**14.1 Medical treatment**

	- 1. Medroxyprogestrone acetate / 30 mg /po /daily
	- 2. Megestrol acetate / 40 mg / po / daily
	- 3. Lynoestrenol / 10 mg / po / daily
	- 4. Dydrogestrone / 20-30 mg / daily

The role of the LNG IUS ( Levonorgestrel intra uterin system ) in management of this common and troublesome disorder has been evaluated by multiple studies.( 78-80)

A pilot study examined the role of LNG IUS as a postoperative adjunct to surgical ablation for endometriosis. When compared with expectant management, the LNG IUS recipients had a reduced rate of recurrence of pelvic pain (2/20 compared with 9/20) and an increased rate of satisfaction (15/20 compared with 10/20). (81) The LNG IUS offers several

Histologic confirmation is essential in the diagnosis of endometriosis. The utility of peritoneal wash cytology for diagnosis of endometriosis has been reported. In most cases, only hemosiderin-laden macrophages are identified. The presence of endometrial cells is more specific but less sensitive than hemosiderin-laden macrophages for the diagnosis of endometriosis. The endometrial cells have been reported in 25%–52% of peritoneal washes done in endometriosis. However, recognition of endometrial cells as well as hemosiderinladen macrophages is essential for diagnosis on morphological basis alone. Histologic examination of the tissue confirmed for endometriosis by the presence of both endometrioid

Treatment must be individualized, and the effect of the kind of treatment on quality of life must be considered. There is not any confidence that a uniform therapeutic way be enough and successful, however in the most of the patients there is not a curative treatment. The choice of treatment is based on various factors such as size, location and extent of the disease, type and severity of the symptomatology, wish for pregnancy, and age of the patient. (77) Planning for the treatment is based on two important symptoms: pain and infertility. All the therapeutic ways divide to two main surgical and medical

1. Selective progestron receptor modulators, progestogens and anti progestins

The role of the LNG IUS ( Levonorgestrel intra uterin system ) in management of this

A pilot study examined the role of LNG IUS as a postoperative adjunct to surgical ablation for endometriosis. When compared with expectant management, the LNG IUS recipients had a reduced rate of recurrence of pelvic pain (2/20 compared with 9/20) and an increased rate of satisfaction (15/20 compared with 10/20). (81) The LNG IUS offers several

common and troublesome disorder has been evaluated by multiple studies.( 78-80)

**13. Histological confirmation** 

glands and stroma (15).

**14. Treatment** 

treatments.

**14.1 Medical treatment** 

(Androgens) 2. Gn-RH agents

5. Chinese Medications 6. Angiogenesis inhibitor

7. Gene Therapy

a. Progestogens

3. COC ( Combined Oral Contraceptives)

4. Aromatase inhibitor & NSAIDs and cox2- inhibitors

8. Modulation of Cytokines , inhibition of Matrix Metalloproteinase

1. Medroxyprogestrone acetate / 30 mg /po /daily

2. Megestrol acetate / 40 mg / po / daily 3. Lynoestrenol / 10 mg / po / daily 4. Dydrogestrone / 20-30 mg / daily

I. Selective progestron receptor modulators, progestogens and anti progestins

advantages for control of pelvic pain associated with endometriosis, including effective contraception, minimal systemic effects, and up to 5 years of benefit, as compared with 6 months, typical of GnRHa treatment.

Dienogest (DNG), a progestin of 19‑nortestosterone derivative, has good oral bioavailability and is highly selective for progesterone receptors. Owing to its antiovulatory, antiproliferative activities in endometrial cells, and its inhibitory effects on the secretion of cytokines, DNG is expected to be an effective treatment for endometriosis. Progesterone receptor-binding affinity is higher for DNG than for progesterone.


Treatment with a GnRH-a followed by long-term dienogest therapy maintains the relief of endometriosis-associated pelvic pain achieved with GnRH-a therapy for at least 12months. This regimen reduces the amount of irregular uterine bleeding that often occurs during the early phase of dienogest therapy.(83)

Complex mechanisms involving promoter regulation may be responsible for the observed aberrations in (Estradiol Receptor a, b) ERa, ERb, and PR (progesterone Receptor) expression in endometriosis. The stromal cell component of endometriotic tissue may be the primary site of these abnormalities. In endometriotic stromal cells, ERb promoter is pathologically hypomethylated and therefore hyperactive, leading to very high ERb levels. ERb suppresses ERa expression and results in strikingly high ERb-to-ERa ratios in endometriotic cells.

