Doses Of Ethinyl Estradiol Research Articles

Effects of two contraceptives containing drospirenone on blood pressure in normotensive women: a randomized-controlled trial.

Drospirenone (DRSP) is a progestogen derived from spironolactone with antimineralocorticoid action that seems to exert a favorable effect on blood pressure (BP); however, when associated with ethinylestradiol (EE), this effect does not seem to occur. This study aimed to assess possible differences in BP associated with the use of combined oral contraceptives containing DRSP with different doses of EE. This open-label parallel-group randomized clinical trial involved women randomized to use either 30 mcg of EE+DRSP (n=22) or 20 mcg of EE+DRSP (n=22). Daytime, nighttime, and 24-h BP were evaluated by ambulatory blood pressure monitoring at the beginning of the trial and 6 months after drug therapy. The groups were similar in terms of demographic characteristics. The mean 24-h systolic blood pressure and diastolic blood pressure (DBP) were similar between the groups before and after treatment (P>0.05). With respect to day and nighttime systolic blood pressure and DBP, no statistically significant difference was observed in BP values between the two groups either before or after treatment, except for the daytime DBP in the 30EE+DRSP group. In this group, a decrease of 2 mmHg (3%) in daytime DBP was observed after 6 months of drug therapy (P=0.04). There was no difference in BP associated with the use of combined oral contraceptives containing DRSP irrespective of the EE dose used.

A two-centre, open-label, randomised study of ovulation inhibition with three transdermal contraceptive patches, each containing different amounts of ethinyl estradiol and gestodene in healthy, young women

Here we report the findings of a two-centre, open-label, randomised, Phase IIa study designed to investigate whether an ethinyl estradiol (EE)/gestodene (GSD) patch that has been developed (referred to herein as the ‘EE/GSD patch’) reliably inhibits ovulation in comparison with patches delivering lower doses of these hormones. The study rationale was to provide justification of the doses of EE and GSD selected for the EE/GSD patch. Healthy women, aged 18–35 years, were randomised to receive treatment with either the EE/GSD patch, a ‘reduced-GSD patch’ (delivering similar amounts of EE and approximately half the amount of GSD) or a ‘reduced-EE/GSD patch’ (delivering half the amount of EE and GSD). Treatment was administered for three 28-day cycles (three × 7 patch-wearing days, plus a 7-day patch-free interval). The primary pharmacodynamic variable was the percentage of women with ovulation in at least one of Cycles 2 and/or 3, as indicated by Hoogland score. Pharmacokinetic parameters for EE and GSD were also measured. Results indicated that the EE/GSD patch effectively suppressed ovulation, while patches delivering lower doses of EE and GSD were less effective for this purpose. All three patches showed comparable tolerability.

Body mass index does not affect the efficacy or bleeding profile during use of an ultra-low-dose combined oral contraceptive

ObjectivesSafe and effective contraceptive options for obese women are becoming more important due to the obesity epidemic within the United States. This study evaluated the impact of body mass index (BMI) on efficacy, safety and bleeding patterns during use of an ultra-low-dose combined oral contraceptive (COC). Study DesignData are from a Phase 3 clinical efficacy and safety study of an ultra-low-dose COC containing 1.0-mg norethindrone acetate and 10-mcg ethinyl estradiol. Pearl Indices, adverse events and bleeding profile were calculated for BMI ranges of <25, 25–30 and >30 kg/m2. ResultsOf the 1581 participants included in the analysis, 28.3% were overweight, and 18.0% were obese. For women aged 18–45 years, the Pearl Indices were 2.49, 2.32 and 1.89 for women with a BMI <25, 25–30 and >30 kg/m2, respectively. The ultra-low dose of ethinyl estradiol did not impact scheduled bleeding or intensity of bleeding, but we observed a slight decline in amenorrhea and slight increase in unscheduled bleeding in obese women compared with other BMI categories. ConclusionsOur analysis of an ultra-low-dose COC did not find clinically important differences in contraceptive failure rates, adverse events or bleeding profile with increasing BMI. ImplicationsOur analysis of an ultra-low ethinyl estradiol dose COC did not find clinically important differences in contraceptive failure rates, adverse events or bleeding profile with increasing BMI. An ultra-low-dose COC provides another safe and effective contraceptive option for obese women.

Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus

In the United States, more than ten million women use contraceptive hormones. Ethinyl estradiol and levonorgestrel have been mainstay contraceptive hormones for the last four decades. Surprisingly, there is scant information regarding their action on the central nervous system and behavior. Intact female rats received three weeks of subcutaneous ethinyl estradiol (10 or 30μg/rat/day), levonorgestrel (20 or 60μg/rat/day), a combination of both (10/20μg/rat/day and 30/60μg/rat/day), or vehicle. Subsequently, the rats were tested in three versions of the novel object recognition test to assess learning and memory, and a battery of tests for anxiety-like behavior. Serum estradiol and ovarian weights were measured. All treatment groups exhibited low endogenous 17β-estradiol levels at the time of testing. Dose-dependent effects of drug treatment manifested in both cognitive and anxiety tests. All low dose drugs decreased anxiety-like behavior and impaired performance on novel object recognition. In contrast, the high dose ethinyl estradiol increased anxiety-like behavior and improved performance in cognitive testing. In the cell molecular analyses, low doses of all drugs induced a decrease in tyrosine hydroxylase mRNA and protein in the locus coeruleus. At the same time, low doses of ethinyl estradiol and ethinyl estradiol/levonorgestrel increased galanin protein in this structure. Consistent with the findings above, the low dose treatments of ethinyl estradiol and combination ethinyl estradiol/levonorgestrel reduced brain-derived neurotrophic factor mRNA in the hippocampus. These effects of ethinyl estradiol 10μg alone and in combination with levonorgestrel 20μg suggest a diminution of norepinephrine input into the hippocampus resulting in a decline in learning and memory.

Investigation of effects of myricetin on thyroid-gonadal axis of male rats at prepubertal period

The present study is to investigate the effects of myricetin on pubertal development and thyroid hormone concentrations in the male rat. The rats were exposed to 25 and 50mg/kg/day of myricetin by gavage from post natal day (PND) 23 to 53. Preputial separation (PPS), organ weights and biochemical and hormone analysis were investigated. PPS was significantly delayed in low dose myricetin groups. Total serum thyroxine (T4) and, triiodothyronine (T3) levels increased in 25mg/kg myricetin dose group but thyroid-stimulating hormone (TSH) level increased in 0.7μg/kg/day ethinyl estradiol dose groups. Myricetin exposure did not significantly change androgen dependent tissue weights; however myricetin exposure caused congestion, germinal cell debris and tubular atrophy in testis colloidal and tubular degeneration in thyroid gland were observed while there was germinal cell debris in epididymis. This study demonstrated that orally gavages myricetin caused adverse effects on male thyroid-gonadal axis during peripubertal period to pubertal period.

Are hormonal components of oral contraceptives associated with impaired female sexual function? A questionnaire-based online survey of medical students in Germany, Austria, and Switzerland

To investigate in a large cohort of young university women whether different progestins and different ethinyl estradiol (EE) dosages in oral hormonal contraceptives (OHCs) adversely affect sexual function. Female medical students from German, Austrian, and Swiss universities (14/1/1) completed an anonymous online questionnaire comprising the 19 Female Sexual Function Index (FSFI) questions and 17 additional questions concerning demographics, lifestyle, sexual activity, and contraceptive use. OHCs were categorized by EE dose (≤20, <20 to ≤30, and >30µg) and partially androgenic or antiandrogenic progestins. FSFI scores were analyzed by contraceptive method using descriptive statistics and standard nonparametric tests. We analyzed 2612 questionnaires submitted by respondents aged ≤30years [mean age (SD) 23.5 (2.5) years]. Of 2126 contraceptive users, 1535 (72.2%) used OHCs. Median FSFI total scores (ranges) were 28.2 (2.0-36.0) for all respondents. Median FSFI was significantly lower in non-users (24.4) versus users (28.7) of contraception (p<0.001). Stratified analysis showed that 279/486 (57.4%) respondents using no contraceptives, 563/1535 (36.7%) using OHCs, 71/227 (31.3%) using non-oral hormonal contraceptives, and 96/351 (27.4%) using non-hormonal contraceptives were at risk for female sexual dysfunction (FSFI total score <26.55). FSFI scores for the three EE dosage categories and progestin components did not differ significantly. For OHCs, the FSFI score was lower than for other contraceptives but there was no significant association with EE dose or progestins, possibly due to small sample sizes. Further research needs to clarify the role of OHCs in female sexual function.

