Long-term treatment for endometriosis with dienogest: efficacy, side effects and tolerability.

BACKGROUND: Dienogest (DNG) improves endometriosis-associated pain (EAP) and patients' quality of life; however, the modern cornerstone of the management of endometriosis is the long-term adherence of the patient to medical treatment. OBJECTIVE: To evaluate DNG as a long-term treatment of endometriosis, focusing on patients' compliance and side effects, also correlating with different phenotypes of endometriosis. METHODS: This was a cohort study on a group of patients with endometriosis (n = 114) undergoing long-term treatment with DNG. During the follow up visits (12, 24, and 36 months) patients were interviewed: an assessment of EAP was performed by using a visual analogue scale (VAS) and side effects were evaluated by using a specific questionnaire of 15 items. RESULTS: At 12 months, 81% were continuing the DNG treatment, with a significant reduction of dysmenorrhea, dyspareunia, dyschezia, dysuria and chronic pelvic pain. Of the 19% that discontinued the treatment: 62% was due to spotting, reduced sexual drive, vaginal dryness, and mood disorders. The improvement of EAP was significant for all endometriosis phenotypes, especially in patients with the deep infiltrating type. At 36 months, 73% of patients were continuing the treatment, showing a significant reduction of EAP through the follow up, along with an increase of amenorrhea (from 77% at 12 months to 93% at 36 months). In a subgroup of 18 patients with gastrointestinal disorders, DNG was administered vaginally at the same dosage, showing similar results in terms of efficacy and tolerability. CONCLUSIONS: DNG was an effective long-term treatment for all endometriosis phenotypes, with few side effects that caused the discontinuation of the treatment mainly during the first year. Thus, the course of 1-year treatment is a predictive indicator for long-term treatment adherence.

The effects of dienogest and combined oral contraceptives on protein S-specific activity in endometriosis patients.

OBJECTIVE: One serious side effect of combined oral contraceptives (COCs) is venous thromboembolism. Reduced activity in activated protein C-related coagulation pathways is attributable to low protein S activity in one-third of Japanese patients with deep vein thrombosis. Herer, we quantified the behavior of protein S-specific activity in response to dienogest (DNG) and COCs using the protein S-specific activity assay system to explore its potential utility as a thrombosis marker. STUDY DESIGN: This was a prospective cohort study. Female patients aged 20 - 49 years who were starting drug treatment for endometriosis using DNG or COCs were enrolled. Blood samples were taken before treatment and at the first, third, and sixth months of treatment. To analyze the primary endpoints, changes in total protein S antigen levels, total protein S activity, and protein S-specific activity from baseline to each time point were estimated using a linear mixed-effects model. All statistical analyses were performed in the SAS software version 9.4 (SAS Institute, Cary, NC). A two-sided P < 0.05 was considered statistically significant. RESULTS: 64 patients took DNG and 34 patients took COCs. Protein S-specific activity did not change significantly from baseline in the six months after treatment started in either group. In the DNG group, total protein S activity and total protein S antigen levels increased slightly from baseline levels after the treatment. The means for total protein S activity and total protein S antigen levels in the COC group remained within reference limits, but they both decreased markedly in the first month and stayed low. Protein S-specific activity in four women remaind below the reference limit throughout the whole study period, suggesting they may have potential protein S deficiencies. CONCLUSION: The effects of DNG on protein S were negligible, though both total protein S activity and antigen levels decreased soon after COC treatment began and remained low. As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk.

Evaluation of long-term efficacy and safety of dienogest in patients with chronic cyclic pelvic pain associated with endometriosis.

