use for all reasons, and by two years, between 70.5 and 76.5 percent had discontinued the treatment. These rates did not differ between the four treatment groups. However, discontinuation rates for all medical reasons at one and two years, and at two years pregnancy rates and discontinuation rates for bleeding disturbances, were significantly lower in the EE/LNG preparation. The groups receiving the MES/NET, LNG and NET had similar pregnancy rates, discontinuation rates for all medical reasons and all bleeding disturbances. There were two ectopic pregnancies among the 22 pregnancies in the progestogen-only groups. Discontinuation because of headache, dizziness and other central nervous system symptoms were significantly more common in those receiving MES/NET compared to EE/LNG. In contrast, discontinuation for gastro-intestinal disturbances were significantly higher in the EE/LNG combined preparation. Bleeding disturbances in the first few cycles tended to be higher in NET than in the LNG group. The data suggest that greater consideration be given to the benefits and risks of including progestogen-only oral contraceptives in the family planning programmes of some countries.

Adolescent↗

Non-availability of the IUD and contraceptive choice.

The Copper 7 and Lippes Loop IUD are no longer distributed in the United States, and the cost of the Progestasert precludes usage in many family planning clinics. The impact of the loss of this widely used contraceptive method was assessed in a pilot study at the UCLA Family Planning Clinic. The clients who would have selected an IUD at the time of their clinic visit between March and December of 1986 instead chose oral contraceptive pills (55%) or barrier methods (45%) but their level of dissatisfaction with the methods they received was significantly greater than that of all other contraceptors, and this led to their subsequent selection of another method which, in the majority (66%), was of lower efficacy than the IUD. There were two unplanned conceptions amongst twenty women who would have chosen an IUD, both due to non-compliance with oral contraceptive pills; and at the time of survey in March 1987, no clients had opted for sterilization. Women who no longer have their choice of the IUD represent a high risk for contraceptive dissatisfaction and failure, but have not made precipitous decisions to undergo permanent sterilization.

Adolescent↗

A multicenter clinical trial of a progestin-only oral contraceptive in lactating women.

A non-comparative study of a progestin-only oral contraceptive (POC) containing 75 micrograms norgestrel was conducted at 22 sites in 14 countries. This study was designed to evaluate safety, contraceptive efficacy, and the overall acceptability of a POC in breastfeeding women. A total of 4,088 women entered the study over a three-year period and 29,399 woman-months of experience was gathered. Women had follow-up visits at 2, 6, and 11 months after admission. Headaches and vaginal discharge were the medical complaints most commonly reported by women, both prior to and after admission. Menstrual problems were reported by 59% of the women after admission. Of the 3,714 women who returned for at least one follow-up visit, 1,101 (29.6%) discontinued through month 11. The 11-month total discontinuation percentage, including those lost to follow-up (25.3%) was 51.6%. The most common reason given for discontinuation was a woman's desire for a change in contraceptive method. Only 4.9% discontinued pill use for menstrual problems, a percentage far below those generally reported for POCs. Twenty-nine unintended pregnancies occurred through 11 months giving a gross cumulative life table rate of 1.2 per 100 women (Pearl Index = 1.4). The POC appears to be a safe, effective and acceptable contraceptive option for postpartum breastfeeding women.

Adolescent↗

Low-dose oral contraceptives lower plasma levels of apolipoprotein E.

Three different oral contraceptive preparations were studied before and after a 3 month treatment period with respect to their effects on plasma lipoprotein parameters. A total of 58 healthy women requesting oral contraception were randomly assigned to three groups. Each woman received either monophasic preparations containing ethinylestradiol and desogestrel (M-DG); ethinylestradiol and gestodene (M-GD); or a triphasic preparation of ethinylestradiol and levonorgestrel (T-LN). As has been reported in other studies, the concentrations of total plasma cholesterol and apolipoproteins B and A-IV did not change significantly in any group. HDL cholesterol, triglycerides, apolipoproteins A-I and A-II increased or tended to increase. Despite the effects of the three hormone preparations on these lipoprotein parameters, however, each led to a highly significant decrease in apolipoprotein E plasma levels. Considering the recently reported observations that oral contraceptives increase the hepatic uptake of cholesterol-rich remnants, this decrease in apo-E plasma levels may in women that take oral contraceptives be directly correlated with increased hepatic lipoprotein metabolism.

