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![Total body water (TBW) showed no significant differences between EP-treated and control subjects or within each group [25].](publication/269186608/figure/fig3/AS:1088601433616385@1636554215166/Total-body-water-TBW-showed-no-significant-differences-between-EP-treated-and-control.jpg)
Total body water (TBW) showed no significant differences between EP-treated and control subjects or within each group [25].
Source publication
Estroprogestins (EPs) are combinations of estrogen and progestin with several actions on women's health. The different pharmacological composition of EPs is responsible for different clinical effects. One of the most used low-dose EP associations is ethinylestradiol 20 mcg plus levonorgestrel 100 mcg in monophasic regimen (EE20/LNG100). This review...
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Background:
Although most low-dose combined oral contraceptives (COCs) include 7-day hormone-free intervals (HFIs), these COCs could incompletely suppress ovarian activity.
Objectives:
To review the impact of HFIs on ovarian suppression and tolerability, and evaluate the utility of COCs without traditional 7-day HFIs.
Search strategy:
PubMed w...
Alfred O Mueck1, Harald Seeger1, Xiangyan Ruan2 1Department of Endocrinology and Menopause, University Women's Hospital of Tuebingen, Tuebingen, Germany; 2Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China Abstract: No placebo-controlled studies concerning hormonal contr...
Citations
... Эмоциональная лабильность, снижение когнитивной функции, повышенная утомляемость вследствие мышечного гипотонуса нередко становятся причиной снижения либидо и минеральной плотности костной ткани [22]. За счет проандрогенной активности ЛНГ относят к прогестагенам выбора для пациенток с выраженным астено-депрессивным синдромом, сексуальной дисфункцией и остеопорозом в период климактерия [6,23]. ...
... ЛНГ корригирует эстроген-индуцированные клинически значимые изменения соотношений факторов свертывания крови и снижает резистентность к активированному протеину С, не препятствуя защитным эффектам эстрогенов на сосудистую стенку [6,7]. По результатам рандомизированных плацебо-контролируемых исследований МГТ с ЛНГ у женщин в постменопаузе статистически значимо сопровождалась улучшением липидного профиля и не оказывала значительного влияния на параметры коагулограммы и активность фибринолиза [23,26]. ...
Female hypogonadism, as a result of natural or induced shutdown of ovarian function, is a multifaceted problem. A variety of clinical manifestations motivates women to consult doctors of various specialties and solve health problems without focusing on the underlying cause. The financial and economic component of the problem due to a violation of the quality of life of women and a sharp decrease in their ability to work requires the inclusion of the most effective method of treatment. There are a number of MHT regimens and combinations that allow differentiated selection of the drug, taking into account the woman’s health status and her concomitant diseases. The range of biological effects and risks depends on the type and dose of the hormonal drug, duration of use, route of administration, and time of initiation of MHT. As a component of MHT, bioidentical estrogens and gestagens are used, different in their vector of influence, pharmacodynamic and pharmacokinetic profile. The article is devoted to cyclic biphasic MHT using a combination of 17β-estradiol (2 mg) and levonorgestrel (0.15 mg). The experience of using the drug will be presented in the form of a review and our own clinical cases from everyday medical practice.
... In female patients of childbearing potential, oral hormonal contraceptives (OCs) are anticipated to be administered concomitantly with abrocitinib. The metabolism of such OC steroids such as ethinyl estradiol (EE) and levonorgestrel (LN) is mediated by the CYP3A system and Phase 2 enzymes such as uridine diphospho-glucuronosyltransferase (UGT) and sulfotransferase (SULT) [12,13]. Induction of the metabolizing systems involved in metabolism of OCs may result in clinically important reduction in the systemic exposure of these hormonal contraceptives, leading to failure of contraception. ...
Abrocitinib is an oral small-molecule Janus kinase (JAK)-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis. In vitro studies indicated that abrocitinib is a weak time-dependent inhibitor of cytochrome P450 (CYP) 2C19/3A and a weak inducer of CYP1A2/2B6/2C19/3A. To assess the potential effect of abrocitinib on concomitant medications, drug-drug interaction (DDI) studies were conducted for abrocitinib with sensitive probe substrates of these CYP enzymes. The impact of abrocitinib on hormonal oral contraceptives (ethinyl estradiol and levonorgestrel), as substrates of CYP3A and important concomitant medications for female patients, was also evaluated.
Three Phase 1 DDI studies were performed to assess the impact of abrocitinib 200 mg once daily (QD) on the probe substrates of: (1) 1A2 (caffeine), 2B6 (efavirenz) and 2C19 (omeprazole) in a cocktail study; (2) 3A (midazolam); and (3) 3A (oral contraceptives).
