**3. Results**

Of 13 endometriosis patients sequentially treated with GnRHa and dienogest, 7 were associated with coexistent myoma node and adenomyosis; 4 intramural and 2 subserosal types and 1 of adenomyosis. Mean age was 49.9 ± 2.3 (46-52)(Table 1). Volume changes of total myoma and adenomyosis are presented as the percentage change from baseline in Table 1. A remarkable reduction in myoma /adenomyosis volume from baseline was noted:

Sequential Management with Gonadotropin-Releasing Hormone Agonist

perimenopausal women until leading to a natural menopause.

**4. Discussion** 

& Manyonda, 2008).

and Dienogest of Endometriosis-Associated Uterine Myoma and Adenomyosis 487

Uterine myoma/adenomyosis and endometriosis have many common features. Both are estrogen-dependent conditions that can often be the source of pelvic pain and menstrual abnormalities. In addition, both have range of symptom severity that is often poorly correlated to preoperative or operative findings, making surgical planning a challenge (Huang et al, 2010). Recently we found significant shrinkage of myoma nodes coexisted with endometriosis over several months during an administration of dienogest (Ichigo et al, 2011). To our knowledge this retrospective study may be the first study that examined the efficacy and safety of sequential management with dienogest following GnRHa therapy in

Many studies have reported the potential usefulness of the hypoestrogenic state induced by GnRHa for treatment of uterine myoma (Levy, 2008; Parker, 2007; Sankaran & Manyonda, 2008). A GnRHa down-regulates the pituitary-ovarian-gonadal axis, leading to suppression of ovarian steroidogenesis. In the present study our patients revealed an average reduction of 57.5 % in myoma volume in response to leuprolide acetae (1.8mg/month). The results are in agreement with those of previous studies (Levy, 2008; Parker, 2007; Parsanezhad *et al*, 2010; Sankaran & Manyonda, 2008). The GnRHa treatment is often associated with so-called ovarian defect symptoms, including vasomotor instability, vaginal dryness, and significant bone loss, which preclude the long-term use of this compound (Levy, 2008; Parker, 2007; Sankaran & Manyonda, 2008). These limit the standard use of GnRHa to 6 months. The regression of uterine or endometriosis volume is not permanent, with returning to their original size or even enlarging more rapidly upon cessation of GnRHa administration. GnRHa, therefore, can only be used in the short term, as temporizing measures in the perimenopausal woman, or pre-operatively to reduce myoma size, influence the type of surgery, restore hemoglobin levels and apparently reduce blood loss at operation (Sankaran

There may be profound differences among the available progestins according to their structure, metabolites and pharmacodynamic actions (Harada & Taniguchi, 2010; Sasagawa *et al*, 2008; Sitruk-Ware, 2006). It is therefore inappropriate to consider the various effects of the older and newer progestins as class effects. While it has long been established that estrogen promotes myoma growth, many biochemical and clinical studies suggested that older progestins, without an estrogen component, may be effective in the treatment of endometriosis, but not adenomyosis or myomas (Levy, 2008; Parker, 2007; Sankaran & Manyonda, 2008). The newer progestin dienogest demonstrates a modest suppression of estradiol, representing a potential advantage over other therapies, such as GnRHa, which require estrogen add-back if used longer than 6 months (Harada & Taniguchi, 2010; Strowitzki *et al*, 2010a). Also in contrast to GnRHa, dienogest is not associated with an increased incidence of hot flashes (Strowitzki *et al*, 2010a; Strowitzki *et al*, 2010b). More recently the efficacy and safety of long-term usage of dienogest have been demonstrated in previous controlled studies in a large number of patients with endometriosis (Endrikat *et al*, 2007; Momoeda *et al*, 2009; Schindler *et al*, 2010; Sitruk-Ware, 2006). Our previous paper demonstrated that the use of dienogest have several advantages over GnRHa therapy to manage uterine myoma (Ichigo *et al*, 2011). Management of uterine myoma using dienogest is useful in women for whom temporary reduction in myoma volume is aimed and no surgical intervention is planned for any reason. Women with uterine myoma who have pain, pressure effect, hypermenorrhea, or other types of abnormal uterine bleeding who wish to retain the option of childbirth; women who wish to save their uterus; women who are not fit for surgical intervention; and young

the total volume of myoma/adenomyosis declined to 67.6 ± 19.5 % after GnRHa treatment table 1). During the dienogest-period, myoma volume remained as they shrunk; no regrowth occurred. Fig. 1 showed as a representative profile (case 6 of Table 1). One patient (case 7) discontinued therapy because of an unexpected event, onset on ovarian abscess developed in the endometrioma (see Fig.2).

Fig. 2. Bilateral *de novo* ovarian abscesses in a 52-year-old woman with multilobular uterine myoma and bilateral ovarian endometriomas (case 7, table 1).

The patient was treated with leuprolide acetate (1.88mg monthly, Takeda Pharmaceutical, Japan) for 6 months. Axial T2-weighed MR imagings before (a) and after (b) GnRHa treatment showed remarkable shrinkage of uterine myoma and bilateral endometriomas. An attempt to prevent the recurrence submitted the patient to dienogest therapy (2mg daily, Mochida Pharmaceutical, Japan). After two months, she complaint a one-week history of increasing abdominal girth and a two-day history of fever. Axial T2-weighed MR imaging (c) showed two enlarged cystic lesions, one in the left adnexa and the other in the right adnexa. Both lesions were superimposed on the endometrioma with inhomogenous content and the thick wall, while shrunk uterine myoma was detected. There was no history of gynecological interventions including endometrioma aspiration, no had she ever used an intra-uterine device. The clinical and imaging findings and unresponsive to antibiotic therapy proposed the ovarian abscess developed in the endometriomas. At laparotomy, both ovarian cysts were markedly distended and filled with yellow-brown pus, and both ovaries were destroyed by multiple abscess pockets. Histology of the abscess wall confirmed endometriotic nature of the cyst.
