Thirty percent of women will experience abnormal uterine bleeding (AUB) during their lifetime, with adenomyosis and uterine leiomyoma being the two most common benign causes. These two conditions share similar clinical manifestations, yet the choice of treatment regimen directly affects fertility preservation and symptom control outcomes. How to achieve accurate differential diagnosis? Should continuous or intermittent medication regimens be selected for pharmacotherapy?

Source: Scientific Reports

A prospective study (NCT05153928) conducted by a research team from Assiut University in Egypt and published in Scientific Reports in 2025 provided clear answers based on clinical data from 100 cases: hysteroscopy serves as a powerful tool for differential diagnosis, and continuous norethisterone administration yields superior efficacy in controlling menorrhagia! This article summarizes the core evidence to facilitate direct clinical application.

Overview of Key Study Information

01 Study Subjects

A total of 100 premenopausal women with AUB were enrolled, with a mean age of 41.3 years. Among them, 85% had concurrent menorrhagia, 50% suffered from dysmenorrhea, 34% experienced dyspareunia, and 18% had defecation pain (see the figure below for baseline Visual Analogue Scale (VAS) scores).

Source: Scientific Reports

Key Inclusion Criteria: Aged 25–45 years; ultrasound findings suggestive of adenomyosis/submucosal leiomyoma; regular menstrual cycles.

Exclusion Criteria: Pregnancy/lactation, ovarian tumors, pelvic inflammatory disease, and endocrine disorders.

02 Study Design

Diagnostic Method: All patients underwent hysteroscopy, with pathological results as the gold standard, to evaluate the accuracy of hysteroscopy in differentiating adenomyosis from leiomyoma.

Treatment Regimens:

Continuous Group (n=46): Norethisterone was administered continuously from day 5 to day 21 of the menstrual cycle.

Intermittent Group (n=54): Norethisterone was administered continuously for 10 days starting on day 16 of the menstrual cycle.

Follow-up Indicators: Three months after treatment, improvements in dysmenorrhea, dyspareunia, menorrhagia, and defecation pain were assessed using VAS scores.

Core Results: Dual Breakthroughs in Diagnosis and Treatment

01 Hysteroscopy: A Precision Tool for Differentiating Adenomyosis and Leiomyoma

Based on pathological diagnosis as the reference standard, hysteroscopy demonstrated excellent diagnostic performance, with a specificity exceeding 95%, which significantly reduced the misdiagnosis rate.

Clinical Significance: When ultrasound indicates "uterine space-occupying lesion with AUB" but cannot clearly distinguish between adenomyosis and leiomyoma, hysteroscopy enables direct visualization of intrauterine lesions, clarifying the number, size, and location of lesions. This provides an accurate basis for selecting surgical interventions (e.g., myomectomy) or medication regimens.

02 Norethisterone Therapy: Continuous Regimen Is More Effective in Controlling Menorrhagia

Both regimens improved symptoms, but the continuous administration regimen showed significant advantages in addressing the core symptom of menorrhagia.

Key Evidence: Receiver Operating Characteristic (ROC) curve analysis revealed that the Area Under the Curve (AUC) of norethisterone for predicting menorrhagia relief reached 0.793 (sensitivity: 80.43%, specificity: 81.48%), confirming its reliability as a treatment option for AUB.

03 Additional Finding: Symptoms Are More Refractory in Patients with Adenomyosis

A comparison between 15 pathologically confirmed adenomyosis patients and 85 leiomyoma patients showed:

Longer duration of symptoms (8.6 months vs. 6.6 months, P=0.04);

Higher baseline VAS scores for dysmenorrhea, dyspareunia, and defecation pain (all P<0.001);

Lower magnitude of symptom improvement after treatment compared with the leiomyoma group, though no significant difference in therapeutic efficacy was observed between the two norethisterone regimens in adenomyosis patients.

Clinical Implications: 3 Practical Recommendations for Direct Implementation

01 Optimization of Diagnostic Process

Initial Ultrasound Screening: For patients with uterine space-occupying lesions and AUB, first assess the location of lesions (hysteroscopy is preferred for submucosal leiomyomas).

Hysteroscopic Confirmation: Hysteroscopy is prioritized when ultrasound results are inconclusive, fertility preservation is required, or before initiating pharmacotherapy to clarify the lesion type.

Combined Diagnosis: For pre- and postmenopausal AUB, the combination of transvaginal ultrasound and hysteroscopy achieves a diagnostic consistency Kappa value of 0.784 (Kappa=0.475 for ultrasound alone; Kappa=0.669 for hysteroscopy alone).

02 Selection of Norethisterone Regimen

Preferred Continuous Regimen (Days 5–21): Recommended for patients requiring rapid control of menorrhagia that severely impacts quality of life.

Intermittent Regimen (Days 16–25): Suitable for young patients with mild symptoms who wish to maintain regular menstrual cycles.

Precautions: Norethisterone is cost-effective with mild side effects, making it suitable for patients who refuse surgery or require preoperative pretreatment.

03 Management of Special Populations

Adenomyosis Patients: Given their longer symptom duration and more severe pain, extended follow-up is recommended. Combination therapy with other agents (e.g., GnRH agonists) may be necessary if needed.

Leiomyoma Patients: For those with submucosal leiomyomas complicated by menorrhagia, adjuvant norethisterone after hysteroscopic surgery can help prevent recurrence.

Study Limitations and Future Directions

Limitations: This was a single-center study with a sample size of 100 cases and a follow-up period of only 3 months. Long-term efficacy and safety require further verification.

Future Directions: Multicenter, large-sample studies are needed to explore the application value of hysteroscopy in infertile patients, as well as the long-term compliance and side effects of norethisterone use.

Conclusion

Hysteroscopy is a highly effective tool for differentiating adenomyosis from uterine leiomyoma (with specificity >95%), and continuous norethisterone administration is more effective in controlling menorrhagia, the core symptom of AUB. This evidence set provides an integrated "diagnosis + treatment" solution for clinical practice, which is particularly suitable for rapid decision-making in primary hospitals and outpatient settings.

For AUB patients, remember the core principles: choose hysteroscopy when ultrasound results are uncertain, and use continuous norethisterone for menorrhagia. This approach ensures both accuracy and a balance between efficacy and cost-effectiveness.

References

Editor: Lily