Adenomyosis: Symptoms, Types, Causes and Treatment

Adenomyosis is a complex gynecological condition that has long puzzled clinicians and researchers. Characterized by the presence of endometrial tissue within the muscular wall of the uterus, it can significantly impact quality of life and reproductive health. This article explores the key aspects of adenomyosis—its symptoms, types, causes, and treatment options—drawing on the latest evidence-based research to provide a comprehensive overview for patients, clinicians, and anyone interested in this important women's health issue.

Symptoms of Adenomyosis

Adenomyosis manifests in a variety of ways, often making its diagnosis a challenge. While some women may experience significant symptoms that disrupt daily life, others may remain entirely asymptomatic. Understanding the spectrum of symptoms is crucial for prompt recognition and management.

Symptom	Description	Frequency/Significance	Source(s)
Menorrhagia	Heavy/prolonged menstrual bleeding	Most common symptom	3 5 14
Dysmenorrhea	Painful menstruation	Very common, often severe	3 4 5 10
Pelvic Pain	Chronic/non-cyclic pelvic discomfort	Frequent, may be persistent	2 4 5 14
Enlarged Uterus	Uterine enlargement	Common clinical finding	5 9 14
Infertility	Difficulty conceiving	Notable impact in many patients	2 14
Asymptomatic	No noticeable symptoms	Not rare, complicates diagnosis	2 3 13

Table 1: Key Symptoms

Overview of Common Symptoms

Adenomyosis's hallmark symptoms include heavy menstrual bleeding (menorrhagia), painful periods (dysmenorrhea), and chronic pelvic pain. These symptoms often worsen over time and can lead to significant disability and emotional distress 3 4 5 14. However, not all individuals experience every symptom, and up to one-third may have no symptoms at all 2 3 13.

Menorrhagia

• Heavy or prolonged menstrual bleeding is the most frequently reported symptom, affecting the majority of women with adenomyosis.
• This symptom can lead to anemia and fatigue, impacting overall health and well-being 3 5 14.

Dysmenorrhea and Pelvic Pain

• Severe menstrual cramps and non-cyclic pelvic pain are also commonly present.
• The intensity of pain often correlates with the extent and spread of adenomyosis within the uterine wall 4.
• Adolescents with adenomyosis report dysmenorrhea as the most common symptom, particularly when the outer myometrium is involved 10.

Uterine Enlargement

• Many women with adenomyosis have a diffusely enlarged, tender uterus upon examination, sometimes mistaken for fibroids 5 9.

Infertility

• Adenomyosis can impair fertility, making conception more challenging for some patients 2 14.

Asymptomatic Cases

• Importantly, some women exhibit no symptoms, which may delay diagnosis or result in incidental findings during imaging or surgery for other reasons 2 3 13.

Types of Adenomyosis

Adenomyosis is not a uniform disease; it presents in several distinct forms based on its location, pattern, and extent within the uterus. Classification of adenomyosis types is essential for determining the most effective management approach.

Type	Location/Pattern	Key Features	Source(s)
Diffuse	Widespread in myometrium	Uniform thickening, enlarged uterus	2 6 7 9
Focal	Localized (adenomyoma)	Discrete nodules/masses	2 7 9 18
Internal	Inner myometrium/junctional	Associated with HMB, prior surgery	6 8 10
External	Outer myometrium	Linked to younger age, endometriosis	6 8 10
Other Subtypes	Mixed/Indeterminate	Combination or unclear origin	6 7 8

Table 2: Types of Adenomyosis

Diffuse vs. Focal Adenomyosis

Diffuse Adenomyosis

• Characterized by uniform infiltration of endometrial tissue throughout the myometrium.
• Leads to generalized uterine enlargement and a “boggy” texture on examination 2 6 7 9.
• More likely to cause global uterine symptoms such as heavy bleeding and pain.