PURPOSE: To evaluate the efficacy and long-term safety (up to 108 months) of treatment with Dienogest in patients with endometriosis. METHODS: Patients with chronic pelvic pain endometriosis-related were enrolled in this observational study from June 2012 to July 2021. The patients enrolled took Dienogest 2 mg as a single daily administration. Group B of long-term therapy patients (over 15 months) were compared with group A of short-term therapy patients (0-15 months). The effects of the drug on pain variation were assessed using the VAS scale and endometriomas dimensions through ultrasonographic evaluation. Furthermore, has been valuated the appearance of side effects and the effect of the drug on bone metabolism by performing MOC every 24 months in group B. RESULTS: 157 patients were enrolled. The mean size of the major endometrioma progressively decreased from 33.2 mm (29.4-36.9) at T0 to 7 mm (0-15.8) after 108 months of treatment. We found a significant improvement in dysmenorrhea, dyspareunia, dyschezia and non-cyclic pelvic pain. As for the side effects, both groups complained menstrual alterations present in 22.9%. In 27.6% of group B, osteopenia was found. Group B had a higher percentage statistically significant of side effects such as headaches, weight gain and libido reduction compared to group A. 2 CONCLUSION: Long-term therapy with Dienogest has proven effective in controlling the symptoms of the disease and reducing the size of endometriomas, with an increase in the positive effects related to the duration of the intake and in the absence of serious adverse events. Study approved by the "Palermo 2" Ethics Committee on July 2, 2012 No. 16.

Effects of Nandrolone Decanoate on Skeletal Muscle and Neuromuscular Junction of Sedentary and Exercised Rats.

Background and Objectives: Nandrolone decanoate (ND) is the most widely used among the anabolic androgenic steroids (AAS), synthetic substances derived from testosterone, to improve muscular and health gains associated with exercises. The AAS leads to physical performance enhancement and presents anti-aging properties, but its abuse is associated with several adverse effects. Supraphysiological doses of AAS with or without physical exercise can cause morphological and functional alterations in neuromuscular interactions. This study aims to investigate the effects of ND supraphysiological doses in neuromuscular interactions, focusing on the soleus muscle and its neuromuscular junctions (NMJs) in rats, associated or not with physical exercise. Materials and Methods: Forty male Sprague Dawley rats were divided into four groups: sedentary and exercised groups, with or without ND at the dose of 10 mg/kg/week. The animals were treated for eight weeks, with intramuscular injections, and the soleus muscle was collected for morphological analyses. Results: The supraphysiological doses of ND in the sedentary group caused muscle degeneration, evidenced by splitting fibers, clusters of small fibers, irregular myofibrils, altered sarcomeres, an increase in collagen deposition and in the number of type I muscle fibers (slow-twitch) and central nuclei, as well as a decrease in fibers with peripheral nuclei. On the other hand, in the ND exercise group, there was an increase in the NMJs diameter with scattering of its acetylcholine receptors, although no major morphological changes were found in the skeletal muscle. Thus, the alterations caused by ND in sedentary rats were partially reversed by physical exercise. Conclusions: The supraphysiological ND exposure in the sedentary rats promoted an increase in muscle oxidative pattern and adverse morphological alterations in skeletal muscle, resulting from damage or post-injury regeneration. In the ND-exercised rats, no major morphological changes were found. Thus, the physical exercise partially reversed the alterations caused by ND in sedentary rats.

Compare the Efficacy of Dienogest and the Levonorgestrel Intrauterine System in Women with Adenomyosis.

PURPOSE: The goal of this study was to examine the efficacy and safety of the levonorgestrel intrauterine system (LNG-IUS) versus dienogest (DNG) in female subjects with symptomatic uterine adenomyosis. METHODS: This study enrolled 117 women with symptomatic adenomyosis who visited our hospital from May 1, 2019, to June 30, 2022. Participants were randomized to either the LNG-IUS group (n = 48) or the DNG group (n = 79) in an as-controlled clinical trial for 36 months. Visual analog scale (VAS) scores, uterine volume, endometrial thickness, serum carcinoma antigen 125 level, estradiol, follicle-stimulating hormone, luteinizing hormone, and side effects were assessed to compare the efficacy of LNG-IUS and DNG. FINDINGS: The VAS pain score was significantly decreased in both groups after 3 months of treatment. Three months later, patients receiving DNG reported significantly lower VAS scores compared with those treated with LNG- IUS (P < 0.05). Compared with LNG-IUS, DNG effectively controlled uterine volume growth after 12 months of treatment but neither significantly reduced uterine volume. During the treatment period, endometrial thickness in both groups was maintained at 0.4 to 0.7 cm. IMPLICATIONS: Both DNG and LNG-IUS significantly improved adenomyosis-associated pain after 3 months of treatment. Compared with LNG-IUS, DNG was shown to continuously relieve the symptoms of pain and effectively control the growth of uterine volume.

