What is the first‑line medical management for symptomatic adenomyosis in women who wish to preserve the uterus?

Medical Management for Adenomyosis

The levonorgestrel-releasing intrauterine device (LNG-IUD 20 μg/d) is the first-line medical therapy for symptomatic adenomyosis in women wishing to preserve the uterus, providing 71-95% reduction in menstrual blood loss and superior symptom control compared to all other medical options. 1

First-Line Therapy: LNG-IUD

The LNG-IUD stands out as the optimal initial choice based on multiple advantages 1:

• Reduces menstrual blood loss by 71-95%, with efficacy comparable to endometrial ablation 1
• Provides significant improvement in both pain and bleeding, demonstrated superior to combined oral contraceptives in randomized controlled trials 1
• Offers local mechanism of action with lower systemic hormone levels, long duration after placement, and user independence 1
• Does not eradicate adenomyosis lesions but provides effective temporary symptom relief 2

The American College of Radiology specifically recommends the LNG-IUD as first-line therapy for patients with adenomyosis, including those with concurrent fibroids and endometriosis 1. Recent long-term data shows dienogest and LNG-IUD maintain efficacy over three years, though 49% of dienogest patients and 15% of LNG-IUD patients required treatment switches 3.

Second-Line Medical Options

When LNG-IUD fails or is contraindicated, proceed algorithmically:

Combined Oral Contraceptives

• Reduce painful and heavy menstrual bleeding in randomized controlled trials, though less effective than LNG-IUD 1, 4
• Provide only symptomatic management without curing underlying disease 2

High-Dose Progestins

• Dienogest (2 mg daily) significantly reduces dysmenorrhea, dyspareunia, and heavy menstrual bleeding with maintained efficacy over three years 3
• Drospirenone (4 mg) and desogestrel (75 mcg) improve symptoms, though desogestrel has higher discontinuation rates due to reduced long-term efficacy 3
• Progestins demonstrate antiproliferative and anti-inflammatory effects, making them particularly effective for pain control 5

GnRH Antagonists (Elagolix, Linzagolix, Relugolix)

• Highly effective for heavy menstrual bleeding, even with concomitant adenomyosis 2, 1
• Reduce fibroid volume by 18-30% 1
• Mandatory combination with low-dose estrogen and progestin add-back therapy to mitigate hypoestrogenic effects including hot flushes, headaches, and bone mineral density loss 2, 1
• Consider as second-line therapy due to hypoestrogenic limitations 2

GnRH Agonists

• Effective at reducing both bleeding and bulk symptoms 2
• Require add-back therapy with long-term use to prevent bone mineral loss 2
• Provide equivalent pain relief to danazol but with better tolerability 4

Non-Hormonal Alternatives

Tranexamic Acid

• Provides significant reduction in menstrual blood loss as a nonhormonal option 1
• Ideal for patients who cannot or prefer not to use hormonal therapy 1

NSAIDs

• Reduce menstrual blood loss and bleeding symptoms 1
• Avoid in women with cardiovascular disease 1

Interventional Options for Medical Failures

When medical management fails and uterus preservation remains desired:

Uterine Artery Embolization (UAE)

• Provides 94% short-term and 85% long-term symptom improvement 2, 4
• Long-term symptomatic relief (median follow-up 27.9 months) ranges from 65-82% in pure adenomyosis 1
• More recent studies report symptomatic control in 73-88% of patients with median follow-up 24-65 months 1
• Only 7-18% of patients require subsequent hysterectomy for persistent symptoms 4
• Comprehensive data on fertility and pregnancy outcomes after UAE is lacking; counsel patients accordingly 4

Endometrial Ablation

• Has high failure rates in the presence of adenomyosis 2
• Not recommended as primary intervention for adenomyosis 2

Critical Pitfalls and Caveats

No medical therapy eradicates adenomyosis lesions—all provide only temporary symptom relief with rapid recurrence after discontinuation 1, 6, 5. This is the most important counseling point for patients.

Additional warnings:

• Surgical recurrence is common, with up to 44% experiencing symptom recurrence within one year after conservative surgery 2, 4
• Myomectomy alone does not address adenomyosis and is ineffective for this condition 2
• Ensure endometrial biopsy has been performed to rule out endometrial cancer or hyperplasia, especially in perimenopausal women 2
• Medical therapies will not treat bulk symptoms associated with fibroids 1
• There is no evidence that medical treatment affects future fertility in women with adenomyosis 4

Follow-Up Protocol

• Reassess symptoms at 3 months after initiating medical therapy 4
• If inadequate response, switch to alternative progestin formulation or route of administration before escalating to GnRH therapy 3
• Norethisterone acetate serves as effective second-line treatment in cases of intolerance or inadequate response to first-line progestins 3