Focal Adenomyosis (Adenomyoma)

• Presents as isolated nodules or masses within the uterine wall.
• May mimic fibroids on imaging but has different tissue characteristics 2 7 9 18.
• Often associated with more localized symptoms or may be asymptomatic.

Internal vs. External Adenomyosis

Internal Adenomyosis

• Involves the inner myometrial layer, near the junctional zone (JZ) of the uterus.
• Frequently associated with heavy menstrual bleeding and a history of uterine surgery 6 8 10.
• Imaging shows thickening of the JZ, sometimes with small cystic spaces.

External Adenomyosis

• Affects the outer myometrial layer, often separated from the JZ.
• More common in younger and nulliparous women.
• Strongly linked to concurrent endometriosis 6 8 10.
• Pain symptoms may not differ significantly from internal adenomyosis, but heavy bleeding is less frequent.

Classification Systems and Imaging

• Recent advances in ultrasound and MRI have enabled more precise classification based on location (anterior, posterior, lateral, fundal), extent (focal vs. diffuse), and depth (inner vs. outer myometrium) 7 9 10.
• Some classification systems also grade the severity (mild, moderate, severe) based on how much of the uterus is affected 10.

Mixed and Indeterminate Types

• Mixed or indeterminate types occur when both internal and external layers are involved, or when the disease does not fit neatly into other categories 6 7 8.
• These cases may be more advanced and present with a combination of symptoms.

Causes of Adenomyosis

The exact cause of adenomyosis remains under investigation. Several theories have been proposed to explain why endometrial tissue becomes embedded within the uterine muscle. Understanding these mechanisms helps guide future research and potential prevention strategies.

Cause/Theory	Description	Key Evidence or Factors	Source(s)
Endometrial Invasion	Invagination of endometrial tissue into muscle	Most widely supported theory	2 11 14
Müllerian Remnants	Embryologic misplaced tissue develops later	Accounts for focal types	6 11 14
Uterine Injury	Trauma from surgery, childbirth, abortion	Higher risk with prior procedures	1 8 14
Hormonal Factors	Estrogen dependence, hormonal dysregulation	High estrogen promotes growth	2 11 12
Genetic/Developmental	Myometrial formation defects, gene changes	Tamoxifen exposure in animals	12
Associated Conditions	Endometriosis, fibroids	Frequent co-occurrence	2 8 11

Table 3: Proposed Causes of Adenomyosis

Endometrial Invasion Theory

• The most widely accepted mechanism is the direct invagination or invasion of endometrial glands and stroma into the myometrium.
• This can be facilitated by uterine trauma, high intrauterine pressure, or a “weakness” in the smooth muscle tissue 2 11 14.

Embryologic/Müllerian Remnant Theory

• Some cases, especially focal adenomyosis, may arise from misplaced embryonic cells (Müllerian remnants) that later differentiate into endometrial tissue within the muscle wall 6 11 14.
• This theory is supported by the presence of adenomyotic tissue in unusual or extrauterine locations.

Uterine Injury and Surgical Factors

• Procedures such as cesarean section, dilation and curettage, or previous uterine surgeries increase the risk of adenomyosis by disrupting the endometrial-myometrial interface 1 8 14.
• A notable correlation exists between adenomyosis and a history of pregnancy termination or uterine surgery 1 8.

Hormonal and Immune Factors

• Adenomyosis is considered an estrogen-dependent condition, with high local estrogen levels promoting the growth and survival of ectopic endometrial tissue 2 11.
• Immune dysfunction may also play a role, allowing abnormal tissue survival and invasion 11.

Genetic and Developmental Factors

• Animal studies show that exposure to certain drugs (e.g., tamoxifen) during uterine development can cause adenomyosis, likely due to impaired myometrial differentiation 12.
• Specific gene expression changes affecting the development and structure of the uterus have been implicated 12.

Association with Other Diseases

• There is frequent overlap between adenomyosis, endometriosis, and uterine fibroids, suggesting shared or related pathogenic mechanisms 2 8 11.

