Management of uterine leiomyoma and adenomyosis: role of hysteroscopy in diagnosis and norethindrone in the treatment

Characteristics of studied patients. Data expressed as mean (SD), frequency (percentage). This was a prospective cohort study conducted on 100 women with mean age was 41.3 years. A total of 50 (50%) of patients had dysmenorrhea, with average VAS of (3.2 ± 3), (34%) had dyspareunia, with average VAS of (1.4 ± 0.9), (85%) had Menorrhagia, with average VAS of (3.9 ± 1.9), and (18%) had Defecation pain, with average VAS of (0.9 ± 0.01). Hysteroscopic and histopathological data and drug intervention. Data expressed as mean (SD), frequency (percentage). Regarding Hysteroscopy data; 15 (15%) and 87 (87%) of patients had hysteroscopic appearance suggestive of adenomyosis and fibroid, respectively. Histopathology data; 15 (15%) and 85 (85%) of patients had adenomyosis, and fibroid, respectively. Characteristics of patients based on histopathology. Data expressed as mean (SD), frequency (percentage). P value was significant if < 0.05. * p  < 0.05, ** p < 0.01. Patients with adenomyosis had significantly longer duration of symptoms. At baseline and during follow up as regard clinical data there was significant differences between both groups with exception of menorrhagia at baseline. Hysteroscopy and intervention based on histopathology. Data expressed as mean (SD), frequency (percentage). P value was significant if < 0.05. * p  < 0.05, ** p < 0.01. There was significant difference between both groups as regard hysteroscopic findings but both of them were comparable as regard drug therapy. Logistic regression model for the Factors affecting different clinical data. Other factors excluded from the model as ( P value > 0.1). OR: odds ratio. * p  < 0.05, ** p < 0.01. The decrease in age; and the increase in Adenomyosis in hysteroscopy; had an independent effect on increasing the probability of dysmenorrhea occurrence. The decrease in age; and the increase in Gravidity, Duration of symptoms and adenomyosis in hysteroscopy were predictors for dyspareunia occurrence. The decrease in duration of symptoms; and the increase in adenomyosis in hysteroscopy were predictors of menorrhagia. The increase in endometrial depth and adenomyosis in hysteroscopy were predictors for defecation pain. Roc-curve of hysteroscopy usage to predict diagnosis. ROC (Receiver operating characteristic), AUC; Area under curve. * p  < 0.05, ** p < 0.01. ROC curve of hysteroscopy usage (Adenomyosis). ROC curve of hysteroscopy usage (Fibroid). By using ROC-curve analysis hysteroscopy usage had 73.33% sensitivity for prediction of adenomyosis and fibroid with 95.29% and 97.65% specificity for prediction of adenomyosis and fibroid, respectively. Role of Norethindrone in each diagnosis. * p  < 0.05, ** p < 0.01. Both groups showed highly significant decrease in follow up menorrhagia pain, in continuous norethindrone group. Roc-curve of Norethindrone administration to predict follow up obstetric data ROC (Receiver operating characteristic), AUC; Area under curve. * p  < 0.05, ** p < 0.01. ROC curve of Norethindrone administration (Menorrhagia pain). By using ROC-curve analysis, norethindrone administration showed non-significant predictive values regarding dysmenorrhea, dyspareunia and defecation pain except for menorrhagia pain with AUC was 0.793.

