Adenomyosis – An Overview

Adenomyosis is a benign uterine disorder in which there is a pathological presence of endometrial glands and stroma in the myometrium. Symptoms can include abnormal uterine bleeding, dysmenorrhea, dyspareunia, or infertility; one-third of women, however, remain asymptomatic. ^{1 2} Since many of these symptoms also occur in other gynecological diseases such as endometriosis and uterine fibroids, which often co-exist with adenomyosis, making a clinical diagnosis can be difficult. In the past, adenomyosis was only diagnosed on histopathology after a hysterectomy. With the combination of a patient's risk factor profile, clinical symptoms, and imaging diagnostic tools such as transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI), clinicians are able to identify adenomyosis in a non-invasive way. ^{1 3 4 5} The diagnosis of adenomyosis has been increasing in young women of reproductive age and conservative treatment is essential in those who prefer to maintain fertility. ^{1 5} Since adenomyosis greatly impacts quality of life, it is important for clinicians to properly diagnose and treat these women to optimize clinical outcome.

Epidemiology of Adenomyosis

Uterine adenomyosis is primarily seen in women 30–50 years old. ⁶ There is a discrepancy in the literature about true incidence and prevalence of adenomyosis for two reasons: many patients are asymptomatic, and there are no agreed upon standard diagnostic criteria. ³ In a retrospective population-based cohort study of women aged 16–60 years, it was reported that the overall adenomyosis incidence was 1.03% with the overall prevalence being 0.8%. ² However, another study reported that it adenomyosis is estimated to affect 10–80% of premenopausal women, with an even highly incidence and prevalence in women with infertility and chronic pelvic pain. ⁷ The most common known risk factors are age greater than 40 years old, multiparity, prior cesarean section, or uterine surgery. ¹

Rationale for Endovascular Treatment?

Since adenomysosis is difficult to diagnose, has a diffuse nature of disease, and there is little evidence-based literature needed to standardize treatment, hysterectomy has been the definitive treatment. ⁵ Because the diagnosis has been increasing in young women of reproductive age, it is important that they have the option to undergo a uterine-sparing option if they desire future fertility. ¹ For women who prefer a uterine-sparing option, uterine artery embolization (UAE) may be considered. Uterine artery embolization has the benefit of being minimally-invasive, and has been reported to be effective in some women in palliating symptoms related to adenomyosis, in one study, for example, UAE was shown to induce more than 34% necrosis within adenomyotic tissues. ⁴ The benefits of UAE include minimal side effects, cost-effectiveness benefits, and retention of fertility. ⁸

Although there is no US Food and Drug Administration-approved medical therapy for adenomyosis, medical management is typically the first line therapy for adenomyosis. ² Nonhormonal therapy such as non-steroidal anti-inflammatory drugs (NSAIDs) have been used to control adenomyosis associated pain, while some hormonal treatments such as progestins, oral contraceptives (OCP), and gonadotropin-releasing hormone (GnRH) analogues are often used off-label for abnormal uterine bleeding in adenomyosis. ⁹ While these therapies provide women with temporary symptomatic relief without the need to undergo surgery, however there is risk of side effects with these medical therapies. ⁵ Side effects of GnRH analogues can include menopausal symptoms, reduced bone mineral density, genital atrophy, and mood instability; side effect of progestin therapy is breakthrough bleeding; and side effects of combined OCPs can include spotting, headache, and thromboembolic events. ⁹

The levonorgestrel-releasing intrauterine system (LNG-IUS) has also been successfully used to treat adenomyosis without the need of surgical intervention. This medication works by reducing the thickness of the myometrial junction zone and total uterine volume, therefore decreasing menstrual blood loss and pelvic pain. The benefits of using the LNG-IUS is that it has been demonstrated to be cost-effective, reversible, and a long-term treatment for women with adenomyosis-associated pelvic pain. The side effects of this system include irregular bleeding and amenorrhea. ⁹ In a three-year follow up study of adenomyosis, women treated with LNG-IUS reported an overall satisfaction of 72%, with a continued significant decrease in dysmenorrhea and uterine volume compared with baseline. ¹⁰ Another randomized control trial of 75 women reported a significant improvement in hemoglobin levels for women receiving the LNG-IUS device when compared with hysterectomy in the treatment of adenomyosis-associated menorrhagia during the first post-procedure year. ¹¹