It is possible that this consequence of PR-B deficiency is only the tip of the iceberg with regard to pathogenesis of endometriosis, and that numerous other molecular aberrations may also contribute to the development of resistance to hormone treatments in women with endometriosis. Selective ERb ligands that target high levels of ERb in endometriotic tissue may be clinically beneficial via disrupting this mechanism.(84) PR deficiency is likely responsible for increased levels of E2 in endometriosis because progesterone fails to induce the E2-metabolizing enzyme HSD17B2 in endometriotic tissue. Some conclusion resonates with gene expression microarray studies performed on eutopic endometrium of women with endometriosis compared with that from disease-free women.(85, 86) These studies on eutopic endometrium identified distinct molecular defects that are consistent with the progesterone resistance hypothesis.

ER b agonists act as immunomodulators, enhancing the immunologic response to the explants; a second possible explanation lies an antiangiogenic effect because ER b are

Endometriosis 17

GnRH antagonists offer the theoretical advantage of working faster and more effectively than GnRH agonists, with better patient compliance because of earlier amelioration of

Hormone therapy obtains a good initial response, is well tolerated by patients, and can be discontinued if there are adverse effects. Combined hormone therapy with estrogens and progesterone [91] has been used for small lesions, with total or partial remission of the symptoms in a high percentage of cases. Medical treatment alone does not lead to the definitive cure of deep, severe endometriosis but only induces temporary disappearance of

These drugs can be used conventionally in a cyclic regimen or may be used continuously, without a break for withdrawal menses. The continuous regimen may be preferable for its decreased frequency of menses for women who fail to achieve pain relief with cyclic COC therapy. To maintain relief from pelvic pain while minimizing hypoestrogenic side effects, several regimens are proposed. Oral contraceptives plus dienogest, a novel progestogen, or a gonadotropin-releasing hormone agonist with estrogen supplementation (add-back therapy) can be used in long-term administration. The relief from pelvic pain achieved with a gonadotropin-releasing hormone agonist can be sustained by long-term administration of a tapered dose of danazol or medium-to-low doses of oral contraceptives. Local treatment with the levonorgestrel-releasing intrauterine system is an option for long-term suppression of pelvic pain.(93) For patients with recurrent ovarian endometriosis after conservative surgery or conservative surgery plus medical therapy, LNG-IUS and COC (combined oral contraceptives) may be used to control and reduce endometriotic cysts, relieve pain and reduce the level of CA125. LNG-IUS has the advantages of a greater convenience and minor systemic side effects (94). Long-term OCP therapy can be a reliable adjuvant post-operative measure to prevent or reduce frequency/severity of recurrent dysmenorrhoea and anatomical relapse of endometriosis. Since both continuous and cyclic OCP administration regimens seem to have comparable effects, the choice of regimen can be modulated according to patient preferences. The protective effect seems to be related to the duration of

Large quantities of estrogen can be produced locally within ectopically located endometrium via an intracrine mechanism, via the expression of the enzyme aromatase. This enzyme, not expressed in normal endometrium, is stimulated by prostaglandin E2 (PGE2); the resulting estrogen production then stimulates PGE2, further enhancing estrogen. An obvious therapeutic target would thus be this aromatase enzyme and aromatase inhibitors were tested in the rodent endometriosis model, with good success

The expression of COX-2 was recently demonstrated in ectopic endometrial cells, showing higher concentration with respect to the eutopic endometrium [97]. COX-2 selective inhibitor given at the minimal dosage is effective against the pelvic pain symptoms (dysmenorrhoea, dispareunia, and chronic pelvic pain) associated to endometriosis [98].

symptoms (90).

active lesions [92]

treatment.(95)

[96].

IV. Aromatase inhibitor & NSAIDs and cox2- inhibitors

III. COC (Combined Oral Contraceptives)

present in endothelial cells of endometrial vasculature. Finally, it is possible that b receptor acts intracellularly as an ERa inhibitor, by dimerizing with the ERa molecules to form a faulty product (87).