This was a prospective study in the management of uterine leiomyoma and adenomyosis. This study has been conducted in the Department of Obstetrics and Gynecology, Ghamra Military Medical Hospital in Cairo. The duration of the study was from January 2021 to January 2023. Clinical assessment with complete history taking and systemic examination of 100 patients of reproductive age group was done and relevant findings were recorded with informed consent. In this study hysteroscopy was done in a minor operation theatre under sedation to evaluate abnormal uterine bleeding and dysmenorrhea in the reproductive age group women suspected of fibroid or adenomyosis. Patients diagnosed by US who has submucous fibroid and adenomyosis with age between 25 and 45 years old and Regular menstrual cycles before administration of norethindrone. Pregnancy and or breast-feeding women Patients with ovarian neoplasm, benign ovarian cyst including endometrioma Pelvic inflammatory disease or other endocrine disease Pregnancy and or breast-feeding women Patients with ovarian neoplasm, benign ovarian cyst including endometrioma Pelvic inflammatory disease or other endocrine disease All patients were subjected to full history taking and clinical evaluation. Baseline blood tests included complete blood count, blood sugar, blood urea, serum creatinine and blood grouping. Abdominal and pelvic ultrasound and anesthetic fitness was obtained. Prophylactic antibiotics with third generation cephalosporins were given in pre operative and post operative period. Hysteroscopy was done in the proliferative phase of the menstrual cycle. The procedure was done with administration of short intravenous anesthesia. It was done based on all standard guidelines The anterior lip of cervix comes to view and is holded with the volelsellam. The hysteroscopy is checked before introducing for the eye-piece, objective lens, clarity and then introduced through the vagina, ectocervix and the endocervical canal. Any lesion found was documented. Illumination of the scope was provided by a high intensity cold light source via a fibro optic cable and the procedure monitored through the video monitor. Then the hysteroscope was introduced into the uterine cavity. The hysteroscopy was guided through the endocervical canal into the uterine cavity under vision, The Ostia of the tubes examined, then the endometrial surface was examined. All the surfaces of uterine cavity, that is the anterior wall, posterior wall, and lateral walls were examined. The appearance of the endometrium, color, any polyps, fibroid, hyperplasia and vascularity noted. The examination was considered complete when all parts were visualized. If any difficulty in visualization due to blood clot was documented then the procedure is considered as incomplete and failed. The hysteroscopic findings was correlated with the histopathology results. Two regimens were used by Norethindrone administration the 1st regimen as continuous manner from day 5 to day 21 46 patients (46%). The 2nd manner was the intermittent type from day 16 and for 10 days 54 patients (54%). The choice between regimens depends on the clinical goal where continuous use is better for menstrual suppression, while intermittent use is preferred for cycle regulation or short-term symptom relief. The main study variables were chronic pain, dysmenorrhea or pain during uterine bleeding assessed using the visual analog scale (VAS) at baseline and then after three months. The study was conducted according to the principles of the Declaration of Helsinki and was approved by the Hospital’s Ethics Committee purpose of the study was explained to all participants, and written informed consent was obtained. The study was approved by Assiut Faculty of Medicine, Institutional Review Board (IRB No. 17200648, 2021). The study was explained to all patients and only patients who were signing an informed consent were participated in study. This study was registered on clinicaltrials.gov with identifier: ( NCT05153928 ). Data entry, processing and statistical analysis was carried out using MedCalc ver. 20 (MedCalc, Ostend, Belgium). Mean, Standard deviation (± SD) and range for parametric numerical data and compared with Student t test, while Median and Inter-quartile range (IQR) for non-parametric numerical data and compared by Mann Whiteny test. Frequency and percentage of non-numerical data. Student’s t test was used to assess the statistical significance of the difference between two study group means. Chi-Square test was used to examine the relationship between two qualitative variables. Logistic regression: useful in the prediction of the presence or absence of an outcome based on a set of independent variables. The ROC Curve (receiver operating characteristic) provides a useful way to evaluate the Sensitivity and specificity for quantitative Diagnostic measures that categorize cases into one of two groups. Confidence interval was kept at 95% and hence, P value was significance if < 0.05.

The current study stated the important use of hysteroscopy in management of abnormal uterine bleeding. Norethindrone looks a good alternative for management of AUB cases. Future studies are warranted to assess these findings particularly regarding the long-term effects and patient adherence to Norethindrone treatment regimens.

In the currents study, Roc-curve of hysteroscopy usage to predict diagnosis; adenomyosis sensitivity was 73.33% and specificity 95.29% and fibroid sensitivity was 73.33% and specificity was 97.65%. Two regimens were used by Norethindrone administration the 1st regimen as continuous manner from day 5 to day 21 46 patients (46%). The 2nd manner was the intermittent type from day 16 and for 10 days 54 patients (54%). Both groups revealed; highly significant decrease in follow up menorrhagia in continuous Norethindrone group ( P  < 0.001). By using ROC-curve analysis; Norethindrone administration predicted decreased menorrhagia pain with fair (70%) accuracy; sensitivity 80% and specificity 81%. Outpatient hysteroscopy as a mode of diagnostic modality for abnormal uterine bleeding has gained popularity and is extremely encouraging. Its high diagnostic reliability, less pain, minimally invasive, office procedure all these make this diagnostic hysteroscopy an ideal method for diagnosis and also for follow up of patients with endometrial hyperplasia 8 . The review of the studies about hysteroscopy in abnormal uterine bleeding and its meta-analysis showed that diagnostic hysteroscopy is accurate in diagnosing intrauterine pathologies. It is highly sensitive and is useful clinically. Moreover, when compared to other studies 9 – 11 . Our review confirms that diagnostic hysteroscopy is safe and no complication has been in our study. Technical failures and patient discomfort were not reported in any of the patients included in our study. All the patients taken for the study underwent hysteroscopy successfully. Hysteroscopy, a minimally invasive technique, allows direct observation of the endometrial thickness and color, the opening of the bilateral fallopian tubes, uterine angles, cavity shape, and cervical canal. Despite its growing popularity, hysteroscopy faces limitations in clinical practice, such as cost, technical complexity, invasiveness, and patient tolerance 12 . Ding et al. 13 demonstrated that combining transvaginal ultrasound, enhanced by the K-means clustering color image segmentation algorithm, with hysteroscopy significantly increased diagnostic sensitivity.In diagnosing AUB caused by endometrial polyps, the concordance rates for hysteroscopy and transvaginal ultrasound were 93.3% and 77.3%, respectively, with the difference being statistically significant indicating hysteroscopy’s superior efficacy in detecting endometrial polyps. The concordance rates for diagnosing AUB caused by normal endometrium, uterine leiomyoma, malignant transformation of the endometrium, adenomyosis, atypical hyperplasia, benign hyperplasia, and other factors did not show a statistically significant difference between the two methods 14 – 16 . This discrepancy from previous findings may be attributable to factors such as small sample size. In diagnosing peri-menopausal AUB, transvaginal ultrasound showed a sensitivity of 89.7%, a specificity of 66.7%, and a negative predictive value of 46.7%. Hysteroscopy demonstrated higher sensitivity, specificity, and negative predictive value of 94.8%, 76.2%, and 66.7%, respectively 16 . The combined diagnostic approach yielded sensitivity and specificity rates of 97.4% and 81.0%, respectively, and a negative predictive value of 81.0%, surpassing the individual use of transvaginal ultrasound and hysteroscopy 17 . The consistency between transvaginal ultrasound results and the pathological diagnosis was moderate (Kappa 0.475), while hysteroscopy showed substantial consistency (Kappa 0.669). The combined use of transvaginal ultrasound and hysteroscopy presented a higher consistency with the pathological diagnosis (Kappa 0.784), suggesting that this combined approach offers superior diagnostic efficacy in the evaluation of peri-menopausal AUB 18 . Bettocchi reported his experience with more than 11,000 hysteroscopic procedures performed using the vaginoscopic technique, eliminating the use of a speculum and a tenaculum. He found that as many as 99.1% of the patients reported no discomfort related to the procedure. The mean pain score was significantly lower in the group without the use of speculum 19 . The current study had some limitations selection bias, being conducted in single center and relatively small sample size. These make difficulty in generalizability of such findings with need for further research.