Uterine Artery Embolization

Uterine artery embolization was initially performed to prevent or limit bleeding prior to myomectomy or in the setting of post-partum hemorrhage. ¹² Since 1995, it has been recognized as an alternative to hysterectomy for patients with symptomatic uterine leiomyomas. In a randomized control trial with 177 patients from 28 Dutch hospitals who underwent UAE for symptomatic leiomyomas, a 10-years post-intervention questionnaire demonstrated that hysterectomy was avoided in 69% of all women undergoing a technically successful UAE. Importantly, health-related quality of life remained stable between the groups. ¹³

In addition to treating uterine leiomyomas, due to its minimally invasive nature and high success rate UAE has been increasingly used in the treatment of post-partum hemorrhage (PPH) patients. In a retrospective study of 33 patients who underwent UAE for PPH, the technical and clinical success rates were 100% and 85%, respectively. In this study, patients who had intractable PPH after UAE were successfully treated with hysterectomy. ¹⁴

Possible side effects include post-embolization syndrome (seen in the majority of patients undergoing UAS for fibroids), isolated pain, nausea, and hematoma at the femoral puncture site. ⁸

Brief Description of Technique

Uterine artery embolization for adenomyosis is performed the same as it is for fibroid embolization. Briefly, arterial access is obtained from either the femoral artery or in some cases (due to operator preference) from the radial artery. ^{15 16} Some operators will choose to perform a superior hypogastric nerve block prior to the embolization procedure to decrease the degree of post-procedural pain and the need to give opiods for analgesia. ^{17 18} Once arterial access is obtained, a curved catheter is used to select one of the internal iliac arteries (ipsilateral or contralateral), and the anterior division is selected. After angiographic visualization of the uterine artery, a microcatheter is advanced to the horizontal portion of the uterine artery deep in the pelvis. Angiography is performed, particularly to visualize the vaginal and cervical branches to avoid nontarget embolization of these vessels. Once angiography confirms appropriate placement of the catheter, embolization is performed with particles (500–700 microns) to the level of near stasis. Intra-arterial lidocaine can also be injected, again to decrease the risk of post-embolization pain. ¹⁹ Once embolization is completed on one side, the other uterine artery is embolized in identical fashion.

Adenomyosis tends to be less vascular than fibroids, so the likelihood of collateral supply to the uterus (such as the ovarian artery) is lower. For this reason, delayed persistent bleeding from the uterus post-embolization is likely lower than that seen with fibroids.

Outcomes of UAE for Adenomyosis

Several studies have reported the outcomes of UAE for adenomyosis in short- and long-term follow-up. A systemic review and meta-analysis of UAE in 30 studies and over 1,000 patients with adenomyosis reported that 83.1% of women had an improvement of clinical symptoms after their uterine artery embolization. However, long term follow-up (>12 months) demonstrated less encouraging observations compared with short-term follow-up (<12 months). ²⁰

In another review of studies, UAE was seen to have favorable short- and long-term outcomes. In the short term, there was an 83.8% improvement of symptoms at an average of 9.4 months after the procedure; for the long term there was a 64.9% improvement of symptoms at an average of 40.6 months. ⁸

A retrospective study of 252 patients also suggested that UAE is effective in the short- and long-term treatment for adenomyosis, and that the degree of vascularity in the adenomyosis lesion is associated with improvement of symptoms after UAE. In this study, short-term follow-up at 12 months demonstrated that 74% of those who had symptoms of dysmenorrhea prior to UAE had reported symptom improvement, and 70.9% of those who had menorrhagia reported symptom improvement. However, 42.9% of patients experienced recurrence of at least one symptom during their short-term follow-up. In the long-term follow-up, 70.4% of patients with dysmenorrhea had symptom improvement, and 68.8% with menorrhagia reported symptom improvement. In the long term, 47.2% had a recurrence of symptoms. This study also concluded that according to the degree of vascularity based on angiography, with the more highly vascularized lesions showing a better response to UAE. ⁶

Future Trends/Conclusion

Another novel and promising uterine-sparing alternative for local and diffuse adenomyosis is high-intensity focused ultrasound (HIFU), which is a non-invasive local thermal ablation technique. ²¹ This is used to reduce adenomyosis lesions, pain and bleeding symptoms, and improve a patient's quality of life. However, there is limited evidence regarding the impact of HIFU on ovarian reserve and pregnancy outcome,s, and further studies should be performed to ensure its efficacy and safety for women who desire future fertility or uterine preservation. ²²

Lastly, endometrial ablation or resection can be used for adenomyosis depending on the depth of penetration. For those who have only minimal endometrial penetration (superficial adenomyosis), endometrial ablation can have good results. Those women who have a deep endometrial penetration (deep adenomyosis), however, should be offered a hysterectomy over repeat ablation due to the persistence of problems. ²³