Effects of Pre_Operation Desogestrel Estradiol in Endometrial Preparation at Hysteroscopic Polypectomy.

Background: Hysteroscopic surgery is a common gynecologic process in many conditions. Endometrial thinning is the main successful key for this process associated with many preoperative preparations. This study aimed to evaluate DE (Desogestrel-estradiol) to reduce endometrial thickness in comparison with the control group. Materials and Methods: This Randomized clinical trial was done on the patients candidate for polypectomy that were randomly divided into two groups of intervention and control; the first group received DE OCP (oral contraceptive pill with 30 microgram Ethinyl estradiol + 150 micro gram Desogestrel) once daily from the 1st to 5th day of the menstrual cycle for 21 days and then in the first day of next menstruation cycle, the drug was used up to one day before hysteroscopy done in the 5th to 8th day of the cycle. The second group received no drugs. Hysteroscopy was done in the early follicular phase in both groups and all the subjects received one dosage of Misoprostol a night before surgery. Results: There were no significant differences between the parity, polyp size, and BMI (Body Mass Index) in the two groups. The mean duration of surgery, mean endometrial thickness before hysteroscopy, the quality of endometrial tissue, and surgeon satisfaction were significantly difference between the two groups. However, the quality of the surgeon's vision in the intervention group was better than the control group but there was no significant difference between the two groups. Conclusion: Pre-operation endometrial thinning by oral contraceptives such as DE could be an effective method and reduce the duration of surgery.

Cerebral venous sinus thrombosis due to desogestrel intake in a young lady: A case report.

Cerebral Venous Sinus Thrombosis (CVST) is a subtype of venous thromboembolism, which occurs in the dural venous sinuses. Blockage of the venous drainage of the brain leads to the development of hemorrhages. Strokes can hence develop in any individual, irrespective of age or sex. CVST is a very serious condition requiring immediate thrombolysis to prevent residual neurological deficits. We report the case of a lady aged 25 years, who presented to the emergency department with a severe diffuse headache for 4 days, associated with vomiting. This was followed by multiple episodes of seizures and altered sensorium the previous day. She had been taking desogestrel for the past 2 months. On examination, the patient was unconscious and febrile (102.8 F). On admission, Glasgow Coma Scale score of E2V2M3 and bilateral extensor plantar response were noted. Signs of meningeal irritation were absent. Her pupils were mid-dilated, sluggishly reactive to light, and papilledema was present bilaterally. Based on imaging studies, she was diagnosed with a case of CVST. Her homocysteine levels were elevated. She recovered on appropriate treatment and was discharged on Ryle's feeding tube after 26 days of hospital stay with a Glasgow Coma Scale score of E4V5M6 and a flexor plantar response. The case emphasizes the need to rule out CVST in young adult females on oral contraceptive pills (OCP) presenting with severe neurological dysfunction. Vigilant screening, clinical suspicion and timely management can help cut down the associated mortality and morbidity in such cases.

Higher baseline heart rate variability in CCHS patients with progestin-associated recovery of hypercapnic ventilatory response.

After a fortuitous observation of two cases of chemosensitivity recovery in women with congenital central hypoventilation syndrome (CCHS) who took desogestrel, we aimed to evaluate the ventilatory response to hypercapnia of five CCHS patients with or without treatment consisting of desogestrel (DESO) or levonorgestrel (LEVO). Only two patients became responsive to hypercapnia under treatment, according to their basal vagal heart rate variability. These results suggest that heart rate variability may be promising tool to discriminate patients susceptible to become responsive to hypercapnia under DESO-LEVO treatment.Clinical Trials Identifier NCT01243697.

The Uncharted Link Between Desogestrel and Hypercalcemia.

This report presents a unique case of hypercalcemia with an elusive etiology. A 37-year-old Caucasian female with a history of gonadotropin-secreting pituitary microadenoma and recurrent nephrolithiasis was found to have hypercalcemia, hypercalciuria, elevated 1,25-dihydroxyvitamin D levels, and low parathyroid hormone levels. Extensive investigations were conducted to identify the cause, including ruling out sarcoidosis and other granulomatous disorders. Imaging and diagnostic testing revealed normal results. The patient's condition considerably improved after the cessation of an oral contraceptive pill containing desogestrel. This surprising association raises the possibility that the use of desogestrel could result in hypercalcemia as one of the side effects. To ensure proper care and avoid consequences linked to severe hypercalcemia, a high index of suspicion is needed to detect the underlying cause of hypercalcemia, even in the absence of usual indications.

