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Purpose To investigate the histological efficacy of ranibizumab and zoledronic acid in an experimentally induced endometriosis model as compared with danazol, buserelin acetate and dienogest. Methods Endometrial implants were introduced in 52 female Wistar albino rats, which were then randomly divided into six groups. The animals were, respectively, given dienogest, danazol, buserelin acetate, zoledronic acid, ranibizumab and 0.9% NaCl. After 4 weeks, the volumes and histopathological properties of the implants were evaluated and the implants were excised completely at the third laparotomy. A histopathological scoring system was used to evaluate the preservation of epithelia. Endometrial explants were evaluated immunohistochemically. Results Among the groups, the histological score was significantly lower in the zoledronic acid and ranibizumab groups compared with the controls (p < 0.001). There were no significant differences regarding ellipsoidal volume levels between groups (p > 0.05). However, there was a statistically significant difference regarding cell numbers according to the degree of Bcl-2, NF-kappa B, and CD31 staining (p < 0.001). There was no statistically significant difference in Bcl-2, CD31, or NF-kappa B staining in the binary comparisons between the other groups (p > 0.05). For Bcl-2 staining, the staining rate of the group treated with zoledronic acid was significantly lower compared with the dienogest and danazol groups (p < 0.05). The staining rates of CD31 and NF-kappa B were significantly lower in the zoledronic acid and ranibizumab groups compared with the controls (p < 0.05). Conclusion According to these results, zoledronic acid and ranibizumab may be putative candidates for the treatment of endometriosis., Technological and Scientific Research Council of Turkey (TUBITAK) [213S002], This study was funded by The Technological and Scientific Research Council of Turkey (TUBITAK) (213S002).

To compare the efficacy of dienogest with the combined oral contraceptive pill (COC) Yasmin for the control of endometriosis-associated pelvic pain.Seventy women with endometriosis-associated chronic pelvic pain, dysmenorrhoea or both for6 months were randomized to either dienogest (Visanne) 2 mg/day or monophasic COC (Yasmin, 0.03 mg ethinyl estradiol and 3 mg drospirenone) for 24 weeks. The primary efficacy variable was change in non-cyclic pelvic pain and dysmenorrhoea from baseline to end of treatment, assessed using a visual analogue scale (VAS). The secondary efficacy variable was change in the Biberoglu and Behrman (BB) scale scores for chronic pelvic pain, dysmenorrhoea and dyspareunia. Health-related quality of life (HRQoL) was evaluated using the Endometriosis Health Profile-30 (EHP-30) questionnaire at baseline and 24 weeks. Safety variables included incidence of side-effects, bleeding pattern and treatment tolerability.Both treatments improved the mean VAS score for endometriosis-associated pelvic pain significantly: mean difference 6.0 [95% confidence interval (CI) 4.9-7.1; p 0.0001] in the dienogest group and 4.54 (95% CI 3.1-5.9; p 0.0001) in the COC group; the difference between them was not significant (p = 0.111). Similarly, both dienogest and COC improved HRQoL in various core and modular segments of the EHP-30 questionnaire with comparable requirements for supplemental pain medication (p = 0.782 and 0.258 at 12 and 24 weeks, respectively), and redistribution of the BB severity profile for chronic pelvic pain (p = 0.052 and 0.526 at 12 and 24 weeks, respectively), dysmenorrhoea (p = 0.521 and 1 at 12 and 24 weeks, respectively) and dyspareunia (p = 0.376 and 0.835, respectively). Nevertheless, dienogest was associated with fewer side-effects, and hence had a better safety and tolerability profile than COC.Dienogest (2 mg/day) is comparable to the COC Yasmin for the relief of endometriosis-associated pelvic pain and improvement in HRQoL.Clinicaltrials.gov under number NCT04256200; date of registration 15/1/2020 (registered retrospectively).

Aim: to evaluate the effectiveness of the argonoplasmic coagulation method in the treatment of external genital endometriosis (GE) in women. Materials and methods. An open, prospective, controlled, clinical and experimental study was conducted. 50 women with genital endometriosis aged 20 to 50 years and older were examined (the average age was 35±15 years). The following forms of GE were identified: peritoneal endometriosis - in 21 (42%) patients; extraperitoneal endometriosis - in 15 (30%); uterine body endometriosis - in 9 (18%); retrocervical endometriosis - in 5 (10%) patients. Clinical, laboratory (blood test, urinalysis, biochemical studies, hemostasiogram, bacteriological and microscopic studies of the cervical canal and vagina, cytological studies); instrumental and special research methods were used. By the method of enzyme immunoassay (ELISA), studies were conducted for the presence of infections: toxoplasmosis, herpes and cytomegalovirus, chlamydia, mycoplasma, ureaplasma infections, rubella. Results. For the treatment of external genital endometriosis, a combined treatment regimen was applied: argonoplasmic coagulation of endometrioid heteropathies using the FOTEK EA 141M apparatus, followed by the prescription of a course of hormone therapy including dienogest (visanna), which contributed to improving the general condition and quality of life, relieving clinical symptoms, reducing the frequency of relapses, improving the hormonal status of the women. With a mild form of external genital endometriosis, argonoplasmic coagulation of endometrioid heteropathies was carried out in the "spray" mode at a power of 37-42 W, at a depth of 0.1-1 mm with a time interval of exposure of 2-4 seconds. In the moderate-severe form of external genital endometriosis, argonoplasmic coagulation of endometrioid foci located at a depth of 1-2 mm was carried out in the "spray" mode at a given power of 42-50W, with a time interval of exposure to an argon torch of 3-5 seconds. In severe external genital endometriosis, argonoplasmic coagulation was performed in the "filgur" mode at a given power of 57-64 watts with a time interval of exposure of 4-7 seconds, at a distance of no more than 2.5-3.0 mm. Conclusions. The use of APC using the FOTEK EA 141M device ensures the effectiveness of treatment that enables to avoid the formation of rough scars, adverse reactions and / or complications, shortening of the time interval, absence of pain syndrome, microbial contamination, risk of massive bleeding. The use of dienogest group is effective in preventing relapses after surgical treatment of severe forms of genital endometriosis.

PURPOSE To study the efficacy and safety of the dienogest and the gonadotropin-releasing hormone agonist (GnRH-a) in symptomatic females with uterine adenomyosis. METHODS A total of 127 patients with adenomyosis with a chief complaint of dysmenorrhea were recruited. The first group received 2 mg of dienogest (DNG) daily, whereas the second group received goserelin acetate (GS) (3.6 mg/4 weeks) for 12 weeks. Outpatient follow-up was undertaken after 12 weeks. RESULTS Among 127 women, 56/63 (88.9%) patients completed the treatment in the DNG group, whereas 62/64 (96.9%) patients completed the treatment in the GS group. A significant decrease in dysmenorrhea symptoms as measured by the visual analog scale (VAS) and Carcinoma antigen125 (CA125) after 12 weeks of treatment was observed in both groups (p

AIM: The aim of this study was to determine the 25(OH)D status in patients with genital endometriosis compared to the control group and to analyze the clinical efficacy of cholecalciferol implication as a combined targeted therapy of the disease. MATERIALS AND METHODS: The main group included 440 patients with genital endometriosis (mean age 33.75.8 years) with various degrees of disease prevalence. The control group consisted of 30 women with the normal ovulatory menstrual cycle (mean age 26.33.1 years) in whom gynecological pathology was not revealed. Peripheral blood (PB) 25(OH)D level was assessed in all the participants included into the study. In 49 women from the main group, the level of 25(OH)D in the peritoneal fluid (PF) was determined. Comparative evaluation of the clinical efficacy of cholecalciferol intake in combination with gonadotropin-releasing hormone agonist (aGnRH) 3.75 mg injections or with dienogest 2 mg oral administration, as well as monotherapy in comparison with standard hormone-modulating treatment was carried out. Prior to the start of treatment, the patients had pain syndrome of varying severity, which was evaluated using the McGill Pain Questionnaire with the Visual Analogue Scale for pain. The psycho-emotional status was assessed using the Hospital Anxiety and Depression Scale. The Excel, Statistica 10, and Jamovi software programs were used to process the obtained data. RESULTS: The level of 25(OH)D in PB of patients with endometriosis was significantly lower compared to the control group (p 0.001). Women with Grades III and IV genital endometriosis were characterized by lower PB 25(OH)D levels compared to the patients with Grades I and II of the disease, but the difference was not statistically significant. Relationships were revealed between 25(OH)D levels in the PB and PF (p 0.001), as well as PF 25(OH)D level and the disease prevalence (p = 0.004). Significantly more pronounced pain reduction and stabilization of the psycho-emotional status were observed in patients receiving combined therapy with cholecalciferol. CONCLUSIONS: Insufficient level of vitamin D and vitamin D deficiency can be considered as factors that play a role in the progression of genital endometriosis. The use of cholecalciferol in combination with aGnRH 3.75 mg or dienogest 2 mg may more effectively reduce the severity of pain and stabilize the psycho-emotional status in patients with genital endometriosis compared to standard hormone-modulating therapy.

