Thrombotic microangiopathy caused by oral contraceptives in a kidney transplant recipient.

Thrombotic microangiopathy (TMA) after kidney transplantation has various aetiologies, including acute antibody-mediated rejection, bacterial or viral infection and immunosuppressive drugs, particularly calcineurin inhibitors. We present the case of a 28-year-old woman who developed TMA 30 months after the transplantation of an ABO-incompatible kidney from a living unrelated donor. The patient developed a sudden onset of allograft renal dysfunction and became uremic. She was transferred to our institution from a community hospital with strongly suspected acute allograft rejection. Intensive treatments for both T- and B-cell mediated acute rejection, including steroid pulse therapy, double-filtration plasmapheresis, antithymocyte globulin (1.5 mg/kg × 14 days) and rituximab (100 mg), were initiated during haemodialysis. However, her renal allograft function did not improve. Histopathological analysis 8 days after the treatment indicated TMA, despite the absence of apparent acute T-cell- or acute antibody-mediated rejection. There were no symptoms of infectious diseases, such as intestinal haemorrhagic colitis or viral infection. We concluded that the use of oral contraceptives, which had been initiated 3 weeks before TMA onset for the treatment of irregular vaginal bleeding, was the aetiologic agent.

Effects of chronic treatment with cyclooxygenase inhibitor, indomethacin on oral contraceptive-induced high blood pressure in female rats.

The present study sought to investigate the effects of prostaglandins synthesis inhibition with indomethacin on blood pressure, heart rate, cardiac weight, plasma electrolytes and cardiovascular responses to arterial baroreceptor stimulation in Oral contraceptive (OC) treated female Sprague-Dawley rats. Oral administration of synthetic oestrogen, ethinyl oestradiol in combination with progestogen, norgestrel for ten weeks significantly increased blood pressure and cardiac weight compared with those of the control rats. Concomitant treatment with indomethacin significantly abrogated increase in blood pressure but did not affect the increase in cardiac weight induced by OC. Heart rate, plasma sodium and potassium concentrations were not affected by OC and/or indomethacin treatment. OC treatment did not alter sympathetic-mediated pressor and tachycardiac responses caused by bilateral carotid baroreceptors unloading. However, these responses were significantly attenuated by indomethacin treatment. These results demonstrated that rat model of OC-induced high blood pressure developed cardiac hypertrophy that is not associated with altered sympathetic-mediated cardiovascular responses to arterial baroreceptor stimulation. The finding that indomethacin prevented OC-induced high blood pressure, but not associated cardiac hypertrophy implies that synthesis of prostaglandins may be an important determinant of OC-induced hypertension, while associated cardiac hypertrophy may not be pressure overload-dependent.

A clinical study of transdermal contraceptive patch in Thai adolescence women.

OBJECTIVE: To study cycle control, compliance and safety of a transdermal contraceptive patch in adolescent Thai women. MATERIAL AND METHOD: Fifty-eight healthy women were assigned to receive 3 cycles of contraceptive patch (ethinyl estradiol 20 microg and norelgestromin 150 microg/day). All participants aged 16-20 years were invited to participate from the family planning clinic at King Chulalongkorn Memorial Hospital. Data were collected on adverse effects, perceived advantages and disadvantages, body weight, blood pressure, patch detachments and compliance. Data were analyzed using mean, percentage and student's t-test. RESULTS: The participants' average age was 19.4 years, height 158.8 cm, weight 51.8 kg, BMI 20.8 Kg/m2. The most location of patch application was the abdomen and the most adverse event was breast tenderness (31.0%) followed by application site reaction, nausea vomiting and headache respectively. The breast symptom was mild in severity. The participants reported decrease in dysmenorrhea and shorter duration of bleeding. There were no significant changes in body weight and blood pressure. The improvement of their facial acne was reported. There were no pregnancies during use and the adhesion of the contraceptive patch is excellent. Partial patch detachment was reported in only 6.9%. No completed patch detachment was found. CONCLUSION: The present study found an overall positive impression of a new transdermal contraceptive patch. The good compliance and few side effects were demonstrated. The adhesive patch contraceptive was excellent.

Contraceptive, cerebral vein thrombosis and choked discs.

