Adenomyosis

Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%–35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Diagnosis is often made with pelvic imaging. Usually, transvaginal ultrasound is adequate, though MRI can be helpful in indeterminate cases. Management is based on the patient’s preference regarding future childbearing and may include hysterectomy (definitive treatment), other surgical options, or medical hormonal suppression (usually with progestins).

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Overview

Definition

Adenomyosis is the presence of ectopic endometrial glands and stroma located within the myometrium:

  • May be diffuse or focal (discrete lesions are known as adenomyomas)
  • 1 of the structural causes of abnormal uterine bleeding (AUB) in the PALM-COEIN classification structure

Classification of abnormal uterine bleeding and its causes

Image by Lecturio.

Epidemiology

  • Prevalence: up to 20%–35% of reproductive-age women 
  • Average age: 40–50 years 
  • Often coexists with other uterine pathology, especially:
    • Leiomyomas (fibroids)
    • Endometriosis

Etiology

The exact etiology is unknown.

  • Theories: 
    • Invagination or disruption around the junctional zone, allowing endometrial proliferation within the myometrium
    • As an embryo, pluripotent Müllerian stem cells undergo inappropriate differentiation (some differentiate into endometrium within the myometrium).
  • Hormone effects:
    • Estrogen:
      • Endometrium is stimulated by estrogen.
      • ↑ Estrogen exposure → ↑ adenomyosis
    • Other hormones that may play a role:
      • Prolactin
      • Oxytocin
      • Follicle-stimulating hormone (FSH)
  • Other potential factors:
    • Growth factor dysregulation
    • Abnormalities of angiogenesis

Risk factors

  • ↑ Estrogen exposure:
    • ↑ Parity
    • Early menarche
    • Short menstrual cycles
    • Obesity
    • Tamoxifen use
    • Oral contraception pill (OCP) use
  • Prior uterine surgery:
    • Cesarean section
    • Dilation and curettage
    • Myomectomy

Pathophysiology

Inappropriate endometrial tissue proliferation within the myometrium can lead to heavy menstrual bleeding (HMB) and dysmenorrhea.

Pathophysiology of HMB

  • ↑ Estrogen production within adenomyosis implants
  • ↑ Total endometrial surface area 
  • ↑ Vascularization within the uterus
  • Abnormal uterine contractions

Pathophysiology of dysmenorrhea

  • Endometrial tissue is responsible for prostaglandin production → ↑ prostaglandins → trigger menstrual contractions 
  • Bleeding and swelling within the myometrium during menses as the ectopic endometrial tissue sheds
  • Overexpression of inflammatory mediators within implants

Clinical Presentation

Symptoms

  • Dysmenorrhea
  • Abnormal uterine bleeding/heavy menstrual bleeding (AUB/HMB)
  • Chronic pelvic pain
  • Dyspareunia
  • May be asymptomatic (up to 33% of women)

Physical exam

Physical exam may reveal a uterus that is:

  • Symmetrically enlarged
  • Tender
  • Globular
  • Boggy
  • Mobile (as opposed to fixed, which may occur with endometriosis)

Diagnosis

The diagnosis relies on history, exam, and imaging. Laboratory evaluation is not helpful.

Pelvic/transvaginal ultrasound 

  • Considered the preferred imaging modality
  • The following findings are suggestive of adenomyosis:
    • Enlarged uterus
    • Myometrial cysts
    • Asymmetrical thickening of the myometrium (typically at the fundus or posterior wall)
    • ↑ Myometrial heterogeneity
    • Loss of a clear endomyometrial border
    • Thickening of the junctional zone
    • Linear striations radiating out from the endometrium
    • Doppler assessment shows ↑ vascularity in the myometrium.

Transvaginal ultrasound demonstrating a uterus with adenomyosis:
A: ultrasounds of normal uterus
B: ultrasound images in a patient with adenomyosis: Notice the asymmetric thickening of the myometrium, particularly posteriorly. The arrows point to the junctional zone, which appears thickened and irregular.

Image: “Evaluation of the junction zone” by J. M. Puente. License: CC BY 4.0

Pelvic MRI

  • Slightly more sensitive and specific than pelvic ultrasound
  • Rarely required
  • Indications:
    • When an accurate diagnosis will change management
    • Assist in surgical planning when uterus-sparing surgery is planned
  • Findings: same as those seen on ultrasound

Pelvic MRI of a uterus with adenomyosis:
This MRI shows thickening of the junctional zone, which is most marked posteriorly (arrow). Several small cystic spaces can be seen within it.