After multiple doses of abrocitinib 200 mg QD, there is a lack of effect on the pharmacokinetics of midazolam, efavirenz and contraceptives. Abrocitinib increased the area under the concentration time curve from 0 to infinity (AUCinf) and the maximum concentration (Cmax) of omeprazole by approximately 189 and 134%, respectively. Abrocitinib increased the AUCinf of caffeine by 40% with lack of effect on Cmax.
Based on the study results, abrocitinib is a moderate inhibitor of CYP2C19. Caution should be exercised when using abrocitinib concomitantly with narrow therapeutic index medicines that are primarily metabolized by CYP2C19 enzyme. Abrocitinib is a mild inhibitor of CYP1A2; however, the impact is not clinically relevant, and no general dose adjustment is recommended for CYP1A2 substrates. Abrocitinib does not inhibit CYP3A or induce CYP1A2/2B6/2C19/3A and does not affect the pharmacokinetics of contraceptives.
ClinicalTrials.gov registration IDs: NCT03647670, NCT05067439, NCT03662516.
... В связи с представленным разнообразием прогестагенов перед практикующим врачом встает вопрос выбора препарата в комбинации с эстрогеном. И здесь важным фактором становятся предъявляемые пациенткой жалобы: одна из наиболее часто встречаю щихся -снижение качества жизни в связи с наличием астенодепрессивного синдрома, что обеспечивает наш выбор в пользу левоноргестрела (ЛНГ) [16][17][18]. Механизм действия ЛНГ отличается в зависимости от дозы и метода доставки в организм (оральный, трансдермальный или внутриматочный). Биодоступность оральной формы ЛНГ составляет примерно 90-100%, поскольку он подвержен метаболизму первого прохождения [19]. ...
... Прогестаген левоноргестрел обладает 100%-ной биодоступностью и высокой гестагенной активностью, положительно влияя на метаболическое состояние пациентки [17,26]. В рамках XIV конгресса 2-й Глобальной конференции Европейского общества по контрацепции и репродуктивному здоровью 2016 г. обсуждались риски возникновения венозных тромбозов, ассоциированных с применением различных гестагенов в сочетании с одним и тем же эстрогеновым компонентом в препаратах КОК [27]. ...
... Одним из важных фармакокинетических параметров является биодоступность, которая, как уже говорилось, у ЛНГ составляет 100% [17,26]. Это позволяет поддерживать стабильные концентрации ЛНГ в крови, не требуя создания «запаса дозы». ...
Determining the role of menopausal hormone therapy in the era of covid infection is an urgent task. The reasons for the lower rate of severe outcomes in women against the background of covid infection compared to men are currently being discussed. This is suggestive of the idea that the female body has the protection that accounts for this advantage. that Scientific literature data were reviewed to select the best combination of estrogen and progesterone when used as menopausal hormone therapy in the present setting. During the analysis of the literature on the use of estrogens and progestins as menopausal hormone therapy published in recent years, we used the following sources: PubMed, E-libary, Scopus. The body of material, which we studied, led us to a conclusion about the preference for the gestagen component when menopausal hormone therapy was prescribed. Gestagen should have the lowest risks in the development of thrombosis, as well as level the pronounced symptoms of peri- and postmenopause. According to the sources we studied and the authors’ own clinical experience, levonorgestrel-containing menopausal hormone therapy preparations have a high safety profileImproving physicians’ literacy about the criteria for prescribing menopausal hormone therapy, including drugs containing two components, estrogen and levonorgestrel in a cyclic regimen, will allow the use of hormone therapy in a wider range of patients in the perimenopausal and postmenopausal periods.
... Baratloo et al 44 study which did not show any serious side effects like venous thromboembolism (VTE) after use of second generation oral contraception. LNG containingEstroprogestins (Eps) as being linked to a lower VTE risk than EPs containing other progestins.45 ...
Background
Combined oral contraception was used in many studies for treatment of acne and hirsutism. However, levonorgestrel (LNG) alone has not been evaluated before.
Objective
To evaluate the efficacy of oral contraceptive pills containing LNG and EE compared with LNG only for the treatment of acne and hirsutism in a randomized, controlled prospective clinical trial.
Methods
Eighty females (20 with acne, 20 with hirsutism and 40 healthy females) received LNG + EE or LNG only for six months. Assessment of acne by Global Acne Grading system (GAGS) and hirsutism by Modified Ferriman Gallwey grading system (MFGS) and serum free testosterone was measured before and 6 months after treatment.
Results
Serum free testosterone was significantly higher before treatment in acne and hirsutism patients compared to control group (P<0.000). In acne patients, after 6 months of treatment with LNG/EE, serum free testosterone and (GAGS), were significantly decreased compared to LNG only (P<0.000). In hirsutism group, after 6 months of treatment with LNG/EE, serum free testosterone and (MFGS), were non‐significantly decreased compared to LNG only.