PURPOSE: To raise awareness of the importance of prompt and appropriate imaging in patients presenting with signs and symptoms suggestive of idiopathic intracranial hypertension. METHODS: Case report with diagnostic tests and discussion of management options. RESULTS: A 15-year-old girl presenting with bilateral optic disc swelling was noted to have extensive thrombosis of intracerebral venous sinuses with the clot extending along the internal jugular vein as inferior as the root of the neck demonstrable on magnetic resonance venography. CONCLUSIONS: Ophthalmologists should be vigilant in obtaining appropriate imaging in cases of optic disc swelling.

[Hormonal contraception and cervix of the uterus pathology].

The effect of hormonal contraception on cervix of the uterus of young nullipara women with ectopia was investigated. Cohort study was carried out by using simple blind method. By means of statistical data manipulation correlation between the application of hormonal contraceptives and changes of colposcopy pictures in the zone of pathology was displayed. Excluton showed low percent anomalous colpscopy picture in pathology zone. Excluton was declared as medicine of choice for nullipara women with ectopia. Still it is necessary to conduct a strong dynamic control of cervix of the uterus (colposcopy and pap-smear test) in order to avoid complications.

Activation of cardiac renin-angiotensin system and plasminogen activator inhibitor-1 gene expressions in oral contraceptive-induced cardiometabolic disorder.

CONTEXT: Clinical studies have shown that combined oral contraceptive (COC) use is associated with cardiometabolic disturbances. Elevated renin-angiotensin system (RAS) and plasminogen activator inhibitor-1 (PAI-1) have also been implicated in the development of cardiometabolic events. OBJECTIVE: To determine the effect of COC treatment on cardiac RAS and PAI-1 gene expressions, and whether the effect is circulating aldosterone or corticosterone dependent. METHODS: Female rats were treated (p.o.) with olive oil (vehicle) or COC (1.0 µg ethinylestradiol and 10.0 µg norgestrel) daily for six weeks. RESULTS: COC treatment led to increases in blood pressure, HOMA-IR, Ace1 mRNA, Atr1 mRNA, Pai1 mRNA, cardiac PAI-1, plasma PAI-1, C-reactive protein, uric acid, insulin and corticosterone. COC treatment also led to dyslipidemia, decreased glucose tolerance and plasma 17ß-estradiol. CONCLUSION: These results demonstrates that hypertension and insulin resistance induced by COC is associated with increased cardiac RAS and PAI-1 gene expression, which is likely to be through corticosterone-dependent but not aldosterone-dependent mechanism.

Long-term safety of an extended-cycle oral contraceptive (Seasonale): a 2-year multicenter open-label extension trial.

OBJECTIVE: The purpose of this study was to assess the long-term safety of Seasonale, 91-day extended-cycle oral contraceptive (OC). STUDY DESIGN: Following completion of a 1-year Phase 3 multicenter trial, patients from selected centers were invited to participate in this 2-year extension trial. In this open-label study all participants received the 91-day extended-regimen OC, Seasonale. RESULTS: There were 189 study participants enrolled from 27 sites. Patient exposure included 1130 completed 91-day cycles. Overall rates of study discontinuation and the incidence of adverse events were similar to the earlier Phase 3 clinical trial. Seasonale was well tolerated and the number of reported bleeding and/or spotting days reported diminished during the course of the study. CONCLUSION: This study confirms the findings from the previous clinical trial and demonstrates that Seasonale is a safe and effective therapy for long-term use.

[Ectopia of cervix of the uterus and hormonal contraception].

The aim of the study was the investigation of impact of different hormonal contraceptive drugs on cervix of uterus of young nullipara women with ectopia. Cytologic smears were examined using Pappanikolau method. Cohort study was carried out by using simple blind method. The data were treated by statistics packet (SPSS). The results displayed correlation between taking the hormonal contraceptives Rigevidon and Marvelon and in transformation of ectopia into micro glandular hyperplasia, which did not occur in taking medicine Exluton. Drug Exluton is recommended for young nullipara women with ectopia to exclude micro glandular hyperplasia. In case of prescribing monophase contraceptives for young nullipara women with ectopia cytological control of endo- and exo-cervix is recommended.

Concomitant administration of lumiracoxib and a triphasic oral contraceptive does not affect contraceptive activity or pharmacokinetic profile.

