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One of the most used low-dose EP associations is ethinylestradiol 20 mcg plus levonorgestrel 100 mcg in monophasic regimen (EE20/LNG100). This review summarizes clinical pharmacology, cycle control, and effects on lipid and glucose metabolism, coagulation, body weight/body composition, acne, and sexuality of EE20/LNG100.

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3 РОЗЫ,3 ГЕРБЕРЫ,2 РОМАШКИ,1 КУСТОВАЯ ХРИЗАНТЕМА,2 СОЛИДАГО И САЛАЛ Table of Contents Alerts To receive news and publication updates for International Journal of Endocrinology, enter your email address in the box below.
This is an open access article distributed under thewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The different pharmacological composition of EPs is responsible for different clinical effects.
Introduction Estroprogestins EPs are pharmaceutical compounds containing estrogen and progestin.
вот ссылка progestogen compounds can be classified as first- e.
Estrogen can decrease follicle-stimulating hormone and luteinizing hormone, even if firstly it was added to progestin to reduce or avoid symptoms which follow ovarian blockage and to improve cycle control.
The roles of progestin are to decrease luteinizing hormone levels through a negative feedback mechanism, to thicken cervical mucus, and to decrease the endometrial proliferation after estrogen mitotic stimulation.
Different EPs can show different clinical effects and different risk profile according to their specific pharmacological composition i.
Selection of Evidence Key papers for inclusion in this paper were collected by browsing MEDLINE using pertinent keywords e.
Ethinylestradiol EE is the most used estrogen in EPs.
It is more potent than estradiol, due to the presence of the 17 α-ethinyl group, which can prevent the oxidation of 17 β-hydroxy group Figure.
The 17 α-ethinyl group can be oxidized, with the formation of an intermediate element which inhibits the cytochrome P450 isoenzymes e.
Figure 1: Structural formula of the 17 β-estradiol derivative ethinylestradiol EE.
After oral administration, besides oxidative metabolism, EE undergoes glucuronidation and sulphatation by specific enzymes e.
The reduction of enzymatic inactivation results in the dose-dependent hepatic modulation of a 5 of activity, such as protein synthesis.
Hepatic metabolism yields EE conjugated and metabolites circulating into blood vessels.
Of the oral dose, about 1% circulates as EE and is bound by 98.
Enterohepatic recirculation is important in the EE pharmacokinetics PKand the metabolic passages are based on hydroxylation at C2 and C4, with formation of catechol estrogens, which can be metabolized into 2- and 4-methoxy-EE.
EE metabolites are excreted by feces and urine.
Levonorgestrel LNG Figure по этому сообщению rapidly absorbed when administered orally.
The bioavailability is about 100%, with no relevant first-pass effect, and the peak plasma-level is obtained between 1 and 3 hours after oral administration.
LNG is bound to SHGB by 47.
Figure 2: Structural formula of the progestin levonorgestrel.
LNG has a marked progestin activity, no mineralocorticoid or glucocorticoid effects, and an antiestrogenic action at hepatic level.
LNG and its metabolites glucurono- and sulphoconjugated 5 excreted by urine and feces.
These results suggest the important antigonadotropic effect exerted by LNG.
Serum maximum concentration was reached, for both EE and LNG, between 1 and 2 hours after single and repeated administration on a daily basis.
The serum concentration of EE increased after multiple daily administrations, with about twofold accumulation.
In addition, serum concentrations of LNG increased following 5 administrations, with steady-state being reached after 11 days since the intake of the first tablet.
By comparing the AUC 0—24 values after the first and the last tablet, LNG showed an accumulation by a factor of 3 during a cycle of treatment.
The PKs for steady state of LNG were similar after the end of the first and the third cycle of administration, thus indicating no further accumulation over a long-term intake.
The clearance and distribution volume of LNG decreased and half-life increased after multiple daily administration.
Mean levels of LH, FSH, 17beta-estradiol, and progesterone were suppressed during treatment, with a normal ovulation restored in posttreatment cycles; these results were confirmed also by an ultrasound examination.
Interestingly, even if 5 subject values were reported occasionally outside the normal reference range, there were no subjects with relevant alterations in the lipid pattern, and the changes in lipid profile were similar to those observed with other low-dose EPs.
Lipid changes were no longer significant at 24 months.
Interestingly, the wide majority of lipid values remained within the normal reference range.
Another study, by Endrikat et al.
Also the study by Skouby et al.
No significant differences between the treatment groups for any подробнее на этой странице the carbohydrate metabolism variables were disclosed.
Even if not confirmed by several studies, the perception of this problem remains in clinical practice among patients and, sometimes, among clinicians.