The first medication approved for the treatment of endometriosis in the United States was the androgen danazol. The predominant mechanism of action appears to be suppression of midcycle luteinizing hormone (LH) surge, creating a chronic anovulatory state as a result, danazol creates a hypoestrogenic, hyperandrogenic state, inducing endometrial atrophy in endometriotic implants. The recommended dosage of danazol is 600 to 800 mg daily. Unfortunately, significant androgenic side effects develop at this dosage and include acne, hot flashes, hirsutism, adverse serum lipid profiles, voice deepening (possibly irreversible), elevation of liver enzymes, and mood changes. Moreover, due to possible teratogenicity, this medication should be taken in conjunction with effective contraception. Because of this adverse side-effect profile, danazol is prescribed less frequently, and when administered, its duration should be limited. Gestrinone (ethylnorgestrienone; R2323) is an antiprogestational agent prescribed in Europe for the treatment of endometriosis. Gestrinone equals the effectiveness of danazol and of GnRH agonists for relief of endometriosis-related pain. Mifepristone is a PA (Progestron Antagunist) currently approved only for use in medication abortion and, in some countries, as an emergency contraceptive, but 3 small trials have demonstrated a reduction in endometriosis symptoms with Mifepristone therapy.(88 ,89)


Treatment with GnRHa for 3 months is as effective as the 6-months treatment as far as pain is concerned, and when combined with estro-progestational agents ('add-back therapy') up to a maximum of 2 years, is effective for pain and safe in terms of protecting bone density.(77)

Like GnRH agonists, the GnRH antagonists share some homology with the native GnRH molecule. These drugs act by blocking the GnRH receptor directly and preventing it from activating. This result in a downregulation of the pituitary gland, a reduction of gonadotropin secretion, and a suppression of ovarian steroid production Unlike GnRH agonists, however, these drugs do not cause an initial stimulation of gonadotropin and ovarian hormone secretion. At the molecular level, GnRH antagonists interrupt the basic activation process of the GnRH receptor, blocking the receptor dimerization synthesis and secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Given the high binding affinity, relative abundance and long half-life of the antagonist, these molecules monopolize the GnRH receptors. As a result of the above characteristics, the

present in endothelial cells of endometrial vasculature. Finally, it is possible that b receptor acts intracellularly as an ERa inhibitor, by dimerizing with the ERa molecules to form a

The first medication approved for the treatment of endometriosis in the United States was the androgen danazol. The predominant mechanism of action appears to be suppression of midcycle luteinizing hormone (LH) surge, creating a chronic anovulatory state as a result, danazol creates a hypoestrogenic, hyperandrogenic state, inducing endometrial atrophy in endometriotic implants. The recommended dosage of danazol is 600 to 800 mg daily. Unfortunately, significant androgenic side effects develop at this dosage and include acne, hot flashes, hirsutism, adverse serum lipid profiles, voice deepening (possibly irreversible), elevation of liver enzymes, and mood changes. Moreover, due to possible teratogenicity, this medication should be taken in conjunction with effective contraception. Because of this adverse side-effect profile, danazol is prescribed less frequently, and when administered, its duration should be limited. Gestrinone (ethylnorgestrienone; R2323) is an antiprogestational agent prescribed in Europe for the treatment of endometriosis. Gestrinone equals the effectiveness of danazol and of GnRH agonists for relief of endometriosis-related pain. Mifepristone is a PA (Progestron Antagunist) currently approved only for use in medication abortion and, in some countries, as an emergency contraceptive, but 3 small trials have demonstrated a

reduction in endometriosis symptoms with Mifepristone therapy.(88 ,89)

Treatment with GnRHa for 3 months is as effective as the 6-months treatment as far as pain is concerned, and when combined with estro-progestational agents ('add-back therapy') up to a maximum of 2 years, is effective for pain and safe in terms of protecting bone

Like GnRH agonists, the GnRH antagonists share some homology with the native GnRH molecule. These drugs act by blocking the GnRH receptor directly and preventing it from activating. This result in a downregulation of the pituitary gland, a reduction of gonadotropin secretion, and a suppression of ovarian steroid production Unlike GnRH agonists, however, these drugs do not cause an initial stimulation of gonadotropin and ovarian hormone secretion. At the molecular level, GnRH antagonists interrupt the basic activation process of the GnRH receptor, blocking the receptor dimerization synthesis and secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Given the high binding affinity, relative abundance and long half-life of the antagonist, these molecules monopolize the GnRH receptors. As a result of the above characteristics, the


faulty product (87). b. Antiprogestins:

II. Gn-RH agents

density.(77)





#### III. COC (Combined Oral Contraceptives)

Hormone therapy obtains a good initial response, is well tolerated by patients, and can be discontinued if there are adverse effects. Combined hormone therapy with estrogens and progesterone [91] has been used for small lesions, with total or partial remission of the symptoms in a high percentage of cases. Medical treatment alone does not lead to the definitive cure of deep, severe endometriosis but only induces temporary disappearance of active lesions [92]

These drugs can be used conventionally in a cyclic regimen or may be used continuously, without a break for withdrawal menses. The continuous regimen may be preferable for its decreased frequency of menses for women who fail to achieve pain relief with cyclic COC therapy. To maintain relief from pelvic pain while minimizing hypoestrogenic side effects, several regimens are proposed. Oral contraceptives plus dienogest, a novel progestogen, or a gonadotropin-releasing hormone agonist with estrogen supplementation (add-back therapy) can be used in long-term administration. The relief from pelvic pain achieved with a gonadotropin-releasing hormone agonist can be sustained by long-term administration of a tapered dose of danazol or medium-to-low doses of oral contraceptives. Local treatment with the levonorgestrel-releasing intrauterine system is an option for long-term suppression of pelvic pain.(93) For patients with recurrent ovarian endometriosis after conservative surgery or conservative surgery plus medical therapy, LNG-IUS and COC (combined oral contraceptives) may be used to control and reduce endometriotic cysts, relieve pain and reduce the level of CA125. LNG-IUS has the advantages of a greater convenience and minor systemic side effects (94). Long-term OCP therapy can be a reliable adjuvant post-operative measure to prevent or reduce frequency/severity of recurrent dysmenorrhoea and anatomical relapse of endometriosis. Since both continuous and cyclic OCP administration regimens seem to have comparable effects, the choice of regimen can be modulated according to patient preferences. The protective effect seems to be related to the duration of treatment.(95)

#### IV. Aromatase inhibitor & NSAIDs and cox2- inhibitors

Large quantities of estrogen can be produced locally within ectopically located endometrium via an intracrine mechanism, via the expression of the enzyme aromatase. This enzyme, not expressed in normal endometrium, is stimulated by prostaglandin E2 (PGE2); the resulting estrogen production then stimulates PGE2, further enhancing estrogen. An obvious therapeutic target would thus be this aromatase enzyme and aromatase inhibitors were tested in the rodent endometriosis model, with good success [96].

The expression of COX-2 was recently demonstrated in ectopic endometrial cells, showing higher concentration with respect to the eutopic endometrium [97]. COX-2 selective inhibitor given at the minimal dosage is effective against the pelvic pain symptoms (dysmenorrhoea, dispareunia, and chronic pelvic pain) associated to endometriosis [98].

Endometriosis 19

implantation. In human endometrium, the expression of HOXA10 and HOXA11 is driven by sex steroids, with peak expression occurring at time of implantation in response to rising progesterone levels. However, the maximal HOXA10 and HOXA11 expression fails to occur in women with endometriosis resistance to progesterone which can explain inhospitable implantation environment and medical treatment failures in endometriosis. Alterations in progesterone receptor expression and decreased HOX gene expression secondary to hypermethylation of its promoter region are the possible mechanisms of the progesterone resistance. A gene therapy approach involving the manipulation of HOXA10 expression or by using DNA demethylation agents to restore methylation aberrations can potentially have

A new study compared women suffering chronic pelvic pain (CPP) secondary to endometriosis with women experiencing CPP due to either myofascial abdominal/pelvic pain or pelvic adhesions to determine if there are specific psychological variables uniquely associated with endometriosis .No differences were obtained across the three groups for any of the outcome measures. Effect size computation supported the absence of clinical differences across the groups for these measures. These findings fail to support the presence of a unique psychological profile or disproportionate psychological disturbance for women with CPP due to endometriosis. These data illustrate the importance of considering control groups that include chronic pain when exploring psychological contributions to specific

In rats with experimental endometriosis, recombinant human TNF-α-binding protein can

In nude mice, suppression of MMPs by progesterone or by a natural inhibitor slows the

The goal of surgery is to excise all visible endometriotic lesions and associated adhesionsperitoneal lesions, ovarian cysts, deep rectovaginal endometriosis-and to restore normal