Adolescent↗

A comparative randomized trial on the impact of two low-dose oral contraceptives on ovarian activity, cervical permeability, and endometrial receptivity.

In a double-blind randomized study, the suppression of ovarian activity and anti-conceptive effects on the cervix and endometrium were assessed during administration of two low-dose monophasic oral contraceptives (20 micrograms ethinyl estradiol [EE], 500 micrograms norethisterone--Eve 20 [Grünenthal, Aachen, Germany]; 20 micrograms EE, 150 micrograms desogestrel --Lovelle [Organon, Munich, Germany]). One hundred eighteen healthy women (ages: 18-35 years) were studied in 10 investigation centers during medication with either Eve 20 (n = 59) or Lovelle (n = 59). During three treatment cycles, ovarian activity was evaluated by sonographic determination of follicle-like structures (FLS) and by simultaneous assessment of serum endocrine profiles (gonadotropins LH and FSH, ovarian steroids estradiol [E2] and progesterone [P]). While on either treatment, no ovarian activity (as judged by no FLS and/or reduced sex steroid levels) was found in 90.8% (Eve 20) and 97.2% (Lovelle) of all investigated cycles. Follicular activity or cyst formation were detected in 18 of 173 cycles (Eve 20) and in 5 of 175 cycles (Lovelle), respectively. Gonadotropin levels were suppressed (LH < 6 IU/L, FSH < 8 IU/L) in most treatment cycles (Eve 20 76.6% vs. Lovelle: 84.8%). Serum E2 concentrations exceeding 0.1 nmol/L indicated residual follicular activity in 19.3% (Eve 20) versus 12.2% (Lovelle) of all cycles. An estimated by serum P levels over 5 nmol/L, ovulation had presumably occurred in 4.1% (Eve 20) versus 2.9% (Lovelle) of treatment cycles. However, when the sonographical and endocrinological data were combined, no ovulation was documented in any pill cycle. The quality and quantity of the cervical mucus was found to be minimal in the majority of women. Moreover, the endometrial layer was determined to be low by ultrasound during most pill cycles, indicating equally strong suppressive effects on endometrial receptivity by the two contraceptives. These observations suggest that ovarian activity is suppressed in the majority of cycles during use of low-dose contraceptives. This effect may mainly be medicated by pronounced suppression of serum gonadotropin levels. Strong anti-conceptive effects of these formulations on both cervical permeability and endometrial receptivity are additional factors ensuring the contraceptive efficacy of these formulations.

Adult↗

Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy.

PURPOSE: Because enzyme-inducing antiepileptic drugs (AEDs) can affect pharmacokinetics of oral contraceptives and thereby cause contraceptive failure, the potential effect of topiramate, a new AED, on the pharmacokinetics of the combination oral contraceptive norethindrone/ethinyl estradiol was evaluated. METHODS: Twelve women receiving stable valproic acid (VPA) monotherapy for epilepsy received a combination norethindrone 1.0 mg/ethinyl estradiol 35-microg tablet daily for 21 days followed by seven daily doses of inert tablets for four 28-day cycles. After a baseline cycle (cycle 1), topiramate 100, 200, and 400 mg every 12 h was administered in cycles 2 through 4, respectively. Serial blood samples were obtained on day 20 of each cycle and were analyzed for norethindrone, ethinyl estradiol, and progesterone by using validated radioimmunoassay methods. RESULTS: Compared with cycle 1, none of the norethindrone pharmacokinetic parameters changed significantly in the presence of topiramate, 100-400 mg every 12 h. Individual patient serum progesterone concentrations measured during each cycle were at or close to the limit of quantification with no apparent differences among cycles. However, mean area under the concentration-versus-time curve over the 24-h period (AUC(0-24)) values for ethinyl estradiol were 18-30% lower in cycles 2 through 4 compared with cycle 1 (p < or = 0.05 for all pairs), whereas mean oral serum clearance (CL/F) values were 14.7-33.0% higher (p < or = 0.05 for cycles 2 and 4 vs. cycle 1). Mean time of peak concentration (T(max)) values determined during topiramate therapy were not significantly different from those at baseline. CONCLUSIONS: When prescribing an oral contraceptive for patients receiving topiramate, clinicians should consider initial therapy with an agent containing > or = 35 microg of ethinyl estradiol.

Adult↗

Review of newer contraceptive agents.