Endometriosis features and dienogest tolerability in women with depression: a case-control study.

OBJECTIVE: Primary aim of this study was to investigate endometriosis characteristics of patients with psychiatric conditions or depression. The secondary aim was to study tolerability of dienogest in this context. METHODS: This observational case-control study included endometriosis data from patients visiting our clinic from 2015-2021. We collected information from patient charts and in phone interviews based on a structured survey. Patients with surgical confirmed endometriosis were included. RESULTS: 344 patients fulfilled the inclusion criteria: n = 255 no psychiatric disorder, n = 119 any psychiatric disorder and n = 70 depression. Patients with depression (EM-D, p=.018; p=.035) or psychiatric condition (EM-P, p=.020; p=.048) suffered more often from dyspareunia and dyschezia. EM-P patients had more often primary dysmenorrhoea with higher pain scores (p=.045). rASRM stage or localisation of lesions did not differ. EM-D and EM-P patients discontinued dienogest treatment more often related to worsening of mood (p= .001, p=.002). CONCLUSION: EM-D or EM-P had a higher prevalence of pain symptoms. This could not be attributed to differences in rASRM stage or location of endometriosis lesions. Strong primary dysmenorrhoea might predispose to develop chronic pain-based psychological symptoms. Therefore, early diagnosis and treatment are relevant. Gynaecologist should be aware of the potential impact of dienogest on mood.

Women with endometriosis and psychiatric disorders especially have more dyschezia and dyspareunia, independent from rASRM stage, depth of infiltration and localisation of endometriosis lesions. Dienogest has an impact on mood especially in already prone patients.Trial registration: trial registration number: NCT04816357. https://clinicaltrials.gov/ct2/show/NCT04816357Date of registration: 22.03.2021, date of enrolment of the first subject: 25.03.2021.

The Efficacy of Dienogest in Reducing Disease and Pain Recurrence After Endometriosis Surgery: a Systematic Review and Meta-Analysis.

The objective of this study is to determine whether dienogest therapy after endometriosis surgery reduces the risk of recurrence compared with placebo or alternative treatments (GnRH agonist, other progestins, and estro-progestins). The design used in this study is systematic review with meta-analysis. The data source includes PubMed and EMBASE searched up to March 2022. A systematic review and meta-analysis were performed in accordance with guidelines from the Cochrane Collaboration. Keywords such as "dienogest," "endometriosis surgery," "endometriosis treatment," and "endometriosis medical therapy" were used to identify relevant studies. The primary outcome was recurrence of endometriosis after surgery. The secondary outcome was pain recurrence. An additional analysis focused on comparing side effects between groups. Nine studies were eligible, including a total of 1668 patients. At primary analysis, dienogest significantly reduced the rate of cyst recurrence compared with placebo (p < 0.0001). In 191 patients, the rate of cyst recurrence comparing dienogest vs GnRHa was evaluated, but no statistically significant difference was reported. In the secondary analysis, a trend toward reduction of pain at 6 months was reported in patients treated with dienogest over placebo, with each study reporting a significantly higher reduction of pain after dienogest treatment. In terms of side effects, dienogest treatment compared with GnRHa significantly increased the rate of spotting (p = 0.0007) and weight gain (p = 0.03), but it was associated with a lower rate of hot flashes (p = 0.0006) and a trend to lower incidence of vaginal dryness. Dienogest is superior to placebo and similar to GnRHa in decreasing rate of recurrence after endometriosis surgery. A significantly higher reduction of pain after dienogest compared with placebo was reported in two separate studies, whereas a trend toward reduction of pain at 6 months was evident at meta-analysis. Dienogest treatment compared with GnRHa was associated with a lower rate of hot flashes and a trend to lower incidence of vaginal dryness.

Effects of estradiol- and ethinylestradiol-based contraceptives on adrenal steroids: A randomized trial.