Validation of 24-hour trough concentration as a proxy for intensive pharmacokinetic measurements for a combined oral contraceptive pill containing desogestrel.

OBJECTIVES: To confirm that 24-hour steady-state trough measurements (C24) are high-quality proxies for gold standard pharmacokinetic measurements (area under the curve [AUC]) of a combined oral contraceptive pill (COCP). STUDY DESIGN: We conducted a 12-sample, 24-hour pharmacokinetic study in healthy reproductive-age females taking a COCP containing 0.15-mg desogestrel (DSG) and 30-µg ethinyl estradiol (EE). As DSG is a pro-drug for etonogestrel (ENG), we calculated correlations between steady-state C24 and 24-hour AUC values for both ENG and EE. RESULTS: Among 19 participants at steady state, C24 measurements were highly correlated with AUC for both ENG (r = 0.93; 95% CI 0.83-0.98) and EE (r = 0.87; 95% CI 0.68-0.95). CONCLUSIONS: Steady-state 24-hour trough concentrations are high-quality proxies for gold standard pharmacokinetics of a DSG-containing COCP. IMPLICATIONS: Use of single-time trough concentration measurements at steady state provides excellent surrogate results for gold standard AUC values for both DSG and EE among COCP users. These findings support that large studies exploring interindividual variability in COCP pharmacokinetics can avoid the time- and resource-intensive costs associated with measuring AUC. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT05002738.

Can a 3 months treatment with oral Desogestrel prior to insertion of the etonogestrel-releasing contraceptive implant improve continuation rate at 1 year? A randomized trial.

OBJECTIVE: To evaluate if daily oral 75 µg of Desogestrel (DSG) for 3 months prior to the insertion of etonogestrel-releasing contraceptive implant (ENG-IMPLANT) might help reduce its premature discontinuation. RESULTS: A total of 66 women were randomized in the ENG-IMPLANT group (26) and in the DSG + ENG-IMPLANT group (40), respectively, in the Geneva University Hospitals and Basel University Hospital, from August 15th, 2016 through September 30th, 2019. In the DSG + ENG-IMPLANT group, patients were given a 3 months' supply of 75 µg of DSG before the insertion of the ENG-IMPLANT. All women were seen after 3 months for bleeding and satisfaction evaluation, and at 12 months post ENG-IMPLANT insertion. Higher levels of satisfaction at 12-months were found in the ENG-IMPLANT group compared to the DSG + ENG-IMPLANT group (8.5 ± 1.7 vs. 6.6 ± 2.9, p = 0.012). There were no statistically significant differences regarding tolerance (7.8 ± 2.5 vs 6.8 ± 2.6, p = 0.191) and contraceptive continuation (80% vs 72.4%, p = 0.544) between groups. CONCLUSION: DSG prior to insertion of the ENG-IMPLANT did not improve its continuation rate neither its satisfaction at 1 year. Trial registration NCT05174195. Retrospectively registered, the 30th December 2021.

The progestin-only pills drospirenone 4 mg and desogestrel 0.075 mg as an option for the management of dysmenorrhea and mastodynia.

INTRODUCTION: Dysmenorrhea and mastodynia are the most common gynecologic pain causes in women of all ages and races during their reproductive life. The following study aimed to show the influence of two POP´s in the development of dysmenorrhea and mastodynia after nine months of use. MATERIAL AND METHODS: A total of 858 women with 6691 drospirenone (DRSP) cycles and 332 women with 2487 desogestrel (DSG) cycles were analyzed. Women included in this study were all child-bearing potentials, at risk of pregnancy, agreeing to use only the study medication for contraception for the duration of the study medication treatment, aged 18 to 45. RESULTS: At screening, 168 (19.6%) of the 858 patients using DRSP and 64 (19,3%) of the DSG patients reported that they had suffered from dysmenorrhea within six cycles prior to the first visit before starting with the medication. 20,2% of the DRSP and 10,9% of the DSG group had a sever dysmenorrhea. After 9 cycles this was reduced to 0,6% and 3,1% respectively. In total, 96 women (11.2%) in the DRSP and 49 (14,8%) experienced mastodynia within six cycles before the screening. Of these 91.6% in the DRSP group and 91,8% in the DSG group had no or mild mastodynoa at follow-up. DISCUSSION: The progestins 4 mg and desogestrel 0,075 mg showed a marked effect in the non-contraceptive aspects of dysmenorrhea and mastodynia so that new possibilities are opened for these two benign gynecological diseases. Future studies must reaffirm these first data.