Understanding the cognitive impact of the contraceptive estrogen Ethinyl Estradiol: Tonic and cyclic administration impairs memory, and performance correlates with basal forebrain cholinergic system integrity

Ethinyl Estradiol (EE), a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives, and is found in at least 30 different contraceptive formulations currently prescribed to women as well as hormone therapies prescribed to menopausal women. Thus, EE is prescribed clinically to women at ages ranging from puberty to reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection, modeling the daily rise and fall of serum EE levels with oral regimens. Study II also investigated the impact of low, medium and high doses of EE on the basal forebrain cholinergic system. The low and medium doses utilized here correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. We evaluate cognition using a battery of maze tasks tapping several domains of spatial learning and memory as well as basal forebrain cholinergic integrity using immunohistochemistry and unbiased stereology to estimate the number of choline acetyltransferase (ChAT)-producing cells in the medial septum and vertical/diagonal bands. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; tonic delivery of low EE, a dose that corresponds to the most popular doses used in the clinic today, did not impact cognition on any measure. Both medium and high injection doses of EE reduced the number of ChAt-immunoreactive cells in the basal forebrain, and cell population estimates in the vertical/diagonal bands negatively correlated with working memory errors.

Epidemiology of hormonal contraceptives-related venous thromboembolism.

For many years, it has been well documented that combined hormonal contraceptives increase the risk of venous thromboembolism (VTE). The third-generation pill use (desogestrel or gestodene (GSD)) is associated with an increased VTE risk as compared with second-generation (levonorgestrel) pill use. Other progestins such as drospirenone or cyproterone acetate combined with ethinyl-estradiol (EE) have been investigated. Most studies have reported a significant increased VTE risk among users of these combined oral contraceptives (COCs) when compared with users of second-generation pills. Non-oral combined hormonal contraception, such as the transdermal patch and the vaginal ring, is also available. Current data support that these routes of administration are more thrombogenic than second-generation pills. These results are consistent with the biological evidence of coagulation activation. Overall, the estrogenic potency of each hormonal contraceptive depending on both EE doses and progestin molecule explains the level of thrombotic risk. Some studies have shown a similar increased VTE risk among users of COCs containing norgestimate (NGM) as compared with users of second-generation pill. However, for this combination, biological data, based on quantitative assessment of sex hormone-binding globulin or haemostasis parameters, are not in agreement with these epidemiological results. Similarly, the VTE risk associated with low doses of EE and GSD is not biologically plausible. In conclusion, newer generation formulations of hormonal contraceptives as well as non-oral hormonal contraceptives seem to be more thrombogenic than second-generation hormonal contraceptives. Further studies are needed to conclude on the combinations containing NGM or low doses of EE associated with GSD.

Research in brief

Research in brief

Combined oral contraceptives: venous thrombosis

Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. We selected studies including healthy women taking COC with VT as outcome. The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk. All combined oral contraceptives investigated in this analysis were associated with an increased risk of venous thrombosis. The effect size depended both on the progestogen used and the dose of ethinylestradiol. Risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate and drospirenone were similar, and about 50-80% higher than with levonorgestrel. The combined oral contraceptive with the lowest possible dose of ethinylestradiol and good compliance should be prescribed-that is, 30 μg ethinylestradiol with levonorgestrel.

Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague Dawley Rats From Gestation Day 6 Through Postnatal Day 90

Bisphenol A (BPA) is a high production volume industrial chemical to which there is widespread human oral exposure. Guideline studies used to set regulatory limits detected adverse effects only at doses well above human exposures and established a no-observed-adverse-effect level (NOAEL) of 5 mg/kg body weight (bw)/day. However, many reported animal studies link BPA to potentially adverse effects on multiple organ systems at doses below the NOAEL. The primary goals of the subchronic study reported here were to identify adverse effects induced by orally (gavage) administered BPA below the NOAEL, to characterize the dose response for such effects and to determine doses for a subsequent chronic study. Sprague Dawley rat dams were dosed daily from gestation day 6 until the start of labor, and their pups were directly dosed from day 1 after birth to termination. The primary focus was on seven equally spaced BPA doses (2.5-2700 μg/kg bw/day). Also included were a naïve control, two doses of ethinyl estradiol (EE2) to demonstrate the estrogen responsiveness of the animal model, and two high BPA doses (100,000 and 300,000 μg/kg bw/day) expected from guideline studies to produce adverse effects. Clear adverse effects of BPA, including depressed gestational and postnatal body weight gain, effects on the ovary (increased cystic follicles, depleted corpora lutea, and antral follicles), and serum hormones (increased serum estradiol and prolactin and decreased progesterone), were observed only at the two high doses of BPA. BPA-induced effects partially overlapped those induced by EE2, consistent with the known weak estrogenic activity of BPA.

Pituitary and ovarian hormone activity during the 7-day hormone-free interval of various combined oral contraceptive regimens

ObjectiveThe objective was to investigate changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) during the hormone-free interval (HFI) of 6 combined oral contraceptives (COCs). DesignBlood samples were obtained from 62 women. ResultsWhen COCs were grouped by ethinyl estradiol (EE) dose, there was a significant positive mean slope for LH and FSH during the HFI for the 30- and 35 mcg-EE doses, whereas 20 showed a gradual nonsignificant slope. All E2 slopes were significant. P remained suppressed with all doses. ConclusionA more rapid rebound of gonadotropin levels is found with higher doses of EE during the HFI. ImplicationsThis study showed a more rapid rebound of pituitary hormone levels among women using higher-EE-dosage formulations, which was demonstrated by the statistically significant slope for mean LH and FSH from day 1 to day 7 of the HFI. The degree of suppression did not vary across progestin generations. It remains to be established whether women who experience side effects during their HFI may benefit from using a COC with a lower EE dose to minimize changes in endogenous pituitary hormone levels.

Effect of combined oral contraceptive (Duofem) on platelet indices in female wistar rats

This research is aimed at determining the effect of low dose combined oral contraceptive (Duofem) on platelet count and mean platelet volume. Methods: 80 female wistar rats weighing 180 to 250g were used for the study. They were divided into four groups of 20 rats each (each group containing 10 treated and 10 control rats). The treated rat received 0.66mg/kg body weight of combined oral contraceptive intragastrically, for 36, 48, 60 and 72 days in five-day cycles (four-day treatment with one-day break). Rats in control groups remain a standard chow and water. Platelet count and mean platelet volume were determined using Symex Kx21-N Haematology auto analyzer. Results: There were no significant difference in platelet count and MPV in all the treated groups compare to the control (P<0.05). Conclusion: Low dose ethinylestradiol in combined oral contraceptive (Duofem) produces no changes in platelet count and mean platelet volume.

Selective Estrogen Receptor Modulator Effects of Epimedium Extracts on Breast Cancer and Uterine Growth in Nude Mice

Epimedium is popularly used in traditional Chinese medicine to treat sexual dysfunction, menstrual irregularity, and osteoporosis. The estrogenic effects of the prenylated flavonoids of Epimedium make it an attractive alternative for hormone replacement therapy. Here, we examined the therapeutic potential of the estrogenic herb extract of Epimedium brevicornum as an alternative to hormone replacement therapy in a breast cancer mouse model. To that end, athymic and ovariectomized female nude mice were subcutaneously injected into the mammary fat pads with MCF-7 breast cancer cells, randomly grouped and fed with soy-free feeds, alone or in combination with ethinyl estradiol or different doses of the estrogenic herb extract of E. brevicornum. Our findings demonstrate that unlike ethinyl estradiol, it did not promote the growth of breast cancer xenograft volume and weight, with the highest dose showing a significant reduction in growth and ERα protein content. Moreover, the extract increased uterine weight at the lowest dose, while higher doses had no effects. Put together, our data shows for the first time that despite the estrogenic activity of E. brevicornum, its action is largely tissue specific and dose-dependent. Our data on E. brevicornum presents in vivo evidence for its selective estrogen receptor modulator effect and warrants exploration of its use as an alternative to hormone replacement therapy in menopausal women.

Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis

Objective To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives.Design Systematic review and network meta-analysis.Data sources PubMed, Embase, Web of Science,...

Clinical efficacy and metabolic impact of two different dosages of ethinyl-estradiol in association with drospirenone in normal-weight women with polycystic ovary syndrome: A randomized study

The estrogenic component of estro- progestin (EP) is responsible for a negative impact on the metabolic and lipid assessment in women with polycystic ovary syndrome (PCOS). To evaluate the risk/benefit ratio of two EP combinations, containing the same progestin (3 mg drospirenone) and a different dose of ethinyl-estradiol (EE) (20 vs 30 μg) and to compare their effects on the clinical and endocrine-metabolic parameters in normal-weight PCOS women. In this randomized pilot study, we enrolled 30 young normal-weight PCOS women. Fifteen subjects were allocated to group A (20 μg EE) and 15 PCOS subjects to group B (30 μg EE). Hirsutism score, hormonal assays, oral glucose tolerance test, euglycemic hyperinsulinemic clamp and lipid profile were performed at baseline, and after 6 and 12 months of therapy. Main outcome measures were signs of hyperandrogenism, glucose and insulin metabolism, lipid profile. Both treatment regimens induced a significant improvement in hirsutism score, testosterone, DHEAS, and SHBG levels. Androstenedione significantly dropped only in patients of Group A, while 17(OH)P only in those from Group B. Both the formulations did not significantly modify gluco-insulinemic metabolism. Total cholesterol, LDL cholesterol, and HDL cholesterol levels significantly increased in both groups. Triglycerides levels, which increased as well, resulted more markedly influenced by the formulation with 30 μg EE. In association with drospirenone, 20 μg EE results as effective as 30 μg in improving clinical and hormonal features of normal-weight PCOS women, while exhibiting a milder influence on lipidic parameters.

Investigation of the Hemostatic Effect of a Transdermal Patch Containing 0.55 mg Ethinyl Estradiol and 2.1 mg Gestodene Compared with a Monophasic Oral Contraceptive Containing 0.03 mg Ethinyl Estradiol and 0.15 mg Levonorgestrel: An Open-Label, Randomized, Crossover Study

BackgroundTransdermal delivery of contraceptives offers several advantages over combined oral contraceptives (COCs), including effective absorption and the provision of relatively constant serum concentrations. Ethinyl estradiol (EE) and the progestin gestodene are well-absorbed through the skin and, therefore, well-suited for use in a transdermal contraceptive patch.ObjectiveThe objective of this study was to investigate the impact of a once-weekly transparent, transdermal patch delivering low doses of EE and gestodene equivalent to a COC containing 0.02 mg EE and 0.06 mg gestodene on hemostasis parameters compared with a monophasic COC containing 0.03 mg EE and 0.15 mg levonorgestrel.MethodsIn this single-center, open-label, randomized, crossover study, 30 women (aged 18–35 years) received three cycles of each treatment, separated by a two-cycle washout period. The primary outcome measure was the absolute change from baseline in prothrombin fragments 1 + 2 and d-dimer.ResultsFor both treatments, prothrombin fragments 1 + 2 remained stable during the first treatment period, and increased only slightly in the second period (mean absolute change 0.025 and 0.028 nmol/L in the novel Bayer patch and COC groups, respectively). Increases in d-dimer were observed in both periods (mean absolute change 107.0 ± 147.2 ng/L for the novel Bayer patch and 113.7 ± 159.0 ng/L for the COC). There were no statistically significant treatment differences in prothrombin 1 + 2 or d-dimer (p = 0.667 and p = 0.884, respectively) and no statistically significant treatment sequence or period effects.ConclusionA COC containing 0.03 mg EE and 0.15 mg levonorgestrel and the novel Bayer patch have comparable influence on hemostatic endpoints. Both treatments were well-tolerated by subjects.

