**3.4 Gonadotropin-releasing hormone antagonists**

Regarding to initial flare effect of GnRH agonist administration and probably exacerbation effect on endometriosis and a delay between their administration and real hypo estrogenic state and their intolerable side effects in some patients, GnRH antagonists became an suitable substitute for GnRH agonists. Weekly subcutaneous 3-mg cetrotide (GnRH antagonist) injection had been shown clinical efficacy without pseudo menopausal side effects (Finas etal, 2006; Kupker etal, 2002).There are some published advances in oral GnRH antagonist production: Elagolix (C.Chen et al, 2008). In a double blind study in 55 patients, weekly usage of this drug , results effective suppression of gonadal hormonal production (Struthers etal,2009), which could be a promising development in endometriosis treatments modalities instated of injectable options.

#### **3.5 Androgens**

Danazol is a derivation from testosterone which effect on endometriosis from several ways. Danazol inhibit some steroidogenic enzymes and elevate free testosterone and reduce estrogen level (Barbieri etal, 1981). Also, danazol inhibit mid cycle LH surge (Tamura etal, 1991) and PG F2α production in ovary (Kogo etal,1992),which both of them result chronic anovulation and decrease the chance of new peritoneal seeding.Danazol with 400-800 mg/daily recommended dosage regress the endometriotic implants (Telimaa etal,1987), but severe side effects prevent such dosage administration for an effective period (6 months) (Miller etal,1998).Oily skin, acne, hirsutism, irreversible voice deepness, variation in lipid profile, vaginal atrophia and hot flash limited it's prescription (Hayashi etal,2001).

#### **3.6 Aromatase inhibitors**

In opposition to other hormonal therapeutic options which reduce ovarian estrogenic production, aromatase inhibitors act not only locally on endometriotic implants, but also on all of estrogenic producers: ovary, brain, adipose tissues (Attar&Bulun, 2006). Anastrazole 1mg or letrozole 2.5mg daily could be effective in pain relief associated with endometriosis (Nothnick, 2011; Shippen&West, 2004). Because of stimulatory action of aromatase inhibitors in FSH secretion, in premenopausal women they could cause ovarian cysts;

down regulation state and after suppression of FSH and LH production, menstruation and ovulation had been stopped and therefore, low estrogenic environment achieved which inhibits the proliferation in endometriotic implants. Beside initial flare effect, pseudo menopausal situation produce minor side effects like hot flashes, vaginal atrophia and dryness, headache and other vasomotor signs and symptoms (Dlugi etal,1990) which could be managed by add-back therapy, but after 6 or more continues cycles of drug administration, bone mineral density is going to be reduced sometimes in an irreversible manner (Taga etal,1996); but there is an interesting report about ten years usage of GnRH agonist with add-back therapy without any bone mineral loss (Bedaiwy etal,2006). Unlike the progestins and danazole, GnRH agonists had not adverse effects on lipid profile (Burry etal,1989).Several kinds of injectable GnRH agonists and nasal spray form are available with

Regarding to initial flare effect of GnRH agonist administration and probably exacerbation effect on endometriosis and a delay between their administration and real hypo estrogenic state and their intolerable side effects in some patients, GnRH antagonists became an suitable substitute for GnRH agonists. Weekly subcutaneous 3-mg cetrotide (GnRH antagonist) injection had been shown clinical efficacy without pseudo menopausal side effects (Finas etal, 2006; Kupker etal, 2002).There are some published advances in oral GnRH antagonist production: Elagolix (C.Chen et al, 2008). In a double blind study in 55 patients, weekly usage of this drug , results effective suppression of gonadal hormonal production (Struthers etal,2009), which could be a promising development in endometriosis treatments

Danazol is a derivation from testosterone which effect on endometriosis from several ways. Danazol inhibit some steroidogenic enzymes and elevate free testosterone and reduce estrogen level (Barbieri etal, 1981). Also, danazol inhibit mid cycle LH surge (Tamura etal, 1991) and PG F2α production in ovary (Kogo etal,1992),which both of them result chronic anovulation and decrease the chance of new peritoneal seeding.Danazol with 400-800 mg/daily recommended dosage regress the endometriotic implants (Telimaa etal,1987), but severe side effects prevent such dosage administration for an effective period (6 months) (Miller etal,1998).Oily skin, acne, hirsutism, irreversible voice deepness, variation in lipid profile, vaginal atrophia and hot flash limited it's prescription (Hayashi

In opposition to other hormonal therapeutic options which reduce ovarian estrogenic production, aromatase inhibitors act not only locally on endometriotic implants, but also on all of estrogenic producers: ovary, brain, adipose tissues (Attar&Bulun, 2006). Anastrazole 1mg or letrozole 2.5mg daily could be effective in pain relief associated with endometriosis (Nothnick, 2011; Shippen&West, 2004). Because of stimulatory action of aromatase inhibitors in FSH secretion, in premenopausal women they could cause ovarian cysts;

equal efficacy (Prentice etal,2000).

modalities instated of injectable options.

**3.5 Androgens** 

etal,2001).

**3.6 Aromatase inhibitors** 

**3.4 Gonadotropin-releasing hormone antagonists** 

therefore they administrate with GnRH agonist or OCPs or progestins. This method could reduce the concern about their disadvantage in prolong usage: bone loss (Ferrero etal ,2009).
