Endometriosis is a condition where tissue similar to the lining inside the uterus grows outside of it. These misplaced lesions commonly attach to organs like the ovaries, fallopian tubes, and the outer surface of the uterus, but can also appear in other pelvic areas or distant sites. Their presence often causes symptoms such as chronic pelvic pain, unusually painful and heavy menstrual periods, pain during sexual activity, and difficulty conceiving.
What Endometriosis Is
This tissue behaves similarly to the uterine lining, thickening and bleeding in response to hormonal changes. However, unlike menstrual blood that exits the body, blood from these external growths becomes trapped. This leads to inflammation, irritation, and the formation of scar tissue and fibrous bands called adhesions. While the exact cause remains unclear, theories include retrograde menstruation, where menstrual blood flows backward into the pelvic cavity, carrying endometrial cells that then implant and grow.
Estrogen’s Influence on Endometrial Tissue
Estrogen is a primary female sex hormone that regulates the menstrual cycle. It stimulates the growth and thickening of the uterine lining, preparing it for potential pregnancy. In endometriosis, the misplaced tissue also responds to estrogen. Research indicates that individuals with endometriosis often have elevated estrogen levels, particularly estradiol, which can intensify inflammation and pain associated with the condition.
How Estrogen Contributes to Endometriosis Progression
Estrogen not only promotes the physical growth of endometriotic lesions but also contributes to the inflammatory environment that characterizes the condition. A key factor in this progression is the ability of endometriotic lesions to produce their own estrogen locally, independent of ovarian production. This occurs through the aberrant expression of an enzyme called aromatase within the lesion tissue itself, which converts precursor hormones into estrogen.
This local estrogen production creates a self-sustaining cycle, where estrogen stimulates the production of prostaglandins, which in turn further enhance aromatase activity, leading to more estrogen and inflammation. Estrogen also influences the formation of new blood vessels, a process called angiogenesis, within the lesions, which is necessary for their survival and growth. It also contributes to nerve innervation, increasing the density of pain-sensing nerves within the lesions and surrounding tissues, thereby intensifying the chronic pain experienced.
The endometriotic lesions also exhibit an altered response to hormones, particularly an overexpression of estrogen receptor-beta (ERĪ²) and a diminished expression of progesterone receptors. This hormonal imbalance makes the tissue more sensitive to estrogen’s growth-promoting effects and less responsive to progesterone’s inhibitory actions, contributing to the persistence and severity of the disease. This unique hormonal profile helps explain why endometriosis continues to thrive in an estrogen-rich environment.
Therapeutic Strategies Targeting Estrogen
Given estrogen’s influence on endometriosis, many medical treatments aim to reduce estrogen levels or block its effects. Hormonal therapies are often used to create a low-estrogen environment or to counteract estrogen’s actions on the lesions. These treatments do not cure endometriosis but help manage its symptoms and slow its progression.
One common approach involves hormonal contraceptives, such as birth control pills, patches, or rings, which provide a steady level of hormones that can suppress the natural hormonal fluctuations that stimulate endometriosis. These can lead to lighter or absent periods, reducing pain and growth of the lesions. Progestin-only therapies also work by thinning the uterine lining and suppressing the growth of endometrial implants, often by inhibiting ovulation and menstruation.
Other therapies include GnRH (gonadotropin-releasing hormone) agonists and antagonists, which reduce estrogen production by temporarily inducing a menopause-like state. These medications block the signals that tell the ovaries to produce estrogen, causing the endometriotic tissue to shrink. Aromatase inhibitors are another class of medications that specifically target the aromatase enzyme, thereby reducing the local production of estrogen within the endometriotic lesions themselves.