Background Endometriosis is a chronic inflammatory condition with varied presentation, which ultimately leads to chronic pelvic pain and infertility. It is a psychological and economic burden to the women and their families. Main body of abstract The literature search was performed on the following databases: MEDLINE, Google Scholar, Scopus, EMBASE, Global health, the COCHRANE library, and Web of Science. We searched the entirety of those databases for studies published until July 2020 and in English language. The literature search was conducted using the combination of the Medical Subject heading (MeSH) and any relevant keywords for “endometriosis related infertility and management” in different orders. The modalities of treatment of infertility in these patients are heterogeneous and inconclusive among the infertility experts. In this article, we tried to review the literature and look for the evidences for management of infertility caused by endometriosis. In stage I/II endometriosis, laparoscopic ablation leads to improvement in LBR. In stage III/IV, operative laparoscopy better than expectant management, to increase spontaneous pregnancy rates. Repeat surgery in stage III/IV rarely increases fecundability as it will decrease the ovarian reserve, and IVF will be better in these patients. The beneficial impact of GnRH agonist down-regulation in ART is undisputed. Dienogest is an upcoming and new alternative to GnRH agonist, with a better side effect profile. IVF + ICSI may be beneficial as compared to IVF alone. Younger patients planned for surgery due to pain or any other reason should be given the option of fertility preservation. Short conclusion In women with endometriosis-related infertility, clinician should individualize management, with patient-centred, multi-modal, and interdisciplinary integrated approach.

Dienogest (DIE) and drospirenone (DRO) are two fourth-generation synthetic progestins widely used as oral contraceptives. Despite their increasing detection in wastewaters and surface waters, their fate during biological wastewater treatment is unclear. Here, we investigated DIE and DRO biotransformation with representative activated sludge batch incubations and identified relevant transformation products (TPs) using high-resolution mass spectrometry. DIE exhibited slow biotransformation (16-30 h half-life) and proceeded through a quantitative aromatic dehydrogenation to form TP 309 (molar yields of ∼55%), an aromatic TP ∼30% estrogenic as 17β-estradiol. DRO experienced more rapid biotransformation (

Purpose To evaluate the efficacy of two progestins, levonorgestrel intrauterine system (LNG‐IUS) and dienogest (DNG), for adenomyosis. Methods This study enrolled 157 women with adenomyosis, randomized to either LNG‐IUS (n = 76) or DNG (n = 81) groups as a controlled clinical trial for 72 months. Participants were classified by three different localizations of adenomyosis: diffuse, focal, and extrinsic. VAS (Visual analog scale) score, days, and amount of uterine bleeding were assessed. Uterine volume or bone mineral density (BMD) were measured by three‐dimensional ultrasonography or dual‐energy X‐ray absorptiometry. Results LNG‐IUS and DNG comparably reduced pain scores in patients with adenomyosis. With regard to pain control, DNG offered greater efficacy than LNG‐IUS in 3 months of treatment. In all types of adenomyosis, the days of bleeding after 12 months with DNG were significantly decreased compared to those with LNG‐IUS. The decrease of whole uterine body was transient in any subtypes. A comparable decrease in BMD due to age‐related changes in both groups was observed. Conclusions LNG‐IUS and DNG could be useful for long‐term management of adenomyosis. In terms of durations of uterine bleeding, DNG was superior to LNG‐IUS for 6 years., We described the efficacy of two progestins, levonorgestrel intrauterine system (LNG‐IUS) and dienogest (DNG) in the treatment of adenomyosis as a first controlled clinical trial. Patients were classified by three different localizations of adenomyosis: diffuse, focal, and extrinsic. DNG proved superior to LNG‐IUS in terms of the duration of uterine bleeding.

Systematic review and Meta-analysis of efficacy and safety of dienogest in treatment of endometriosis

A low dose of dienogest (DNG) 1 mg/day is useful for treating dysmenorrhea in young women. However, the effect of DNG on bone turnover during bone growth and formation, rather than at maturity, is currently unknown even at low doses. We investigated change in bone turnover after 3 months of DNG 1 mg/day. This retrospective cohort study included young women aged 10–24 years with dysmenorrhea and irregular menstruation. Gonadotropins and the bone metabolism markers TRACP-5b and BAP were compared before and at 3 months after administration of DNG 1 mg/day. There were no significant changes in TRACP-5b (before, 455.6 ± 323.6 mU/dL, 3 months after, 462.1 ± 346.1 mU/dL), BAP (before, 24.7 ± 19.0 μg/L, 3 months after, 25.2 ± 22.3 μg/L), or the TRACP-5b/BAP ratio (before, 22.1 ± 7.0, 3 months after, 21.5 ± 6.3). Administration of DNG 1 mg/day had no significant effect on bone turnover after 3 months during the bone-growth phase in young women.

Introduction: Women with endometriosis require individualized, long-term treatment. Analyzing prescription choices, medication switches, discontinuations, and breaks can describe real-world treatment patterns and optimize pathways for women. To our knowledge, the Visanne Post-approval Observational Study (VIPOS) is the largest real-world, non-interventional study examining the safety of hormonal treatments for the routine clinical management of endometriosis. We present data from VIPOS on endometriosis drug utilization patterns, including treatment discontinuation due to treatment failure. Methods: VIPOS was a prospective, long-term, controlled, non-interventional cohort study in six European countries (Germany, Switzerland, Russia, Poland, Ukraine, and Hungary) conducted between 2010 and 2018. Women self-reported medical and gynecological history and symptoms and treatment information via comprehensive questionnaires. Results: Overall, 27,840 women were enrolled via gynecologists or specialized centers. Inter-country variance in treatment prescription patterns suggests the influence of differential management strategies and guidelines on prescribing behavior and diagnostic methods. Most enrolled women were receiving combined hormonal contraceptives. Women receiving dienogest 2 mg or gonadotropin-releasing hormone agonists more often had a surgical diagnosis of endometriosis compared to other treatments, while most women receiving combined hormonal contraceptives, other progestins or danazol had a symptom-based diagnosis. Although treatment changes during follow-up were common, only 4733 discontinuations out of 42,342 treatment starts were reported due to side effects or treatment ineffectiveness. Conclusion: VIPOS provides valuable insights into the considerable inter-country variance in endometriosis treatment prescription and potential role of differing management guidelines and practices strategies. Findings presented here suggest the need greater alignment of clinical practice to optimize patient management.

Combined oral contraceptives (COC), as drugs containing hormones, can negatively affect sexual function in women of reproductive age. Various causes of sexual dysfunction when taking COC have been studied: a decrease in the concentration of testosterone in the blood due to an increase in globulin, which binds sex steroids, under the influence of oral contraceptives. This mechanism is realized due to the action of two components of COC, both estrogenic and progestogenic. Female sex hormones are known to play an important role in the physiology of sexual desire and behavior. The importance of the most important of them, estrogens, in the sexual behavior of women is to prevent atrophic processes in the vagina, enhance vaginal and vulvar blood circulation, as well as to maintain sensory peripheral perception and the beneficial effect of these processes on the central nervous system. The presented clinical case demonstrates the positive effect of Claira (a drug that is a COC containing estradiol valerate in combination with dienogest with a dynamic dosage regimen) on sexual function. The content of this oral contraceptive of estrogen, identical to natural, eliminates the negative impact of COC on sexual function. Estradiol and estriol, formed during the metabolism of estradiol valerate, actively bind to receptors and have their effects in the tissues of the urogenital tract, having a positive effect on the manifestations of sexual dysfunction. Switching to the drug Clair from other COCs can normalize the condition of women who have decreased sexual function when taking a contraceptive of a different composition and mechanism of action, which was confirmed by this clinical study.

Endometriosis is now considered as benign disease. However, a correlation was found between endometriosis and several types of cancer. Endometriomas are found in 17–44% of patients with endometriosis and can be frequent precursors of ovarian cancer (endometrioid and clear cell ovarian tumors are more common). This process can be realized through several mechanisms: predominance of certain cytokines, oxidative stress and local hyperestrogenia, genetic mutations including PTEN, PIK3CA, ARID1A, Wnt/β-catenin, microsatellite instability, Src and KRAS.There are no generally accepted approaches to non-invasive early diagnosis of ovarian cancer, especially in borderline tumors and early stages of malignancy. The lack of accurate screening programs for ovarian cancer emphasizes the importance of identifying high-risk, moderate-risk, and low-risk groups. Screening is not recommended in the general population in the low-risk group. Annual CA125 evaluation and transvaginal pelvic ultrasound with general and special gynecological examination are recommended in the moderate-risk group in postmenopause. Transvaginal ultrasound of the pelvic organs with CA125 evaluation is performed every 6 months in the high-risk group, starting from 30 years or 5–10 years before the youngest age of ovarian cancer onset in relatives. The main method of diagnosing tumors is expert ultrasound of the pelvic organs (simultaneously with transabdominal ultrasound). The main tumor markers are CA125 (single evaluation has low diagnostic value), risk malignancy index (RMI) and HE4.Clinical trials are going on and various methods of prevention, screening and treatment of these diseases are being developed. Probably, dienogest can help to solve the problem. Existing results of research are promising, but insufficient since they show both the positive effects of progestin therapy and minor cases of cancer detection during therapy that are not related to the use of progestins, but probably indicate unknown mechanisms of transformation in endometriosis.

