**2. Hormonal therapy**

262 Gastrointestinal Endoscopy

endoscopic, surgical or interventional radiological therapy.

The aim of this chapter is to give an overview of current scientific evidence supporting the use of pharmacological therapy in these, often difficult to treat, OGIB patients. The standard diagnostic and therapeutic approach involving endoscopic and radiological techniques, the management of concomitant antiplatelet and anticoagulant drugs and the supportive care of anemia in OGIB patients, are described elsewhere. Up to date, data regarding pharmacological agents for OGIB are scarce and exclusively based on case reports and small uncontrolled studies. The available evidence suggests a potential role for pharmacological therapy as an adjunctive measure in patients with either multiple comorbidities or in whom lesions are inaccessible or refractory to endoscopic therapy. However, their clinical utility remains to be proven in randomized controlled trials. Similarly, the appropriate dose and schedule required for long-term therapy are also unknown. The different pharmacological agents

2. Diffuse vascular lesions in the small bowel or extended to

3. Relative unaccesible location of lesions for endoscopy.

1. Patients who are not candidates or do not respond to

upper or lower segments.

4. Unknown source of bleeding.

Table 1. Indications for pharmacological therapy in OGIB

used for OGIB reported in the literature are listed in Table 2.

Long acting release (LAR) octreotide

Recombinant activated factor VII

Non selective beta-blockers

Table 2. Pharmacological agents used in OGIB

Antifibrinolytics (aminocaproic acid, tranexamic acid)

**Hormonal therapy Somatostatin analogues** 

**Antiangiogenic drugs** 

Octreotide

Lanreotide

Thalidomide Lenalidomide Bevacizumab **Miscellaneous** 

Danazol Desmopressin

Tamoxifen

Estrogen-progesterone combination was proposed for OGIB because of preliminary reports of improvement of epistaxis in patients with HHT during pregnancy and further relapse in the puerperium.3 Its effect, which is not immediate, seems to be estrogen dose-dependent and acts by enhancing microvascular circulation, coagulation, and vascular endothelial integrity. The most common combination schedule has been ethynil estradiol 0.01-0.05 mg and noresthisterone 1-3 mg.4 This therapy should be used over six-month periods with pauses to reduce the incidence of adverse effects, mostly due to the estrogen component (vascular thrombosis, gynecomastia and loss of libido in men, breast tenderness and vaginal bleeding in women). However, the two largest placebo-controlled studies addressing the impact of hormonal therapy on GI bleeding from angiodysplasias failed to demonstrate any significant benefit. In the first study, patients with out-of-reach bleeding small-bowel angiodysplasias were treated using high-dose estrogens, estrogen-progesterone or placebo, but no statistical improvement of transfusion requirements was observed amongst the groups.5 Additionally, in the second study, the authors failed to identify any significant effect of hormonal therapy compared to placebo in 72 non-cirrhotic patients bleeding from documented angiodysplasia6. This latter study, however, has setbacks such as the use of low doses of ethynil estradiol and the exclusion of patients with vascular ectasia associated to cirrhosis and HHT. Overall, the effectiveness of hormonal therapy remains unclear and both negative controlled trial results and serious and frequent side effects strongly limit its use in OGIB. Recent reports on the effectiveness of other agents with an improved safety profile displace hormonal therapy as first-line therapeutic option for OGIB.