Long-term treatment of endometriosis-related pain among women seeking hormonal contraception.

OBJECTIVE: To evaluate the different effects of a progestin-only contraceptive with desogestrel (DSG) vs combined oral contraceptives (COCs) for a first line long-term treatment of endometriosis-related pain among patients seeking hormonal contraception. METHODS: An observational retrospective cohort study was conducted in collaboration with a local outpatient clinic for endometriosis among a group of nulliparous young women (n = 216) with endometriosis-related pain and seeking contraception. The cohort was subdivided into a group (n = 73) treated as first line by DSG and another group (n = 75) treated by a COC. During the study, clinical symptoms, side effects and possible changes in OC type use were recorded. RESULTS: No significant difference was found between the two groups in terms of clinical characteristics and pain scores before treatment. After 6 months both treatments were effective in reducing endometriosis-related pain, and those treated with DSG showed lower levels of dysmenorrhea, dyspareunia and nonmenstrual pelvic pain than COCs group (p < .01). After 12 months, in DSG Group some patients (15%) switched from DSG to a COC for breakthrough bleeding, whereas in COC Group 48% of patients switched to another type of COC for reduced efficacy on pain and/or for side effects. After 3 years of OC treatment, in DSG Group 79% of patients maintained the same therapy, whereas in COC Group only 14% continued the same COC type, 37% switched to another COC and 47% to DSG. CONCLUSIONS: A progestin-only contraceptive with DSG is a valid option for long term management of endometriosis-related pain in patients seeking hormonal contraception.

Effects of Ethinyl Estradiol in Combined Oral Contraceptives on Cell Proliferation and Apoptosis in Ectopic Endometrial Tissue: A Randomized Controlled Study.

Objective: Since endometriosis is an estrogen-dependent disease; therefore, combined oral contraceptives (COCs) may not be the best choice for the treatment of endometriosis. The objective of the present study was to investigate the effects of ethinyl estradiol (EE) and desogestrel (DSG) in COCs on cell proliferation and apoptosis in ectopic endometrial tissue as compared to DSG alone. Materials and methods: Forty-five women of reproductive age with at least one endometriotic cyst were recruited into this single-blind randomized controlled trial study and randomly divided equally into three groups. EE-DSG and DSG groups received EE (0.03 mg) and DSG (0.15 mg) or DSG alone daily for 28-35 days before surgery. The control group was prescribed nothing. Endometriotic cyst tissues were collected during ovarian cystectomy for immunohistochemistry. Results: Levels of Ki-67 positive cells in the ectopic endometrial tissue of the EE-DSG group were significantly higher than the DSG group (median [IQR]; 1.4[1.2] vs 0.6 [0.7], P <0.016). There were significantly more TUNEL-positive cells in the EE-DSG group compared to the DSG group (median [IQR]; 2.8[0.7] vs 1.8[1.4], P < 0.016, respectively). Moreover, the number of TUNEL-positive cells in the EE-DSG and DSG groups were significantly higher than the control (median [IQR]; 2.8[0.7] vs 0.2[0.2] and 1.8[1.4] vs 0.2[0.2], P <0.016). The levels of cells that positively stained for Bcl2 were not different among all groups. Conclusion: Progestin alone increased cell apoptosis in ectopic endometria. However, concurrent EE in COCs enhanced proliferation and promoted a greater apoptotic effect in ectopic endometria compared to progestin alone.

Provision of the progestogen-only pill by community pharmacies as bridging contraception for women receiving emergency contraception: the Bridge-it RCT.