Endometriosis is a common disease, the diagnosis and treatment of which is still a matter of debate. One of the main symptoms of endometriosis -pelvic pain is a particular problem due to the difficulties in identifying the cause and the lack of sufficient effect from surgical and medical treatment. The literature review presents current data on the prevalence, clinical characteristics and methods of individualized therapy in patients with pelvic pain established or presumably associated with endometriosis.

Background: New vessel formation or neovascularization has been recognized as a feature of endometriosis. Treatment with cabergoline suppresses cell proliferation and vascular-endothelial-growth-factor-mediated angiogenesis, thereby promoting regression of endometriotic lesions. Dienogest, a fourth-generation progestin currently in use for the treatment of endometriosis significantly decreases the volume of endometrial implants. Objective: The objective of the study was to see if cabergoline is as effective as dienogest in reducing the size of endometriomas and pelvic pain in women with endometriosis. Methods: The prospective comparative study was carried out on 56 women with endometrioma (diagnosed by ultrasound), divided by odd and even numbers into two groups. Cabergoline, 0.5 mg tablet twice weekly, was given to 28 women for 3 months. Dienogest, 2 mg tablet daily, was given to 28 women for the same duration. Pre- and post-treatment assessment of endometrioma size by transvaginal sonography and pelvic pain using the 10-cm visual analog scale (VAS) were recorded. Results: The percentage reduction in endometrioma size in women given dienogest was twice that compared to the women given cabergoline. Mean VAS score after 3 months was significantly lower in the cabergoline group compared to dienogest ([Formula: see text] ¡ 0.05). The incidence of nausea, vomiting, and headache were similar in cabergoline and dienogest group. There was polymenorrhea in the cabergoline group and irregular spotting in the dienogest group. Conclusions: Reduction of the size of endometrioma is less apparent with cabergoline than dienogest after 3 months of treatment. Cabergoline yields better results in decreasing pelvic pain compared to dienogest.

Endometriosis refers to a chronic, often recurrent disease that requires the appointment of a long-term management plan and the patient with the appointment of therapy that effectively affects the clinic of this disease, at the same time having good tolerability, ensuring the patient's adherence to this method of treatment. This dictates the need for careful selection of a drug that meets such requirements. Moreover, studies of drug therapy for endometriosis should also be prolonged. In this case, they allow you to qualitatively assess the effectiveness of a particular type of treatment in the context of routine clinical practice. The main clinical manifestations of endometriosis of the uterine body-adenomyosis are pain syndrome, manifested by various types of pain (dysmenorrhea, dyspareunia, dyschesia, chronic pelvic pain) and the presence of abundant uterine bleeding. The presented clinical case demonstrates the effectiveness of long-term (for 36 months) use of dienogest at a dosage of 2 mg per day (the drug Vizanna) in a continuous mode in the treatment of a patient with adenomyosis. By the 4th month of therapy, the pain syndrome, manifested by dysmenorrhea and dyspareunia, which is the leading clinical manifestation of this pathology in the patient, was completely stopped. The proposed type of therapy has also demonstrated its effectiveness in relation to another clinical manifestation of the disease - heavy uterine bleeding. By the 6th month of therapy, the patient had developed persistent amenorrhea. Good tolerability and the absence of side effects, along with a pronounced clinical effect, led to a high adherence of the patient to this type of drug therapy and allowed her to continue it in the future with dynamic monitoring.

Menopausal Hormone Therapy in women with other underlying diseases: how to proceed? Abstract. Postmenopausal women frequently suffer, in addition to classical climacteric symptoms, from other diseases. Therefore, it is important to know when, in which form, and with which dosage menopausal hormone therapy (MHT) may be prescribed with regard to the underlying chronic disease. All women's health specialists have to know when MHT is contraindicated. To minimize the risks of MHT in the presence of a chronic disease, the following basic rules should be kept in mind: If there is no absolute contraindication, MHT should be started within the "window of opportunity" (age

The review presents the psychosocial characteristics of young women in todays millennial generation and survey data regarding their hormonal contraceptive requirements. The results of randomized clinical trials and real-life studies of the use of the combined oral contraceptive (COC) Qlaira containing estradiol valerate and dienogest (E2V/DNG) in a dynamic dosing regimen were analyzed, in which the reliability of the contraceptive effect of the drug was identified and confirmed, the restoration of fertility was population level after drug withdrawal, its minimal effect on metabolism and a reduced risk of cardiovascular complications (venous and arterial thrombosis) when using Qlaira COC in comparison with other COCs. The absence of a negative effect of COC E2V/DNG on body weight, sexual function and vaginal microbiocenosis in most women has been proven. The data on satisfactory characteristics of menstrual bleeding (lighter and shorter) in users of Qlaira COC and a decrease in symptoms associated with a hormone-free interval, which often occur when taking other COCs in the 21/7 regimen, are presented. The favorable efficacy and safety profile of COC E2V/DNG in real conditions, the advantages of estrogen bioidentical to the endogenous, in the composition of the drug, the dosage regimen 26/2, the positive effect on the lifestyle, determine the significant satisfaction of young women, including young women with children, and the ability to use the drug for a long time until menopause.

Objective: Endometriosis is a common disease that affects 5%-15% of women of reproductive age. This study aimed to evaluate the effect of dienogest (DNG) on improving pain scores of patients with endometriosis.Methods:Data of 77 women who were admitted to the endometriosis clinic from March 1, 2015, to March 1, 2017, were evaluated. Patients were divided into 2 groups: DNG group (n=46) or group that denied use of any medication (expectant management group, n=31). The main presenting symptoms were graded using the visual analog scale (VAS). Age, parity, gravidity, body mass index (BMI), VAS scores, and further surgery requirement of the study groups were compared.Results:The most common presenting symptom was dysmenorrhea (79.2%), and the least common was dysuria (7.8%). No statistically significant difference was found between the study groups in terms of age, parity, gravidity, BMI, and further surgery requirement. A significant difference was found in the reduction of dysmenorrhea, dyspareunia, dyschezia, and pelvic pain VAS scores between the study groups, and more reduction was observed in the DNG group after 6 months of follow-up (p

Background Extragonadal endometriosis is a rare condition, and its disease manifestation and long-term prognosis have not been elucidated. We report an extragonadal endometriosis case controlled by drug therapy for 14 years with analysis of the sex hormone receptor expression and PIK3CA mutation. Case presentation The patient was diagnosed with bladder endometriosis at age of 30 years, and underwent bilateral nephrostomy and GnRHa therapy with add-back therapy. The patient was switched to dienogest therapy at age 35 and had hematuria and bloody stools at age 38. PET-CT revealed a 6-cm mass in the bladder with fluorodeoxyglucose accumulation and the diagnosis of endometriosis in the bladder, sigmoid colon, and cecum was confirmed after the biopsy result. The lesion’s tubular structures were positive for the estrogen receptor, but only 30% positive for the progesterone receptor, and the H1047R mutation in PIK3CA was found in tubular structures of the bladder lesion. GnRHa therapy caused the tumors to shrink. Conclusion Decreased progesterone receptor expression and oncogenic mutations may influence the course of less common and rare site endometriosis. Rare site endometriosis often requires long-term hormone therapy, and management should be tailored to the patient's life stage, keeping in mind complications, such as decreased bone density.

Background Endometriosis affects the responsiveness to ovarian stimulation. This study aimed to assess the role of Dienogest pretreatment for endometriosis suppression as compared to Gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis pursuing IVF treatment. Methods In this randomized controlled trial, 134 women with endometriosis-related infertility were randomly allocated to group A (n = 67) who had monthly depot GnRHa for 3 months before ovarian stimulation in IVF treatment (Ultra-long protocol), and Group B (n = 67) who had daily oral Dienogest 2 mg/d for 3 months before starting standard long protocol for IVF. The primary outcome measure was the number of oocytes retrieved. The secondary outcome measures included the number of mature oocytes, fertilization rate, quality of life assessed by FertiQoL scores, cost of treatment, and pregnancy outcomes. Results Although there was no statistically significant difference between both groups regarding ovarian stimulation, response parameters, and pregnancy outcomes, the Dienogest group had a lower cost of treatment (2773 vs. 3664 EGP, P P P P Conclusion Our study indicates that Dienogest is a suitable and safe substitute for GnRHa pretreatment in endometriosis patients. Trial registration NCT04500743 “Retrospectively registered on August 5, 2020”.