Conclusion
Oral contraceptives containing either LNG/EE or LNG seem to be effective and safe treatment for acne and hirsutism.
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... Group IV rats served as the control and received 5 ml/kg body weight of distilled water orally. Group V rats served as the positive control and received 0.3 mg/kg body weight of Levonorgestrel -a progesterone based contraceptive that has antigonadotropic effects thus preventing folliculogenesis and ovulation [23] . Group VI rats served as a negative control and received 50 mg/kg body weight of Clomiphene -a pro-fertility drug that enhances the serum level of FSH and LH with a resultant effect of improving folliculogenesis and ovulation [24] . ...
Background: the increasing prevalence of infertility worldwide necessitated studies to elucidate its etiology and to profer solutions. This study evaluated the effects of Super7 – a polyherbal antimalarial drug - on female Wister rats’ gonadotropin hormones. Methods: Phytochemical analysis and acute toxicity test of Super7 were done. The test animals were randomly allocated into six groups I-VI (n=7). Group I – III received 507.3 mg/kg, 1,014.6 mg/kg and 2,029.2 mg/kg body weight of Super7 respectively. Group IV, V and VI rats served as the general, positive and negative controls and received 5 ml/kg body weight of distilled water, 0.3 mg/kg body weight of Levonorgestrel, 50 mg/kg body weight of Clomiphene respectively. Treatments were administered daily for 30 days. Body weights, daily food and water intakes were measured. Both pre-treatment and post-treatment gondotropin hormonal assays were conducted. Anti oxidant properties were also tested. Results: The LD50 was > 5,000 mg/kg body weight with no signs of acute toxicity. Tannins, alkaloids, flavonoids, saponins, cardiac glycosides, steroids and terpenoids were present while proteins were absent; flavonoids being the most abundant in Super7. Groups I - V had increases in body weights which were statistically significant (P < 0.05). Group VI had none statistically significant increase in body weights (P > 0.05). The test drug showed positive gonadotropin properties and good antioxidant potentials by increasing post treatment LH levels and mean superoxide dismuthase enzyme units respectively. Conclusion: Super7 has a pro-fertility effect that is comparable to that of Clomiphene.
... DG does not affect androgen, which distinguishes it from other contraceptive drugs [1,3,4]. Moreover, it improves the high-density lipoprotein (HDL) and oestrogen antagonistic activity, significantly inhibits ovulation, changes cervical mucus concentration, and suppresses endometrium development [5]. The affinity of DG and its major metabolite, 3-ketone, for the progesterone receptor is much higher than its affinity for progesterone, norethindrone, and linezolid progesterone [6,7]. ...
The aim of this study was to explore the synthesis parameters of desogestrel-polylactic acid nanoparticles (DG-PLA-NPs), optimise the preparation technology, and elucidate the in vitro release characteristics. Considering encapsulation efficiency (EE) and drug loading as the main evaluation indexes, DG-PLA-NPs were prepared using the modified emulsion solvent diffusion method and single factor and orthogonal design tests were performed to investigate the influencing factors and optimise the preparation method. Morphology of the nanoparticles was observed using transmission electron microscopy (TEM), average particle diameter and distribution were determined using dynamic laser particle size analysis, and the EE and drug loading were measured using reversed-phase high-performance liquid chromatography. Among the eight factors, the drug-to-material ratio, water-to-organic phase ratio, and polyvinyl alcohol (PVA) concentration significantly affected the NP EE. In the optimised formulation, the PLA/DG ratio, PVA concentration, and oil-to-water phase ratio were 5, 0.5%, and 5, respectively. The DG-PLA-NPs prepared with the optimised formulation were round or spherical with an average diameter of 209 nm, 79.60% EE, and 6.81% drug loading capacity. The polydispersity index was 0.181, and the zeta potential was −27.37 mV. The in vitro releases of both DG and DG-PLA-NPs conformed to the Weibull equation. The DG-PLA-NPs released desogestrel rapidly in the early stages but slowly at later stages, indicating that compared to DG, the DG-PLA-NPs had obvious sustained-release effects. The DG-PLA-NPs prepared by the modified emulsion solvent diffusion method were small, simple to prepare, and had high drug loading with promising application prospects.
... 28 The estrogen ethinylestradiol and the progestin levonorgestrel are among the most commonly prescribed contraceptives and both are metabolized through CYP3A, sulfotransferases, and uridine 5 -diphospho-glucuronosyltransferases. 29,30 Drugs that have pharmacokinetic interactions with oral contraceptives can potentially result in failure of contraception through induction of metabolism or increased incidence of the side effects through inhibition of metabolism. [31][32][33] Given the wide use of hormonal contraceptives, this study was conducted to characterize any potential effect of upadacitinib on ethinylestradiol and levonorgestrel pharmacokinetics to inform safety of coadministration in patients. ...