INTRODUCTION: Unless women start effective contraception after using emergency contraception, they remain at risk of unintended pregnancy. Most women in the UK obtain emergency contraception from community pharmacies that are unable to provide ongoing contraception (apart from barrier methods which have high failure rates). This means that women need an appointment with a general practitioner or at a sexual and reproductive health clinic. We conducted a pragmatic cluster randomised cohort crossover trial to determine whether or not pharmacist provision of a bridging supply of a progestogen-only pill plus the invitation to attend a sexual and reproductive health clinic resulted in increased subsequent use of effective contraception (hormonal or intrauterine). METHODS: Twenty-nine pharmacies in three UK cities recruited women receiving emergency contraception (levonorgestrel). In the intervention, women received a 3-month supply of the progestogen-only pill (75 µg of desogestrel) plus a card that provided rapid access to a local sexual and reproductive health clinic. In the control arm, pharmacists advised women to attend their usual contraceptive provider. The primary outcome was reported use of an effective contraception (hormonal and intrauterine methods) at 4 months. Process evaluation was also conducted to inform any future implementation. RESULTS: The study took place December 2017 and June 2019 and recruited 636 women to the intervention (n = 316) and control groups (n = 320). There were no statistically significant differences in demographic characteristics between the groups. Four-month follow-up data were available for 406 participants: 63% (198/315) of the control group and 65% (208/318) of the intervention group. The proportion of participants reporting use of effective contraception was 20.1% greater (95% confidence interval 5.2% to 35.0%) in the intervention group (58.4%, 95% confidence interval 48.6% to 68.2%) than in the control group (40.5%, 95% confidence interval 29.7% to 51.3%) (adjusted for recruitment period, treatment arm and centre; p = 0.011). The proportion of women using effective contraception remained statistically significantly larger, when adjusted for age, current sexual relationship and history of past use of effective contraception, and was robust to the missing data. There were no serious adverse events. CONCLUSION: Provision of a bridging supply of the progestogen-only pill with emergency contraception from a pharmacist and the invitation to a sexual and reproductive health clinic resulted in a significant increase in self-reported subsequent use of effective contraception. This simple intervention has the potential to prevent more unintended pregnancies for women after emergency contraception. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70616901. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 27. See the NIHR Journals Library website for further project information.

The emergency contraceptive pill can prevent pregnancy following unprotected sex or a burst condom; however, unless women start a regular method of contraception they remain at risk of pregnancy. Most women obtain emergency contraception from a community pharmacy (chemist), but then require an appointment with a general practitioner or at a sexual and reproductive health clinic for ongoing contraception. Getting an appointment can take time and unintended pregnancies can occur during this time. If a pharmacist could give women a small supply of a progestogen-only pill or 'mini-pill' with their emergency contraception, together with help to get an appointment at a clinic, then this might help more women to start effective contraception. We undertook a study in 29 pharmacies in Lothian, Tayside and London among women receiving emergency contraception. Pharmacists provided either their standard advice about contraception (control group) or the intervention. The intervention was a 3-month supply of the progestogen-only pill plus a rapid-access card, which, if presented at a sexual and reproductive health clinic, would help women get an appointment for contraception. The order in which the pharmacy provided either control or intervention was randomised. We conducted telephone interviews with the women 4 months later to find out what contraception they were using. A total of 636 women took part in the study, 316 in the intervention group and 320 in the control group. The proportion who said that they were using an effective method of contraception was around 20% larger in the intervention group. In addition, fewer women in this group said that they had used emergency contraception again. This study shows that community pharmacy provision of a small supply of progestogen-only pills and the invitation to attend a sexual and reproductive health clinic results in a large increase in the use of effective contraception after emergency contraception. If this became routine practice then it could help prevent unintended pregnancies.

Oral Desogestrel as Endometrial Preparation before Operative Hysteroscopy: A Systematic Review.

The pharmacologic preparation of the endometrium before hysteroscopy may be achieved with the use of various drugs. This systematic review aims to summarize the available evidence regarding the use of desogestrel for endometrial preparation before hysteroscopic procedures. A literature search for suitable articles published in English language from inception of the database until August 2019 was performed using the following databases: PubMed/MEDLINE, EMBASE, the Cochrane Library, and Google Scholar. All original articles concerning desogestrel-only pretreatment before hysteroscopic surgery were considered eligible. Reviews, case reports/series, conference papers, studies including the use of combined hormonal preparation, and articles in languages other than English were excluded from the analysis. The literature search retrieved 3 studies that met all the inclusion criteria. The data demonstrated that desogestrel may be considered as a hormonal pretreatment drug before hysteroscopic procedures. The drug was distinctly effective and assessed as helpful by the operating surgeon in numerous patients who were administered the pretreatment of 75 µg daily. Oral desogestrel is a cheap, easily available, safe, and quite efficient alternative for endometrial preparation before hysteroscopic procedures.

