Adenomyosis

# Overview
Adenomyosis is a medical condition characterized by the presence of ectopic endometrial tissue (the inner lining of the uterus) within the myometrium (the thick, muscular layer of the uterus). The condition is typically found in women between the ages between 35 and 50.  Patients with adenomyosis can have painful and/or profuse menses (dysmenorrhea & menorrhagia, respectively).
Adenomyosis may involve the uterus focally, creating an adenomyoma, or diffusely.  With diffuse involvement, the uterus becomes bulky and heavier.

# Historical Perspective
- Adenomyosis was first discovered by Carl von Rokitansky, a German pathologist, in 1860 when he found endometrial glands in the myometrium and designated this finding as 'cystosarcoma adenoids uterinum'.
- In 1892 the first systematic investigation of adenomyosis was carried out by 'Thomas Stephen Cullen', a gynecologist. He distinguished 3 types of adenomyoma: intramural, subperitoneal and submucous adenomyoma.
- In 1893, Kelly and Cullen described the pathogenesis of adenomyoma. The 'gradual ascendancy of Cullens mucosal theory' stated that endometrium invades the inner myometrium through the presence in it of chinks, or fissures.
- In 1892, Cullen described that abdominal hysterectomy is indicated for treatment as the endometrial growths are interwoven with the normal muscle of the uterus.

# Classification
- Adenomyosis can be classified according to its histopathology into 2 groups:
- Diffuse adenomyosis: Uniformly enlarged boggy uterus.
- Focal adenomyosis (adenomyoma): Grossly it resembles fibroid but without a surrounding pseudocapsule.
- Other variants of adenomyosis include juvenile cystic adenomyosis; which is the presence of endometrial cysts > 1cm in diameter within the myometrium. It is usually seen in young women <30 years old .

# Pathophysiology
- The pathogenesis of Adenomyosis is poorly understood. There two theories that explain the possible pathogenesis:
- Endomyometrial invagination of the endometrium; due to weakness of the uterine smooth muscles.
- De novo development of adenomyosis from mullerian rests due to metaplasia.
- The basic Fibroblast Growth Factor (bFGF) receptor/ligand system has shown to be upregulated in adenomyosis which explain the abnormal uterine bleeding and menorrhagia.
- Estrogen and progesterone hormones play a role in the pathogenesis of adenomyosis. Other hormones such as oxytocin , FSH, and prolactin also contribute to the pathogenesis of the disease.
- On gross pathology, there is a globular enlargement of the myometrium of the uterus showing cysts filled with hemolysed red blood cells and sideroblasts.
- On microscopic histopathological analysis, there are endometrial glands, and stroma surrounded by hypertrophic smooth muscle bundles haphazardly scattered within the myometrium.

# Causes
The cause of adenomyosis is unknown, although it has been associated with any sort of uterine trauma that may break the barrier between the endometrium and myometrium, such as:
- Caesarean section
- Tubal ligation
- Abortion
- Pregnancy

# Differentiating adenomyosis from other Diseases
For further information about the differential diagnosis, click here.

# Epidemiology and Demographics
- It is generally estimated that adenomyosis is present in 20-35% of women.
- The incidence and prevalence of adenomyosis are, however, difficult to be accurately estimated and biased by studying only women undergoing hysterectomy, so the total population of women having the disease is not known.

## Age
- Adenomyosis is more commonly observed among women aged 40-50 years in those undergoing hysterectomy for diagnosis.
- Adenomyosis is less commonly diagnosed in adolescents who undergo pelvic imaging by transvaginal ultrasound or MRI rather than a hysterectomy for diagnosis.

## Race
- There is no racial predilection for adenomyosis.
- Almost all cases of adenomyosis present in multiparous women, however there is no clear causal relationship between multiparty and the development of the disease

# Risk Factors
- Similar to the epidemiology, the risk factors of adenomyosis are unknown and difficult to be accurately determined as diagnosis is based on examining pathological specimens only in women undergoing hysterectomy.
- Adenomyosis often coexists with other pelvic diseases namely endometriosis and leiomyoma, so it is unknown whether it exhibits specific risk factors.
- Prior uterine surgery has been shown to be a possible risk factor for the development of adenomyosis.