Background: A number of works provide information on the effectiveness of dienogest in uterine adenomyosis. However, information on the use of the drug at various degrees of the adenomatous nodes, is not presented in the available literature. Aim: The aim of the study was to evaluate the clinical efficacy of dienogest in the treatment of patients with adenomyosis 2nd and 3rd stage and chronic pelvic pain. Materials and methods: A comprehensive clinical survey and treatment of 46 patients with signs of adenomyosis were carried out. Patients were divided into two groups: 28 patients with stage 2 adenomyosis, 18 patients with type 3 adenomyosis were included in the 2nd group. On the first phase of the menstrual cycle all patients underwent hysteroscopy for endoscopic verification of the diagnosis using the traditional Karl Storz hysteroscopic stand with separate treatment and diagnostic curettage of the uterine cavity and cervical canal, followed by histological examination. After surgical treatment all patients received dienogest at a dose 2 mg/day for 6 months. The treatment was performed during 6 months. After 3, 6, and 12 months of the study, the patients included in the survey underwent a comprehensive examination with a clinical assessment of the manifestations of the disease. The level of pain manifestations was evaluated on a visual analog scale (VAS) with a range of 0–10 points. During pain assessment, its manifestations were differentiated—pain due to dyspareunia, dysmenorrhea, dyschezia, and chronic pelvic pain were evaluated. Results: In the group of patients with 2nd adenomyosis stage, the intake of dienogest for 6 months led to the absence of manifestations of uterine bleeding and dyschezia, a decrease in the frequency of dyspareunia—by 7.7 times. In patients with the 3rd stage of the disease, the decrease in the symptoms of adenomyosis was less pronounced, however, after taking the drug, a decrease in the frequency of uterine bleeding was found to be 6 times, dyspareunia 4 times, and dyschezia 5 times. Twelve months after the start of observation (6 months after the end of treatment), none of the patients with 2nd stage of disease showed severe pelvic pain, in the group with 3rd stage of adenomyosis there were only two of these patients (11.1%). At the same time, the vast majority of patients included in the study did not have manifestations of chronic pelvic pain—78.6% of patients with 2nd stage of adenomyosis and 55.6% of patients with 3rd stage of disease, the remaining 21.4% and 33.3% of patients of the first and second groups reported a significant decrease in the severity of pain. Conclusions: The inclusion of dienogest in the combined treatment of adenomyosis is clinically effective, contributing to the rapid and reliable relief of the main manifestations of the disease in patients with adenomyosis with grade 2 and 3 nodes. Treatment of adenomyosis with the use of dienogest is clinically effective, contributing to the rapid and reliable relief of the main manifestation of the disease.

The aim of this study was to evaluate the changing pattern of bone mineral density (BMD) levels after 3 years of dienogest use post endometrioma surgery and investigate the possible predictive factors for BMD reduction. This retrospective study included 44 reproductive-aged women who took dienogest (2 mg/day) and followed up BMD for 3 years after laparoscopic endometrioma surgery from July 2013 to December 2018. In addition, to investigate the predictive factors in the group with decreased BMD, analysis was added for patients with decreased BMD after taking dienogest for 1 year post laparoscopic endometrioma surgery. After 3 years of treatment with dienogest, BMD of both the lumbar spine (- 4.4%) and femur neck (- 3.6%) decreased significantly compared to the baseline levels. Bone loss predominantly occurred during the first year of treatment in the lumbar spine (- 2.4%) and gradually decreased with time during the treatment period. The predictive factors for BMD reduction after dienogest use were evaluated based on a 1-year change in BMD levels of 160 women, but no associated factors were found. This study demonstrated that dienogest use for 3 years was associated with a significant and gradual decrease in BMD and no predictive factors for BMD reduction during the first year of treatment with dienogest were found. These results may be useful in counseling patients regarding long-term effects of dienogest use on reducing BMD levels so that appropriate preventive measures can be taken.

Dienogest (DNG), is an effective and widely used progestin used in the treatment of endometriosis, yet clinically, a subset of cases show resistance to DNG treatment. During a previous investigation on the effect of DNG of cytokines and growth factor production, we incidentally found that endometriotic cyst fluid did not demonstrate inhibitory effects to DNG in a subset of cases. To clarify the mechanisms of this resistance to DNG, we performed proteomics analysis to compare the protein expression between DNG-sensitive and resistant cases. Based upon our results, several proteins were extracted that relate to neutrophil granulocyte activation marker (myeloperoxidase, lactotransferrin), inflammation (azurocidin, neutrophil gelatinase-associated lipocalin, etc.), and others biological processes reflecting the clinical environment of the endometriotic cyst. Among these proteins, azurocidin (AZU) is perhaps most interesting one as azurocidin is a protease that cleaves insulin-like growth factor-1 (IGFBP-1) associated with clear cell carcinoma of the ovary. We propose that the proteins extracted in the present study warrant further investigation in their relationship to carcinogenesis of endometrioma.

Peritoneal inclusion cysts, which are also known as ‘peritoneal mesothelial cysts’ and ‘residual ovarian syndrome’, often form in the peritoneum or the pelvis after surgery or as a result of endome...

Objective: Endometriosis is a common gynecological condition that affects many women of reproductive age worldwide and is a major cause of pain and infertility. Treatment of endometriosis can be either surgical, aiming to restore normal anatomy by removing endometriotic lesions, or hormonal. Various medical treatments with different doses, formulations, delivery systems, and regimens have been tested. The main objective of this study was to compare the efficacy and tolerability of dienogest and dienogest plus ethinylestradiol on endometriosis-related pain. Additionally, the effects on endometrioma size were examined.Study Design: A total of 81 patients with clinically diagnosed endometrioma, who had chronic pelvic pain, dysmenorrhea, or deep dyspareunia between January 2015 and December 2018 were studied retrospectively. The patients were divided into two main groups: continuous oral dienogest (n=43) (Visanne®, 2 mg/day) and continuous oral dienogest plus ethinylestradiol (n=38) (Dienille®, 2 mg/0.03 mg/day). The intensity of pain symptoms was evaluated before therapy, then after 3 and 6 months of treatment using a 10-point numerical rating scale (0 = no pain and 10 = worst possible pain) (NRS) provided to the patients in advance.Results: The pain scores related to chronic pelvic pain decreased 36% for dienogest and 49% for dienogest plus ethinylestradiol (p

Amac:Polikistik over sendromlu kadinlarda hirsutizm tedavisinde drospirenon ve dienogest iceren iki oral kontraseptifin klinik etkinligini karsilastirmak icin prospektif randomize bir calisma yapildi. Hastalar ve Yontem:Bu calismaya orta-siddetli hirsutizm tanisi olan 50 kadin alindi. Yirmi bes hastaya 6 ay boyunca oral 0,03 mg etinil estradiol ve 3 mg drospirenon 21/7 (Grup 1) verildi. 25 hastalik bir baska gruba 6 ay boyunca oral 0,03 mg etinil estradiol ve 2 mg dienogest 21/7 (Grup 2) verildi. Hirsutizm, 6 ay sonra Ferriman-Gallwey (FG) puanlama sistemi kullanilarak degerlendirildi. Her iki tedavinin de 6 ayinin sonrasinda gorulen hormonal seviyeler bazal degerlerle ve birbirleriyle karsilastirildi. Bulgular:Hirsutizm icin F-G skorlarinda (ortalama ± SD) Grup 1\'de (19,3±6,2\'den 9,7±3,5’ye, p

Background Massive hemorrhagic ascites caused by endometriosis is exceedingly rare, and the treatment strategy remains controversial. Here, we report a case of endometriosis with massive hemorrhagic ascites treated with a novel triple therapy including conservative surgery, gonadotropin-releasing hormone agonist, and then dienogest. Case summary A 28-year-old nulliparous patient was admitted to Shengjing Hospital of China Medical University, and exploratory laparoscopy was performed. A total of 9500 mL of brown ascites was aspirated from the pelvic cavity, the bilateral ovaries strongly adhered to the posterior of the uterus and were fixed to the pelvic floor, and endometriotic cysts were not observed in either ovary. The pelvic and abdominal peritonea were covered with patchy red, white, and brown endometriotic lesions and defects. Partial surgical resection of endometriotic lesions on the peritoneum was performed while we simultaneously collected multiple peritoneal biopsies. The final pathological diagnosis was endometriosis coupled with hemorrhagic necrotic tissue. Conclusion Postoperative injection of gonadotropin-releasing hormone agonist was provided three times, followed by dienogest administration, and we will continue to follow up with this ongoing treatment.

