Endometriosis refers to the ectopic presence of endometrial tissue that then induces chronic inflammatory reactions. It is the second most gynaecological condition (after fibroids) with approximately 10% of women in the UK having it.
Pathophysiology
The aetiology of endometriosis is not entirely certain at this point, however, it is believed to be a combination of the following:
- Retrograde menstruation - endometrial cells flow from the uterine cavity back up through the fallopian tubs and then get deposited on pelvic organs where they begin to grow. However, seeing as endometriosis can occur in women who have had a hysterectomy or in men who have received oestrogen hormonal therapies, this does not quite explain it.
- Lymphatic/circulatory spread of endometrial tissue - this may explain how we can get pulmonary endometrial tissue.
- Genetic predisposition - there is a correlation between siblings having endometriosis that may support a genetic predisposition.
- Metaplasia - cells elsewhere in the body shift into an endometrial-like cell. This can explain how endometrial cells appear spontaneously in the body and how it can occur after hysterectomy or with men taking hormonal treatment.
- Mullerian rests - mullerian rests are cells that embryo logically derive from the paramesonephric ducts (also known as the Müllerian ducts) which are the cells that form the uterus, cervix and upper vagina. These mullerian rests are stimulated by oestrogen once the hypothalamic-pituitary-ovarian axis matures.
- Environmental factors - dioxins are a group of chemically related compounds that are persistent pollutants in the environment and have been shown to increase the incidence and severity of the disease in animals exposed to these chemicals.
- Immune dysfunction - it remains if this a cause or consequence of endometriosis.
Women with endometriosis also display central sensitivity which means they feel more pain due to sensory amplification of the pain. However, the pain demonstrated does not correlate with degree of involvement always. Pain may occur due to fibrosis that takes place with chronic inflammation → adhesion formation and distortion of the normal anatomy. Neuropathic pain may also occur due to nerve entrapment that may occur also. So as we can see, it is a complex mix of factors that lead to the symptoms of endometriosis.
Endometrial deposits respond to the hormonal cycle, and when there is a drop in oestrogen and progesterone they also shed, similar to the normal shedding of the uterine lining. This causes local inflammation and irritation due to the bleeding.
⚠️ Risk factors
- Reproductive age
- Family history
- Nulliparity/delayed parity
- Mullerian anomalies - as mentioned, the Müllerian ducts develop into the female reproductive organs. Anomalies in the development of these structures is known as a Mullerian anomaly.
- Early menarche and late menopause - due to increased oestrogen exposure.
- Low BMI
- Smoking - smoke contains dioxins which may precipitate the disease potentially.
- Previous C-section
- Late first sexual encounter - although a 2018 study showed that sexual and physical abuse early on in life is associated with a higher risk of endometriosis.
- Autoimmune disease
😷 Presentation
- Chronic and cyclical pelvic/abdominal pain prior to menstruation
- Dysmenorrhoea - painful periods. The pain is severe as the ectopic endometrial tissue also bleeds during menses. It is referred to as secondary dysmenorrhoea as it is a cause of pain during menstruation that is not due to the menstruation itself (other causes include PID or fibroids, for example).
- Deep dyspareunia - if there is endometriosis that is found within the posterior fornix.
- Dyschezia - painful defecation. This is when there is rectal endometriosis.
- Subfertility - a large proportion of women with endometriosis struggle with fertility. This is not entirely clear, but it may be due to scarring and adhesions that occur with the chronic inflammation. It may be due to altered pelvic anatomy.
- Pelvic mass
- Asymptomatic - about 30% of women are completely asymptomatic.
- Extrapelvic endometriosis - cyclical presentation of such symptoms may indicate extrapelvic endometriosis manifestations.
- Haemoptysis, cough, chest pain, pneumothorax - may be indicative of pulmonary endometriosis.
- Haematuria, dysuria, urgency, frequency - all indicative of urinary tract endometriosis.
- Subcutaneous mass - often blue, black, brown or red in colour. This may indicate cutaneous endometriosis.
- Changes to bowel habit, dyschezia - indicate rectal endometriosis.
- Tender blue nodules - often located in the posterior fornix.
- Fixed and retroverted uterus - this is due to the scarring and endometrial tissue on the uterosacral ligaments which pulls the uterus backwards and immobilises it.
- Tenderness in the lateral and posterior fornices - due to additional pressure applied to the uterosacral ligaments once again.
