Thromboxane Function in Women With Endometriosis

Cardiovascular disease (CVD) is the leading cause of death worldwide. Endometriosis is an independent risk factor for CVD that affects an estimated one in ten women in the world. Endometriosis is a gynecologic condition characterized by invasive extrauterine endometriotic lesions, chronic pain, and systemic inflammation. The expression of thromboxane A2 (TxA2), a product of the inflammatory cyclooxygenase pathway, is upregulated in endometriotic lesions. In the vasculature, TxA2 blocks vasodilation, and induces vasoconstriction. TxA2 diffuses across the innermost layer of cells in the blood vessels, the endothelium, to act directly on its receptors in the vascular smooth muscle. It also inhibits endothelial nitric oxide synthase, thereby decreasing nitric oxide (NO)-mediated vasodilation --endothelial dysfunction which is regarded as a critical early event in the development of atherosclerosis and overt cardiovascular disease. Women with endometriosis demonstrate marked endothelial dysfunction compared with healthy controls, but the potential role of TxA2 and its receptors (TP) in this dysfunction have not been investigated. Furthermore, TP play a key role in sensitizing the sensory afferent nerve fibers in pre-clinical models of cardiovascular disease, leading to an exaggerated blood pressure responses to sympathoexcitatory maneuvers including the exercise pressor reflex. The exercise pressor reflex is the reflex increase in blood pressure in response to the mechanical and metabolic stimuli of exercise. The exaggeration of this reflex response is a strong predictor of major adverse cardiovascular events in cardiovascular disease patients. However, the reflex response to sympathoexcitatory maneuvers has not been characterized in women with endometriosis. Furthermore, TxA2 is a key component in the clotting cascade. An increased production of TxA2 in the platelet cells of women with endometriosis indicates altered platelet function. However, platelet activity in women with endometriosis has not been characterized.

Inclusion criteria

• Born with a uterus
• 18-45 years old
• With and without endometriosis

Exclusion criteria

• Currently pregnant or breastfeeding
• Diagnosed cardiovascular disease
• BMI over 35
• Nicotine use (e.g., smoking, chewing tobacco, vaping, etc.)
• Currently using hormone replacement therapy (or have used within previous 6 months)
• Known skin allergies or current rash, skin disease, disorders of pigmentation
• Diabetes
• Renal disease, renal artery stenosis, renal impairment
• Liver disease
• Stage II Hypertension (blood pressure >140/>90 mmHg)
• Hypotension (blood pressure < 90/60 mmHg)
• Raynaud's syndrome
• Any current medications which could conceivably alter cardiovascular responses (e.g. antihypertension medication, diuretic, digoxin)
• Allergy or hypersensitivity to investigational agents
• Immunosuppressed/immunocompromised