Endometriosis & Adenomyosis

Three main theories regarding etiology of endometriosis?

(1) Halban theory: endometrial tissue *transported via the lymphatic system* to various sites in the pelvis, where it grows ectopically. (2) Meyer: multipotential cells in peritoneal tissue undergo *metaplastic transformation* into functional endometrial tissue. (3) Sampson suggests that endometrial tissue is transported through the fallopian tubes during *retrograde menstruation*

American Society for Reproductive Medicine Revised Classification of Endometriosis

...

Incidence of endometriosis?

10-15%

The incidence of adenomyosis is

15%.

Adenomyosis - clinical manifestations

30% asymptomatic / secondary dysmenorrhea (30%), menorrhagia i.e. incr heavy prolonged periods (50%) or both (20%) / pressure on bladder/rectum due to an enlarged uterus

What does adenomyosis due to the uterus?

Adenomyosis causes the uterus to become *diffusely enlarged and globular* due to *hypertrophy and hyperplasia of the myometrium adjacent to the ectopic endometrial tissue*. The disease is usually most extensive in the fundus and posterior uterine wall.

Adenomyoma

Adenomyosis may also present as a well-circumscribed, isolated region known as an adenomyoma - well-circumscribed collection of endometrial tissue within the uterine wall. They may also contain smooth muscle cells and are not encapsulated. Adenomyomas can also extend into the endometrial cavity in the form of a polyp.

Risk factors for adenomyosis?

Adenomyosis, endometriosis, and uterine fibroids frequently coexist. About 15% to 20% of patients with adenomyosis also have endometriosis, and 50% to 60% of patients with adenomyosis also have uterine fibroids. Patients with dyspareunia, dyschezia, and menorrhagia or menometrorrhagia have an increased probability of having adenomyosis.

Definitions - adenomyosis?

An extension of endometrial tissue into the uterine myometrium leading to menorrhagia or metromenorrhagia. The uterus becomes soft, globular.

PE findings in adenomyosis

Diffusely *enlarged globular uterus*. The uterus can be 2 to 3 times normal size but is usually <14 cm. The consistency of the uterus is typically softer and boggier than the firmer, rubbery uterus containing fibroids. The adenomyomatous uterus may be mildly tender just before or during menses but should have normal mobility and no associated adnexal pathology.

Does the severity of symptoms correlate with the amount of endometriosis?

No. Women with widely disseminated endometriosis or a large endometrioma may experience little pain, whereas women with minimal disease in the cul-de-sac may suffer severe pain.

Not necessary

Peritoneal biopsy is not necessary but is helpful in histologically confirming the diagnosis of endometriosis.

PE findings for endometriosis?

Suble or non-existent. Do PE during early menses when implants are largest and most-tender. If more dissem may find uterosacral nodularity on rectovaginal exam or fixed retroverted uterus.

Cause of adenomyosis?

The cause of adenomyosis is not known. The current theory is that *high levels of estrogen stimulate hyperplasia of the basalis layer of the endometrium*. For unknown reasons, the barrier between the endometrium and myometrium is broken and the endometrial cells can then invade the myometrium. Because this disease occurs most frequently in parous women, it is thought that subclinical endomyometritis may be the first insult to the endometrial-myometrial barrier and eventually predisposes the myometrium to subsequent invasion.

DDX for adenomyosis

The differential diagnosis for adenomyosis includes disease processes resulting in uterine enlargement, menorrhagia, and/or dysmenorrhea including uterine fibroids, polyps, menstrual disorders, endometrial hyperplasia, endometrial cancer, pregnancy, and adnexal masses.

DDX for endometriosis

The differential diagnosis for endometriosis includes other processes that result in recurrent pelvic pain such as pelvic inflammatory disease, recurrent acute salpingitis, adenomyosis, fibroids, adhesions, hemorrhagic corpus luteum cysts, ectopic pregnancy, and ovarian neoplasms

Adenomyosis gen occurs in what kind of women? (epi)

The disease generally develops in *parous women* in their late 30s or early 40s. Itoccurs very infrequently in nulliparous women.

Diagnosing endometriosis?

The only way to definitively diagnose endometriosis is through direct visualization with laparoscopy or laparotomy.

What's a chocolate cyst?

The ovary itself can develop large cystic collections of endometriosis filled with thick, dark, old blood known as endometriomas or chocolate cysts

Adenomyoma vs fibroids?

Unlike uterine fibroids, which have a characteristic pseudocapsule, *individual areas of adenomyosis are not encapsulated*. Instead, adenomyosis can infiltrate throughout the myometrium giving the uterus a characteristic *boggy* feel on palpation.

Risk factors for endometriosis

Women with *first-degree relatives* (mother or sisters) with endometriosis are seven times more likely to develop the disorder than women without this risk factor. A relationship has also been demonstrated between endometriosis and some *autoimmune disorders (e.g., lupus).* Less common in Black women.

GnRH agonists like Lupron can be costly and often have limited insurance coverage. Therefore, the use of these medications is generally limited to 6 months. Fortunately, newer treatment regimens known as *add-back therapy* have been designed for use in conjunction with GnRH agonists. These do what?

add a small amount of estrogen to the GnRH agonist to minimize the symptoms caused by estrogen deficiency such as hot flashes and bone density loss. With add-back therapy, the patient receives the benefits of the GnRH agonist (endometriosis suppression and relief of pelvic pain and dysmenorrhea) while the small dose of estrogen minimizes the adverse effects of hypoestrogenation.

