**3.7 Prolactin secretion inhibitors**

Suppression of cellular immunity and NK cell activity in endometriotic patients has been well known. Also, in stressful situations inhibition of NK cell had been found (Chrousos etal, 2000). Prolactin and cortisol levels in serum are stress indicators. Of course the mechanism of hyper prolactinemia in response to stress isn't so clear, elevated level of serum prolactin had been found in endometriosis like other stressful conditions (Lima etal, 2006, Wang etal, 2009). Interestingly the mean serum prolactin levels are higher in advance stages in endometriotic patients (Gregoriou etal ,1999). Quinagolide as a dopamine receptor 2 agonist by reduction in VEGF receptor (a main factor for angiogenesis) could decrease the size of peritoneal lesions and in some cases could eradicate all of endometriotic implants (Gomez etal, 2011). From another aspect quinagolide, is a valuable option for hyper prolactinemia like other dopamine agonists (bromocriptine or caberguline) (Barlier&Jaquet,2006); therefore this drug could be effectively administrated in endometriosis.

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**28** 

 *Japan* 

**Sequential Management with** 

**Uterine Myoma and Adenomyosis** 

*Institute of Endocrine-Related Cancer, Matsunami General Hospital,* 

**Gonadotropin-Releasing Hormone Agonist** 

**and Dienogest of Endometriosis-Associated** 

Atsushi Imai\*, Hiroshi Takagi, Kazutoshi Matsunami and Satoshi Ichigo

Uterine leiomyoma and adenomyosis represent the most common benign tumors of the female reproductive system (Levy, 2008; Parker, 2007; Sankaran & Manyonda, 2008). These tumors are estrogen dependent, develop during the reproductive period, and are suppressed with menopause. Traditional treatments for myomas and adenomyosis have been various types of surgical techniques. Medical management of these tumors is an approach that has been used recently and is attractive for many gynecologists because of its relative ease and lack of complications (pelvic organ adhesion) compared with surgery. Indications for therapy are similar to those for surgical removal of these tumors and focus on preserving fertility and/or the patient's desire to maintain her uterus. Medications used include androgens, antiprogestogens (mifepristone), raloxifen, and gonadotropin-releasing hormone agonist (GnRHa) (Levy, 2008; Parker, 2007; Sankaran & Manyonda, 2008; Schweppe, 1999). At present, considering efficiency and safety issues, none of the above agents obtained adequate popularity except for GnRHa. However, GnRHa also have disadvantages including bone loss and menopausal symptoms. The effect of GnRHa is transient and reversal of estrogen deprivation occurs soon after discontinuation of the GnRHa and most myoma and

adenomyosis returns to their initial size within several months after discontinuation.

Dienogest is a selective progestin that combines the pharmacologic properties of 19 norprogestins and progesterone derivatives, offering potent progestogenic effects without androgenic, mineral corticoid, or glucocorticoid activity (Harada & Taniguchi, 2010; Sasagawa *et al*, 2008; Sitruk-Ware, 2006). Previous trials demonstrated that dienogest provides effective reductions in endometriosis-associated pelvic pain and laparoscopic measures of pathology (Harada *et al*, 2009; Köhler *et al*, 2010; Schindler *et al*, 2006; Strowitzki *et al*, 2010b). Recently, the new progesterone 2 mg daily demonstrated equivalent efficacy to GnRHa (e.g. buserelin acetate and leuprolide acetate) for relieving the pain of endometriosis in two 24-week, randomized studies (Harada *et al*, 2009; Strowitzki *et al*, 2010a; Strowitzki *et al*, 2010b). Because uterine myoma/adenomyosis and endometriosis have many common

\* Corresponding author: Institute of Endocrine-Related Cancer, Matsunami General Hospital, Kasamatsu,

**1. Introduction** 

Japan.