A study by Hite et al.
More interestingly, in terms of body composition, the combination had no impact on fat mass, fat-free mass, total body water, intracellular water, and extracellular water versus baseline and versus lack of treatment Figure.
There was an incidence % of the cycles; total number of cycles valid for analysis: 7508 of 4.
The mean length of withdrawal bleeding was 4.
The mean bleeding intensity was generally reported as mild.
With regard to the most common side effects considered possibly drug related, headache was reported in 14% 5 the subjects, metrorrhagia in 8%, dysmenorrhea in 7%, and nausea in 7%; moreover, abdominal pain was pointed out in 4%, breast pain in 4%, emotional lability in 3%, acne in 3%, depression in 2%, amenorrhea in 2%, and vaginal moniliasis in 2%.
No relevant cardiovascular events were reported during the study.
The results from по ссылке two preparations were compared with a standard preparation containing EE 30 mcg + LNG 150 mcg.
In this study, while cycle control was good with the two combinations with LNG, less favorable profile was obtained with the EP containing NET.
Comprehensively, spotting was present in 9.
Moreover, the incidence of IMB decreased from 18.
Amenorrhea was reported more frequently in the first cycles of observation and then decreased over time.
The incidence over the study 13 cycles was 7.
Dysmenorrhea improved during this study, the incidence being highest at baseline and decreasing to 2.
Figure 4: Analysis of cycle control parameters: percentage of subjects with no IMB, S episodes, or BTB.
In the study by Coney et al.
No clinically relevant changes in laboratory findings, blood pressure, and body weight were reported.
Factor X increased significantly from baseline during cycles 3 and 6 and cycle 12whereas a significant decrease in factor VII concentration was seen at cycle 3.
In particular, the coagulation activation marker thrombin-antithrombin TAT complex did not change significantly during читать далее study.
At cycles 3, 6, and 12 total protein S and antithrombin antigen levels decreased from baseline.
Protein S activity decreased from baseline at cycles 3 and cycle 6 but was no longer different from baseline at cycle 12.
Antithrombin activity or free protein 5 antigen did not show any significant changes from baseline during the />Plasminogen antigen and activity levels increased significantly during the observation, while fibrinogen was not significantly modified.
D-dimer increased significantly at cycles 3, 6, and 12, with a smaller increase at cycle 12.
Altogether, only sporadic individual values Amouage Dia for Men парфюмерная вода 100 ml тестер (муж) antigen and activity were outside the normal reference range, and no subject showed clinically important variation in hemostatic profile.
The increase of plasminogen antigen and activity were seen in this study as a manifestation of increased fibrinolysis, and the general changes in haemostatic parameters were regarded as consistent with those of other low-dose oral EPs by the authors.
Also D-dimer did not show any significant change between baseline and cycle 13.
Plasminogen a profibrinolytic marker was increased by 31.
On the other hand, some procoagulatory markers were increased fibrinogen +16.
Overall, hemostatic parameters showed minor changes, all within the normal range of variation, thus indicating only a new and different источник between coagulation and fibrinolysis.
The median concentration of prothrombin fragments 1 + 2 considered as a marker for changes in coagulation did not change significantly versus baseline, while D-dimer a marker of fibrinolysis did so.
Moreover, the changes of all hemostatic variables were all within the normal ranges.
It was suggested by some reports since the 1990s that EPs containing second-generation progestins e.
For instance, in 5 6-year cohort study, the following odds rations for VTE were reported: gestodene versus levonorgestrel, 1.
A possible explanation for this lower VTE risk with 5 EPs containing LNG is that LNG exerts a stronger antiestrogenic effect at hepatic level than the other progestins for which a greater risk is reported, according to the concept that estrogenic component of EPs is the main reason for VTE risk in a dose-dependent manner.
On the other 5, other studies report different results.
In any case, patients with a personal or family history of venous thromboembolism should not take combined EPs.
With respect to the risk of myocardial infarction and thrombotic stroke arterial thromboembolism linked to the use of EPs, it is well known that this risk is very rare among EPs users, and a recent work by Lidegaard et al.
Moreover, a study by Coenen et al.
EP, by blocking the ovulation, decreases further ovarian production of androgens.
Interestingly, in a study by Coney et 5 />This combination по этому сообщению a mild or no significant effect from a metabolic i.
Conflict of Interests The authors declare that there is no conflict of interests regarding the publication of this paper.
Acknowledgments Editorial assistance for the preparation of this paper was provided by Luisa Granziero, PhD, and Luca Giacomelli, PhD, on behalf of Content Ed Net; this assistance was посетить страницу источник by Pfizer.
Van Hylckama Vlieg, F.

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