Prior to treating adenomyosis in pts > 35

any patient or older age 35 with irregular menses should have an endometrial biopsy and TSH to rule out other causes for irregular menses

How do endometrial implants cause symptoms?

by disrupting normal tissue, forming adhesions and fibrosis, and causing severe inflammation.

Hallmark clin symptom of endometriosis?

cyclic pelvic pain beginning 1 or 2 weeks before menses, peaking 1 to 2 days before the onset of menses, and subsiding at the onset of flow or shortly thereafter. Other symptoms associated with endometriosis are dysmenorrhea (often after yrs of pain-free cycles), dyspareunia, abnormal bleeding, and *infertility*. Endometriosis is one of the most common diagnoses in the evaluation of infertility.

Patients can also be placed in a reversible state of pseudomenopause with the use of ... How do they work?

danazol (Danocrine), an androgen derivative, or gonadotropin-releasing hormone (GnRH) agonists such as leuprolide acetate (Lupron) and nafarelin (Synarel). Both classes of drugs suppress follicle-stimulating hormone (FSH) and luteinizing hormone (LH). As a result, the ovaries do not produce estrogen, which would normally stimulate endometrial implants. Subsequently, existing endometrial implants atrophy, and new implants are prevented.

What's adenomyosis

extension of endometrial tissue into the uterine myometrium

endometrioma PE finding?

fixed adenexal mass

Complications of endometriosis include ...

intra-abdominal inflammation and bleeding that can cause scarring, pain, and adhesion formation, which can lead to infertility and chronic pelvic pain.

Side effects associated with OCPs and progestin agents include ...

irritability, depression, breakthrough bleeding, and bloating

Endometriomas are best treated using ...

laparoscopic cystectomy with removal of as much of the cyst wall as possible

What progestin is used in med management?

medroxyprogesterone i.e. megestrol i.e. Megace

Symptoms of adenomyosis?

menorrhagi, metromenorrhagia

Draw back to danazol?

patients may experience some androgen-related, anabolic side effects including acne, oily skin, weight gain, edema, hirsutism, and deepening of the voice.

Definitive surgical therapy includes

total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO), lysis of adhesions, and removal of endometriosis lesions. This therapy is reserved for cases in which childbearing is complete and for women with severe disease or symptoms that are refractory to conservative medical or surgical treatment.

Most common sites?

Endometrial tissue can be found anywhere in the body, but the most common sites are the ovary and the pelvic peritoneum. Other common sites are in the most dependent parts of the pelvis including the uterosacral ligaments, the anterior and posterior cul-de-sacs, and the posterior uterus and broad ligaments. Although not commonly found, endometriosis has been identified in the lung and brain.

What's an endometrioma?

Endometriosis in the ovary.

What's endometriosis?

Endometriosis is the presence of endometrial tissue (glands and stroma) outside the endometrial cavity.

SE GnRH agonists like Lupron?

Estrogen deficiency i.e. menopause symptoms i.e. hot flashes, decreased bone density, HA, vag atrophy, dryness.

How is endometriosis treated?

Expectant Management if minimal symptoms of it pt trying to conceive. Medical management = temporizing measures 2/2 recurrence = suppression/atrophy of endometrial tissue = *NSAIDs, OCPs, Progestins"

Definitive treatment for adenomyosis?

Hysterectomy

Conception Rates after Ablation of Endometrial Implants

If mild extent of disease and stage 1-2 = 75% concept rate Mod, stage 3, 50% Severe, stage 4 - 35%

Treating adenomyosis?

If symptoms not bad treat with NSAIDs, OCPs, menstrual suppression with progestins or continuous OCPs. But hysterectomy is the only definitive treatment. R/o concomitant endometrial hyperplasia/carcinoma before hysterectomy.

How do the medical treatments work?

Induce state of pseudopregnancy. by suppressing both ovulation and menstruation and by decidualizing the endometrial implants, thereby alleviating the cyclic pelvic pain and dysmenorrhea. This therapy is believed best for patients with mild endometriosis who are not currently seeking to conceive.

Age group?

It is found almost exclusively in women of reproductive age, and is the single most common reason for hospitalization of women in this age group. Approximately 20% of women with chronic pelvic pain and 30% to 40% of women with infertility have endometriosis.

Surgical treatment for endometriosis can be classified as either conservative or definitive. Conservative surgical therapy typically involves ...

Laparoscopy and fulguration of any visible endometrial implants. With conservative therapy, the *uterus and ovaries are left in situ to allow for future fertility*. For these, the pregnancy rate after conservative surgical treatment depends on the extent of the disease at the time of surgery. For patients with pain who do not desire immediate pregnancy, pain control can be optimized and recurrences delayed by starting or restarting medical therapy immediately after surgical treatment.

Leiomyoma

Local proliferations of smooth muscle cells within the uterus, often surrounded by a pseudocapsule. Also known as fibroids, these benign growths may be located on the intramural, subserosal, or submucosal portion of the uterus.

How to diagnose adenomyosis?

MRI but expensive so usually start with pelvic US and if + then go to MRI. Goal to dist adenomyosis from fibroids. Ultimately though hysterectomy is the only definitive means of diagnosing adenomyosis.

If pt trying to conceive?

No role for medical management. Medical management does not improve conception rates and only serves to delay attempts at conception and/or employment of surgical treatments that have been shown to improve conception rates.

Why isn't adenomyosis gen responsive to regulation with OCPs or other hormonal agents?

Because the endometrial tissue in adenomyosis extends from the basalis layer of the endometrium, it does not undergo the proliferative and secretory changes traditionally seen in normally located endometrium or in endometriosis.