# Natural History, Complications and Prognosis
- Early clinical features of adenomyosis include dysmenorrhea, heavy menstrual bleeding, and chronic pelvic pain.
- Some reported complications of adenomyosis are preterm birth and miscarriage in young women diagnosed by pelvic imaging. The relationship of adenomyosis to infertility is controversial.
- Prognosis is generally good as surgical treatment by hysterectomy is often curable unless there is another associated uterine pathology that requires further attention. There is no increased risk for secondary development of endometrial carcinoma.

# Diagnosis
Adenomyosis is a histopathological diagnosis that is made after hysterectomy. The preoperative diagnosis is suggested by pelvic imaging such as transvaginal ultrasound and MRI along with the classical presentation of heavy menstrual bleeding, dysmenorrhea, and uniformly enlarged globular uterus.

## Symptoms
- Symptoms of adenomyosis may include the following:
- Heavy menstrual bleeding
- Dysmenorrhea
- Chronic pelvic pain

## Physical Examination
- Bimanual pelvic examination may be remarkable for:
- Diffusely enlarged uterus (Boggy soft uterus)
- Uterus is mobile (not fixed as in endometriosis)
- Uterine tenderness may be noted.

## Pelvic Imaging
The uterus may be imaged using ultrasound (US) or magnetic resonance imaging (MRI).  Transvaginal ultrasound is the most cost-effective and most available.  Either modality will show an enlarged uterus.  On ultrasound, the uterus will have a heterogeneous texture, without the focal well-defined masses that characterize uterine fibroids.

### Ultrasonography
- Typical appearances of adenomyosis at transvaginal ultrasound include poorly marginated hypoechoic and heterogeneous areas within the myometrium, myometrial cysts, and a globular or enlarged uterus with asymmetry.
Image courtesy of RadsWiki
- US: Adenomyosis
- US: Adenomyosis
- US: Adenomyosis

### Computed Tomography
Images courtesy of RadsWiki
- CT: Adenomyosis
- CT: Adenomyosis

### Magnetic Resonance Imaging
- MRI provides better diagnostic capability due to the increased spatial and contrast resolution, and to not be limited by the presence of bowel gas or calcified uterine fibroids (as is ultrasound).  In particular, MRI is better able to differentiate adenomyosis from multiple small uterine fibroids.
- MRI can be used to classify adenomyosis based on the depth of penetration of the ectopic endometrium into the myometrium.
- Adenomyosis appears as either diffuse or focal thickening (greater than 12 mm )of the junctional zone forming an ill-defined area of low signal intensity, occasionally with embedded bright foci on T2-weighted images.
- Histologically, areas of low signal intensity correspond to smooth muscle hyperplasia, and bright foci on T2-weighted images correspond to islands of ectopic endometrial tissue and cystic dilatation of glands.
Images courtesy of RadsWiki
- T2: Adenomyosis
- T2: Adenomyosis
- T2: Adenomyosis
- T1 fat sat contrast: Adenomyosis
Images courtesy of RadsWiki

# Treatment

## Surgery
- Surgery is the mainstay of therapy for adenomyosis.
- Hysterectomy with preservation of the ovaries is the most common approach to the treatment of adenomyosis, and it is done via abdominal, transvaginal, laparoscopic approach, or robotic surgery. .
- Unlike Leiomyoma, there is no plane of cleavage to excise adenomyomas and preserve the uterus. Uterus sparing resection is an investigational approach especially for young women seeking future pregnancy.

## Medical Therapy
- Medical treatment for dysmenorrhea and menorrhagia can be prescribed as a temporary alternative for young women in the child-bearing period.
- Hormonal therapy to control the symptoms includes levonorgestrel-releasing IUD (most preferred method), combined oral contraceptive pills, GnRH analogs, and oral GnRH antagonists.
- Levonorgestrel-IUD has a direct action on the uterus. It alleviates dysmenorrhea and menorrhagia.
- Once the hormonal therapy is stopped to conceive, symptoms recur within six months.

## Uterine artery embolization
- In women who decline hysterectomy or have contraindications for hysterectomy or women who failed hormonal therapy, uterine artery embolization can be an alternative to control dysmenorrhea and heavy menstrual bleeding..
- The outcomes of the procedure are significantly correlated with the lesion vascularity..