Double-Dose Desogestrel: Is it Effective in Adolescent Menstrual Dysfunction?

STUDY OBJECTIVE: Adolescent menstrual dysfunction (AMD) is a common cause of iron deficiency anemia and absences from school. The management of AMD with single- and double-dose desogestrel is largely on the basis of anecdotal evidence. Our aim was to describe the effectiveness and safety of both dosing strategies in our clinic cohort to help guide future management. DESIGN: Local service evaluation with retrospective analysis of clinic notes. SETTING: Adolescent gynecology clinic in a tertiary pediatric center in the North West of England. PARTICIPANTS: Adolescent girls (10-18 years of age) with AMD (n = 129). INTERVENTIONS: Single-dose (75 µg) desogestrel vs double-dose (150 µg) desogestrel. MAIN OUTCOME MEASURES: Prevalence of amenorrhea and light spotting, side effects, and discontinuation rates of both dosing regimens. RESULTS: Forty-three of 87 (49%) adolescent girls who started treatment with a double dose of desogestrel were amenorrheic/experienced light spotting, compared with 7/40 (18%) of girls who started treatment with a single dose (P = .001). Patients taking a double dose of desogestrel were less likely to discontinue overall (double: 45/89 [51%]; vs single: 35/40 [88%]; P < .001) and there was no evidence of an increase in nonbleeding side effects (double: 30/89 [34%]; vs single: 15/40 [38%]; P = .68). CONCLUSION: Our findings provide evidence that a double dose of desogestrel is associated with a higher prevalence of amenorrhea and light spotting compared with a single dose in adolescent girls with AMD. However, larger studies are needed to further inform clinical guidelines.

Desogestrel and Severe Psychiatric Disorders: A Retrospective Analysis of Federal Adverse Event Reporting System and EudraVigilance.

BACKGROUND: Several studies have been published which stated that there is some connection between severe psychiatric disorders and contraceptive drug "desogestrel". However, nothing in the summary of product characteristics (SmPC) or patient information leaflets of desogestrel about anxiety, more severe anxiety leading to panic attacks, or about risks of severe depression leading to suicidal thoughts or suicide attempts. OBJECTIVE: To examine the safety and risk association between hormonal contraceptive desogestrel among women with psychiatric disorders using adverse drug reaction database of FDA Adverse Events Reporting System (FAERS) and EudraVigilance (EV). METHODS: Individual case safety reports (ICSRs) of only female patients from Jan 1999 to Nov 2019 and Jan 2004 to Nov 2019 were downloaded from FAERS and EV database, respectively. Reports of drug desogestrel, dienogest, norgestimate, cyproterone acetate and drospirenone were downloaded. Disproportionality method of data mining was used to calculate the risk association. RESULTS AND DISCUSSION: The lower limit of 95% CI of PRR is -0.28 and 2.02, PRR is 1.08 and 9.18, ROR is 1.09 (95%CI: 0.74, 1.59) and 9.26 (95% CI: 7.21, 11.89), Chi square value is 1.21 and 433.68, and IC-2SD is -0.27 and 2.60, respectively for data obtained from FAERS and EV. CONCLUSION: From this study, we conclude that there is no new emerging signal for the drug-event pair studied. Further study and continuous monitoring are required in future to know more about this drug-event pair association, as severe psychiatric disorders are not yet mentioned or included in SmPC and patient leaflet of desogestrel.

Effectiveness of Low-dose Ethinylestradiol/Cyproterone Acetate and Ethinylestradiol/Desogestrel with and without Metformin on Hirsutism in Polycystic Ovary Syndrome: A Randomized, Double-blind, Triple-dummy Study.

