Pathogenesis of Endometriosis: The Origin of Pain and Subfertility

Abstract

Endometriosis (EM) and adenomyosis (AM) are common conditions with pain and infertility as the principal symptoms. The pathophysiology of pain in EM and AM comprises sensory and somatoform pain mechanisms. Over time, these may aggravate and lead to individual complex disease patterns if not diagnosed and treated. Despite the known facts, several years often pass between the onset of symptoms and diagnosis. Chronic pain disorders with changes on a neuronal level frequently arise and are linked to depressive disorders, with the process becoming a vicious cycle. Additionally, women with EM and AM suffer from sub- and infertility. Low fecundity rates are caused by anatomical changes in combination with behavioral changes in the sexual activity of women with chronic pain as well as local proinflammatory factors that not only decrease implantation rates but also promote early abortions.

Keywords: adenomyosis; endometriosis; infertility; inflammation; ovarian reserve; pain; pathophysiology.

Figure 1

Pathophysiological pathways and clinical consequences. The underlying biological key concepts of EM include hormonal imbalance, activation of stem cells, changes on genetic and epigenetic levels, tissue injury and repair mechanisms, hyperperistalsis, epithelial-mesenchymal transition, and fibroblast to myofibroblast transition. In consequence, the formation of adhesions, fibrosis, inflammation, and local invasion arise. This coexistence of different pathways and their interactions triggers the clinical outcomes that affect multiple organ systems. EM patients present with complaints that include pain, infertility and sterility, complications in pregnancy, and even malignant transformation of preexisting lesions as ovarian cancer.

Figure 2

Pathogenesis of spinal hyperalgesia. Patients suffering from chronic pain have an increased risk of developing spinal hyperalgesia, chronic pain syndromes, and pelvic floor dysfunction. Glutamate upregulation and spinal cord modulation occur. After a latency of two years, changes at the central level may develop. This process explains severe pain that accompanies patients, even in the absence of pathological findings.