Pathophysiology of the Uterus – Comprehensive Study Notes

Preamble to Reproductive Lectures (Page 3)

• Reproductive pathophysiology lectures cover typical male and female systems but acknowledge variations such as:

  • Intersex variations: born with physical sex characteristics not fitting typical female/male norms.

  • Transgender individuals may have reproductive organs different from typical male/female descriptions.

• These variations are not exhaustively covered in these lectures.

• Emphasizes avoiding heteronormativity by identifying and challenging heteronormative and cisnormative language and practices within the context of the reproductive system.

Learning Objectives

• Describe the pathophysiology of common conditions of the uterus:

  • Endometrium: endometritis, endometriosis, hyperplasia, and neoplasia

  • Myometrium: fibroids

• Describe the pathogenesis, clinical features, and complications of common uterine conditions.

Endometritis

• Definition: infectious inflammation localized to the endometrium.

• Significance: can cause severe long-term complications if not correctly diagnosed or treated.

• Extension: Infection that extends to uterine tubes (salpingitis), ovaries, or pelvic peritoneum is termed pelvic inflammatory disease (PID).

• Classification: two types – acute and chronic.

• Postpartum endometritis: subtype of acute endometritis associated with pregnancy.

• Clinical features: endometrium appears red and granular; hysteroscopic finding of chronic endometritis can be seen in women with a history of repeated implantation failure.

Acute Endometritis

• Definition: endometrial infection present for < 30 days.

• Common etiologies: sexually transmitted infections (Chlamydia trachomatis and Neisseria gonorrhoeae) or bacterial vaginosis (BV).

• Associations: may be linked to retained products of conception/placenta (most common) or instrumentation.

• Microbiology: usually bacterial; histology shows endometrium with prominent intraluminal neutrophils and neutrophil infiltration destroying glandular epithelium.

• Signs and symptoms: fever; abnormal bleeding; purulent discharge; pelvic pain.

Chronic Endometritis

• Definition: mild infectious inflammation of the endometrium lasting > 30 days.

• Microbiology: polymicrobial infections (commonly Strep., Escherichia coli, Staph., Mycoplasma, Gardnerella vaginalis, and Candida); presence of plasma cells.

• Associations: commonly linked to IUDs, history of multiple pregnancies, and previous abortions.

• Possible associations: unexplained infertility, recurrent miscarriages, repeated implantation failure after IVF embryo transfer.

• Signs and symptoms: often asymptomatic but may include abnormal uterine bleeding, dyspareunia, pelvic pain; may be associated with moderate to severe intrauterine adhesions.

Endometriosis

• Definition: ectopic endometrial tissue deposits outside the uterine cavity.

• Epidemiology: affects >11% of women in Australia.

• Common locations: ovaries and pelvic peritoneum; can be present elsewhere (bowel, bladder).

• Hormonal responsiveness: estrogen-responsive tissue; functional and undergoes cyclical menstrual changes.

• Pathophysiology: lesions enlarge and become haemorrhagic, causing inflammation, scarring, fibrosis, peritoneal irritation, and pain.

• Clinical impact: can cause infertility; may lead to cystic lesions called “chocolate cysts.”

• Diagnostics: detected via ultrasonography and MRI.

• Key imaging features (illustrative): endometriotic implants and deep lesions with classic appearances such as powder-burn lesions, blue-black lesions, and adhesions in relation to ovarian and uterine structures.

• Contributing concept: retrograde menstruation is one proposed mechanism.

Endometriotic Implants (visual reference)

• Common descriptive appearances include reddish-brown to bluish small areas and deep deep lesions near the posterior uterus in the pouch of Douglas; multiple characteristic patterns noted on imaging.

• Associated anatomy: ovary, bladder, rectum, sigmoid colon, and peritoneal cavity; may form cysts (endometriomas) in the ovary.

Endometriosis Signs and Symptoms

• Extrauterine (ectopic) endometrial tissue growth in:

  • Ovary, peritoneum, uterine tube, uterine serosa, bladder, and intestines.

• Pelvic pain features:

  • Dysmenorrhea (painful menses); lower abdominal, vaginal, posterior pelvic, and back pain.

  • Dyspareunia (pain during intercourse).

  • Pain on defecation.

  • Excessive bleeding leading to anemia and fatigue.

Endometrial Hyperplasia

• Definition: thickening of the endometrium; pathology shows a hyperplastic endometrium.

• Pathophysiology: associated with excess or unopposed estrogen.