Laparoscopy is the gold standard for diagnosis and the primary means of treatment at this time. Laparoscopy is used with different goals such as diagnosis, ablation, excision and lysis

 Excisional removal of ovarian endometriomas seems superior to drainage and ablation for both improved spontaneous pregnancy rates and improved pain symptoms. Laparoscopic treatment of endometriosis carries a long-term substantial relief of symptoms for a significant percentage of women. (114) Laser ablation does not appear to be more effective

Radical procedures such as oophorectomy or total hysterectomy are indicated only in severe situations and can be performed either laparoscopically or by laparotomy. Laparotomy should be reserved for patients with advanced-stage disease who cannot undergo a laparoscopic procedure and for those in whom fertility conservation is not necessary.

a role in the future treatment of endometriosis.(108-110)

VIII. Modulation of Cytokines, lnhibition of Matrix Metalloproteinase

reduce 64% of the size of endometriosis-like peritoneal lesions (112).

establishment of ectopic lesions by human endometrium. (113)

than conventional electrosurgical ablation of endometriosis.

chronic pain conditions.(111)

**14.2 Surgical treatments** 

anatomy.

of adhesions.

Aromatase inhibitors have similar hypoestrogenic side-effect profiles as GnRH agonists, but hold promise in severe, refractory cases of endometriosis.

Treatment of rats with induced endometriosis using the nonsteroidal aromatase inhibitor fadrozole hydrochloride or YMsl l resulted in a dose-dependent volume reduction of endometriosis transplants.(99, 100)

In a pilot study, preliminary data were generated suggesting a potential future use of this drug, but randomized controlled trials are needed to confirm these data.(101) The effect of medical treatment in terms of pain relief in women with rectovaginal endometriosis appear substantial.(102)

V. Chinese Medications (CM)

In recent years, the Chinese medicine treatment of EM has won favorable therapeutic effects with few adverse reactions. The CM treatment of EM puts stress on therapy according to syndrome differentiation, varying the treatment for different individuals and emphasizing different sides in different stages of a menstrual cycle. It is non-traumatic with less adverse effect and good long-term effectiveness. It is favorable in combination with various approaches like acupuncture and moxibustion, retention enema and Western medical treatment, and could be extensively applied in clinical practice to function effectively in improving clinical symptoms and physical signs of patients and raising their quality of life.(103) Dong, et al treated EM with Guizhi Fuling capsule combined with intervention paracentesis implemented under ultrasonographic guidance to achieve good efficacy. The patients' cystic fluid was drawn out through puncturing and then the cystic cavity was washed repeatedly with 0.5% Lidocaine, then absolute alcohol was injected into the cavity The outcome shows that the therapeutic efficacy in the two groups was the same, but adverse reaction of Guizhi Fuling Capsule was significantly less than that of Gestrinone.(104)

Xue treated 41 patients with Mifepristone (25 mg/d, starting from the 1st day of the menstruation) combined with Chinese decoction, consisting of chuanxiong, dragon's blood, peach kernel, achyranthes root, yanhusuo rhizome, typha, trogopterus dung, red peony root, Chinese angelica root, cyperus tuber, red sage root, etc., one dose a day for 6 successive months, and the total effective rate obtained was 92.7%, which was better than that of Mifepristone or Chinese herbal medicine alone.(105)

Yu used Xiaoyi Zhitong Decoction combined with Mifepristone to treat 76 patients for 3 months, which resulted in a total effective rate of 92% and a recurrent rate of 5.3%.(106)

VI. Angiogenesis inhibitors

The most prominently studied among angiogenic factors is the vascular endothelial growth factor (VEGF), which is responsible for inducing early vascular growth. In any event, one logical therapeutic step would be to attempt inhibition of these new vascular structures as a way of deterring the development of endometriosis. The only human study thus far conducted with an angiogenesis inhibitor was the treatment of endometriosis associated pain with thalidomide; pain relief was noted in these patients [107].

