What is the recommended management for a perimenopausal woman (age 40‑55) presenting with dysfunctional uterine bleeding after excluding structural lesions and obtaining appropriate laboratory evaluation?

Treatment of Dysfunctional Uterine Bleeding in Perimenopause

The levonorgestrel-releasing intrauterine device (LNG-IUD) is the most effective first-line medical treatment for perimenopausal dysfunctional uterine bleeding, reducing menstrual blood loss by 71-95% with efficacy comparable to endometrial ablation. 1

Mandatory Initial Evaluation Before Treatment

Before initiating any therapy, you must exclude malignancy and structural lesions through a systematic diagnostic approach:

Endometrial Sampling Requirements

• All perimenopausal women (age ≥45 years) with abnormal uterine bleeding require endometrial biopsy regardless of ultrasound findings. 1, 2 This is non-negotiable because chronic anovulation in this age group creates unopposed estrogen exposure that markedly raises the risk of endometrial hyperplasia and carcinoma. 1

• Office endometrial biopsy using Pipelle achieves 99.6% sensitivity for detecting endometrial carcinoma when adequate tissue is obtained. 2

• If the initial biopsy is inadequate, non-diagnostic, or symptoms persist despite a benign result, escalate immediately to hysteroscopy with directed biopsy or fractional D&C under anesthesia because blind sampling has a 10% false-negative rate and frequently misses focal lesions such as polyps. 2

Imaging Protocol

• Obtain transvaginal ultrasound combined with transabdominal imaging to assess endometrial thickness and identify structural causes (polyps, fibroids, adenomyosis). 1, 3

• If focal lesions are suspected or visualization is inadequate, proceed to saline infusion sonohysterography, which provides 96-100% sensitivity for detecting endometrial pathology. 1, 3

Laboratory Assessment

• Measure thyroid-stimulating hormone (TSH) and prolactin levels to exclude reversible endocrine causes of anovulatory bleeding. 1, 3

• Check hemoglobin and iron levels if heavy bleeding is present. 4

• Obtain β-hCG in all reproductive-age women to exclude pregnancy. 1, 3

First-Line Medical Management Algorithm

Once malignancy and structural lesions requiring surgery are excluded, proceed with medical therapy:

Preferred Option: Levonorgestrel-Releasing IUD

• The LNG-IUD (20 µg/day) is the single most effective medical treatment, reducing menstrual blood loss by 71-95% and achieving quality-of-life outcomes equivalent to hysterectomy. 1, 5 This represents the highest-quality evidence for medical management.

• The LNG-IUD provides minimal systemic absorption, making it the preferred option for women with cardiovascular disease or contraindications to systemic hormones. 1

• Counsel patients that irregular bleeding patterns may occur initially but typically improve over 3-6 months. 3

Alternative Hormonal Options

Combined hormonal contraceptives (CHCs):

• Use CHCs for women who desire contraception and have no contraindications (no history of thromboembolism, stroke, migraine with aura, uncontrolled hypertension, or breast cancer). 1, 3

• CHCs are particularly effective for anovulatory bleeding and can be combined with NSAIDs to further reduce bleeding volume. 1

• Perimenopausal non-smokers without vascular disease may use low-dose combination oral contraceptives. 6, 7

Cyclic oral progestins:

• Administer medroxyprogesterone acetate 10 mg daily for 10-14 days each month (or 21 days per month for greater efficacy) when estrogen is contraindicated. 1, 6

• Critical FDA caveat: Injectable medroxyprogesterone acetate is NOT recommended for dysfunctional uterine bleeding due to its prolonged action and unpredictable withdrawal bleeding; oral therapy is required. 8

• Cyclic progestin therapy reduces menstrual blood loss by approximately 87% in women with heavy cyclic bleeding. 1

Non-Hormonal Medical Options

Tranexamic acid:

• Tranexamic acid is the most effective non-hormonal medical therapy, significantly reducing menstrual blood loss. 1, 5, 4

• Avoid in women with cardiovascular disease or history of thrombosis due to increased MI and thrombotic risk. 1

NSAIDs:

• NSAIDs reduce bleeding by 20-50% and are most effective for ovulatory menorrhagia. 3, 4

• Avoid in women with cardiovascular disease due to MI risk. 1

Surgical Management When Medical Therapy Fails

Indications for Surgical Intervention

• Failed medical management after adequate trial (typically 3-6 months). 3

• Medical therapy contraindicated or not tolerated. 1, 3

• Patient preference for definitive treatment. 3

• Endometrial sampling showing atypical hyperplasia or malignancy. 3

Surgical Options

Endometrial ablation (second-generation techniques):

• Endometrial ablation is a less invasive alternative to hysterectomy with efficacy comparable to LNG-IUD. 1

• Appropriate for women who have completed childbearing and desire uterus preservation. 3, 4

• Critical pitfall: Endometrial ablation carries long-term risks including postablation Asherman syndrome, cervical stenosis, and potential delayed diagnosis of endometrial cancer; provide thorough informed consent. 1

• Endometrial ablation is associated with high risk of pregnancy complications and should never be performed in women desiring future fertility. 9

Hysterectomy:

• Hysterectomy provides definitive resolution and significantly better health-related quality of life compared to other therapies. 3, 5

• Choose the least invasive surgical route (vaginal, laparoscopic, or abdominal) based on uterine size and surgical expertise. 3

• Hysterectomy is the most appropriate treatment when medical management fails or is contraindicated, particularly in perimenopausal women with symptomatic fibroids. 1

Special Considerations and Common Pitfalls

Cardiovascular Disease

• In women with cardiovascular disease or post-spontaneous coronary artery dissection, systemic hormonal therapy is relatively contraindicated. 1

• The LNG-IUD becomes the preferred and often only safe option due to minimal systemic absorption. 1

• Avoid NSAIDs and tranexamic acid in this population. 1

Coexisting Adenomyosis

• Adenomyosis frequently coexists with fibroids in women in their 40s and presents with heavy menstrual bleeding, dysmenorrhea, and dyspareunia. 1

• The LNG-IUD is particularly effective for adenomyosis-related bleeding. 4

When to Reassess

• If bleeding persists despite initial medical therapy, further investigation with imaging or hysteroscopy is mandatory—never accept treatment failure without tissue diagnosis. 1

• Hysteroscopy allows visualization of the endometrial cavity and diagnosis of focal lesions possibly missed by endometrial sampling. 1

Contraception Counseling

• When prescribing progestogen therapy, assess the need for non-hormonal contraception because ovulation may still occur in up to 20% of patients despite treatment. 1

Evidence Quality Summary

The recommendation for LNG-IUD as first-line therapy is based on high-quality guideline evidence from the American College of Obstetricians and Gynecologists (2026) 1 and supported by systematic reviews demonstrating equivalent quality-of-life outcomes to hysterectomy 5. The mandatory endometrial sampling in women ≥45 years is supported by high-quality evidence from ACOG, NCCN, and ESMO guidelines 1, 2. The FDA contraindication for injectable medroxyprogesterone acetate in dysfunctional uterine bleeding represents the highest level of regulatory evidence 8.