Advances in contraceptive technology have made birth control more effective, convenient, and safe. We review the newer products and some under development, including the latest oral contraceptives, injectable progesterone, subdermal progestin implants, progesterone-releasing IUDs, emergency contraception, and male contraception.

Absorbable Implants↗

A low-dose triphasic oral contraceptive.

Controlled clinical investigations of a three-phase, low-dose oral contraceptive combination of levonorgestrel and ethinyl estradiol were conducted at 17 sites in the United States and 60 sites in the United Kingdom. A day 1 start in cycle one with no backup contraception was used. A total of 3546 female volunteers participated in 35,036 cycles. Medication was missed in 2688 (7.7%) cycles. Nine pregnancies were reported for an uncorrected use-effectiveness rate of 0.33 per 100 woman-years. Cycle control was excellent, bleeding irregularities were minimal, and the incidence of side effects was very low. No clinically significant variations in blood pressure means or weight means were observed. Carbohydrate and lipid metabolism studies were limited to 6 months and showed minimal alterations. Subject compliance with the preparation was excellent. It is concluded that this triphasic oral contraceptive with its varying ratios of levonorgestrel and ethinyl estradiol is an effective, predictable, and well-tolerated combination oral contraceptive.

Adolescent↗

The effect of oral contraceptives on mononuclear cell cholesteryl ester hydrolase activity.

The influence of sex steroids on mononuclear cell cholesteryl ester hydrolase (CEH) activity in premenopausal women and women on combined estrogen-progestin oral contraceptives has been studied. In addition, plasma and mononuclear cell cholesterol and esters were measured along with plasma estrogen and progesterone levels. Mononuclear cell CEH activity in control women is highest on Day 20 of their menstrual cycle. The control women had significantly higher CEH activities than women on oral contraceptives. Plasma esters were higher in the oral contraceptive group. However, in mononuclear cells, free cholesterol but not cholesteryl esters were higher in women on oral contraceptives.

Adult↗

Fibrinopeptide A plasma levels during low-estrogen oral contraceptive treatment.

In a group of healthy women taking oral contraceptives containing 30 micrograms ethinylestradiol combined with two different progestogens (desogestrel and gestoden), Fibrinopeptide A (FPA) plasma levels were evaluated both before and after 3, 6 and 9 months of therapy. FPA levels, which represent an index of thrombin action in vivo, were also determined in untreated subjects during the follicular and the luteal phases of the menstrual cycle. While no modifications of FPA levels were found during the menstrual cycle, a significant increase of this peptide was observed during oral contraceptive treatment. These data suggest that low-dose oral contraceptives, by enhancing the rate of conversion of fibrinogen to fibrin by thrombin, increase the risk of venous thrombosis. Since some mechanisms which compete with the thrombin activity are also increased by oral contraceptives, the significance of this change in the induction of thrombosis cannot be completely clarified.

Adolescent↗

Effects of two oral contraceptive combinations, 0.125 mg desogestrel + 0.050 mg ethinylestradiol and 0.125 mg levonorgestrel + 0.050 mg ethinylestradiol on the adrenal function of healthy female volunteers.

The effects of the oral contraceptive combinations of 0.125 mg desogestrel + 0.050 mg ethinylestradiol (EE), and of 0.125 mg levonorgestrel + 0.050 mg EE on serum cortisol and the urinary excretion of 17-oxogenic steroids and free cortisol were studied in 16 healthy females. Adrenal responsiveness was studied by the metyrapone test. Both contraceptive combinations increased (P less than 0.001) serum cortisol concentrations but the rhythmic fluctuation at different times of the day remained unchanged. The urinary excretion of 17-oxogenic steroids was lower (P less than 0.01) during treatment than before or after treatment with both contraceptive combinations. The metyrapone test showed normal adrenal responsiveness during the treatment cycles. The urinary excretion of free cortisol was unchanged when desogestrel + EE was used, but increased (P less than 0.01) during treatment with levonorgestrel + EE. However, even then, the urinary free cortisol was within the normal range of the population. All the test results of hormone determinations normalized soon after finishing the contraceptive treatments. It is suggested that the abnormalities seen were due to an increased serum binding capacity of cortisol induced by EE and not a sign of pathological changes in adrenal function. No major differences in the biological effects of the two combinations tested were seen.

17-Hydroxycorticosteroids↗