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Endometriosis is an inflammatory disease that affects one in ten women, where ectopic endometrial cells grow outside of the uterus. Lesions are estrogen dependent but progesterone resistant due to decreased progesterone receptor activity. This study investigated whether a combination of dienogest, a synthetic progesterone, and calcitriol, vitamin D’s active form, had an additive or synergistic effect in the therapy of endometriosis. Experiments were conducted on immortalized endometriotic epithelial (12Z) and stromal (22B) cell lines. Results revealed that the combination therapy effectively inhibited cell viability in spheroids, limited proliferation, and reduced cell migration in cell monolayers of lipopolysaccharide- induced cells. Concentrations of prostaglandin E2, a key inflammatory cytokine, were measured from the supernatants of 12Z cells. The combination did not alter CD44 and progesterone receptor levels on the surface of 12Z cells. Further testing in a mouse model is necessary to determine the efficacy of the combination in vivo., 2023, Includes bibliography., Degree granted: Thesis (MS)--Florida Atlantic University, 2023., Collection: FAU Electronic Theses and Dissertations Collection

Bakgrund: Endometrios är en sjukdom beroende av östrogen där endometriotisk vävnad tillväxer utanför livmodern, i exempelvis bäcken eller äggstockarna. Symtomen är bäckensmärta, dysmenorré och djup dyspareuni som kommer under skov. Infertilitet kan också vara ett symtom vid endometrios. Prevalensen för sjukdomen är 10%. Behandling av endometrios sker främst för att förhindra smärta och vidare utveckling av sjukdomen. Läkemedel som sätts in kan vara ickesteroida antiinflammatoriska läkemedel (NSAID), orala kombinerade preventivmedel, gonadotropinfrisättande hormonanaloger (GnRH), progestiner, aromatasinhibitorer, selektiva östrogenreceptormodulatorer (SERM) eller behandling med kirurgi. Läkemedlet dienogest är ett progestin och har som verkningsmekanism att binda och aktivera progesteronreceptorer vilket leder till minskad syntes av östrogen. Syfte: Syftet med examensarbetet var att undersöka läkemedlet dienogests effekt vid behandling av endometrioskopplad bäckensmärta (EAPP). Metod: Denna litteraturstudie baserades på 5 vetenskapliga artiklar som valdes ut från databasen PubMed efter att sökorden ”endometriosis” tillsammans med ”dienogest” angivits. Av artiklarna jämförde 4 av de dienogest med placebo varav 2 av artiklarna var förlängningsstudier. Sista artikeln som valdes ut jämförde dienogest med orala kombinerade preventivmedlet Yasmin (0,03 mg etinylestradiol och 3 mg drospirenon). Resultat: Resultatet från studierna visade att dienogest 2 mg reducerade endometrioskopplad bäckensmärta effektivt. I studie 1 och 2 var dienogest statistiskt signifikant bättre i att reducera endometriosassocierad bäckensmärta jämfört med placebo. Vid förlängning av dienogestbehandling i studie 3 och 4 blev reduceringen i bäckensmärta också effektiv men lik placebo. Vid jämförelse av dienogest med orala kombinerade preventivmedlet Yasmin visade både läkemedlen förbättring av EAPP. Biverkningar som uppkom var i majoritet milda till medel-svåra och exempel på biverkningar som uppkom, Background: Endometriosis is a disease dependent on estrogen where endometriotic tissue develops outside the uterus, such as the pelvic or the ovaries. Symptoms associated with endometriosis are pelvic pain, dysmenorrhea and deep dyspareunia which can show up under different relapses. Another symptom of the disease is dealing with infertility. The prevalence of endometriosis is 10%. The goal with the treatment of endometriosis is primarily to prevent pain and the development of the disease. General treatment includes non steroidal anti-inflammatory drugs (NSAID), combined oral contraceptives, gonadotropin-releasing hormone analogs (GnRH), progestins, aromatase inhibitors, selective estrogen receptor modulators (SERM), or surgery. The drug dienogest is a progestin that acts by binding and activating progesterone receptors, leading to a lower estrogen synthesis. The aim: This literature study aimed to investigate the effect of dienogest on the treatment of endometriosis-associated pelvic pain (EAPP). Method: This literature review is based on five randomized controlled trials (RCT) from the database PubMed. The search was made with the keywords “endometriosis” and “dienogest.” Four of the articles compared dienogest 2 mg with placebo for treatment of EAPP. Out of these four articles, two were extension studies. The fifth article compared dienogest 2 mg with the oral contraceptive Yasmin (0,03 mg ethinylestradiol och 3 mg drospirenone) for the treatment of EAPP. Results: The results from the studies showed that dienogest 2 mg reduced EAPP effectively. In the first and second trials, dienogest was statistically significantly better at reducing EAPP than placebo. The extension studies showed that dienogest had long-term effects in improving EAPP, but the improvement in long-term treatment was also achieved with placebo. When dienogest was compared to the oral contraceptive Yasmin, both treatments affected EAPP by reducing the pain. Side effects were in the majority m

Bakgrund: Endometrios är en sjukdom beroende av östrogen där endometriotisk vävnad tillväxer utanför livmodern, i exempelvis bäcken eller äggstockarna. Symtomen är bäckensmärta, dysmenorré och djup dyspareuni som kommer under skov. Infertilitet kan också vara ett symtom vid endometrios. Prevalensen för sjukdomen är 10%. Behandling av endometrios sker främst för att förhindra smärta och vidare utveckling av sjukdomen. Läkemedel som sätts in kan vara ickesteroida antiinflammatoriska läkemedel (NSAID), orala kombinerade preventivmedel, gonadotropinfrisättande hormonanaloger (GnRH), progestiner, aromatasinhibitorer, selektiva östrogenreceptormodulatorer (SERM) eller behandling med kirurgi. Läkemedlet dienogest är ett progestin och har som verkningsmekanism att binda och aktivera progesteronreceptorer vilket leder till minskad syntes av östrogen. Syfte: Syftet med examensarbetet var att undersöka läkemedlet dienogests effekt vid behandling av endometrioskopplad bäckensmärta (EAPP). Metod: Denna litteraturstudie baserades på 5 vetenskapliga artiklar som valdes ut från databasen PubMed efter att sökorden ”endometriosis” tillsammans med ”dienogest” angivits. Av artiklarna jämförde 4 av de dienogest med placebo varav 2 av artiklarna var förlängningsstudier. Sista artikeln som valdes ut jämförde dienogest med orala kombinerade preventivmedlet Yasmin (0,03 mg etinylestradiol och 3 mg drospirenon). Resultat: Resultatet från studierna visade att dienogest 2 mg reducerade endometrioskopplad bäckensmärta effektivt. I studie 1 och 2 var dienogest statistiskt signifikant bättre i att reducera endometriosassocierad bäckensmärta jämfört med placebo. Vid förlängning av dienogestbehandling i studie 3 och 4 blev reduceringen i bäckensmärta också effektiv men lik placebo. Vid jämförelse av dienogest med orala kombinerade preventivmedlet Yasmin visade både läkemedlen förbättring av EAPP. Biverkningar som uppkom var i majoritet milda till medel-svåra och exempel på biverkningar som uppkom, Background: Endometriosis is a disease dependent on estrogen where endometriotic tissue develops outside the uterus, such as the pelvic or the ovaries. Symptoms associated with endometriosis are pelvic pain, dysmenorrhea and deep dyspareunia which can show up under different relapses. Another symptom of the disease is dealing with infertility. The prevalence of endometriosis is 10%. The goal with the treatment of endometriosis is primarily to prevent pain and the development of the disease. General treatment includes non steroidal anti-inflammatory drugs (NSAID), combined oral contraceptives, gonadotropin-releasing hormone analogs (GnRH), progestins, aromatase inhibitors, selective estrogen receptor modulators (SERM), or surgery. The drug dienogest is a progestin that acts by binding and activating progesterone receptors, leading to a lower estrogen synthesis. The aim: This literature study aimed to investigate the effect of dienogest on the treatment of endometriosis-associated pelvic pain (EAPP). Method: This literature review is based on five randomized controlled trials (RCT) from the database PubMed. The search was made with the keywords “endometriosis” and “dienogest.” Four of the articles compared dienogest 2 mg with placebo for treatment of EAPP. Out of these four articles, two were extension studies. The fifth article compared dienogest 2 mg with the oral contraceptive Yasmin (0,03 mg ethinylestradiol och 3 mg drospirenone) for the treatment of EAPP. Results: The results from the studies showed that dienogest 2 mg reduced EAPP effectively. In the first and second trials, dienogest was statistically significantly better at reducing EAPP than placebo. The extension studies showed that dienogest had long-term effects in improving EAPP, but the improvement in long-term treatment was also achieved with placebo. When dienogest was compared to the oral contraceptive Yasmin, both treatments affected EAPP by reducing the pain. Side effects were in the majority m