... A total of 22 female subjects were enrolled in the study, and 20 subjects completed both periods 1 and 2. The subjects enrolled in the study had mean age of 41.1 years (range, 21-53), mean weight of 72.7 kg (range, 58-84), mean body mass index of 26.6 kg/m 2 (range, [19][20][21][22][23][24][25][26][27][28][29][30], and mean height of 165 cm (range, 156-174). One subject discontinued the study in period 1 (prior to upadacitinib administration) due to an adverse event. ...
Upadacitinib is a novel selective oral Janus kinase 1 (JAK) inhibitor being developed for treatment of several inflammatory diseases. Oral contraceptives are anticipated to be a common concomitant medication in the target patient populations. This study was designed to evaluate the effect of multiple doses of upadacitinib on the pharmacokinetics of ethinylestradiol and levonorgestrel in healthy female subjects. This phase I, single‐center, open‐label, 2‐period crossover study evaluated the effect of multiple doses of 30 mg once daily extended‐release upadacitinib on the pharmacokinetics of a single oral dose of ethinylestradiol/levonorgestrel (0.03/0.15 mg; administered alone in period 1 and on day 12 of a 14‐day regimen of upadacitinib in period 2) in 22 healthy female subjects. The ratios (90% confidence intervals) for maximum plasma concentration and area under the plasma drug concentration–time curve from time zero to infinity following administration of ethinylestradiol/levonorgestrel with upadacitinib compared with administration of ethinylestradiol/ levonorgestrel alone were 0.96 (0.89–1.02) and 1.1 (1.04–1.19), respectively, for ethinylestradiol, and 0.96 (0.87–1.06) and 0.96 (0.85–1.07), respectively, for levonorgestrel. The harmonic mean terminal half‐life for ethinylestradiol (7.7 vs 7.0 hours) and levonorgestrel (37.1 vs 33.1 hours) was similar in the presence and absence of upadacitinib. Ethinylestradiol and levonorgestrel were bioequivalent in the presence and absence of upadacitinib. Therefore, upadacitinib can be administered concomitantly with oral contraceptives containing ethinylestradiol or levonorgestrel.
Delineating the relationship between human neurodevelopment and the maturation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty is critical for investigating the increase in vulnerability to neuropsychiatric disorders that is well documented during this period. Preclinical research demonstrates a clear association between gonadal production of sex steroids and neurodevelopment; however, identifying similar associations in humans has been complicated by confounding variables (such as age) and the coactivation of two additional endocrine systems (the adrenal androgenic system and the somatotropic growth axis) and requires further elucidation. In this paper, we present the design of, and preliminary observations from, the ongoing NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty. The aim of this study is to directly examine how the increase in sex steroid hormone production following activation of the HPG-axis (i.e., gonadarche) impacts neurodevelopment, and, additionally, to determine how gonadal development and maturation is associated with longitudinal changes in brain structure and function in boys and girls. To disentangle the effects of sex steroids from those of age and other endocrine events on brain development, our study design includes 1) selection criteria that establish a well-characterized baseline cohort of healthy 8-year-old children prior to the onset of puberty (e.g., prior to puberty-related sex steroid hormone production); 2) temporally dense longitudinal, repeated-measures sampling of typically developing children at 8-10 month intervals over a 10-year period between the ages of eight and 18; 3) contemporaneous collection of endocrine and other measures of gonadal, adrenal, and growth axis function at each timepoint; and 4) collection of multimodal neuroimaging measures at these same timepoints, including brain structure (gray and white matter volume, cortical thickness and area, white matter integrity, myelination) and function (reward processing, emotional processing, inhibition/impulsivity, working memory, resting-state network connectivity, regional cerebral blood flow). This report of our ongoing longitudinal study 1) provides a comprehensive review of the endocrine events of puberty; 2) details our overall study design; 3) presents our selection criteria for study entry (e.g., well-characterized prepubertal baseline) along with the endocrinological considerations and guiding principles that underlie these criteria; 4) describes our longitudinal outcome measures and how they specifically relate to investigating the effects of gonadal development on brain development; and 5) documents patterns of fMRI activation and resting-state networks from an early, representative subsample of our cohort of prepubertal 8-year-old children.
Oral contraceptive pills (OCPs) are considered the first-line pharmacological therapy for hyperandrogenic PCOS patients who are not trying to conceive [1, 2]. However, all the other different kind of treatments are discussed in this chapter, too.