BACKGROUND: The effectiveness of different combined oral contraceptive pills and metformin in reducing hirsutism in patients with polycystic ovary syndrome (PCOS) remains unclear. OBJECTIVE: We sought to determine the effects of ethinylestradiol (35µg)/cyproterone acetate (2mg) (EE/CPA) and ethinylestradiol (20µg)/desogestrel (0.15mg) (EE/DES), alone or with metformin, on hirsutism in PCOS. METHODS: A randomized, double-blind, triple-dummy study was conducted on women with PCOS and hirsutism (N=107) who received one of four drug combinations (Arm A: EE/CPA; Arm B: EE/DES; Arm C: EE/CPA plus metformin; or Arm D: EE/DES plus metformin). Hirsutism was assessed at baseline, six months, and 12 months by using five outcomes variables. RESULTS: No outcomes variable showed a significant difference between the four arms at 12 months. There was a significant reduction in both hair density and modified Ferriman-Gallwey score (mFGS) in Arm A, mFGS in Arm B, hair density in Arm C, and diameter of sideburn hair in Arm D, respectively. Separately, there was a significant increase noted in the hair growth rate of chin and an improvement in patients' perceptions of hirsutism in all four study arms. CONCLUSION: EE/CPA and EE/DES were equally effective in improving hirsutism in PCOS, with no added benefit from low-dose metformin. Sri Lanka Clinical Trials Registry (http://www.slctr.lk) registration no. SLCTR/2015/007.

Development of a simple liquid chromatography method for dissolution testing of low dose desogestrel and ethinylestradiol tablets.

Accurate quantitation of low dose, multi-active dissolution samples poses unique challenges in the pharmaceutical industry, often resulting in separate HPLC methods for each active or the use of multiple detectors for increased sensitivity. In this study, we report a fast, isocratic HPLC method utilizing only UV detection for dissolution testing of low dose desogestrel and ethinylestradiol tablets. Rapid separation is completed in 5 min using isocratic elution at a flow rate of 0.45 mL/min, with a column temperature at 30 °C, an injection volume of 50 µL and the detection wavelength at 200 nm. After extensive method development and optimization, the cyano stationary phase was used to overcome the large difference in hydrophobicity for desogestrel and ethinylestradiol, providing balanced retention for both analytes under isocratic elution. Chromatography modeling software was used to provide a rapid analysis of multiple columns and chromatography conditions. The optimized method boasts fast and efficient separation through use of a short, small I.D. column and a large injection volume of dissolution solution to achieve high sensitivity. The stable baseline from an isocratic separation allows low detection wavelengths to be used, resulting in accurate and precise quantitation of both desogestrel and ethinylestradiol. The method has been successfully validated for specificity, linearity, accuracy and precision in the range of 75 - 600 ng/mL for desogestrel and 10 - 80 ng/mL for ethinylestradiol using both HPLC and UHPLC systems. The method robustness was characterized using a design of experiment approach, and the operational design region of the method was established.

Biotransformation of contraceptive drug desogestrel with Cunninghamella elegans, and anti-inflammatory activity of its metabolites.

Biotransformation of an orally active contraceptive drug, desogestrel (1), with Cunninghamella elegans yielded a new metabolite, 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17ß-ol-3,6-dione (2), along with five known metabolites, i.e., 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3ß,6ß,17ß-triol (3), 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6ß,17ß-diol-3-one (4), 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17ß-ol-3-one (5), 13ß-ethyl-11-epoxy-18,19-dinor-17α-pregn-4-en-20-yn-17ß-ol-3-one (6), and 13ß-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-10ß,17ß-diol-3-one (7). The structure of new metabolite 2 was elucidated by using 1H-, 13C-, and 2D-NMR, EI-, and HREI-MS, IR, and UV spectroscopic data. Compounds 1-7 were evaluated for anti-inflammatory activities, i.e., inhibition of T-cell proliferation, and pro-inflammatory cytokine (TNF-α). Compounds 1 (IC50 = 1.12 ± 0.03 µg/mL), 2 (IC50 = 1.15 ± 0.05 µg/mL), 3 (IC50 = 1.15 ± 0.05 µg/mL), 4 (IC50 = 1.40 ± 0.03 µg/mL), 5 (IC50 = 1.78 ± 0.08 µg/mL), and 6 (IC50 = 1.36 ± 0.07 µg/mL) were identified as potent inhibitors of T-cells proliferation, in comparison to the standard drug, prednisolone (IC50 = 3.51 ± 0.03 µg/mL). Compound 7 (IC50 = 6.18 ± 0.04 µg/mL) showed a good activity. In addition, substrate 1 (IC50 ≤ 1 µg/mL), and its metabolites 2 (IC50 = 4.1 ± 0.60 µg/mL), and 6 (IC50 = 6.8 ± 0.8 µg/mL) also showed a potent inhibition of pro-inflammatory cytokine (TNF-α) production, as compared to the standards drug, pentoxifilline (IC50 = 94.8 ± 2.1 µg/mL). Whereas compounds 3 (IC50 = 57.9 ± 7.6 µg/mL), and 5 (IC50 = 27.2 ± 6.8 µg/mL) showed a moderate inhibition of TNF-α production, while compounds 4 and 7 showed no inhibition. Compounds 1-7 were found to be non-cytotoxic to 3T3 normal cell line (mouse fibroblast).

