**1. Introduction**

Urgent innovations are demanded in endometriosis management, which should start by deeper undestanding of disease core features, with disease different phenotypes and idiosyncrasies. Endometriosis, a chronic inflammatory and immune disease, dependent on environement factors, genes- *Hox* genes

code (HOXA10/HOXA11), epigenetics, and ovarian steroid hormones, with their receptors and coregulators in the eutopic endometrium and ectopic sites, was demonstrated to have a long duration of progress from intrauterine life, latency in childhood, and acme during reproductive years [1–3] with reappearance in postmenopause when hormone replacement therapy, or even without [4]. This fact permits therapeutic intervention to correct endometrial abnormal functions during menstrual cycle, to prepare decidua receptivity for successful egg implantation in women with minimal or mild to moderate endometriosis, in order to avoid the severe stages, and lack of response to therapy, considering that progesterone resistance is an acquired property of eutopic endometrium [5]. The therapeutic aims are to prevent, or at least to stop the progressive damages induced by ectopic endometriotic lesions in the uterus, entire genital tract, and in extra-uterine sites by the endometrial mezenchymal stromal/stem/progenitor cells with their specific migratory, adhesive, and invasive properties, with their genome changes when are outside the uterus, to influence the self- protected endometriotic lesions [6] and to ensure a normal eutopic endometrial cycle functioning, with normal ovarian steroid hormones receptors distribution during menstrual cycle. The aims can be individually accomplished if therapy is started from early stages of illness, by moving from pure hormonal therapy to drug combination, or novel molecules- SERMs, SPRMs which can escape the disrupted homeostatic mechanisms characteristic for endometriosis [7].

One may propose and discuss a perspective "timing" of endometriosis treatment, to maintain or for an early restoration of endometrial estrogen- progesterone receptors natural balance [8] being recognized a still delay in diagnosis, and treatment [9] delay that permits the evolution of genital damages by progressing endometriosis, and in time the risk of atypical endometriosis, and cancers which is very difficult to be assessed clinically, without specific biochemical markers [10].

The incidence of endometriosis of one case in 10 women of reproductive age [11, 12] or around 17% [13] is increasing when one assseses infertility and chronic pelvic pains up to 50% [14] respectively up to 60% [15] recently being estimated 176 million women worldwide, making endometriosis as common as diabetes mellitus [16].

There are three distinct forms of disease according to ectopic sites of endometrial-like tissue location (peritoneal, ovarian and rectovaginal endometriosis), each of them being associated with specific symptoms, although dysmenorrhea, and chronic non-menstrual pelvic pains, dyschezia, dyspareunia are the most frecquent [17]. The literature makes some differences regarding the score of endometriosis, namely the ENZIAN classification/score describes superficial (less than 1 mm), intermediate (2 to 4 mm), deep (greater than or equal to 5 mm), and very deep implants (greater than 10 mm) [18]. The ENZIAN score was proposed of the revised American Society of Reproductive Medicine score (1996) [19], which was demonstrated to be less adequate to clinics, and the ENZIAN score was recently reviewed by experts in imagistic and surgical diagnosis [20]. So endometriosis has a similarity to oncology with 4 stages of evolution, with the difference of missing nuclear atypia [21] but with possible evolution to malignancy in 1% cases [1, 22] or further it may be associated to hematopoietic and breast cancer (HR of 1,3–95% CI 1.1–1.4, in Swidish women) [23] and ovarian cancer, − OR of 1.73, (95% CI: 1.10−2.71) on a pool of women from different continents- Australia, Canada, Denmark, USA, during 10 years (1989–1999) with previous endometriosis [24]. The natural history of endometriosis is uncertain, e.g. it is not known whether superficial peritoneal endometriosis (SPE) can progress to become another subtype, regress spontaneously, or whether disease progression (or lack of treatment) can lead to problems with infertility, and there is poor correlation between pain severity and the amount, location, and subtype of the ectopic lesions [16].

#### *Potential Therapeutic Options and Perspectives for Alleviation of Endometrial Estrogen… DOI: http://dx.doi.org/10.5772/intechopen.100039*

The literature does not mention a conclusive noninvasive diagnostic available tool to allow early detection of endometriosis, the delay in detection being of 7–12 years of latency from symptoms onset to the definitive diagnosis, and even in the best medical centres the full extent of the disease may be unknown [25] and up to 2017 it was not identified any fully validated, symptom-based, patient- reported questionnaire for endometriosis screening in adult women with potential endometriosis [26]. One must think to endometriosis in adolescent girls with family history, abnormal characteristics of menstrual cycles with the aim to avoid the structural and functional abnormalities progression induced in women's endometrial genes mainly *Hox* codes for steroid hormones receptors, ligands, and co-regulators.

The next pages will discuss concepts, theories or hypothesis of potential therapeutic options and perspectives for prevention, normalization or restoration the endometrial estrogen- progesterone balance, and their receptors in the epithelium and stroma, because many years there were recommended ovarian supressing drugs, and surgery.