Context: Limited studies have compared the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones. Objective: To compare estradiol valerate (EV) + dienogest (DNG), EE + DNG, and DNG alone (active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, anti-Müllerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the free androgen index (FAI). Methods: This spin-off study from a randomized trial enrolled 59 healthy, 18 to 35-year-old ovulatory women, outpatients at Helsinki and Oulu University Hospitals, Finland, who were randomized to EV 2 mg + DNG 2‐3 mg (n = 20); EE 0.03 mg + DNG 2 mg (n = 20); and DNG 2 mg (n = 19) for 9 weeks. Blood samples were drawn at baseline, and at 5 and 9 weeks. Age and BMI were comparable between groups; 3 women discontinued. Results: EV + DNG suppressed FSH by −27% (−51% to −3%) (median [95% CI]) vs EE + DNG, −64% (−78 to −51), P = 0.04, but AMH levels decreased similarly by −9% (−18 to −0.1) vs −13% (−28 to 0.2), P = 0.38, respectively. EV + DNG increased SHBG levels by 56% (30% to 82%) and EE + DNG by 385% (313% to 423%), P < 0.001. Total testosterone decreased by 16% (−27% to −5%) in the EV + DNG group but it did not decrease in the EE + DNG group, whereas the FAI decreased by −39% (−54% to −25%) vs −72% (−78% to −67%), P < 0.001. DNG alone did not induce changes in any of these parameters. Conclusions: Compared with EE + DNG, treatment with EV + DNG resulted in milder pituitary downregulation and reduced induction of hepatic SHBG synthesis—potentially carrying more beneficial health effects.

Introduction: Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E₂] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin. Material and methods: We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2–3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover). Clinical trial registration: NCT02352090. Results: Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change −24%, 95% confidence interval [CI] −32% to −15%; p < 0.01) and time to thrombin peak (−26%, 95% CI −37% to −16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%–67% vs +147%,95% CI 96%–198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%–38% vs +64%, 95% CI 5

Bakgrund: Endometrios är en kronisk östrogenberoende sjukdom som innebär att livmodervävnad tillväxer utanför livmodern och karakteriseras av symtom såsom smärta, trötthet och infertilitet. Mål vid behandling är god funktionalitet och ökad livskvalitet. Behandlingsalternativ inkluderar icke-steroida antiinflammatoriska läkemedel (NSAIDs), kombinerade orala preventivmedel, gonadotropinfrisättande hormonanaloger (GnRHa) och progestiner. Progestinet dienogest aktiverar progesteronreceptorn medan GnRH-antagonisten elagolix blockerar GnRH-receptorn. Båda läkemedlen minskar därmed frisättningen av follikelstimulerande hormon (FSH) och luteiniserande hormon (LH), varvid frisättningen av könshormonet östrogen minskar. Syfte: Syftet med arbetet var att utvärdera och jämföra effekten av läkemedlen dienogest och elagolix vid behandling av endometriosassocierad bäckensmärta. Metod: Denna litteraturstudie är baserad på sju randomiserade kontrollerade vetenskapliga studier (RCT) som hämtats från den medicinska databasen PubMed. De sökord som använts är ”endometriosis”, ”pain”, ”elagolix” och ”dienogest”. Resultat: Dienogest i dosen 2mg gav upphov till statistiskt signifikant större förbättringar avseende endometriosassocierad bäckensmärta jämfört med placebo. I de studier där 2mg dienogest var den enda interventionen, d.v.s. inga jämförelser med placebo utfördes, uppvisades förbättringar avseende endometriosassocierad bäckensmärta. De studier som utvärderade elagolix var inte helt entydiga. I en studie gav elagolix i doserna 150mg och 250mg en gång dagligen inte upphov till statistiskt signifikanta förbättringar avseende endometriosassocierad bäckensmärta jämfört med placebo. I en annan studie där elagolix i doserna 150mg en gång dagligen respektive 200mg 2 gånger dagligen undersöktes uppkom statistiskt signifikant större förbättringar jämfört med placebo avseende endometriosassocierad bäckensmärta. I en förlängningsstudie där endast elagolix undersöktes (d.v.s. inga jämförelser, Background: Endometriosis is a chronic oestrogen-dependent disease where endometrial tissue grows outside the uterus and is characterised by symptoms such as pain, fatigue, and infertility. The purpose of treatment is achieving functionality as well as increasing quality of life. Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), combined oral contraceptives, gonadotropin-releasing hormone analogues (GnRHa) and progestins. The progesterone dienogest activate the progesterone receptor while the GnRH-antagonist elagolix blocks the GnRH-receptor. Both drugs result in decreased release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Thereby the release of the sex hormone oestrogen decreases. Purpose: The aim of this study was to evaluate and compare the effects of dienogest and elagolix for the treatment of endometriosis-associated pelvic-pain (EAPP). Method: This work is a literary review based on seven randomized controlled trials (RCT) that were retrieved from the medical database PubMed.gov using the keywords ("Endometriosis"[Mesh]) AND ("Pain") AND ("Dienogest" OR "Elagolix"). Results: Dienogest in the dose of 2mg resulted in statistically significant improvement compared to placebo with regards to EAPP. In studies solely evaluating 2mg dienogest, i.e. when no comparison with placebo was performed, improvements of EAPP arose. The studies evaluating the effects of elagolix were not fully conclusive. One study showed that elagolix in the doses 150mg and 250mg once daily did not show statistically significant improvements with respect to EAPP compared to placebo. Another study showed 150mg elagolix once daily respectively 200mg elagolix twice daily to be statistically significant better at reducing EAPP than placebo. A third study showed numerical improvement with respect to EAPP when elagolix was the sole study treatment, i.e. when the effect of elagolix was not compared to the effect of placebo. Conclusion: This literatur

Bakgrund: Endometrios är en kronisk östrogenberoende sjukdom som innebär att livmodervävnad tillväxer utanför livmodern och karakteriseras av symtom såsom smärta, trötthet och infertilitet. Mål vid behandling är god funktionalitet och ökad livskvalitet. Behandlingsalternativ inkluderar icke-steroida antiinflammatoriska läkemedel (NSAIDs), kombinerade orala preventivmedel, gonadotropinfrisättande hormonanaloger (GnRHa) och progestiner. Progestinet dienogest aktiverar progesteronreceptorn medan GnRH-antagonisten elagolix blockerar GnRH-receptorn. Båda läkemedlen minskar därmed frisättningen av follikelstimulerande hormon (FSH) och luteiniserande hormon (LH), varvid frisättningen av könshormonet östrogen minskar. Syfte: Syftet med arbetet var att utvärdera och jämföra effekten av läkemedlen dienogest och elagolix vid behandling av endometriosassocierad bäckensmärta. Metod: Denna litteraturstudie är baserad på sju randomiserade kontrollerade vetenskapliga studier (RCT) som hämtats från den medicinska databasen PubMed. De sökord som använts är ”endometriosis”, ”pain”, ”elagolix” och ”dienogest”. Resultat: Dienogest i dosen 2mg gav upphov till statistiskt signifikant större förbättringar avseende endometriosassocierad bäckensmärta jämfört med placebo. I de studier där 2mg dienogest var den enda interventionen, d.v.s. inga jämförelser med placebo utfördes, uppvisades förbättringar avseende endometriosassocierad bäckensmärta. De studier som utvärderade elagolix var inte helt entydiga. I en studie gav elagolix i doserna 150mg och 250mg en gång dagligen inte upphov till statistiskt signifikanta förbättringar avseende endometriosassocierad bäckensmärta jämfört med placebo. I en annan studie där elagolix i doserna 150mg en gång dagligen respektive 200mg 2 gånger dagligen undersöktes uppkom statistiskt signifikant större förbättringar jämfört med placebo avseende endometriosassocierad bäckensmärta. I en förlängningsstudie där endast elagolix undersöktes (d.v.s. inga jämförelser, Background: Endometriosis is a chronic oestrogen-dependent disease where endometrial tissue grows outside the uterus and is characterised by symptoms such as pain, fatigue, and infertility. The purpose of treatment is achieving functionality as well as increasing quality of life. Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), combined oral contraceptives, gonadotropin-releasing hormone analogues (GnRHa) and progestins. The progesterone dienogest activate the progesterone receptor while the GnRH-antagonist elagolix blocks the GnRH-receptor. Both drugs result in decreased release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Thereby the release of the sex hormone oestrogen decreases. Purpose: The aim of this study was to evaluate and compare the effects of dienogest and elagolix for the treatment of endometriosis-associated pelvic-pain (EAPP). Method: This work is a literary review based on seven randomized controlled trials (RCT) that were retrieved from the medical database PubMed.gov using the keywords ("Endometriosis"[Mesh]) AND ("Pain") AND ("Dienogest" OR "Elagolix"). Results: Dienogest in the dose of 2mg resulted in statistically significant improvement compared to placebo with regards to EAPP. In studies solely evaluating 2mg dienogest, i.e. when no comparison with placebo was performed, improvements of EAPP arose. The studies evaluating the effects of elagolix were not fully conclusive. One study showed that elagolix in the doses 150mg and 250mg once daily did not show statistically significant improvements with respect to EAPP compared to placebo. Another study showed 150mg elagolix once daily respectively 200mg elagolix twice daily to be statistically significant better at reducing EAPP than placebo. A third study showed numerical improvement with respect to EAPP when elagolix was the sole study treatment, i.e. when the effect of elagolix was not compared to the effect of placebo. Conclusion: This literatur

La endometriosis es una entidad frecuente en ginecología para la que desafortunadamente aun no se tiene un tratamiento del todo efectivo. En los últimos años se ha propuesto el uso de Dienogest, una progestina selectiva, con buenos resultados. Objetivo: Realizar una revisión sistemática de la literatura para determinar la efectividad del Dienogest para el tratamiento de la endometriosis. Materiales y métodos: Se realizó una búsqueda sistemática y ampliada de ensayos clínicos acerca de la efectividad del Dienogest en el manejo de la endometriosis. Resultados: La efectividad del dienogest para el tratamiento de la endometriosis es equiparable al de los análogos de GnRH, tiene un perfil de seguridad adecuado y su uso prolongado no está limitado por la presentación de eventos adversos., Endometriosis is a common disorder in gynecology for which unfortunately has not yet found a fully effective treatment. In recent years it has been proposed the use of dienogest, a selective progestin, with good results. Objective: To conduct a systematic review of the literature to determine the effectiveness of dienogest for the treatment of endometriosis. Materials and methods: We performed a systematic literature search of clinical trials on the effectiveness of dienogest in the management of endometriosis. Results: The effectiveness of dienogest for the treatment of endometriosis is comparable to that of GnRH analogues, has an adequate safety profile and prolonged use is not limited by the presentation of adverse events.

Endometriosis affects up to 10% of reproductive-aged women; with higher prevalence among patients suffering from dysmenorrhea, infertility and chronic pelvic pain (CPP). Early detection is the basis of targeting at time therapy. Administration of GnRH-agonists (GnRHa) is limited with its safety and portability. Dienogest administration as the stage of preparation to in vitro fertilization (IVF) may provide the preparative pre-gravid reserve. Fifty-six infertile patients with adenomyosis and previous IVF failures were recruited for prospective cohort study. The treatment followed the unique algorithm created using clinical experience. Post-transfer support was also considered. The aims included evaluation of dienogest effectiveness for different stages of adenomyosis; working out the schemes of dienogest therapy prior to IVF; evaluation of IVF effectiveness after dienogest administration. Patients with adenomyosis grade I-II demonstrated encouraging results: normalisation of menstrual function in 68.6% cases; decreasing of CPP in 74.3% of patients; better uterine vascularisation in 48.6% cases; IVF effectiveness increased up to 48.6%. Thus, in cases of adenomyosis and previous IVF failures dienogest should be administrated prior to IVF, which results in higher IVF effectiveness. © 2015 © 2015 Taylor & Francis.