Up to one-third of women will experience abnormal uterine bleeding (AUB) in their life, with irregularities most commonly occurring at menarche and perimenopause. A normal menstrual cycle has a frequency of 24–38 days, lasts 7–9 days, with 5–80 millilitres of blood loss 1 . Fibroids can either present as an asymptomatic incidental finding on imaging, or symptomatically. Common symptoms include abnormal uterine bleeding, pelvic pain, disruption of surrounding pelvic structures (bowel and bladder), and back pain 2 . Adenomyosis is a gynecologic condition characterized by ectopic endometrial tissue within the uterine myometrium.The definitive treatment for women who no longer desire pregnancy is hysterectomy, while a variety of other medical and minimally invasive therapies are available for those who want to preserve fertility or want to avoid more extensive surgery 3 . Hysteroscopy is an essential diagnostic tool, particularly in cases where transvaginal ultrasound findings are inconclusive or equivocal. This is especially relevant in evaluating suspected FIGO type 0, 1, and 2 submucosal myomas, where ultrasound may not clearly differentiate fibroids from endometrial polyps or other intracavitary lesions. Hysteroscopy allows for direct visualization of the uterine cavity, providing definitive identification of the number, size, and precise location of myomas relative to the endometrial surface. In cases where ultrasound raises suspicion but does not confirm the diagnosis, hysteroscopy can clarify the pathology and guide clinical decision-making, particularly when surgical planning or fertility preservation is a concern 4 . Similarly, in patients with suspected subendometrial or internal myometrial adenomyosis and inconclusive imaging, hysteroscopy can offer additional diagnostic insights. While it is not the primary modality for diagnosing adenomyosis, it can reveal subtle endometrial surface irregularities, vascular anomalies, or cystic changes that may reflect underlying disease 4 . These findings, when correlated with clinical symptoms and imaging, can strengthen diagnostic confidence. Thus, hysteroscopy holds significant diagnostic value as a second-line investigation when ultrasound does not provide definitive answers, enhancing accuracy and helping tailor individualized management strategies 5 . Hysteroscopy is widely regarded as the gold standard for diagnosing and treating intrauterine pathology and may be particularly beneficial for women with infertility or recurrent pregnancy loss. While some guidelines and studies support its use as a routine screening tool during infertility evaluation, others advise limiting its use to cases with specific clinical indications 6 . The effectiveness of diagnostic or operative hysteroscopy in improving reproductive outcomes—especially in women with unexplained subfertility or suspected uterine cavity abnormalities, and in those undergoing IUI or IVF—remains uncertain, highlighting the need for further high-quality research to clarify its role in enhancing fertility outcomes 6 . The role of norethindrone acetate (NA) offers promise as an effective and well tolerated drug in the management of symptomatic adenomyosis. NA may be a much cheaper alternative to other treatment options for adenomyosis, with fewer and milder side effects 7 . The choice between regimens depends on the clinical goal where continuous use is better for menstrual suppression, while intermittent use is preferred for cycle regulation or short-term symptom relief. Continuous use may lead to more breakthrough bleeding initially, but better long-term control, whereas intermittent use maintains cyclic bleeding {Kaldewey, 2021 #2786}. The current study aimed to evaluate the diagnostic accuracy of hysteroscopy in differentiating between uterine adenomyosis and fibroids. Also, to compare between continuous versus intermittent administration of Norethindroneto control both uterine adenoxmyosis and leiomymatosis.