Image: “Sagittal T2W MRI image” by Department of Radiology, Norfolk & Norwich University Hospital, Colney Lane, Norwich, Norfolk, NR4 7UY, United Kingdom. License: CC BY 2.0

Management and Complications

Management

Management is directed primarily by the patient’s desire for future fertility.

  • Non-hormonal medical therapies:
    • NSAIDs: ↓ prostaglandin production → ↓ dysmenorrhea
  • Hormonal therapies: ↓ estrogenic effects
    • Levonorgestrel intrauterine devices (IUDs): preferred medical treatment
    • Oral contraceptives (all are progestin dominant)
    • Gonadotropin-releasing hormone (GnRH) analogs: 
      • Both agonists and antagonists fully suppress the hypothalamic-pituitary-ovarian axis by disrupting the GnRH pulse.
      • Options: leuprolide, elagolix
    • Danazol (an androgen, rarely used due to androgenic side effects)
    • Aromatase inhibitors
  • Surgical options: All require completion of child-bearing.
    • Hysterectomy
      • Definitive treatment
      • Best option once childbearing is complete
      • Histology specimens will confirm the diagnosis.
    • Endometrial ablation
    • Uterine artery embolization

Complications

  • Correlates with a ↑ risk of infertility (a direct association has not been established)
  • ↑ Risk of pregnancy complications:
    • Miscarriage
    • Preterm birth

Differential Diagnosis

  • Endometriosis: a common disease in which patients have endometrial tissue implanted outside the uterus (anywhere in the pelvis). Endometrial implants are inflammatory, leading to cyclic, chronic pain, adhesions, and an increased risk of infertility. The diagnosis is usually made clinically, though definitive diagnosis requires laparoscopy. Lab work is rarely useful. Standard management involves suppression of endometrial growth with progestins, typically with OCPs.
  • Leiomyomas (fibroids): benign monoclonal tumors arising from smooth muscle cells in the uterine myometrium. Similar to adenomyosis, both conditions present with abnormal bleeding and pelvic pain. Diagnosis is made with pelvic imaging where a fibroid is identified as a hypoechoic, well-circumscribed, round mass. Management for leiomyomas may include surgical resection or medical options to reduce bleeding or bulk.
  • Endometrial hyperplasia or malignancy: Endometrial hyperplasia is abnormal growth of the endometrium, which may progress to adenocarcinoma. The condition is caused by excess estrogen unopposed by progesterone. Patients typically present with heavy menstrual and/or intermenstrual bleeding in the reproductive years, and postmenopausal bleeding when older. Diagnosis is made on biopsy. A hysterectomy is usually the recommended treatment.
  • Polycystic ovary syndrome (PCOS): the most common endocrine disorder of reproductive-aged women, characterized by hyperandrogenism and chronic anovulation. This leads to oligomenorrhea and metabolic dysfunction. Bleeding is usually irregular and may be quite heavy. Diagnosis is one of exclusion, so other causes of AUB and hirsutism should be ruled out with imaging and lab work. Management includes attempting to restore normal ovulation through weight loss, OCPs, and assistance with fertility.

References

  1. Stewart, E.A. (2021). Uterine adenomyosis. In A. Chakrabarti, A. (Ed.), UpToDate. Retrieved March 3, 2021, from https://www.uptodate.com/contents/uterine-adenomyosis 
  2. Gunther, R. (2020). Adenomyosis. In Walker, C. (Ed.), StatPearls. Retrieved March 3, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/42961/ 
  3. American College of Obstetric and Gynecology Committee on Gynecology. (2012). Practice Bulletin No. 128: Diagnosis of abnormal uterine bleeding in reproductive-aged women. ACOG Vol. 120, No.1, pg. 197-203.
  4. Kilpatrick, C. C. (2019). Uterine adenomyosis. [online] MSD Manual Professional Version. Retrieved March 6, 2021, from https://www.msdmanuals.com/professional/gynecology-and-obstetrics/miscellaneous-gynecologic-disorders/uterine-adenomyosis
  5. Ely, L. K., and Truong, M. (2018). Adenomyosis. In Karjane, N.W. (Ed.), Medscape. Retrieved March 6, 2021, from https://emedicine.medscape.com/article/2500101-overview

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