OBJECTIVES: Ethinylestradiol (EE)-based combined oral contraceptives (COC) affect adrenal function by altering steroid and corticosteroid-binding globulin (CBG) synthesis that may contribute to adverse effects related to these drugs. The effects of COCs containing natural estrogens remain unclear. We compared the effects of COCs containing estradiol valerate (EV) and EE on cortisol and other adrenal steroid hormones. STUDY DESIGN: A spin-off study of a randomized, open-label trial. Fifty-nine healthy women were allocated to groups that engaged in the continuous use of EV+dienogest (DNG), EE+DNG, or DNG only for 9 weeks. We measured changes in adrenal steroids, CBG, and the free cortisol index (FCI). RESULTS: Treatment with EE+DNG increased total cortisol (mean increment 668 nmol/L, p < 0.001) and cortisone (10 nmol/L, p= 0.001) levels, whereas the change from the baseline was insignificant for the EV+DNG and DNG-only groups. Dehydroepiandrosterone sulfate decreased by 24% in the EE+DNG group but remained unchanged in the EV+DNG and DNG-only groups. Aldosterone and 17-hydroxyprogesterone levels did not differ between the groups. All preparations increased CBG, but the increase in the EE+DNG group (median increment 42 µg/mL, p < 0.001) was 9- and 49-fold higher than that in the EV+DNG and DNG-only groups, respectively. The FCI remained unchanged in all study groups, indicating that cortisol and CBG mainly increased in parallel, although some individuals demonstrated larger alterations in the cortisol-CBG balance. CONCLUSION: In COCs, EV had a milder effect on circulating CBG and adrenal steroid levels than EE; however, further research is necessary to determine the long-term effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT02352090 IMPLICATIONS: EV-based COC had reduced effects on circulating CBG and adrenal steroids compared to EE, probably due to a lower hepatic impact. Whether the sensitization of the adrenals to ACTH varies according to COC contents and whether it relates to experienced side effects needs to be investigated. These results encourage further research and development of contraceptives containing natural estrogens.

Long-term treatment of dienogest with symptomatic adenomyosis: retrospective analysis of efficacy and safety in clinical practice.

Objective: To evaluate the efficacy and safety of dienogest (DNG) in women with symptomatic adenomyosis.Methods: Women with symptomatic adenomyosis were included in this retrospective observation study. Group 1 (maximum uterine dimension ≥ 100.0 mm) began DNG after 4 months of GnRH-a administration, Group 2 (maximum uterine dimension < 100.0 mm) received DNG with no prior GnRH-a treatment. All women were assessed for their pain symptoms, uterine size, adverse effects and laboratory hematology at baseline and every 6 months during the treatment.Results: 123 women were enrolled in this study, in Group 1 (71 women) with severe uterine enlargement, the median VAS score was 80 mm prior to GnRH-a administration and 10, 10, 10, 20, and 20 mm, respectively, after 0, 6,12,18, and 24 months of DNG treatment. The mean uterine volume decreased from 262.9 ml to 104.7 ml after GnRH-a therapy, and slowly increased from 104.7 ml to 139.5 ml after 24 month-treatment of DNG. Another 52 women with mild uterine enlargement received DNG without prior GnRH-a administration, median VAS score was 70 mm at baseline and decreased to 20, 20, 10, and 10 mm at 6,12,18, and 24 months. The mean uterine volume slightly decreased from 157.9 ml to 153.3 ml after 24 months of DNG treatment (p > 0.05). All laboratory parameters were in the normal range.Conclusions: DNG is effective and well tolerated as a long-term treatment for symptomatic adenomyosis, and it can be used as maintenance therapy after discontinuation of GnRH-a administration.

Impact of Long-Term Dienogest Therapy on Quality of Life in Asian Women with Endometriosis: the Prospective Non-Interventional Study ENVISIOeN.

