Antilipidemic Ezetimibe Induces Regression of Endometriotic Explants in a Rat Model of Endometriosis
Condition: Endometriosis
MeSH terms: Endometriosis
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Current endometriosis therapy is based on interrupting the menstrual cycle and suppression of
      estrogen synthesis in order to induce atrophy of endometrial tissue. Progestins, oral
      contraceptives, androgenic agents, aromatase inhibitors, gonadotropin-releasing hormone
      analogues all play a role in the treatment of endometriosis. However, none of these
      treatments can definitely cure the disease and they require long-term use despite the side
      effects of the drug. It is clear that new treatment methods are needed for this disease, and
      therefore many different new treatment methods are being investigated. Some of the treatment
      methods have focused on inhibiting angiogenesis and inflammation, which seems to play an
      important role in the progression of the disease. In the present study, it was investigated
      whether ezetimibe which is a cholesterol absorption inhibitor with anti-inflammatory and
      antiangiogenic properties, has therapeutic effect on endometriosis in an experimental rat
      model.
    

Detailed description: 
      Endometriosis is a relatively common benign disorder that causes significant health problems
      with yet an unknown etiology. The disease which is defined as the presence of the endometrial
      gland and stroma outside the uterine cavity, was first described by the famous pathologist
      Von Rokitansky in 1860. Since then, new theories about the mechanism of its occurrence have
      been put forward, but no single theory has been holistic enough to explain all clinical
      presentations of the disease. Retrograde menstruation, stem cell theory, immune system,
      genetic and environmental factors are among the proposed theories. However, with the
      widespread use of molecular methods in recent years, more detailed information about its
      etiopathogenesis has been obtained and new approaches have been proposed for its diagnosis
      and treatment. Today, it is accepted that multiple factors, including ectopic endometrial
      tissue, altered immune system response, imbalanced cell proliferation and apoptosis, abnormal
      endocrine signal and genetic factors, play a role in the pathogenesis of endometriosis, which
      is a progressive, estrogen-dependent inflammatory disease.

      In recent years, studies on the inflammatory and angiogenesis mechanisms that play a role in
      the pathogenesis of endometriosis have intensified in the treatment of the disease. Agents
      with anti-inflammatory and antiangiogenic effects have been experimentally shown to partially
      prevent the formation or reduce the size of endometriotic lesions in animal models. Statins
      like atorvastatin and simvastatin have been using in the treatment of coronary artery disease
      with their antilipidemic effects and are shown to have efficacy in animal endometriosis
      models with their anti-inflammatory and antiangiogenic properties.

      Ezetimibe, which is a member of a different class of antilipidemic agents than statins, has
      similarly been shown to inhibit the release of substances that play a key role in the
      inflammatory process such as nuclear factor kappa, TNF-α and interleukin 1, and angiogenesis
      such as VEGF. With this mechanism of action, it may be hypothesized that this agent may have
      a possible therapeutic effect on endometriosis. Therefore in this study it was aimed to
      assess the potential therapeutic role of ezetimibe in the experimental rat endometriosis
      model.
    

Intervention name(s): Surgical induction of endometriotic explants
Intervention type(s): Procedure
Intervention description(s): Surgical induction of endometriosis was done as: A 5-cm vertical midline incision was made and a distal segment 1 cm in length of the right uterine horn was resected. The segment was split longitudinally, and a 5 X 5 mm piece was sectioned.
This piece of uterine tissue was transplanted without removing the myometrium onto the inner surface of the right abdominal wall with the serosal surface apposed and secured with single nonabsorbable 5-0 polypropylene suture at the middle to the abdominal wall. The abdominal incision was closed in two layers
Drug administration:
Vehicle treatment (1 mL/kg/day saline) was administered orally to the control group with the gavage methodology. Ezetimibe (1 mg/kg/day (Ezetrol®, Merck Sharp Dohme, Istanbul, Turkey) was administered orally with gavage methodology to the rats in the study for 28 days postoperatively
Other intervention name(s): Drug (ezetimibe 1mg/kg/day) and placebo (saline 1 ml/kg/day) administration
Intervention MeSH terms: Ezetimibe
Allocation: Randomized
Intervention model: Single Group Assignment
Intervention model description: an experimental rat, randomized, drug versus placebo trial
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: endometriosis, ezetimibe, antilipidemics