What are the recommended medical and surgical treatment options for adenomyosis in a premenopausal woman, considering severity of bleeding, pain, uterine size, age, and desire for future fertility?

Adenomyosis Management

Start with a levonorgestrel-releasing intrauterine device (LNG-IUD 20 μg/d) as first-line therapy for adenomyosis, which reduces menstrual blood loss by 71-95% and provides superior symptom control compared to all other medical options. 1

Medical Management Algorithm

First-Line: LNG-IUD

• The LNG-IUD delivers high local progesterone concentrations directly to the endometrium while minimizing systemic effects, making it the optimal initial choice for managing adenomyosis-related bleeding and pain. 1, 2
• Efficacy is comparable to endometrial ablation with 71-95% reduction in menstrual blood loss. 1
• A randomized controlled trial demonstrated significant improvement in both pain and bleeding in women with adenomyosis treated with LNG-IUD versus combined oral contraceptives. 1
• The LNG-IUD is clinically favored due to its local mechanism of action, lower systemic hormone levels, long duration after placement, and user independence. 1

Second-Line: Oral GnRH Antagonists

• Oral GnRH antagonists (elagolix, linzagolix, relugolix) are highly effective for heavy menstrual bleeding, with a reduction in fibroid volume by 18-30%. 1, 2
• Combination treatment with low-dose estrogen and progestin add-back therapy is mandatory to mitigate hypoestrogenic effects (hot flushes, headaches, bone mineral loss) when using GnRH antagonists. 1, 3
• GnRH agonists provide pain relief comparable to danazol for 3-6 months of treatment. 1
• Up to 44% of women experience recurrence of adenomyosis-related symptoms within one year after stopping GnRH treatment. 1
• GnRH therapy suppresses fertility, making it inappropriate for women actively attempting conception. 1

Third-Line: Combined Oral Contraceptives

• Combined oral contraceptives reduce painful and heavy menstrual bleeding in randomized controlled trials, though less effective than LNG-IUD. 1, 3

Nonhormonal Alternatives

• Tranexamic acid provides significant reduction in menstrual blood loss as a nonhormonal alternative, ideal for patients who cannot or prefer not to use hormonal therapy. 1, 3
• NSAIDs reduce menstrual blood loss and bleeding symptoms, but should be avoided in women with cardiovascular disease. 1, 3

Interventional Options

Uterine Artery Embolization (UAE)

• UAE provides short-term symptom improvement in 94% and long-term improvement in 85% of patients, with symptom control and quality of life improvement maintained up to 7 years. 1, 2, 3
• Long-term symptomatic relief (median follow-up 27.9 months) in patients with pure adenomyosis or adenomyosis with coexistent leiomyomas ranges from 65% to 82%. 1
• More recent retrospective studies (median follow-up ranging from 24 to 65 months) report symptomatic control in 73% to 88% of patients. 1
• If bleeding persists after 6 months of LNG-IUD, consider UAE or GnRH antagonist therapy. 2

Endometrial Ablation

• Endometrial ablation offers greater long-term efficacy than oral medical treatment and reduces pregnancy risk while managing bleeding. 1
• However, endometrial ablation has high failure rates in the presence of adenomyosis. 3

Surgical Management

Hysterectomy

• Hysterectomy provides definitive resolution of all fibroid-related symptoms with patient satisfaction rates up to 90%, and is recommended when medical and interventional therapies fail. 1, 3
• When hysterectomy is performed, the least invasive approach should be chosen, with vaginal or laparoscopic hysterectomy preferred over abdominal approach, offering shorter operating times, faster return to activities, and lower infection rates. 3
• Robotic-assisted hysterectomy shows similar outcomes to traditional laparoscopy. 3
• Ovaries should be left in place to avoid precipitating menopause and associated cardiovascular risks, unless there is an indication for removal. 3
• Even with ovarian conservation, hysterectomy carries risks including cardiovascular disease, mood disorders, osteoporosis, and potentially increased dementia risk. 3

Fertility Preservation Considerations

• Limited evidence supports UAE as a fertility-preserving treatment for adenomyosis; comprehensive pregnancy outcome data are lacking, so patients should be counseled that UAE is not a standard option for preserving fertility. 1
• A retrospective cohort reported spontaneous pregnancy in 29.5% of women at 1 year and 40.1% at 2 years after UAE, with an 81% live-birth rate; however, the cohort included patients with both uterine fibroids and adenomyosis, limiting the applicability to adenomyosis-only cases. 1
• Evidence for MR-guided focused ultrasound (MRgFUS) in adenomyosis is confined to isolated case reports, and a randomized trial was terminated because of insufficient enrollment, indicating a lack of robust data to support its use for fertility preservation. 1
• In patients desiring fertility preservation, alternatives to hysterectomy should be considered, such as UAE, which can provide 94% short-term and 85% long-term symptom improvement. 3

Critical Pitfalls and Caveats

• No medical therapy eradicates adenomyosis lesions; all provide only temporary symptom relief with rapid recurrence after discontinuation. 1, 3
• Medical therapies will not treat bulk symptoms associated with fibroids. 1
• Myomectomy alone does not address adenomyosis and is ineffective for this condition. 3
• Ensure endometrial biopsy has been performed to rule out endometrial cancer or hyperplasia, especially in perimenopausal women with adenomyosis. 3
• Surgical recurrence after conservative surgery is common, with up to 44% experiencing symptom recurrence within one year. 3

Decision Algorithm Based on Clinical Context

For Premenopausal Women with Severe Bleeding/Pain, No Fertility Desire:

1. Place LNG-IUD 1, 2
2. If symptoms persist after 6 months, add GnRH antagonist with add-back therapy or proceed to UAE 1, 2
3. If medical/interventional therapies fail, proceed to hysterectomy 1, 3

For Premenopausal Women with Fertility Desire:

1. Trial LNG-IUD for symptom control (remove when attempting conception) 1
2. Consider UAE with counseling about limited pregnancy outcome data 1
3. GnRH agonists before fertility treatments to improve pregnancy chances 4

For Perimenopausal Women with Adenomyosis and Vasomotor Symptoms:

1. Place LNG-IUD for bleeding control 2
2. Add transdermal estradiol for vasomotor symptoms (LNG-IUD provides endometrial protection) 2
3. If bleeding persists after 6 months, consider UAE or hysterectomy 2

For Women Preferring Nonhormonal Options:

1. Tranexamic acid for bleeding control 1, 3
2. NSAIDs for pain (avoid in cardiovascular disease) 1, 3
3. If inadequate, proceed to UAE or hysterectomy 1, 3