Several clinical trials in women with endometriosis demonstrated that dienogest reduces endometrial lesions and improves health-related quality of life (HRQoL). To assess HRQoL in dienogest-treated patients in real-world setting, we conducted a prospective, non-interventional study in 6 Asian countries. Women aged ≥18 years with clinical or surgical diagnosis of endometriosis, presence of endometriosis-associated pelvic pain (EAPP) and initiating dienogest therapy were enrolled. The primary objective was to evaluate HRQoL using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The secondary objectives included analysis of EAPP, satisfaction with dienogest, endometriosis symptoms and bleeding patterns. 887 patients started dienogest therapy. Scores for all EHP-30 scales improved with the largest mean changes at month 6 and 24 in scale pain (-28.9 ± 27.5 and - 34 ± 28.4) and control and powerlessness (-23.7 ± 28.2 and - 28.5 ± 26.2). Mean EAPP score change was -4.6 ± 3.0 for both month 6 and 24 assessments. EAPP decrease was similar in surgically and only clinically diagnosed patients. From baseline to month 24, rates of normal bleeding decreased (from 85.8% to 17.5%) while rates of amenorrhea increased (from 3.5% to 70.8%). Majority of patients and physicians were satisfied with dienogest. Over 80% of patients reported symptoms improvement. 39.9% of patients had drug-related treatment-emergent adverse events, including vaginal hemorrhage (10.4%), metrorrhagia (7.3%) and amenorrhea (6.4%). In conclusion, dienogest improves HRQoL and EAPP in the real-world setting in women with either clinical or surgical diagnosis of endometriosis. Dienogest might be a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms.NCT02425462, 24 April 2015.

Nandrolone-Induced Tumor Progression in Hormone-Sensitive Prostate Cancer.

ABSTRACT: Hormone-sensitive prostate cancer responds favorably to testosterone suppression induced by GnRH analogs or antagonists. This effect may theoretically be countered by anabolic steroids. We describe a patient of a recurrent hormone-sensitive prostate cancer who was on salvage androgen deprivation therapy with degarelix and developed rapid progression after over-the-counter nandrolone injections.

Anabolic Steroids-Driven Regulation of Porcine Ovarian Putative Stem Cells Favors the Onset of Their Neoplastic Transformation.

Nandrolone (Ndn) and boldenone (Bdn), the synthetic testosterone analogues with strong anabolic effects, despite being recognized as potentially carcinogenic compounds, are commonly abused by athletes and bodybuilders, which includes women, worldwide. This study tested the hypothesis that different doses of Ndn and Bdn can initiate neoplastic transformation of porcine ovarian putative stem cells (poPSCs). Immunomagnetically isolated poPSCs were expanded ex vivo in the presence of Ndn or Bdn, for 7 and 14 days. Results show that pharmacological doses of both Ndn and Bdn, already after 7 days of poPSCs culture, caused a significant increase of selected, stemness-related markers of cancer cells: CD44 and CD133. Notably, Ndn also negatively affected poPSCs growth not only by suppressing their proliferation and mitochondrial respiration but also by inducing apoptosis. This observation shows, for the first time, that chronic exposure to Ndn or Bdn represents a precondition that might enhance risk of poPSCs neoplastic transformation. These studies carried out to accomplish detailed molecular characterization of the ex vivo expanded poPSCs and their potentially cancerous derivatives (PCDs) might be helpful to determine their suitability as nuclear donor cells (NDCs) for further investigations focused on cloning by somatic cell nuclear transfer (SCNT). Such investigations might also be indispensable to estimate the capabilities of nuclear genomes inherited from poPSCs and their PCDs to be epigenetically reprogrammed (dedifferentiated) in cloned pig embryos generated by SCNT. This might open up new possibilities for biomedical research aimed at more comprehensively recognizing genetic and epigenetic mechanisms underlying not only tumorigenesis but also reversal/retardation of pro-tumorigenic intracellular events.

Efficacy of dienogest vs combined oral contraceptive on pain associated with endometriosis: Randomized clinical trial.

OBJECTIVE: To compare the efficacy of dienogest with the combined oral contraceptive pill (COC) Yasmin for the control of endometriosis-associated pelvic pain. STUDY DESIGN: Seventy women with endometriosis-associated chronic pelvic pain, dysmenorrhoea or both for >6 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 (B&B) 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. RESULTS: 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 B&B 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. CONCLUSIONS: Dienogest (2 mg/day) is comparable to the COC Yasmin for the relief of endometriosis-associated pelvic pain and improvement in HRQoL. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov under number NCT04256200; date of registration 15/1/2020 (registered retrospectively).

Dienogest-induced major depressive disorder with suicidal ideation: A case report.