VII. Gene Therapy

HOX genes, encoding homeodomain transcription factors, are dynamically expressed in endometrium, where they are necessary for endometrial growth, differentiation, and

Aromatase inhibitors have similar hypoestrogenic side-effect profiles as GnRH agonists, but

Treatment of rats with induced endometriosis using the nonsteroidal aromatase inhibitor fadrozole hydrochloride or YMsl l resulted in a dose-dependent volume reduction of

In a pilot study, preliminary data were generated suggesting a potential future use of this drug, but randomized controlled trials are needed to confirm these data.(101) The effect of medical treatment in terms of pain relief in women with rectovaginal endometriosis appear

In recent years, the Chinese medicine treatment of EM has won favorable therapeutic effects with few adverse reactions. The CM treatment of EM puts stress on therapy according to syndrome differentiation, varying the treatment for different individuals and emphasizing different sides in different stages of a menstrual cycle. It is non-traumatic with less adverse effect and good long-term effectiveness. It is favorable in combination with various approaches like acupuncture and moxibustion, retention enema and Western medical treatment, and could be extensively applied in clinical practice to function effectively in improving clinical symptoms and physical signs of patients and raising their quality of life.(103) Dong, et al treated EM with Guizhi Fuling capsule combined with intervention paracentesis implemented under ultrasonographic guidance to achieve good efficacy. The patients' cystic fluid was drawn out through puncturing and then the cystic cavity was washed repeatedly with 0.5% Lidocaine, then absolute alcohol was injected into the cavity The outcome shows that the therapeutic efficacy in the two groups was the same, but adverse

reaction of Guizhi Fuling Capsule was significantly less than that of Gestrinone.(104)

Mifepristone or Chinese herbal medicine alone.(105)

pain with thalidomide; pain relief was noted in these patients [107].

VI. Angiogenesis inhibitors

VII. Gene Therapy

Xue treated 41 patients with Mifepristone (25 mg/d, starting from the 1st day of the menstruation) combined with Chinese decoction, consisting of chuanxiong, dragon's blood, peach kernel, achyranthes root, yanhusuo rhizome, typha, trogopterus dung, red peony root, Chinese angelica root, cyperus tuber, red sage root, etc., one dose a day for 6 successive months, and the total effective rate obtained was 92.7%, which was better than that of

Yu used Xiaoyi Zhitong Decoction combined with Mifepristone to treat 76 patients for 3 months, which resulted in a total effective rate of 92% and a recurrent rate of 5.3%.(106)

The most prominently studied among angiogenic factors is the vascular endothelial growth factor (VEGF), which is responsible for inducing early vascular growth. In any event, one logical therapeutic step would be to attempt inhibition of these new vascular structures as a way of deterring the development of endometriosis. The only human study thus far conducted with an angiogenesis inhibitor was the treatment of endometriosis associated

HOX genes, encoding homeodomain transcription factors, are dynamically expressed in endometrium, where they are necessary for endometrial growth, differentiation, and

hold promise in severe, refractory cases of endometriosis.

endometriosis transplants.(99, 100)

V. Chinese Medications (CM)

substantial.(102)

implantation. In human endometrium, the expression of HOXA10 and HOXA11 is driven by sex steroids, with peak expression occurring at time of implantation in response to rising progesterone levels. However, the maximal HOXA10 and HOXA11 expression fails to occur in women with endometriosis resistance to progesterone which can explain inhospitable implantation environment and medical treatment failures in endometriosis. Alterations in progesterone receptor expression and decreased HOX gene expression secondary to hypermethylation of its promoter region are the possible mechanisms of the progesterone resistance. A gene therapy approach involving the manipulation of HOXA10 expression or by using DNA demethylation agents to restore methylation aberrations can potentially have a role in the future treatment of endometriosis.(108-110)

A new study compared women suffering chronic pelvic pain (CPP) secondary to endometriosis with women experiencing CPP due to either myofascial abdominal/pelvic pain or pelvic adhesions to determine if there are specific psychological variables uniquely associated with endometriosis .No differences were obtained across the three groups for any of the outcome measures. Effect size computation supported the absence of clinical differences across the groups for these measures. These findings fail to support the presence of a unique psychological profile or disproportionate psychological disturbance for women with CPP due to endometriosis. These data illustrate the importance of considering control groups that include chronic pain when exploring psychological contributions to specific chronic pain conditions.(111)

VIII. Modulation of Cytokines, lnhibition of Matrix Metalloproteinase

In rats with experimental endometriosis, recombinant human TNF-α-binding protein can reduce 64% of the size of endometriosis-like peritoneal lesions (112).

In nude mice, suppression of MMPs by progesterone or by a natural inhibitor slows the establishment of ectopic lesions by human endometrium. (113)