This study evaluated the effect of lumiracoxib on the pharmacokinetics and pharmacodynamics of ethinyl estradiol (EE) and levonorgestrel (LN) in Triphasil-28 (a triphasic oral contraceptive). Females stabilized on Triphasil-28 continued on Triphasil-28 alone for another month (Treatment Period 1), then also received lumiracoxib (400 mg daily) or placebo for 28 days each (Periods 2 and 3) in a double-blind crossover design. Plasma pharmacokinetic profiles were assessed on Day 21 of Periods 2 and 3. Progesterone and plasma sex hormone binding globulin (SHBG) concentrations were measured before and 2 hours after Triphasil-28 administration on Day 21 of all three treatment periods. Lumiracoxib had no significant effect on EE or LN pharmacokinetics or on progesterone or SHBG concentrations, indicating that anovulation and Triphasil-28 effectiveness was maintained. Adverse events were similar for lumiracoxib and placebo. Therefore, no clinically important consequences are anticipated if lumiracoxib is coadministered with oral contraceptives containing EE or LN.

A comparative and pooled analysis of the safety and tolerability of the contraceptive patch (Ortho Evra/Evra).

OBJECTIVE: To review the safety and tolerability of the contraceptive patch (Ortho Evra/Evra) versus a standard oral contraceptive (Triphasil) and to present the pooled safety and tolerability of the patch across three pivotal studies. DESIGN: Three open-label, contraceptive studies of up to 13 treatment cycles. SETTING: 183 centers. PATIENT(S): Comparative study (812 patch, 605 oral contraceptive); pooled analysis (3,330 patch). INTERVENTION(S): The patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle; the oral contraceptive was dosed according to the U.S. physician package insert. MAIN OUTCOME MEASURE(S): Adverse events, laboratory tests, vital signs, and body weight. RESULT(S): The incidence of most events was similar between the patch and oral contraceptive groups, with the exception of a higher incidence of application site reactions, breast discomfort (cycles 1 and 2 only), and dysmenorrhea in the patch group. Pooled analysis demonstrated that most application site reactions (92%) and breast symptoms (86%) were mild or moderate in severity, and <2% of participants discontinued the patch because of either event. Only 7 (0.2%) participants experienced a serious adverse event classified as possibly, probably, or likely related to the patch. The mean change in body weight from baseline to the end of treatment was an increase of 0.3 kg. CONCLUSION(S): Overall, the contraceptive patch is well tolerated and has a side effect profile similar to an established oral contraceptive.

Ectopic gestation following emergency contraceptive pill administration.

Emergency contraceptive pill prescription following rape is common. We report a case of ectopic gestation after emergency contraceptive pill failure and review the literature on this rare complication. A 26-year-old woman with a normal menstrual period 2 weeks before was administered an emergency contraceptive pill 8 hours after a single sexual assault. The assault was her only sexual activity before and after the emergency contraceptive pill use. Forty-six days following the assault, the patient presented with a right ampullary tubal pregnancy of 59 days gestation and underwent emergent surgery for ectopic gestation. To prevent a delay in the diagnosis of ectopic pregnancy, we recommend that providers and the package insert advise women, that ectopic gestation can occur with emergency contraceptive pill failure.

Biphasic versus triphasic oral contraceptives for contraception.

Side effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. A suggested disadvantage of biphasic oral contraceptive pills compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We examined this potential disadvantage by conducting a systematic review comparing biphasic oral contraceptives with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation because of side effects. We included randomized, controlled trials comparing any biphasic oral contraceptive with any triphasic oral contraceptive when used to prevent pregnancy. Only two trials of limited quality met our inclusion criteria. Larranaga compared two biphasic and one triphasic pills, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation because of medical problems was similar with all three pills. Percival-Smith compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and another triphasic pill containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic pill. The available evidence is limited and of poor quality; the internal validity of these trials is questionable. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. This suggests that the choice of progestin may be more important that the phasic regimen in determining bleeding patterns.

Impact of oral contraceptive use on APC-resistance: a prospective, randomized clinical trial with three low-dose preparations.

The evaluation of the study was of the impact of oral contraceptive (OC) use on activated protein C (APC-resistance). Eight hundred eighteen young fertile women were screened for a study designed to compare three different marketed OC preparations. The women could have used either other oral contraceptive preparations before switching to the study medications (switchers) or were not using hormonal contraceptives (new starters) before the study began. Prior to study drug intake and during treatment, APC-resistance was determined with three different tests. Forty-one of 809 women evaluated (5.07%) carried the Factor V Leiden mutation. Twenty-two further participants (2.72%) had a positive screening test, but did not provide samples for the confirmatory mutation test. Two women with homozygous Factor V Leiden mutations and 39 women with heterozygous mutations were identified. The homozygous carriers were identified in all three of the screening tests employed, whereas none of the tests detected all 39 heterozygotes. In the pretreatment screening tests, previous OC users (switchers) had slightly lower APC ratios than the women using non-hormonal birth control methods (starters). During treatment the difference between starters and switchers was no longer apparent, but the APC ratio values of the screening tests slightly increased for both. The homozygous carriers were not treated. Differences in APC-resistance between users of the three different oral contraceptive preparations were not found. In conclusion, laboratory screening for APC-resistance using Coatest APC, ProC Global, or ProC APC-FV-Leiden clearly identifies homozygous mutant carriers. However, with regard to heterozygous mutant carriers, the sensitivity and specificity of the tests, especially during OC intake, is limited. The results of APC screening tests should have, at present, no impact on contraceptive counseling because the predictive value for thromboembolic risk of the test results and even the mutant status is low.

Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20.

This multicenter study compared the contraceptive efficacy, cycle control, and safety of a new triphasic norgestimate (180/215/250 microg)/ethinyl estradiol 25 microg regimen (Ortho Tri-Cyclen Lo) (n = 1,723) with that of norethindrone acetate 1 mg/ethinyl estradiol 20 microg (Loestrin Fe 1/20) (n = 1,171). Healthy women were treated for up to 13 cycles. Demographics were similar between regimens. Contraceptive efficacy was comparable for Ortho Tri-Cyclen Lo and Loestrin Fe 1/20. The overall and method failure probabilities of pregnancy through 13 cycles were 1.9% and 1.5%, respectively, with Ortho Tri-Cyclen Lo and 2.6% and 2.4%, respectively, with Loestrin Fe 1/20. Breakthrough bleeding and spotting was reported by a significantly lower percentage of participants in the Ortho Tri-Cyclen Lo group compared with the Loestrin Fe 1/20 group. At representative Cycles 1, 3, 6, 9, and 13, breakthrough bleeding and spotting rates were 16.3, 11.5, 10.3, 7.9, and 7.7%, respectively, in the Ortho Tri-Cyclen Lo group and 34.9, 22.9, 22.2, 15.9, and 13.1%, respectively, in the Loestrin Fe 1/20 group. Compliance and safety data were similar for the two regimens.

Rapid improvement of icterus and pruritus by the oral administration of colestimide in two cases of drug-induced hepatitis.

We report two cases of drug-induced hepatitis refractory to therapy of ursodeoxycholic acid and prednisolone, who were relieved of icterus and pruritus immediately by the oral administration of colestimide. Their liver dysfunction was not improved, by withdrawal of causative drugs or by treatment with prednisolone and ursodeoxycholic acid. Colestimide (3.0 g/day), a strong basic anion-exchange resin, was orally taken before breakfast and evening meal, leading to rapid and complete relief of icterus and pruritus. These cases suggested that colestimide would be useful for patients with cholestasis in drug-induced hepatitis, because this agent has few side effects and it is easy to take.

Nutritional and psychological status of young women after a short-term use of a triphasic contraceptive steroid preparation.

The present study was aimed to assess the psychological status of young healthy women after the administration of a triphasic contraceptive steroid preparation for six complete menstrual cycles. Subjects had never used oral contraceptives (OC) and had neither a familial history of depression nor psychological disturbances. OC-induced psychological disturbances were interpreted for years as evidence of pyridoxine (vitamin B6) deficiency. Other nutritional deficiencies, namely in cobalamin, folate and iron, can disturb the functioning of the central nervous system. In addition, a deficiency of any of these nutrients can lead to several anemia-induced symptoms that are highly susceptible to influence the psychological status. For ample evidence, nutritional status was then evaluated in parallel to psychological testing. Blood iron and vitamin levels of interest were found to be adequate and could not have biased the response to a psychological test (MMPI). This study showed that a 6-month Triphasil treatment did not modify significantly the psychological status of subjects. To our knowledge, this is the first psychological study on young never OC-users taking an identical triphasic contraceptive steroid preparation to investigate early psychological side-effects due to OC, at a similar time of the menstrual cycle, when nutritional status was also evaluated.

Oral contraceptive-induced central retinal artery occlusion.

Oral contraceptives are known to have ocular complications including retinal vascular lesions. The authors report a case of central retinal artery occlusion in a young woman on oral contraceptives.

Peliosis hepatis revealed by biliary colic in a patient with oral contraceptive use.

Peliosis hepatis is a rare condition associated with a variety of diseases and drugs. We report a patient who developed peliosis hepatis while taking oral contraceptives. Three months after withdrawal of this oral contraceptive, reduction in size of these lesions was observed.