To assess the effectiveness of using dienogest in combination with postoperative interventions in patients with endometriosis. There were enrolled 102 patients with signs of external endometriosis underwent examination and surgical treatment, subdivided into 2 groups: 67 – main group (after surgical treatment, received dienogest 2 mg/day for 6 months), 35 – comparison group received no hormone therapy in the postoperative period. Surgical treatment included removal of endometrioid ovarian cysts, endometriosis foci on the pelvic peritoneum and sacral uterine ligaments. Course of the early postoperative period (up to 1 month after the intervention) as well as the long-term dynamics of the disease manifestations (3, 6, 12 and 15 months later) were assessed. Dienogest was administered after surgical treatment due to endometriosis that reduced the severity of dyspareunia and intensity of chronic pelvic pain by 3.5- and 2-fold, respectively. The probability of achieving control over uterine bleeding 6 month after the onset of treatment due to endometriosis manifested with metrorrhagia showed that combination treatment (consisting of dienogest) was 3.19-fold higher compared to surgical treatment alone (OR = 3.19; 95 % CI = 1.70–11,0; p < 0,05). Recovery of normal menstrual cycle in 63 (94.0%) women of the main group was established 1.5–2 months after completing of hormonal treatment, while in the comparison group pain and dysmenorrhea relapsed in some patients at the 6-month follow-up. Decreased libido as a side effect in patients who treated with dienogest was observed in 2 (3.0 %) women. Dienogest was highly effective in the combination treatment of patients with verified endometriosis that resulted in reduced severity of pain and metrorrhagia. The drug was featured by low level of side effects. Thus, a combination treatment of endometriosis containing dienogest at a dose of 2 mg/day applied during postoperative period allows to reduce the severity of the disease clinical manifestations and improve treatment outcome.

The major causes of IVF failure in women with endometriosis have been attributed to decreased ovarian reserve, low embryo quality and impaired receptivity of the endometrium. Dienogest (DNG) has anti-inflammatory and anti-angiogenic activity and so may theoretically improve IVF outcomes in women with endometriosis. This study aimed to evaluate the administration of DNG before IVF in women with endometriosis who had previously failed one IVF cycle.This study was based on the retrospective analysis of a prospectively collected database, including 151 women who had failed a previous IVF cycle and all subsequent embryo transfers and had an imaging diagnosis of endometriosis. Patients either directly underwent IVF without receiving hormonal treatment or received 3 months of treatment with DNG (2 mg/daily) before IVF.Eighty-eight (58.3%) patients underwent IVF without previous hormonal treatment, and 63 (41.7%) received pretreatment with DNG. The cumulative implantation, clinical pregnancy and live birth rates were significantly higher in the DNG-treated group (39.7%, 33.3% and 28.6%) than in the non-treated group (23.9%, 18.2% and 14.8%; P = 0.049, 0.037 and 0.043, respectively). The largest diameter of endometriomas significantly decreased after DNG pretreatment (P 0.001). The use of DNG increased significantly the number of oocytes retrieved (P = 0.031), two-pronuclear embryos (P = 0.039) and blastocysts (P = 0.005) in women with endometriomas of diameter ≥4 cm.This study suggest that in patients with endometriosis, IVF outcomes can be improved by pretreatment with DNG. In particular, the use of DNG allows for better oocyte retrieval and blastocysts in patients with large endometriomas.

We present a case of hemorrhagic shock occurred during dienogest therapy for uterine adenomyosis which necessitated an emergency hysterectomy. The patient was a 45-year-old woman with adenomyosis. Magnetic resonance imaging showed type I adenomyosis measuring 10 cm. She had a history of intimal thrombectomy of pulmonary embolism and had been receiving warfarin and aspirin until the onset of the hemorrhagic shock. Following 6-month of gonadotropin-releasing hormone analogue, dienogest was commenced. Nine months after switching to dienogest, the patient experienced a persistent abnormal uterine bleeding for 2 weeks, eventually causing a massive bleeding and was transferred to our emergency room. A diagnosis of hemorrhagic shock with a severe anemia (hemoglobin 3.6 g/dL) was made. Despite blood transfusion and warfarin antagonization, continuous bleeding ≥150 g/h was not controlled. Emergent hysterectomy was opted and enabled hemostasis. Although the number of patients with adenomyosis who can avoid surgery by dienogest is increasing, care must be taken during dienogest therapy, especially in patients with anticoagulants and after gonadotropin-releasing hormone analogue treatment. To prevent such a critical event, careful management including patient education should be carried out.

Objective To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis. Patients and methods Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, BMI, insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random-effects model. We performed subgroup analyses by study duration ( Results Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel (P < 0.001) to 35.1 mg/dL for chlormadinone (P < 0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, P < 0.001) and drospirenone (+7.4 mg/dL, P < 0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL (P < 0.001). Levonorgestrel (+6.8 mg/dL, P < 0.001) and norgestimate (+11.5 mg/dL, P = 0.003) increased LDLc, while dienogest decreased it (–7.7 mg/dL, P = 0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration. Conclusion Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.

The article is devoted to the extremely pressing issue of the treatment of endometriosis, which is the object of a thorough study by scientists around the world. There is no drug that is 100% effective against endometrioid heterotopias and has no pronounced side effects either in our country, or abroad. In addition, the quality of evidence base generated on the basis of randomized clinical trials on the effectiveness of drug therapy for endometriosis is not sufficient in terms of research methodology. The Russian clinical guidelines for the management of endometriosis postulate that operational intervention is the main stage in the treatment of this disease. The treatment of endometriosis is aimed to remove the endometriotic lesion, reduce pain intensity, treat infertility, prevent progression or recurrences of the disease. There is currently no universal drug therapy for endometriosis, and the drug therapy used to treat it is nonspecific and primarily aims to reduce the severity of existing symptoms. The drug therapy for endometriosis is chosen on case-by-case basis, depending on the extent of the disease, clinical symptoms and the patient’s needs. In addition to the above, the choice of hormone therapy for endometriosis should take into account the efficacy of a drug, its individual tolerance, the cost of treatment, the doctor’s experience in using this drug, the patient’s compliance with the doctor’s recommendations. The article presents possible algorithms for choosing strategies in the treatment of endometriosis using surgical and pharmaceutical methods. The authors discussed the principles and mechanisms of action of hormonal drugs intended for the treatment of endometriosis. The review and analysis of modern clinical data on the problem of treatment of endometriosis is presented.

To demonstrate an outpatient vaginoscopic technique for treating multiple vaginal polyps.Demonstration of surgical technique using slides, pictures, and video.Private hospital.Thirty-two-year-old nulligravid woman presenting to the gynecology clinic with one episode of intermenstrual bleeding, regular menstrual cycles with normal flow, and no history of dysmenorrhoea or dyspareunia. The genital local examination was normal, and speculum examination showed multiple vaginal lesions like polyps in the proximal posterior two-thirds and right lateral vaginal walls. Her transvaginal ultrasound read a normal uterus with a right ovarian simple cyst.The surgeon performed an outpatient operative vaginoscopy using a 5-mm continuous flow office hysteroscope with a 2.9-mm rod lens optical system and a 5F working channel. Distension of the vagina was achieved with a normal saline solution, and an intrauterine pressure of 50 to 60 mm Hg was maintained by an irrigation and aspiration electronic pump. An inspection of the vaginal walls, fornices, and the external cervical os (Fig. 1) revealed 10 vaginal lesions like polyps in the proximal two-thirds of the posterior and right lateral vaginal wall. The vaginal lesions (Fig. 2) varied in size from 0.5 cm to 4 cm. An excisional biopsy was performed and the sample sent for histopathologic evaluation. The vaginal lesions2 cm in length were excised by cutting the base with scissors or using a bipolar vaporization electrode, which was connected to an electrocautery unit by a bipolar high-frequency cord. Vaginal lesions2 cm were excised with the TruClear 5C Hysteroscopic Tissue Removal System (HTRS) with a zero-degree scope using the 2.9-mm incisor with a 5-mm cutting window at one end attached to a reusable handpiece with two connectors-one to the motor unit and second to the suction bottle with a collection bag. The overall diameter of TruClear 5C is 5.7 mm, and the optic size is 0.8 mm. The same irrigation pump is compatible with HTRS, and the pressure was increased to 150 mm Hg to maintain vaginal distension. Three factors influenced our decision to use the HTRS intraoperatively: the number and size of the vaginal lesions and the surgical time in the outpatient setting. A mechanical system that works on the principle of excising and aspirating tissue, the HTRS incisor has a rotatory action with the excising window placed against the most distal part of the vaginal lesions. The cutting action is controlled via a foot pedal attached to a motor control with 800 rotations per minute. The handpiece remains stationary while the polyp is excised and aspirated through the window into the collection bag. Minimal bleeding occurred and stopped spontaneously. The institutional ethics committee exempted this case report from review, and we obtained informed written consent from the patient.All vaginal lesions excised in an outpatient setting via vaginoscopy technique without anesthesia.The operative time with the Bettocchi hysteroscope was 14 minutes, and HTRS was 6 minutes. The patient did not complain of pain but did describe minimal discomfort, rated on the visual analog scale as 2 (where ≥5 is severe pain). She was discharged 1 hour later. The histopathology was reported as vaginal endometriosis (ectopic presentation of endometriosis is rare, accounting for 0.02% of cases). After surgery, she was started on cyclical oral contraceptive pills (OCP) in the combination of 30 mg of ethinyl estradiol + 2 mg of dienogest because she desired to delay pregnancy by 1 year. She remained asymptomatic for 6 months. These contraceptive hormones are available in the form of oral pills, vaginal rings, and transdermal patches, and a physician can provide OCP continuously or cyclically. Continuous OCP is more efficacious for control of dysmenorrhoea, but cyclical OCP is preferred because it is affordable, tolerable, effective, produces no unpredictable bleeding, and slows the progression of the disease. (A cohort study found the contraceptive vaginal ring to be more effective for symptom-control in rectovaginal endometriosis with higher patient satisfaction than the transdermal patch; vaginal rings or transdermal patches are not available in some countries.) CONCLUSION(S): Vaginoscopy allows a more in-depth visualization of the vagina with complete inspection and removal of all polyps. Vaginoscopy is feasible in the outpatient setting and allows a comfortable, ergonomic position for the surgeon. Vaginoscopy or no-touch technique avoids the use of a speculum or tenaculum and results in minimal pain during the outpatient procedure.

