Endometriosis=Newer drugs on the horizon

Endometriosis :--Limitations of medical Therapy--Almost all currently available treatments of endometriosis are suppressive, not curative. They are associated with the temporary relief of symptoms during treatment. On treatment discontinuation, recurrence of the symptoms is the rule. For instance, endometriosis-associated pain can continue after medical treatment or conservative surgery. After medical treatment or surgical treatment, the recurrence of endometriosis was estimated to be 21.5% at 2 years and 40% to 50% at 5 years .The treatment goals for endometriomas include pain relief, avoiding rupture or torsion, excluding malignancy, and preventing symptomatic or expanding endometriomas. Several reports have indicated that current medical therapy does not resolve endometriomas More than 60% in patients with chronic pelvic pain (CCP) may be due to recurrent sloughing of the estrogen-dependent ectopic endometrial tissue , This leads to a chronic inflammatory process mediated by the overproduction of inflammatory mediators such as cytokines and prostaglandins. That inflammation, with its resultant adhesions and scarring, mediates the patient's symptoms of pain and other morbidities such as infertility After medical treatment or surgical treatment, the recurrence of endometriosis was estimated to be 21.5% at 2 years and 40% to 50% at 5 years(  Fertility & Stterility)

Treatement modality/ Principle: Whatever the modality treatment (medical or surgical) all are suppressive in nature and it’s an incurable disease, To add to this limitations of endometriosis therapy there are again another important point to  consider, That is whether she wants like restoration of fertility at an early date. Additionally al drugs used for endometriosis are costly and efficacy is doubtful. Based on the above facts there are three kinds of treatment  

Category A) Surgery is a must : Endometriomata> 4 cm, Bowel endometriosis, scar endometriosis, What are the risks of surgery?? When surgery is a must?? . Laparoscopic removal of endometriomata has an adverse effect on ovarian reserve as determined by serum antimüllerian hormone (AMH) levels, There was a statistically significant postoperative fall of AMH concentration (with a weighted mean difference of −1.13 ng/mL) )SourceFertility & Sterility : March 2017Volume 107, Issue 3, Pages 555–565)

Category B) Not desirous of conceiving now A) suppressing estrogen production successful treatment of endometriosis-associated pain is based on suppressing estrogen production and inducing amenorrhea. This creates a relatively hypoestrogenic environment that inhibits ectopic endometrial growth and prevents disease progression .Such drugs are 1) GnRH agonists 2) Inj Depoprovera This is, in part, mediated by blocking the hypothalamopituitary-ovarian axis and inducing a suppression of ovulatory function. GnRH agonists are usually the first-line agents because they are highly effective at suppressing ovarian hormone production and inhibiting the growth of the extrapelvic endometrial tissue. Oral GnRH antagonists produce a dose-dependent hypoestrogenic environment by direct pituitary gonadotropin suppression. This inhibits endometriotic cell proliferation and invasion while maintaining sufficient circulating estradiol levels to avoid vasomotor symptoms, vaginal atrophy, and bone demineralization. Several studies have evaluated the use of elagolix for the management of endometriosis-associated pain with this partially suppressed estrogen paradigm in mind.

1.                Category C)) Desirous of conceiving now: nonsteroidal anti-inflammatory drugs (NSAIDs) appear to be the only medical option consistent with the maintenance of fertility .There is also a RCT that suggested a multidisciplinary approach (physiotherapy and psychological therapy) may offer additional benefits as well as Tricyclic antidepressants. What is an ideal medical agent for endometriosis?? Ideally, medications for endometriosis should be curative rather than suppressive. In addition, they should effectively treat pain and have an acceptable side-effect profile. Long-term use should be safe and affordable. Moreover, they should not be contraceptive and not interfere with spontaneous ovulation and normal implantation of the endometrium to enhance spontaneous conception. Furthermore, they should have no teratogenic potential in case of inadvertent use during the first trimester of a pregnancy. They should suppress the growth of already existing lesions and prevent the development of new ones to limit the need for repeat surgery and prevent the complications associated with advanced endometriosis. Finally, they should be efficacious for all disease phenotypes, including superficial disease, endometriomas, deep infiltrating endometriosis, extrapelvic disease, and adenomyosis

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· Endometriosis : A brief Iist  of newer agents:: . 1 ) Mifepristone, (a SPRM)   2) Asoprisnil( At dose of 5, 10, 25 mg significantly reduces pain) , 3) Ulipristal—(Decreases COX-2 experation -)---4) , Raloxifine( SPRM)  5) Fenofibrate , Simvatatin  7)  Anastrazole at dose of 5, 10, 25 mg significantly reduces non-menstrual pelvic pain/dysmenorrhea, 8) Bromocriptin,9)  Letrozole, 10) Bazedoxifene 11)  Danazol (  View administration of nasal nafarelin as compared with oral danazol for endometriosishas been copared)) . N Engl J Med. 1988; 318: 485–489 : 12)  Tricyclic antidepressant (view Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. Pain. 2012; 153: 1006–1014) 13) Chloroindazole , Oxabicycloheptene Oxabicycloheptene(ER-dependent antiproliferative effect) 14( and many more are on trial.