Progestogen-only pills: which progestogen would be ideal.

Compared with nonuse, combined hormonal contraceptives containing estrogen and a progestogen are associated with a roughly 2- to 3-fold increased risk of venous and a 2-fold increased risk of arterial thromboembolism, including stroke and acute myocardial infarction. These events are, however, overall rare among women of reproductive age. Historically, progestin-only pills were not thought to be linked with any thromboembolic risk increase. Therefore, these preparations may be valuable options in women who are ineligible to take combined hormonal contraceptives. Until recently, only progestogens with partial androgenic activities were available. As demonstrated in animal studies, more modern progestogens such as drospirenone with its anti-mineralocorticoid effects may be associated with even more favorable aspects, which have to be clinically demonstrated, however, in future studies.

Research Advances on Therapeutic Approaches to Congenital Central Hypoventilation Syndrome (CCHS).

Congenital central hypoventilation syndrome (CCHS) is a genetic disorder of neurodevelopment, with an autosomal dominant transmission, caused by heterozygous mutations in the PHOX2B gene. CCHS is a rare disorder characterized by hypoventilation due to the failure of autonomic control of breathing. Until now no curative treatment has been found. PHOX2B is a transcription factor that plays a crucial role in the development (and maintenance) of the autonomic nervous system, and in particular the neuronal structures involved in respiratory reflexes. The underlying pathogenetic mechanism is still unclear, although studies in vivo and in CCHS patients indicate that some neuronal structures may be damaged. Moreover, in vitro experimental data suggest that transcriptional dysregulation and protein misfolding may be key pathogenic mechanisms. This review summarizes latest researches that improved the comprehension of the molecular pathogenetic mechanisms responsible for CCHS and discusses the search for therapeutic intervention in light of the current knowledge about PHOX2B function.

Effect of desogestrel 75 µg on headache frequency and intensity in women with migraine: a prospective controlled trial.

Objective: In contrast with combined hormonal contraception, progestin-only contraception is not associated with an increase in venous thromboembolism or stroke. Women with migraine are at increased risk of ischaemic stroke. Several studies have reported a reduction in migraine frequency and intensity with desogestrel 75 µg, a progestin-only pill. At present the quality of data is limited by retrospective study designs, lack of control groups and small sample sizes. We present the first prospective nonrandomised controlled trial. Methods: A total of 150 women with migraine visiting our clinic for contraceptive counselling were screened. The intervention group comprised women who opted for contraception with desogestrel (n = 98); the control group comprised women who continued their usual contraceptive (n = 36). Participants completed daily diaries for 90 days before the intervention and 180 days after the intervention. Results: In the intervention group, we found improvements in migraine frequency (p < .001), migraine intensity (p < .001) and the number of triptans used (p < .001). These improvements were already significant after 90 days of desogestrel use (p < .001). Disability scores also decreased significantly. No improvement was seen in the nonintervention group. Conclusion: These data demonstrate for the first time in a prospective controlled setting that daily use of the progestin desogestrel is associated with a decrease in migraine frequency, migraine intensity and pain medication use in women with migraine, with and without aura, who had previously been experiencing at least three days of migraine per month. Trial registration: The study is registered in the University of Zürich database ( www.research-projects.uzh.ch/unizh.htm ).