- Ovarian enlargement - as endometriosis within the ovary can form a type of cyst known as an endometrioma which is colloquially known as a chocolate cyst due to its brownish contents.
🔍 Investigations
It is important to obtain a good history to identify the chronic and cyclical pain that worsens prior to menstruation. A bimanual examination and speculum may show the nodules mentioned above as well as indicate tenderness of the adnexa and vagina.
- 🥇 Transvaginal ultrasound - may be confirmatory for an ovarian endometrioma. Although they may be insignificant it should be taken before undergoing surgical exploration.
- 🏆 Laparoscopy + biopsy - this is the gold-standard, definitive diagnostic method. It also has the benefit of enabling removal of the endometrial tissue which may aid the patient’s symptoms.
🧰 Management
We will discuss the following aspects in this section:
- Analgesia
- Hormonal therapies
- Surgical therapies
- Fertility treatments
Analgesia
🥇 We can provide pain relief in the form of NSAIDs and paracetamol. NSAIDs are particularly useful as they help reduce pain that is brought on by prostaglandin secretion during the luteal phase. NICE recommends a short trial initially (e.g. 3 months).
🥈 If this is not sufficient, we can use stronger analgesics in line with the WHO pain ladder.
Hormonal therapy:
Hormonal treatments aim to limit oestrogen production as oestrogen promotes endometrial growth and shedding. By limiting oestrogen we can shrink the endometrial tissue in the body and reduce the pain associated with endometriosis. However, it cannot help improve fertility nor does it help with the complications of adhesions.
- 🥇 Combined oral contraceptive pill (COCP) - this is particularly useful when pain is strictly related to the menstrual cycle.
- 🥇 Progestogens - such as medroxyprogesterone, levonorgestrel, dienogest or even the levonorgestrel intrauterine device (LNG-IUD) (Mirena coil). The LNG-IUD is good for long-term use. They work by thinning the endometrial lining and preventing endometrial proliferation → regression and shedding. They also have anti-inflammatory effects which relieve the pain.
- 🥈 GnRH analogues - by the term “analogues” we mean both agonists and antagonists. Continuous administration of analogues desensitise the pituitary gonadotrophs temporarily which leads to a reversible hypogonadotrophic hypogonadic state (i.e. chemical menopause) that prevents endometrial tissue growth.
- GnRH agonists - goserelin or leuroprelin.
- GnRH antagonists - elagolix.
- Adverse effects include: hot flushes, increased serum lipids, osteoporosis.
- 🥉 Danazol - a testosterone derivative that produces a hypo-oestrogenic effect and hypo-progestogenic state as well (pseudomenopause) which can lead to endometrial regression and atrophy. Adverse effects include: acne, hirsutism.
Surgical management:
- Radical excision of affected areas + restoration of normal anatomy is the preferred method. It should be performed laparoscopically.
- Hysterectomy - if there is adenomyosis (more on this at the end) or menorrhagia that is unresponsive to other treatments. It should be done without oophorectomy.
- Excision or ablation of endometriosis + adhesiolysis - if fertility is a priority.
- Laparoscopic ovarian cystectomy - to remove endometriomas as this improves chance of spontaneous pregnancy.
Fertility treatments:
If a lady desires fertility they should avoid hormonal treatments as they reduce fertility.
- 🥇 To improve fertility, we need to induce ovarian hyperstimulation using:
- Clomiphene - a SERM that antagonise the oestrogen receptors in the hypothalamus → increased GnRH secretion → increased FSH → ovulation.
- Letrozole - as it is an aromatase inhibitor, it decreases circulating oestrogen levels which leads to increased GnRH secretion → increased FSH → ovulation.
🥈 An alternative would be IVF treatment.
🚨 Complications
- Infertility
- Adhesions
- Bowel obstruction
- Chronic pain
Adenomyosis was previously called endometriosis interna as it is essentially the presence of endometrium in the underlying myometrium. It is associated with endometriosis and fibroids and is most common around 40 years of age.
It is another oestrogen-dependent condition, but its pathogenesis is unclear. Symptoms subside after menopause as a result.
😷 Presentation
- Dysmenorrhoea
- Menorrhagia
- Enlarged, tender uterus
🔍 Investigations
- 🥇 Ultrasound
- 🏆 Post-hysterectomy histological analysis
🧰 Management
- LNG-IUD (Mirena coil) or COCP ± NSAIDs - this may control the dysmenorrhoea and menorrhagia.
- 🏆 Hysterectomy