Background: One of the chronic disabling illness affecting approximately 10% of women in midst of their reproductive period is Endometriosis. The treatment goal of endometriosis is to activate decidualization within the hormonally dependent ectopic endometrium and is regularly given to alleviate pain symptoms and reduce its recurrence among women. Objectives: The aim of the study was to evaluate the effectiveness of dienogest in reducing pain and its influence on (QOL) quality of life among women affected with endometriosis. Materials and Methods: A prospective observational cohort study was conducted at Karpaga Vinayaga Institute of Medical Sciences and Research Centre including fifty patients with endometriosis treated with dienogest two mg per day for three months.We assessed the pelvic pain symptoms by visual analogue scale and (QOL)quality of life was determined by physical and mental index before and after 3 months of use of dienogest. Study Design: To perform statistical analysis, we used paired t test. Results: Women were on average 33.18 + 4.43 years. The mean +SD of VAS of 7.72 (0.73) in women with endometriosis was progressively decreased to 4.34(0.66) after 3 months of treatment with dienogest. The physical index score values increased significantly from 31.94 to 42.77 (p increased from 35.07 to 45.86 (p acne, hot flushes and weight gain. Conclusion: The results suggest that among women with endometriosis, dienogest has a relatively favorable safety profile and is well accepted in bettering the quality of life (QOL). Keywords: Endometriosis, (QOL) Quality of life, Dienogest, Pelvic pain.

Pedachenko N. Yu., Shemelko T. L., Tukhtarian R. A. How the therapy for endometriosis affects the hormonal status in female infertility. Journal of Education, Health and Sport. 2020;10(8):505-517. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.08.062 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.08.062 https://zenodo.org/record/4064093 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 04.08.2020. Revised: 14.08.2020. Accepted: 31.08.2020. How the therapy for endometriosis affects the hormonal status in female infertility N. Yu. Pedachenko1, T. L. Shemelko2, R. A. Tukhtarian1 1Shupyk NMAPE 2State Institution “Ciscarpathian Centre for Human Reproduction”, Health Ministry of Ukraine Pedachenko Natalia, MD, Dr Sci., Professor, Professor of Obstetrics, Gynecology and Perinatology Department of the Shupik National Medical Academy of Postgraduate Education; 9 Dorogozhitska Str Kyiv 02000 Ukraine; Clinical facility - Kyiv City Maternity Hospital No1, 5 Arsenalnaya Str,. Tel. +380 (44) 2850424, email: clinicnv@gmail.com ORCID 0000-0002-0821-2943 Shemelko Taras, obstetrian-gynecologist, Ciscarpathian Centre for Human Reproduction, Health Ministry of Ukraine ORCID 0000-0002-6333-0328 Tukhtarian Roksana, intern-doctor, Department of the Shupik National Medical Academy of Postgraduate Education ORCID 0000-0003-1452-8677 Abstract Aim. To determine changes in the values of pituitary and ovarian hormones in women with endometriosis-associated infertility, as well as to evaluate the impact of endometriosis therapy on hormonal parameters Materials and Methods. Sixty-nine women with small-sized endometriomas with adenomyosis (target group) and 50 women with tubal infertility (controls) were examined. The values of pituitary (luteinizing and follicle-stimulating hormones, prolactin) and ovarian (estradiol, tubular antimullerian hormone) hormones were studied. The comparison of quantitative indicators between the studied groups of women was carried out using the Mann-Whitney U-test, the statistical significance of the results was assessed at a level of not less than 95% (risk of error not more than 5% - p Results Infertile women with endometrioma and adenomyosis have lower AMH levels than infertile women with tubal factor. Among patients with endometriosis, there is an increase in serum FSH, LH, prolactin and estradiol compared with women without endometriosis. Dienogest moderately inhibits the secretion of FSH and LH; it has almost no effect on blood AMH and estradiol values. The use of dienogest can moderately increase the level of prolactin, It is noteworthy that these indicators are within the reference range. The use of diferelin for the treatment of endometriosis has a more active effect on the hormonal status of patients, given the decrease in such indicators as FSH and LH, AMH, estradiol and prolactin Conclusions. Women with infertility against the background of endometriosis have minor changes in the hypothalamic-pituitary-ovarian system, which indicates the need to develop medical measures in order to correct them. The use of dienogest compared to diferelin affects the hormonal status of patients with endometriosis to a lesser extent, given the pronounced anti-proliferative effect. Key words: endometriosis; pituitary hormones; ovarian hormones; hypothalamic-pituitary-ovarian system; infertility; dienogest; a-GnRH; diferelin.

Objective Dienogest (DNG) 2 mg (Visanne) was launched for endometriosis treatment in Europe in 2010. The Visanne Post-approval Observational Study (VIPOS) was designed to assess the safety of DNG 2 mg/day compared to other hormonal endometriosis treatments, focusing especially on clinically relevant depression and anemia. Study design Large, prospective, non-interventional, active surveillance study in six European countries. Participants were recruited via gynecologists or specialized centers routinely prescribing endometriosis medication. Self-administered questionnaires during study entry and follow-up collected information on baseline characteristics, health status and endometriosis treatment. Patient-reported anemia and depression cases were validated by health care professionals. Inferential statistics were based on Cox proportional hazards models and crude and adjusted hazard ratios (HR) between cohorts were calculated (including 95% confidence intervals [CI]). Adjustment for potential confounding was performed by including predefined prognostic factors as covariates in the Cox models. Results Out of 26,430 participants, 11.4% used DNG, 12.8% used other approved endometriosis medications (OAED) and 75.7% used hormonal treatments not approved but frequently used for endometriosis treatment (NAED). At baseline, DNG users more frequently reported a surgically confirmed endometriosis diagnosis, severe endometriosis-associated pain and a history of depression, compared to the other cohorts. Baseline characteristics showed large inter-country variability. Overall, the number of confirmed anemia and depression events were substantially lower than expected. The adjusted HRs for anemia were 1.1 (95% CI, 0.4–2.6) for DNG vs OAED and 1.3 (95% CI, 0.7–2.4) for DNG vs NAED. The adjusted HRs for new or worsening depression were 1.8 (95% CI, 0.3–9.4) for DNG vs OAED and 1.5 (95% CI, 0.8–2.8) for DNG vs NAED. Conclusion The main limitations encountered (low number of confirmed events and considerable inter-country variability) made a robust statistical analysis and a solid interpretation of the results challenging. However, no safety signal regarding anemia for DNG users could be detected, whereas a slight increase in depression risk cannot be excluded but might be explained by baseline severity of endometriosis or unknown country-specific confounding variables. VIPOS reflected routine use of hormonal endometriosis medications and provided real-world insights into endometriosis management in Europe.