Treatment of Adenomyosis

Managing adenomyosis requires a personalized, patient-centered approach, considering the severity of symptoms, reproductive desires, age, and overall health. Treatment options range from conservative medical therapies to surgical interventions.

Treatment Type	Approach/Examples	Suitability/Outcome	Source(s)
Medical Therapy	Hormonal treatments (OCPs, LNG-IUD, GnRH)	First-line for symptom control	3 14 17
Conservative Surgery	Excision/ablation, adenomyomectomy	Fertility-sparing, focal disease	15 16 18
HIFU	High-intensity focused ultrasound	Non-invasive, symptom relief	19
Hysterectomy	Removal of uterus	Definitive, for severe cases	3 14 17

Table 4: Treatment Options

Medical Management

• Hormonal Therapies:
  • Oral contraceptive pills (OCPs), high-dose progestins, levonorgestrel-releasing intrauterine devices (LNG-IUD), GnRH agonists, selective estrogen/progesterone receptor modulators, aromatase inhibitors, and danazol can all suppress symptoms by reducing endometrial activity 3 14 17.
  • These options are typically first-line for women wishing to avoid surgery or preserve fertility.
  • Symptom relief is often temporary; symptoms may return once medication is stopped 3.

Conservative and Uterus-Sparing Surgery

• Adenomyomectomy:

  • Surgical excision of focal or localized adenomyosis while sparing the uterus 15 16 18.
  • Appropriate for women with focal disease or those seeking to retain fertility.
  • High rates of symptom relief (over 75%) and promising pregnancy outcomes have been reported, though recurrence is possible 15 16 18.
  • Techniques are evolving to minimize risks such as uterine rupture or adhesions 16.

• Other Conservative Surgical Approaches:

  • Endomyometrial ablation or laparoscopic myometrial excision for selected cases 17.

Non-invasive Techniques

• High-Intensity Focused Ultrasound (HIFU):
  • Uses focused ultrasound energy to thermally ablate adenomyotic tissue without surgery 19.
  • Suitable for both focal and diffuse adenomyosis in carefully selected patients.
  • Benefits include minimal recovery time and preservation of the uterus and fertility 19.
  • Not all patients are candidates; strict selection criteria apply—e.g., absence of extensive pelvic adhesions or large abdominal scars 19.

Hysterectomy

• Definitive Solution:
  • Surgical removal of the uterus remains the only cure for adenomyosis 3 14 17.
  • Reserved for women with severe, refractory symptoms who do not desire future fertility.
  • Offers complete symptom relief but is a major surgery with permanent loss of fertility.

Multidisciplinary Management and Future Directions

• Treatment should be tailored to individual needs, considering symptom severity, fertility goals, age, and comorbidities.
• Emerging imaging techniques and classification systems may allow for more targeted, personalized therapies in the future 2 7 10.

Conclusion

Adenomyosis is a multifaceted condition that can significantly impact women's lives. Recognizing its diverse symptoms, understanding its various forms, and appreciating the complexity of its causes are key to providing effective, patient-centered care. Treatment options have expanded in recent years, offering hope for symptom relief and preservation of fertility for many women.

Key takeaways:

• Symptoms include heavy menstrual bleeding, painful periods, pelvic pain, and sometimes infertility, but can also be absent in some women 3 4 5 14.
• Types of adenomyosis are classified as diffuse, focal, internal, and external, each with unique clinical and imaging characteristics 2 6 7 8 9 10.
• Causes are not fully understood but likely involve a combination of endometrial invasion, developmental errors, uterine injury, hormonal factors, and genetic predispositions 1 2 6 8 11 12 14.
• Treatment ranges from medical management and conservative surgery to innovative non-invasive techniques and, when necessary, hysterectomy 3 14 15 16 17 18 19.

Ongoing research into the pathogenesis, diagnosis, and management of adenomyosis promises to improve the lives of affected women and guide clinicians in offering the most effective, individualized care possible.