Pre-gravid oral contraceptive use and time to pregnancy: a Danish prospective cohort study

Is there an association between oral contraceptive (OC) use (age at the start of use, duration of use, ethinylestradiol dose and generation) and time to pregnancy (TTP)? Although OC use was associated with a transient delay in the return of fertility, we found no evidence that long-term OC use deleteriously affects fecundability. Studies using retrospective data on TTP have reported a short-term delay in the return of fertility after OC use. However, little is known about the long-term OC use and TTP. Data were derived from 'Snart Gravid.dk', a prospective cohort study that enrolled participants from 1 June 2007 to 31 May 2010. The final study population consisted of 3727 women. Eligible women were Danish pregnancy planners, aged 18-40 years, who completed a baseline questionnaire and bimonthly follow-up questionnaires until conception or for 12 months, whichever came first. Cohort retention was 80%. We used proportional probability regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), with adjustment for potential confounders. Compared with barrier methods, the use of OCs as the last contraception method before attempting to conceive was associated with a short-term delay in return of fertility (FR = 0.87, 95% CI: 0.79-0.96). Longer term OC use was associated with higher fecundability: compared with OC use for less than 2 years; FRs were 0.98 (95% CI: 0.83-1.15) for 2-3 years, 1.16 (95% CI: 0.98-1.37) for 4-5 years, 1.10 (95% CI: 0.93-1.29) for 6-7 years, 1.17 (95% CI: 0.99-1.38) for 8-9 years, 1.23 (95% CI: 1.04-1.46) for 10-11 years and 1.28 (95% CI: 1.07-1.53) for ≥12 years of OC use. Because this was a non-experimental study, where study volunteers provided information about their history of contraceptive use at baseline and were followed prospectively to assess their waiting times to pregnancy, there was some potential for error in the reporting of OC use and TTP. Nevertheless, participants reported data on OC use before the occurrence of pregnancy, thereby reducing the potential for systematic bias. Women who have used OCs for many years should be reassured as there was no evidence that long-term OC use has a deleterious affects on fecundability. Both short- and long-term OC users are likely to experience a transient delay in conception compared with those discontinuing barrier methods. This study was supported by the National Institute of Child Health and Human Development (R21050264) and the Danish Medical Research Council (271-07-0338). The authors declare that there are no conflicts of interest.

Contraception and Headache

Most women have used at least 1 method of contraception during their reproductive years, with the majority favoring combined oral contraceptives. Women are often concerned about the safety of their method of choice and also ask about likely effects on their pre-existing headache or migraine and restrictions on using their headache medication. While there should be no restriction to the use of combined hormonal contraceptives by women with migraine without aura, the balance of risks vs benefits for women with aura are debatable. Migraine with aura, but not migraine without aura, is associated with a twofold increased risk of ischemic stroke, although the absolute risk is very low in healthy, nonsmoking women. Although ethinylestradiol has been associated with increased risk of ischemic stroke, the risk is dose-dependent. Low-dose pills currently used are considerably safer than pills containing higher doses of ethinylestradiol but they are not risk-free. This review examines the evidence available regarding the effect that different methods of contraception have on headache and migraine and identifies strategies available to minimize risk and to manage specific triggers such as estrogen "withdrawal" headache and migraine associated with combined hormonal contraceptives. The independent risks of ischemic stroke associated with migraine and with hormonal contraceptives are reviewed, and guidelines for use of contraception by women with migraine are discussed in light of the current evidence.

The effect of triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat

Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in rats exposed to EE and TCS in the uterotrophic assay, whereas TCS alone had no effect. To further characterize this potentiation, we evaluated the effect of co-exposure with lower doses of EE that are comparable to the concentrations in hormone replacement regimens and began to assess the mechanisms by which this potentiation occurs. Changes in uterine weight, epithelial cell growth, and estrogen-sensitive gene expression were assessed. TCS expectedly enhanced the uterotrophic response to EE, however at significantly lower doses of EE. Similarly, TCS increased the EE-induced stimulation of epithelial cell height following cotreatment. Cotreatment also enhanced the estrogen-induced change in gene expression, which was reversed with an ER antagonist. Furthermore, the TCS-induced potentiation was independent of ER activation, as no effects were observed in the ER TA assay.