To compare the effects of preoperative dienogest (DNG) and gonadotropin-releasing hormone (GnRH) agonist administration on the improvement of preoperative symptoms and surgical outcomes in patients who underwent laparoscopic cystectomy for ovarian endometriomas. Seventy patients who were scheduled for laparoscopic surgery were enrolled in the study. They were divided into two groups: 35 patients who received DNG for 4 months preoperatively (group D) and 35 patients who received low-dose sustained-release goserelin acetate for 4 months preoperatively (group G). Preoperative outcomes, including pain score associated with endometriosis, using the numerical rating scale (NRS), adverse events of hormonal therapy and Kupperman index (KI) before and after treatment, surgical outcomes including total surgical duration and blood loss, and postoperative recurrence of endometrioma were compared between the two groups. Regarding preoperative symptoms, NRS and KI at 4 months after preoperative hormonal therapy were significantly lower in group D than in group G (NRS, 5.3 ± 5.5 vs. 2.7 ± 3.9; P = 0.01; KI, 16.0 ± 11.0 vs. 9.2 ± 7.6; P = 0.006). Regarding adverse events, the incidence of hot flashes was significantly lower in group D than in group G (P

Aim. Comparative evaluation of the effectiveness of various types of hormone therapy for the prevention of relapses of endometrioid cysts (EC), based on clinical observation and data analysis. Materials and methods. Retrospective analysis of 122 patients (the average age 31.76.12 years) with laparoscopically confirmed endometriosis. Patients were divided into groups, according to the treatment options aGnRH (n=11), COCs (n=13), dienogest (Visanne) (n=56). A comparison group included 42 patients who did not receive hormone therapy. There were evaluated the number of reccurence in the group without therapy and in groups with different options for hormonal therapy. Results. Among patients treated with hormone therapy, the recurrence rate of EC was 3.75%, among those who have not received therapy 38.1%. Of these, 31.1% of patients had recurrence rate of EC during the first year, 37.8% during 3 years, and 31.1% after 3 years. After suppressive therapy was discontinued, the relapse rate in the aGnRH group was 63.6%, COC 50%, dienogest 24%. Conclusions. In addition to evaluating the ovarian reserve before and after surgical treatment, management tactics for patients with EC should include the long-term administration of dienogest as an anti-relapse therapy.

Aim: to assess the effectiveness of using dienogest in combination with postoperative interventions in patients with endometriosis.Materials and methods. There were enrolled 102 patients with signs of external endometriosis underwent examination and surgical treatment, subdivided into 2 groups: 67 – main group (after surgical treatment, received dienogest 2 mg/day for 6 months), 35 – comparison group received no hormone therapy in the postoperative period. Surgical treatment included removal of endometrioid ovarian cysts, endometriosis foci on the pelvic peritoneum and sacral uterine ligaments. Course of the early postoperative period (up to 1 month after the intervention) as well as the long-term dynamics of the disease manifestations (3, 6, 12 and 15 months later) were assessed.Results. Dienogest was administered after surgical treatment due to endometriosis that reduced the severity of dyspareunia and intensity of chronic pelvic pain by 3.5- and 2-fold, respectively. The probability of achieving control over uterine bleeding 6 month after the onset of treatment due to endometriosis manifested with metrorrhagia showed that combination treatment (consisting of dienogest) was 3.19-fold higher compared to surgical treatment alone (OR = 3.19; 95 % CI = 1.70–11,0; p < 0,05). Recovery of normal menstrual cycle in 63 (94.0%) women of the main group was established 1.5–2 months after completing of hormonal treatment, while in the comparison group pain and dysmenorrhea relapsed in some patients at the 6-month follow-up. Decreased libido as a side effect in patients who treated with dienogest was observed in 2 (3.0 %) women.Conclusion. Dienogest was highly effective in the combination treatment of patients with verified endometriosis that resulted in reduced severity of pain and metrorrhagia. The drug was featured by low level of side effects. Thus, a combination treatment of endometriosis containing dienogest at a dose of 2 mg/day applied during postoperative period allows to reduce the severity of the disease clinical manifestations and improve treatment outcome.

It is known that co‐administration of CYP3A inducers may decrease the effectiveness of oral contraceptives containing progestins as mono‐preparations or combined with ethinylestradiol. In a randomized clinical drug‐drug interaction study, we investigated the effects of CYP3A induction on the pharmacokinetics of commonly used progestins and ethinylestradiol. Rifampicin was used to induce CYP3A. The progestins chosen as victim drugs were levonorgestrel, norethindrone, desogestrel, and dienogest as mono‐products, and drospirenone combined with ethinylestradiol. Postmenopausal women (n = 12–14 per treatment group) received, in fixed sequence, a single dose of the victim drug plus midazolam without rifampicin, with rifampicin 10 mg/day (weak induction), and with rifampicin 600 mg/day (strong induction). The effects on progestin exposure were compared with the effects on midazolam exposure (as a benchmark). Unbound concentrations were evaluated for drugs binding to sex hormone binding globulin. Weak CYP3A induction, as confirmed by a mean decrease in midazolam exposure by 46%, resulted in minor changes in progestin exposure (mean decreases: 15–37%). Strong CYP3A induction, in contrast, resulted in mean decreases by 57–90% (mean decrease in midazolam exposure: 86%). Namely, the magnitude of the observed induction effects varied from weak to strong. Our data might provide an impetus to revisit the currently applied clinical recommendations for oral contraceptives, especially for levonorgestrel and norethindrone‐containing products, and they might give an indication as to which progestin could be used, if requested, by women taking weak CYP3A inducers—although it is acknowledged that the exact exposure‐response relationship for contraceptive efficacy is currently unclear for most progestins.

Introduction: “The aim of our study was to analyze the effect of dienogest on the endometrioid glands in myometrium, a morphological assessment of the effect of the drug, taking into account its safety, as well as an assessment of changes in the quality of life of women associated with a decrease in the severity symptoms of adenomyosis.” Materials and methods: The study included women aged 20–50 years, with histologically confirmed adenomyosis, which was manifested in them by the presence of pelvic pain, abnormal uterine bleeding, painful, and/or heavy menstruation, as well as the presence of anemia. Patients were divided into three groups depending on the name of the drug that they used: 24 patients of Group I received the drug “Visanne” at 2 mg/day for 6 months. In the second group, 24 patients received the combined oral contraceptive drug Klaira, which contains gestagen and estrogen. The third group included 24 patients who received the Jeanine preparation continuously (21–21–21) for 6 months and then received it for an additional 6 months according to the scheme (7 + 21), containing ethinyl estradiol and dienogest. Results: After the appointment of drugs for 6–12 months, bloody discharge from the genital tract in Group I completely stopped in all 10 women; in Group II, the discharge decreased in four women and completely stopped in eight women; and in group III, the discharge decreased in three women and completely stopped in seven women, pain in Group I completely stopped in six women out of eight (75%) and decreased in two women out of eight (25%); in the second group, the pain stopped completely in 7 women out of 12 (58.3 %) and decreased in 5 women out of 12 (41.6%); in the third group, pain completely recovered in 6 women out of 10 (60%) and decreased in 4 women out of 10 (40%). According to the morphological assessment (Figures 1 and 2) of the myometrium section with endometrioid glands before treatment, Group I had 12.2 ± 3.8* glands before treatment and from 1.4 ± 0.8* endometrioid glands after treatment. In the second group, the number of glands before treatment was 10.8 ± 1.4* and after treatment from 3.8 ± 0.7 glands, and in the third group before treatment, 6.7 ± 2.1 endometrioid glands were determined and after treatment 2.7 ± 1.4 glands in the field of view (Figure 1). Conclusion: Dienogest is effective in the treatment of endometriosis and reduces both the clinical manifestations of adenomyosis (abnormal uterine bleeding and chronic pelvic pain) and laboratory blood counts, increasing hemoglobin levels, together with a decrease in the activity of the endometrioid glands in myometrium. Dienogest is a highly selective progestogen against progesterone receptors and has anti-proliferative activity in isolated human endometrial cells. Given the indicators of the 36-Item Short Form Survey questionnaire, the quality of life in all the studied groups improved in all parameters, which indicates the effectiveness of the dienogest-containing drugs used.

Description. The review is presented by modern publications, reflecting the importance of high-quality patient counseling when choosing a method of contraception and the factors that influence it. The choice of combined oral contraceptive (COC) is determined by the need for reliable and safe contraception, expectations for an improved quality of life, and doubts about the frequency of side effects and effects on reproductive and somatic health. Modern COCs containing natural hormone (estradiol valerate), a new gestagen (dienogest) with a dynamic regime and a shortened hormone-free interval (2 days) satisfy the COC requirements of most women from menarche to menopause when contraception is required. An improvement in the profile of menstrual bleeding (a decrease in blood loss in 88% of users) and sexual functioning (increased libido, arousal, and maintaining the cyclical nature of sexual behavior) has been shown. Estradiol valerate does not affect metabolism, has a low risk of thromboembolic events (the adjusted risk of venous thromboembolism compared to other COCs is 0.4) and a low frequency of failure due to side effects (1.7%). This tool is characterized by high efficiency (adjusted Pearl index 0.42) and user satisfaction (78.180.2%). Conclusion. COCs with estradiol valerate/dinogest in 26/2 mode, fully satisfying the requirements of women for contraception, contributes to high adherence to it, that is, consistent and correct use, which contributes to the long-term use of the selected COC and ensures the quality of life of women for many years.

