**4. Discussion**

Adenomyosis is reasonable, although it has not been proven, that matrices with adenomyosis are deficient in activated T-cells, with the result that the basal endometrium in adenomyosis has an advantage in terms of growth potential over nonadenomyotic and lymphoid-rich basal formations. The adenomyosis led to reducing the junctional zone thickness whereas the latter results in the reduction of uterine volume. It remains a major problem that the diagnosis is based on its variable presentation and common coexistence of other gynecologic disorders like fibroids or endometriosis. Growth of adenomyosis focus proved due to contrast-enhanced MRI and TVUS are recommended currently as the most accurate imaging techniques for the diagnosis of the disease. The classical surgical procedure, hysterectomy, is recommended as the only definite treatment modus, while the other treatment alternatives medical and UAE are widely implemented and exist controversially reports [94–98].

Both treatments are reported to be successful, especially in the short term, but there are some long-term reports of UAE adenomyosis treatment being poor in success rate and reaching almost 50% of patients receiving treatment without reporting clinical improvement. Regarding the previously published reports, a recurrence rate of 38% was reported, satisfactory life results were observed in 76% of the participants. However, the question remains unanswered whether such an abnormality is necessarily associated with acquired "morbidity" of the myometrium or whether it is an independent condition for the development of adenomyosis. The exact cause of hyperplasia-hypertrophy of the myometrium, located around the deep foci of the endometrium, is not known [94–98].

Myometrial hyperplasia-hypertrophy may indicate either an attempt to control endometrial penetration or simply represent bundles of smooth muscle fibers displaced by the expanding endometrium. After examination, by immunohistochemical technique, it was found that the myometrium, which surrounds the ectopic endometrium either diffuse (adenomyosis) or focal (adenomyoma), does not show abnormalities. Smooth muscle cells in adenomyotic foci, normal myometrium and leiomyomas, whether or not coexisting with adenomyosis, are rich in actin and desmin [94–98]. Several experimental "models" have been reported to study the pathogenesis of adenomyosis. In one of them, endometrial grafts of the anterior pituitary gland in mice led to the development of adenomyosis [98–100]. Prolactin may amplify this, as the uterine horn that did not contain isografts showed relatively less development of adenomyosis. In this experimental model ovarian resection was prevented, while benzoic estradiol favored the development of adenomyosis.

In another mouse model, which received high doses of diethylstilbestrol (DES) during fetal life, adenomyosis developed. These genera of mice appear to be prone to developing adenomyosis when there are high concentrations of prolactin, estrogen and progestogens. More recently, other researchers have induced adenomyosis in uncastrated rats with hyperprolactinaemia [98–104].

The researchers argued that high concentrations of prolactin cause degeneration of the myometrium, with the concomitant presence of ovarian steroids, which leads to its weakening, resulting in the invasion of the basal layer of the endometrium. Also of great interest were the observations of Mori and Nagasawa in mice, in which the penetration of stromal fibroblasts along the branches of the myometrial blood vessels preceded the invasion of the endometrial glands [105].

In another study, Sakamoto et al., caused severe adenomyosis of the uterus in mice by placing ectopic anterior pituitary lobe isografts [106]. DNA synthesisrelated activities and related enzymes, such as thymidyl synthetase and thymidine kinase, were significantly increased in adenomyosis matrices, compared with controls in the control group. In the same experimental model, it was found that finding low molecular weight metalloproteinases plays a role in the development of adenomyosis, at the level of gene transcription, activation and repression [99–108]. Specific experimental observations suggest that hereditary factors may be involved in the pathogenesis of adenomyosis. For example, the matrices of recombinant SMXA mice automatically develop adenomyosis-like histological changes and contain tenascin around the adenomyotic glands [100–108]. These observations, together with the biological properties of tenascin, reinforce the view of the endometrial origin of adenomyosis and the idea of endometrial penetration into the myometrium, which is genetically predisposed.

Also, compared to SMXA mice, the matrices of F1 mice, a genus found between SMXA and NJL, contain even more obvious spontaneous changes, resembling human adenomyosis. It should be noted, however, that it has not yet been determined whether heredity is an important factor in the development of adenomyosis in humans [100–108]. The early development of adenomyosis from remnants

of Müller's ducts, in positions outside the uterus, is enhanced by the finding of adenomyosis in the rectal septum [100–108]. In this anatomical position can be found endometrial glands and layers, which are associated with hypertrophy of the adjacent smooth muscle fibers and form adenomyotic nodules [100–108]. Although, these nodules can develop as a result of penetration of the peritoneal endometriosis of their origin from remnants of Müller's resources. Thus, according to Nisolle and Donnez, in most cases, adenomyotic nodules are located deep in the septum and in some cases in the muscular layer of the rectum, away from the pelvic peritoneum [106–108]. The co-expression of vimentin and cytokeratin in the endometrium, when it is located in the endometrial cavity and when it is located in adenomyotic foci, is a typical feature of tissue, derived from Müller's ducts. Morphologically and in terms of receptor content, adenomyosis of the atrial septum is similar to that of the myometrium, including poor or no response to the post-ovulatory effect of progesterone. Despite the high doses of progestogens in women with rectal adenomyosis to induce secretory differentiation, hormone therapy has poor results. The definitive treatment of the rectal lesions with surgery also suggests the existence of a metaplastic process from the beginning, from remnants of Müller's ducts in this position, despite the implantation and penetration by peritoneal endometriosis [109–119].

Therefore, as the pathogenetic mechanisms of adenomyosis remain unclear, more studies are needed to reveal the pathophysiology of the disease. In the present study, all patients presented improvement in menorrhagia and had less blood loss during menstruation, while the effectiveness of the method appeared to be higher than that of other conservative surgeries such as intra-myometrial resection/excision and adenoectomy and laparoscopic myometrial electrocoagulation [119–125]. Radical surgery such as hysterectomy was eventually avoided in all participants, in 100% of the 64 patients. We did not observe the occurrence of permanent menopause, except in 0.6% of the participants, while transient amenorrhea within the first 3 months, occurred in the subgroup over the age of 45 years [119–125]. Premature menopause induction and subclinical reduction of ovarian functional reserve after the UAE is a known complication of this procedure, however, we have not observed any cases [119–125]. We know that our study has limitations and that the small sample size precludes a more detailed statistical analysis. Also, when adenomyosis coexists with uterine fibroids, it is very difficult to determine if the symptoms are caused by adenomyosis or the other. The incidence of pure adenomyosis is relatively low and due to a rare condition, individuals with co-existing fibroids were included [119–125].

## **5. Conclusions**

In conclusion, despite the small number of participants, our preliminary study showed promising results with a very high rate of satisfied patients confirming that UAE might be a safe and effective method of treatment for premenopausal women with symptomatic adenomyosis in different if occurs with or without fibroids. It is a non-amputating treatment, alternative to hysterectomy UAE, for the treatment of symptomatic adenomyosis, when conservative treatment fails associated with few complications and allowed an option for the new session for recurrent disease.

## **Conflict of interest**

None.

*Uterine Embolization as a New Treatment Option in Adenomyosis Uteri DOI: http://dx.doi.org/10.5772/intechopen.101480*