RATIONALE: Dienogest is a type of progestin used for the treatment of endometriosis (EM). However, a significant adverse effect of dienogest is depression; therefore, assessing for a history of mood disorders is recommended before prescribing the drug. Herein, we present the case of a patient with no history of psychiatric disorders who was diagnosed with dienogest-induced major depressive disorder. This case emphasizes the importance of close monitoring for negative mood changes in patients taking dienogest. PATIENT CONCERNS: A 41-year-old woman underwent surgery for EM. Postoperatively, her gynecologist prescribed dienogest (2 mg/d) to control EM symptoms. Two months after the initiation of dienogest, she manifested insomnia almost daily, gradually became depressed, lost interest in all activities, had incessant cries, and repeatedly thought of death. She had no history of major physical or psychiatric disorders. DIAGNOSIS: Major depressive disorder, single episode, severe. INTERVENTIONS: A psychiatric consultation was recommended, an antidepressant was prescribed, and dienogest was discontinued. OUTCOMES: Two weeks later, there was significant improvement in the symptoms, and after 4 weeks, she remained in a stable mood with no suicidal thoughts. She was followed up for 13 months with a maintenance dose of escitalopram (5 -10mg/d), until the psychiatrist recommended treatment discontinuation, with a confirmed state of remission. LESSONS: This was a case of dienogest-induced depression in a patient with no history of mood disorders. Clinicians should be aware of the possibility of the occurrence of severe depression in progestin users regardless of their previous history.

Dienogest reduces endometrioma volume and endometriosis-related pain symptoms.

This study aimed to evaluate the efficacy and adverse effects of dienogest for the treatment of endometriomas. Dienogest (2 mg/day) was administered to patients with endometrioma continuously through the 6-month study period. The patients were prospectively examined on the efficacy and side effects at baseline, at third months, and sixth months of the treatment. Twenty-four out of 30 patients were able to complete the study. The mean volume of the endometrioma decreased significantly from 112.63 ± 161.31 cm³ at baseline to 65.47 ± 95.69 cm³ at a 6-month follow-up (-41%) (p = .005). The VAS score for pelvic pain decreased significantly from 7.50 to 3.00 (p < .001) at the sixth months of treatment. The most common side effects were menstrual irregularities. Laboratory parameters did not change during the study. Dienogest considered being effective for 6 months of use in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile.Impact statementWhat is already known on this subject? Laparoscopic excisional surgery for endometrioma is currently the most valid approach in the treatment of endometriomas. However, there are concerns about ovarian reserve damage during surgery.What do the results of this study add? Dienogest considered being effective in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile. Long-term use of dienogest in younger patients with endometriomas who are yet to give birth may reduce the possibility of surgery by reducing the size of the endometriomas and may preserve ovarian reserve.What are the implications of these findings for clinical practice and/or further research? Dienogest may reduce the incidence of infectious complications such as pelvic abscess after oocyte retrieval and the surgical procedures in infertile patients with endometrioma.

Evaluating the safety of dienogest in women with adenomyosis: A retrospective analysis.

AIM: Dienogest (DNG) is highly effective for relieving pain caused by endometriosis and adenomyosis. However, women with severe uterine swelling due to adenomyosis who take DNG usually experience metrorrhagia. This study aimed to examine the safety of DNG usage in women with adenomyosis. METHODS: This study included 20 women who were prescribed DNG for adenomyosis in our hospital from January 2016 to December 2016. We retrospectively analyzed women's clinical background characteristics (age, the use of the gonadotropin-releasing hormone agonist as pre-treatment of DNG, the uterus size [major axis, minor axis, maximum thickness in the myometrium, and length of the uterine body] by transvaginal ultrasonography [TVUS], hemoglobin level, and the presence of metrorrhagia during treatment). These variables were compared between the DNG continuation and discontinuation groups using the Mann-Whitney U test. RESULTS: Thirteen women continued DNG, and seven discontinued DNG within 12 months because of metrorrhagia. The uterine size was significantly larger in the discontinuation group than in the continuation group. All uterine measurements had high Spearman rank correlation coefficients (ρ > 0.8, P < 0.05). In six of seven cases in the discontinuation group, adenomyosis was in the anterior wall. Measuring the uterus size and locating adenomyosis by TVUS are simple methods of predicting DNG discontinuation. CONCLUSION: We consider that DNG can be safely administered in women with adenomyosis if the uterine size is <6 cm in the minor axis and the main lesion of adenomyosis is located in the posterior uterine wall.