56. Adenomyosis and endometriosis. Dysfunctional bleedings. Endometrial hyperplasia. Endometritises
Introduction
The uterine corpus is composed of endometrial mucosa and underlying smooth muscle myometrium. The endometrium is comprised of a functional layer, which proliferates and then sloughs during the menstrual cycle, and a basal layer, from which the functional layer grows each cycle.
Oestrogen is essential for growth of the endometrial glands while progesterone is essential for growth of the endometrial stroma. In normal cycles menstruation occurs because progesterone levels drop as the corpus luteum dies, causing endometrium to be sloughed off.
Abnormal uterine bleeding
Abnormal uterine bleeding refers to any of the following symptoms:
- Menorrhagia – excessive or prolonged bleeding when the period occurs
- Metrorrhagia – bleeding between periods
- Dysmenorrhoea – pain right before or during menstruation
The differential diagnosis for abnormal uterine bleeding depends on the age group of the patient:
| Age group | Causes | |
|---|---|---|
| Prepuberty | Precocious (early) puberty | Hypothalamic or pituitary dysfunction |
| Ovarian germ cell tumors | ||
| Adolescence | Anovulatory cycle | |
| Reproductive age | Complications related to pregnancy | Abortion |
| Gestational trophoblastic disease | ||
| Ectopic pregnancy | ||
| Proliferations | Leiomyoma | |
| Adenomyosis | ||
| Endometrial polyp | ||
| Endometrial hyperplasia | ||
| Endometrial carcinoma | ||
| Anovulatory cycle | ||
| Inadequate luteal phase | ||
| Perimenopause | Anovulatory cycle | |
| Proliferations | Endometrial polyp | |
| Endometrial hyperplasia | ||
| Endometrial carcinoma | ||
| Postmenopause | Endometrial atrophy | |
| Proliferations | Endometrial polyp | |
| Endometrial hyperplasia | ||
| Endometrial carcinoma | ||
An anovulatory cycle is a menstrual cycle without ovulation and luteal phase, causing irregular bleeding. The occur most commonly in both ends of reproductive life, i.e. right after puberty and right before menopause. Anovulatory cycles are not pathological in themselves but they may be caused by endocrine dysfunction or other pathological states.
In anovulatory cycles there is no ovulation, so there is no corpus luteum and therefore no production of progesterone. There is oestrogen however, which will continue to stimulate growth of the endometrium. As the progesterone levels can’t drop the endometrium will continue to grow so much that it will be prone to breakdown and bleeding.
Endometrial hyperplasia
Endometrial hyperplasia is an abnormal proliferation of the endometrium caused by increased oestrogen/progesterone ratio. This increased ratio causes endometrial glands to proliferate more than the endometrial stroma. It’s an important precursor of endometrioid-type endometrial carcinoma. The most characteristic symptom is abnormal uterine bleeding.
Etiology: Any condition that causes oestrogen excess can cause endometrial hyperplasia. As oestrogen drives proliferation of the endometrial glands and progesterone drives proliferation of the stroma, endometrial hyperplasia will only develop if there is excess oestrogen compared to progesterone. The most frequent causes are:
- Anovulatory cycles
- Obesity – adipose tissue produces oestrogen
- Prolonged oestrogen treatment therapy
- Oestrogen producing lesions
- Polycystic ovary disease
- Granulosa cell tumors
- Theca cell tumors
Classification: Endometrial hyperplasia is classified according to its architecture and the degree of atypia. The following subtypes exist:
| Subtype | Risk of progressing into endometrial carcinoma |
|---|---|
| Simple hyperplasia without atypia | 1% |
| Simple hyperplasia with atypia | 5% |
| Complex hyperplasia without atypia | 20% |
| Complex hyperplasia with atypia | 40% |
“Simple” and “complex” here refer to the degree of glandular crowding and architectural complexity. The complex types are characterised by decreased amount of stroma and higher number of glands.
