Figure 6. Female Reproductive System (Winslow, 2009)
Normal Physiology
The inner layer of the uterine wall is known as the endometrium. The endometrium undergoes changes by responding to the female sex hormones estrogen and progesterone throughout the female menstrual cycle. The average length of the menstrual cycle is 27-30 days and consists of two phases known as the follicular and the luteal phases. The follicular phase begins following the cessation of menses. During the mid follicular phase, increasing estrogen levels lead to endometrial thickening. This endometrial thickening continues until ovulation occurs. Ovulation is the release of an ovum from a mature follicle and marks the beginning of the luteal phase. During the luteal phase, a rise in progesterone occurs, causing secretory changes to the endometrium. If implantation of a fertilized ovum does not occur in the uterus, endometrial tissue will break down and menstruation will occur. During menstruation, the functional layer of the endometrium disintegrates and is discharged through the vagina (McCance & Huether, 2019, p. 736).
Figure 7. Illustration of endometrial changes during the menstrual cycle (2017)
Pathophysiology
Figure 8. Common sites of endometriosis (Leonard, 2009)
Endometriosis is the presence of functioning endometrial tissue or implants outside the uterus. Endometrial implants generally occur in the pelvic and abdominal cavities with the most common sites of implantation being the ovaries, uterine ligaments, rectovaginal septum, and pelvic peritoneum. (McCance & Huether, 2019, p. 776).
The displaced endometrial tissue responds to the hormonal fluctuations of the menstrual cycle. The tissue grows in response to estrogen exposure and is resistant to progesterone. With a sufficient blood supply, the ectopic endometrium proliferates, breaks down, and bleeds with the normal menstrual cycle. The bleeding causes inflammation and the triggering of cellular inflammatory mediators, including cytokines, chemokines, growth factors, and protective factors. The inflammation may lead to fibrosis, scarring, and adhesions, resulting in pain (McCance & Huether, 2019, p. 777).
Risk factors for endometriosis include early menarche, nulliparity, family history, and menstrual irregularities including menstrual cycle length of less than 27 days, menstrual bleeding for greater than 7 days, and heavy menses. Endometriosis increases the risk of ovarian cancer.
The cause of endometriosis is unknown, however multiple theories have been proposed. One possible theory, known as retrograde menstruation, proposes that implantation of endometrial cells occurs during the backflow of menstrual fluids through the fallopian tubes and into the pelvic cavity. However, retrograde menstruation occurs in almost all women and not all women develop endometriosis (McCance & Huether, 2019, p. 776).
Another proposed theory involves the possibility that women with endometriosis have impaired cellular and humoral immunity. Alterations in cytokine and growth factor signaling have been identified as well as the depression of cytotoxic T-cell and natural killer (NK) cell activity. Endometrial cell proliferation outside of the uterus is stimulated by an increased number of macrophages (McCance & Huether, 2019, p. 776).
Additional theories include the possibility of a genetic predisposition to endometriosis with a disruption in gene expression during embryogenesis as well as the possibility that endometrial cells may spread outside the uterus during fetal development. It is also possible that endometrial cells travel through the vascular and lymph systems (McCance & Huether, 2019, p. 776).
Clinical Manifestations
Most of the symptoms of endometriosis are caused by the formation of adhesions that occurs with the breakdown and bleeding of ectopic endometrial tissue. The most common symptoms are pelvic pain and infertility. Additional symptoms include dysmenorrhea, dysuria, dyschezia (pain on defecation), and dyspareunia (pain on intercourse). Constipation and abnormal vaginal bleeding may also be present. Symptoms are usually associated with the location of ectopic bleeding endometrial tissue and not related to the degree of endometriosis. The presence of a pelvic mass or retroverted uterus are also sometimes observed (McCance & Huether, 2019, p. 777).
There is a strong link between endometriosis and infertility, however the reason for the infertility is unknown. Possibilities include the presence of adhesions and inflammation causing a mechanical interference with ovulation or an underlying autoimmune disorder. Additional possibilities include the increased macrophage phagocytosis of sperm or a underactive uterine response to progesterone (McCance & Huether, 2019, p. 777).
Figure 9. Laparoscopy (Blausen.com staff, 2014)
Diagnosis and Treatment
Endometriosis is diagnosed using laparoscopy. Once diagnosed, treatment is focused on preventing the spread of ectopic lesions, relieving pain, and restoring fertility. Treatment involves the use of hormonal medications to suppress ovulation and the surgical removal of the ectopic endometrial lesions if possible (McCance & Huether, 2019, p. 777).