Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La...

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Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California

Transcript of Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La...

Page 1: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Endometriosis

R. Jeffrey Chang, M.D.Department of Reproductive Medicine

UCSD School of MedicineLa Jolla, California

Page 2: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Commercial Disclosures (9.9.06)

Entity Activity

Wyeth Research fundingSerono Research supportTakeda Research supportBerlex Research support

Page 3: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Learning Objectives

• Identify the symptoms and consequences associated with endometriosis

• Describe various treatment options in the management of endometriosis

Page 4: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Definition

• Endometriosis is a disease in which endometrial glands and stroma implant and grow in areas outside the uterus

• Most commonly implants are found in the pelvis

• Lesions may occur at distant sites: pleural cavity, liver, kidney, gluteal muscles, bladder, etc

Page 5: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Features of Endometriosis

• Prevalence 2-50% of women; 21-47% of infertility cases

• Exposure to ovarian hormones appears to be essential

• No known racial or socioeconomic predilection

• Severe disease may occur in families

Page 6: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Is Endometriosis Increasing?

• 1965-1984, endometriosis rose from 10 to 19% as

primary indication for hysterectomy

• Simultaneously, a trend of more conservative therapies

was occurring, which suggests a true increase in the

incidence

• Theories include delay of childbearing, less use of OCs,

and exposure to environmental toxins such as dioxin

Page 7: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Etiologies of Endometriosis• Sampson's theory: Retrograde menses and peritoneal

implantation– Most women retrograde menstruate

• Meyer's theory: Coelomic metaplasia– Low incidence of pleural disease

• Halban's theory: Hematogenous or lymphatic spread to distant tissues – Does not explain gravity dependent disease sites

• Immunogenic defect

Page 8: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Normal Pelvic Structures

Page 11: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Endometriosis

Page 12: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Endometriosis

Page 13: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Stage I (Minimal) Stage II (Mild)

Stage III (Moderate) Stage IV (Severe)

Classification of Endometriosis

4* 9

11429

* Revised AFS Score

Page 14: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Clinical Presentation

• Pelvic pain

• Infertility

• Pelvic mass

Page 15: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Pelvic Pain

• Frequency – Cyclic: Variable length prior to and after

menses – Acyclic: constant and unrelenting

• Associated activities– May include dyspareunia, dysuria, or

dyschezia

• Other sites of pain– Muscle regions– Distant tissues

Page 16: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Infertility

• Moderate to severe disease

– Adhesions

– Distortion of normal anatomy

– Prevent sperm-egg interaction

• Minimal to mild disease

– Mild infertility

– Mechanism(s) unknown

Page 17: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Physical Findings

• Tender nodules along the uterosacral ligaments or in the cul-de-sac, especially just before menses

• Pain or induration without nodules commonly in the cul-de-sac or rectovaginal septum

• Uterine or adnexal fixation, or an adnexal mass

Page 18: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Diagnosis of Endometriosis

• Direct visualization of implants– Laparoscopically– Conscious pain mapping

• Imaging of endometriomas– MR appears to be best (3 mm implants)– Ultrasound helpful in office setting

• Biochemical markers – Lack specificity

Page 20: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Endometriosis

Page 24: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Endometrioma

Page 25: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Treatment of Endometriosis

• Management of pain– Surgery – Medical therapy

• Treatment of infertility– Surgery– Ovulation induction– Assisted reproductive technology

Page 26: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Management of Pain

• Surgical treatment

– Ablation of endometrial implants

– Lysis of adhesions

– Ablation of uterosacral nerves

– Resection of endometriomas

• Combined surgical and medical treatment

Page 27: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Endometriosis

Page 28: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Removal of Endometriosis

Page 29: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Dissection of an Endometrioma

Tube

OvaryIncision

Removal Result

Page 30: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Treatment of Pain

• Medical management (ovarian suppression, removal of

estrogen)

– Oral contraceptives, progestin, danazol

– GnRH agonist with add-back

– Alternating GnRH agonist and OCs

– Aromatase inhibitors

Page 31: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Medical Treatment

Ovary Estrogen

EndometriosisTissue

Page 32: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Medical Treatment

Ovary Estrogen

EndometriosisTissueOral contraceptives

DanazolGnRH agonists

Progestin

Page 33: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Role of Estrogen in Endometriosis

Estrogen

Page 34: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Role of Estrogen in Endometriosis

Estrogen

Cell growth

Page 35: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Role of Estrogen in Endometriosis

Aromatase

Estrogen

Cell growth

Page 36: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Role of Estrogen in Endometriosis

Aromatase

Estrogen

Cell growth

PGE2Cytokines

Page 37: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Aromatase In Endometriosis• Aromatase is key for the biosynthesis of

estrogen

• In patients aromatase expression is higher in endometriosis tissue than in normal endometrium

• In endometriosis tissue aromatase activity is stimulated by prostaglandin

• Estrogen synthesized by endometriotic tissue stimulates growth of lesions

Page 38: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Role of Estrogen in Endometriosis

Aromatase

Estrogen

Cell growth

PGE2Cytokines

Aromatase Inhibitors • Letrozole

• Exemestane • Anastrozole

Page 39: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Role of Estrogen in Endometriosis

Aromatase

Estrogen

Cell growth

PGE2Cytokines

Aromatase Inhibitors • Letrozole

• Exemestane • Anastrozole• Danazol

Page 40: Endometriosis R. Jeffrey Chang, M.D. Department of Reproductive Medicine UCSD School of Medicine La Jolla, California.

Treatment of Infertility• Removal of disease

– Surgery improve conception rates at all stages

• Ovulation induction– Gonadotropins with ovarian suppression – Insemination with either clomiphene or FSH

• Medical suppression of ovarian function– No benefit

• Assisted reproductive technology