Progression: Endometrial hyperplasia may eventually acquire mutations that allow them to function even if the oestrogen-producing etiology is removed. This is the first step towards progressing into carcinoma. Mutations in the PTEN gene is especially important in this progression.
Treatment: People who are diagnosed with complex hyperplasia with atypia should undergo hysterectomy to prevent development of cancer. The less severe types of endometrial hyperplasia can be treated with synthetic progesterone therapy.
Endometritis
Inflammation of the endometrium can be acute or chronic, and the causes differ in obstetric populations and non-obstetric populations. Endometritis unrelated to pregnancy is a component of pelvic inflammatory disease. On histology endometritis can be classified as acute or chronic depending on whether there is neutrophil or plasma cell infiltration. Lymphocytes are normally present in the endometrium so chronic endometritis is defined as the presence of plasma cells and not lymphocytes.
Etiology: In the non-obstetric population endometritis is usually caused by bacterial infection, often due to STIs like Neisseria gonorrhoeae or Chlamydia trachomatis. Tuberculosis is a rare cause of granulomatous endometritis. Intrauterine devices may also serve as access points for vaginal bacteria to ascend into the uterus.
In the obstetric population, endometritis is caused by an ascending polymicrobial infection of bacteria that are normally found in the vagina. This can occur in associating with normal delivery, miscarriage or abortion as products of conception remain behind. These products can for example be a piece of placenta, which acts as a nidus where bacteria can grow.
Symptoms: Endometritis presents with fever, pelvic pain and abnormal menstrual bleeding. It also carries an increased risk for infertility and ectopic pregnancy due to scarring of the fallopian tubes.
Endometriosis
Endometriosis is a common, benign and chronic disease of women in the reproductive age that is characterized by the presence of endometrial glands and stroma in places other than the uterus. It is frequently multifocal and may involve the ovaries, fallopian tubes, cervix, peritoneum and even extrapelvic organs like the lung or skeletal muscle.
Pathogenesis: There are multiple theories as to how endometrial tissue disseminates to other places. The major theory is that retrograde menstruation occurs, where shed endometrium travels into the fallopian tubes and ovaries and implants there instead of being shed out the vagina. This theory doesn’t explain however how some cases present with endometrium in extrapelvic organs. To explain this, other theories exist:
- Coelomic metaplasia – differentiation of pluripotent stem cells in the peritoneum into endometrial cells
- Vascular and lymphatic dissemination – endometrial tissue spreads through lymphatic system or pelvic veins
Symptoms: Regardless of the location of the endometrial tissue it reacts to the hormone cycle in the same way as the normal endometrium. It proliferates under the influence of oestrogen and sheds and bleeds during the decline in progesterone levels, just like normal endometrium. As the endometriotic tissue bleed the blood usually collects in nodules. Endometrium on the ovary forms brown blood-filled cysts called chocolate cysts. Blood may also organize and form fibrosis, which can form adhesions between pelvic structures. These adhesions may close the ending of the fallopian tube, causing infertility.
The clinical symptoms in endometriosis depends on where the distribution of the lesions. The most common symptoms are:
- Chronic pelvic pain that worsens before menses
- Severe dysmenorrhoea
- Painful sexual activity (dyspareunia)
Here are some possible symptoms depending on the location of the abnormal endometrium:
- Douglas pouch – defecation problems, pain
- Bladder wall – urination problems, pain
Adenomyosis
Adenomyosis is a benign disease where the basal layer of the endometrium grows deep into the myometrium. Nests of endometrial stroma and/or glands are found deep in the myometrium. It’s basically endometriosis where the endometrium invades the myometrium. This induces reactive hypertrophy of the myometrium, which results in a diffusely enlarged uterus. The etiology is unknown. Symptoms may be menorrhagia, dysmenorrhea, and pelvic pain before onset of menstruation.
Symptoms include pain before or during menstruation, abnormal menstrual bleeding and pelvic pain.