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 Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding (AUB) in the PALM-COEIN classification structure
Causes of aub

Classification of abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. 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 Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. 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 Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview 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 Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. 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 Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of 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)

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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.
Adenomyosis in infertile women

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
Adenomyosis mri

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 Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility (a direct association has not been established)
  • ↑ Risk of pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care complications:
    • Miscarriage
    • Preterm birth Preterm birth Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth

Differential Diagnosis

  • Endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis: a common disease in which patients have endometrial tissue implanted outside the uterus (anywhere in the pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 "hip" bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis). Endometrial implants are inflammatory, leading to cyclic, chronic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, adhesions, and an increased risk of infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility. The diagnosis is usually made clinically, though definitive diagnosis requires laparoscopy Laparoscopy Laparoscopy is surgical exploration and interventions performed through small incisions with a camera and long instruments. Laparotomy and 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 Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of 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 Endometrial Hyperplasia Endometrial hyperplasia (EH) is the abnormal growth of the uterine endometrium. This abnormal growth may be due to estrogen stimulation or genetic mutations leading to uncontrolled proliferation. Endometrial Hyperplasia and Endometrial Cancer or malignancy: Endometrial hyperplasia Endometrial Hyperplasia Endometrial hyperplasia (EH) is the abnormal growth of the uterine endometrium. This abnormal growth may be due to estrogen stimulation or genetic mutations leading to uncontrolled proliferation. Endometrial Hyperplasia and Endometrial Cancer 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 PCOS Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome): 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 Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. 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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