• Cancer risk: increased risk of progression to endometrial adenocarcinoma.

• Management note: responds to suppression by progesterone hormone therapy.

• Reference: external clinical resource linked for deeper understanding.

Endometrial Cancer

• Epidemiology: the most common gynecological malignancy; usually develops from endometrial hyperplasia.

• Demographics: more commonly seen in premenopausal and postmenopausal women.

• Growth pattern: tumor typically starts in the fundus of the uterus and can spread to the myometrium, cervix, and other reproductive organs.

• Histology: most endometrial cancers are slow-growing adenocarcinomas.

Endometrial Carcinoma: Classifications

• Type I Endometrial Carcinomas (most common):

  • Associated with unopposed estrogen exposure.

  • Characteristically low-grade histology.

  • Often linked with atypical endometrial hyperplasia.

  • Generally good prognosis.

• Type II Endometrial Carcinomas:

  • Occur in older, postmenopausal women.

  • Estrogen-independent.

  • Not associated with endometrial hyperplasia.

  • Poor prognosis.

Endometrial Cancer Risk Factors and Presentation

• High estrogen risk factors:

  • Obesity, nulliparity, infertility, late onset of menopause, unopposed estrogen therapy, diabetes mellitus, hypertension, PCOS, family history of ovarian or breast disease, hormonal imbalances or diseases.

• Signs and symptoms:

  • Abnormal vaginal bleeding (including postmenopausal bleeding); pain in lower pelvic and back; uterine enlargement or mass; abnormal vaginal discharge.

Leiomyomas (Uterine Fibroids)

• Definition: benign tumours composed of smooth muscle cells and fibroblasts in the myometrium.

• Epidemiology: the most common benign tumor of the female genital tract; affect approximately 30-50% of women of reproductive age; incidence increases with age; often multiple.

• Etiology: genetic component with chromosomal rearrangements and gene mutations; hormonal component with estrogens (and possibly oral contraceptives) stimulating growth; these tumors tend to shrink after menopause.

Classification of Leiomyomas

• Common anatomical classifications include:

  • Intramural

  • Subserosal (fundal subserosal, pedunculated subserosal)

  • Submucosal (pedunculated or otherwise)

• Location relative to uterine wall and surface determines clinical presentation and management.

Leiomyomas: Clinical Presentation and Impact

• About 25% are symptomatic; symptoms depend on size and location:

  • Chronic pelvic/abdominal pain

  • Menorrhagia leading to anemia

  • Constipation due to bowel compression

  • Urinary symptoms (incontinence or frequency) due to bladder compression

  • Infertility and poor pregnancy outcomes

Leiomyomas: Risk Factors

• Age: typically affect women of reproductive age; incidence tends to decline after menopause.

• Family history: maternal or sister history increases risk.

• Hormonal factors: estrogen and progesterone promote growth; factors that influence hormones include early menarche, late menopause, nulliparity.

• Obesity: potentially via higher estrogen from adipose tissue.

• Conditions affecting hormones: PCOS.

• Environmental factors: exposure to toxins and endocrine disruptors.

Cervical Cancer

• Overview: cervical cancer is a neoplasm that can be detected early and curably via the cervical screening test.

• Etiology: most tumors are caused by oncogenic strains of Human Papillomavirus (HPV).

• HPV role: detectable in precancerous and cancerous lesions; implicated in other squamous cell carcinomas (vagina, vulva, penis, anus, tonsil).

• Risk factors:

  • Exposure to HPV and persistent HPV infection

  • Early age at first intercourse

  • Multiple sexual partners

  • A partner with multiple sexual partners

Cervical Cancer: Preinvasive and Invasive Disease

• Preinvasive disease: usually asymptomatic; screening detects cellular changes about 10 years before invasive cancer develops.

• Invasive carcinoma signs and symptoms:

  • Abnormal vaginal bleeding

  • Persistent vaginal discharge

  • Pain and bleeding after intercourse

• Spread and metastasis:

  • Direct extension to the vaginal wall

  • Lateral spread to the parametrium and pelvic wall

  • Anteroposterior spread to the bladder and rectum

  • Pelvic lymph node metastasis is more common than distant lymph node spread

Summary: What You Should Be Able To Do

• Describe the pathophysiology of common uterine conditions:

  • Endometrium: endometritis, endometriosis, hyperplasia, and neoplasia

  • Myometrium: fibroids

• Describe the pathogenesis, clinical features, and complications of common uterine conditions.