Pedachenko N. Yu., Shemelko T. L., Tukhtarian R. A. The value of the expression of endometrial receptors for steroid hormones in patients with endometriosis. Journal of Education, Health and Sport. 2020;10(5):321-331. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.05.034 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.05.034 https://zenodo.org/record/4066951 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 04.05.2020. Revised: 16.05.2020. Accepted: 29.05.2020. The value of the expression of endometrial receptors for steroid hormones in patients with endometriosis N. Yu. Pedachenko1, T. L. Shemelko2, R. A. Tukhtarian1 1Shupyk NMAPO 2State Institution “Ciscarpathian Centre for Human Reproduction”, the Ministry of Health, Ukraine Pedachenko Natalia, MD, Dr Sci., Professor of Obstetrics, Gynecology and Perinatology Department of the Shupyk National Medical Academy of Postgraduate Education; 9 Dorogozhitska Str Kyiv 02000 Ukraine; Clinical facility - Kyiv City Maternity Hospital No1, 5 Arsenalnaya Str,. Tel. +380 (44) 2850424, email: clinicnv@gmail.com ORCID 0000-0002-0821-2943 Shemelko Taras, Obstetrian-gynecologist, Ciscarpathian Centre for Human Reproduction, Ministry of Health, Ukraine ORCID 0000-0002-6333-0328 Tukhtarian Roksana, Intern, Obstetrics, Gynaecology and Perinatology Department of the Shupyk National Medical Academy of Postgraduate Education ORCID 0000-0003-1452-8677 Abstract Aim: To elucidate the nature of the expression of progesterone receptors (PR) and estrogen receptors (ER) of the endometrium in patients with endometriosis in order to study the effect of endometriosis therapy on endometrial receptors while taking progestogens and agonists of gonadotropin-releasing hormones (a-GnRH). Materials and Methods. A total of 119 women were examined, including 69 patients with small-sized endometrioma with adenomyosis, who were divided into two subgroups during the study: 35 women received Dienogest therapy, other 34 patients received Diferelin. To study the expression of endometrial steroid receptors, the patients underwent endometrial aspiration biopsy from different points of the uterine cavity before the treatment and after 3 months against the background of the therapy for endometriosis. Results Endometriosis therapy affects the expression pattern of endometrial steroid receptors. While taking Dienogest, the sensitivity of the endometrium to estrogens increases, and the number of cells with a positive response to progesterone receptors is partially reduced. When using gonadotropin-releasing hormone agonists (Dipherelin), the sensitivity of the uterine mucosa to ovarian hormones decreases, which is confirmed by the adequate expression of ER and PR. There is a need for more research on estrogen beta receptors, as well as progesterone receptors A and B, and the related ratios. Key words: endometriosis; estrogen receptor; progesterone receptor; dienogest; a-GnRH

By definition, contraception is the prevention of pregnancy and infection from diseases by mechanical, chemical and other contraceptives and methods. According to World Health Organization (WHO) statistics, up to 40% of women of reproductive age still believe that their needs for family planning services are not met during counseling. When recommending contraception, it is important to consider: the characteristics of the potential consumer, the underlying risk of the disease, possible undesirable drug reactions of various drugs, the cost, availability and preferences of the woman herself. Women are often forced to abandon the use of a contraceptive method in connection with adverse events, for example, when using combined oral contraceptives (COCs), they may feel worse (headaches, mood lability, weight gain, swelling, decreased libido) in a hormone-free interval, especially with the reception mode 21/7. Lack of contraception can lead to an increased risk of an unwanted pregnancy. According to statistics in the Russian Federation in 2018, the absolute number of abortions amounted to 567 183, which, according to the UN classification, corresponds to the average level (level of abortion rate per 1000 women of childbearing age). According to clinical practice, there is a relationship between deterioration of well-being and the duration of the hormone-free interval. At the moment, in our country there is the only COC, which has a hormone-free interval of 2 days, containing bioidentical estrogen estradiol valerate and dienogest. According to the Cochrane Library, COCs with a short hormone-free interval are most effective in relation to the clinical manifestations of the estrogen withdrawal syndrome. WHO calls on clinicians to raise womens awareness of modern methods of contraception.

Background. Most common clinical manifestations of endometriosis (N80) include pelvic pain and infertility, while adenomyosis is associated with abnormal uterine bleeding. At present, approach to the treatment of endometriosis has been revised towards shifting surgery to the second-line therapy; medications are considered as the first-line therapy: gonadotropin releasing hormone agonists, progestogens, aromatase inhibitors. Aim. Comparison of clinical and anamnestic characteristics and therapeutic procedures in women who were treated on an outpatient basis and those who were hospitalized and underwent surgical intervention. Materials and methods. Clinical-anamnestic and morphological characteristics were studied in two groups of women: 1st group (n=27) received drug therapy, 2nd group (n=28) underwent surgical intervention. Results and discussion. In the 1st group, 25.9% of patients received microdosed combined oral contraceptives which contain dienogest as a progestogen component, 44.4% of patients received monotherapy with dienogest, and 22.2% of patients received dydrogesterone in a prolonged mode. In the 2nd group, 39 foci of endometriosis, isolated and in a combination of various loci, were revealed during surgery, of which 30.8% were ovarian cysts, 10.2% were foci on the sacro-uterine ligaments, 23.1% were on the pelvis peritoneum. Surgical approach was determined by the urgency of intervention, an expect localization of endometriosis foci, a comorbidity of endometriosis with another pathology of the internal genitalia, 82.1% of surgery were performed by laparoscopic approach. Conclusions. The choice of treatment method depends on the severity of symptoms, the severity of endometriosis, the woman age and her reproductive intentions. When choosing a surgical treatment, one should be guided not only by the need for the most radical removal of endometriosis foci, but also should consider a surgical approach to minimize discomfort and provide a good quality of life after surgery. A three-stage model for the management of patients with endometriosis is proposed, which includes an assessment of treatment effectiveness and the need to develop a rehabilitation program.

Context Combined oral contraceptives (COCs) alter inflammatory status and lipid metabolism. Whether different estrogens have different effects is poorly understood. Objective We compared the effects of COCs containing ethinyl estradiol (EE) or estradiol valerate (EV) and dienogest (DNG) with those containing DNG only on inflammation and lipid metabolism. Design Randomized, controlled, open-label clinical trial. Setting Two-center study in Helsinki and Oulu University Hospitals. Participants Fifty-nine healthy, young, nonsmoking women with regular menstrual cycles. Age, body mass index, and waist-to-hip ratio were comparable in all study groups at the beginning. Fifty-six women completed the study (EV + DNG, n = 20; EE + DNG, n = 19; DNG only, n = 17). Interventions Nine-week continuous use of COCs containing either EV + DNG or EE + DNG, or DNG only as control. Main Outcome Measures Parameters of chronic inflammation (high-sensitivity C-reactive protein [hs-CRP], and pentraxin 3 [PTX-3]) and lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol). Results Serum hs-CRP increased after 9-week use of EE + DNG (mean change ± standard deviation 1.10 ± 2.11 mg/L) compared with EV + DNG (−0.06 ± 0.97 mg/L, P = 0.001) or DNG only (0.13 ± 0.68 mg/L, P = 0.021). Also, PTX-3 increased in the EE + DNG group compared with EV + DNG and DNG-only groups (P = 0.017 and P = 0.003, respectively). In the EE + DNG group, HDL and triglycerides increased compared with other groups (HDL: EE + DNG 0.20 ± 0.24 mmol/L vs EV + DNG 0.02 ± 0.20 mmol/L [P = 0.002] vs DNG 0.02 ± 0.18 mmol/L [P = 0.002]; triglycerides: EE + DNG 0.45 ± 0.21 mmol/L vs EV + DNG 0.18 ± 0.36 mmol/L [P = 0.003] vs DNG 0.06 ± 0.18 mmol/L [P < 0.001]). Conclusions EV + DNG and DNG only had a neutral effect on inflammation and lipids, while EE + DNG increased both hs-CRP and PTX-3 levels as well as triglycerides and HDL. Trial Registration ClinicalTrials.gov NCT02352090

Purpose of the study: to determine the effect of iron and vitamin D subsidies on the quality of women’s life who receive pathogenetic therapy for abnormal uterine bleedings (AUB) caused by adenomyosis and/or endometrial polyps.Materials and methods. 114 patients with chronic AUB were randomized into two groups. The main group consist of 58 women, including 46 women with chronic AUB and adenomyosis (AUB-A), 12 women with adenomyosis and endometrial polyps (AUB-A,P). Women with AUB-A were prescribed 2 mg dienogest daily for the treatment of adenomyosis, similarly to patients with AUB-A,P after hysteroresection. All women in the main group also took a vitamin complex (iron, folate, iodine, vitamin D3, docosahexaenoic acid). The control group included 56 patients (43 women with AUB-A, 13 women with AUB-A,P) who were prescribed etiopathogenetic treatment (dienogest 2 mg per day and/or hysteroresection for endometrial polyps) without a vitamin complex subsidy. Quality of life was assessed using the SF-36 questionnaire. All patients received serum concentrations of hemoglobin, ferritin and 25(OH)D before and 3 months after treatment.Results. Iron-free dienogest therapy led to an increase serum hemoglobin levels after 3 months (p = 0.001). After three months vitamin complex Pregna-5 added there were significantly increased of hemoglobin levels, ferritin and 25(OH)D. This is accompanied by an improvement in the overall indicator of physical (r = 0.421, p