Chap 15: Endometriosis and Adenomyosis

The cause of adenomyosis is not known.

A current theory is that high levels of estrogen stimulate hyperplasia of the basalis layer of the endometrium. For unknown reasons, the barrier be- tween the endometrium and myometrium is broken and the en- dometrial 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.

Endometrioma

A cystic collection of endometrial cells, old blood, and menstrual debris on the ovary; also known as "chocolate cysts."

Adenomyoma

A well-circumscribed collection of endometrial tissue within the uterine wall. They may also contain smooth muscle cells and are not encapsulated. Adenomyomas can also prolapse into the endometrial cavity similar to a classic endometrial polyp.

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 adeno- myosis also have uterine fibroids. dyspareunia, dyschezia, and menorrhagia (abnormal heavy/prolonged bleeding) or menometrorrhagia (abnormal heavy bleedings at irregular times)

Adenomyosis may also present as a well-circumscribed, isolated region known as an adenomyoma.

Adenomyomas contain smooth muscle cells as well as endometrial glands and stroma. These nodular growths may be located in the myome- trium or extend into the endometrial cavity. Unlike uterine fibroids, which have a characteristic pseudocapsule, individual areas of adenomyosis are not encapsulated. Instead, adenomyo- sis can infiltrate throughout the myometrium giving the uterus a characteristic boggy feel on palpation.

Medical treatment for endometriosis is aimed at suppres- sion and atrophy of the endometrial tissue

Although medical therapies can be quite effective, these are temporizing measures rather than definitive treatments. Endometrial implants and symptoms often recur following cessation of treatment.

Adenomyosis

An extension of endometrial tissue into the uterine myometrium leading to abnormal bleeding and pain. The uterus becomes soft, globular. Progestin-containing IUD and hysterectomy are the most effective means of treatment.

Risk factors for endometriosis

Nulliparity, early menarche, prolonged menses, and müllerian anomalies first-degree relatives (mother or sisters) with endometriosis autoimmune inflammatory disorders such as lupus, asthma, hypothyroidism, chronic fatigue syndrome, fibromyalgia, and allergies.

Endometriosis in the ovary appears as a cystic collection known as an endometrioma.

Other common sites include the most dependent parts of the pelvis such as the posterior uterus and broad ligaments, the uterosacral ligaments, fallopian tubes, colon, and appendix (Fig. 15-1). Although not commonly found, endometriosis has been identified as far away as the breast, lung, and brain.

Symptoms of endometriosis vary depending on the area involved.

Over 75% of women with symptomatic endometriosis will have pelvic pain and/or dysmenorrhea (painful menses)

There are three main theories about the etiology of endo- metriosis.

The Halban theory proposes that endometrial tissue is transported via the lymphatic system to various sites in the pelvis, where it grows ectopically. Meyer proposes that multi- potential cells in peritoneal tissue undergo metaplastic trans- formation into functional endometrial tissue. Finally, Sampson suggests that endometrial tissue is transported through the fallopian tubes during retrograde menstruation, resulting in intra-abdominal pelvic implants.

The pelvic examination of a patient with adenomyosis may reveal a diffusely enlarged globular uterus.

The adenomyomatous uterus may be mildly tender just before or during menses but should have normal mobility and no associated adnexal pathology.

Adenomyosis causes the uterus to become diffusely en- larged 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. 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. Thus, unlike endometriosis, which contains both glandular and stromal endometrial tissue, adenomyosis is less responsive to treatment with OCPs or other hormonal treatments.

Endometriosis

The presence of endometrial cells outside the uterine cavity. The hallmark of this chronic disease is cyclic pelvic pain. These estrogen-sensitive lesions can be treated with NSAIDs, OCPs, progestins, GnRH agonists, or surgery.

GnRH agonists such as Lupron result in estrogen deficiency.

The side effects of these medications are similar to those seen during menopause including hot flashes, decreased bone density, headaches, and vaginal atrophy and dryness. Moreover, these treatments can be costly and often have limited insurance coverage. Therefore, the use of these medications is generally limited to 6 months.

newer treatment regimens known as add-back therapy have been designed for use in conjunction with GnRH agonists

These regimens add a small amount of progestin with or without 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 progestin with or without estrogen minimizes the adverse effects of hypoestrogena- tion allowing the treatment to be continued up to 1 year.

A prevailing theory is that women who develop endometriosis may have an altered immune system that is less likely to recognize and attack ectopic endometrial implants.

These women may even have an increased concentration of inflam- matory cells in the peritoneum that contribute to the growth and stimulation of the endometrial implants. Endometrial implants cause symptoms by disrupting normal tissue, form- ing adhesions and fibrosis, and causing severe inflammation.

When surgical intervention is used, endometrial implants vary widely in terms of size, texture, and appearance.

They may appear as rust-colored to dark brown powder burns or raised, blue-colored mulberry or raspberry lesions. The areas may be surrounded by reactive fibrosis that can lead to dense adhe- sions in extensive disease. The ovary itself can develop large cystic collections of endometriosis filled with thick, dark, old blood and debris known as endometriomas or chocolate cysts. Peritoneal biopsy is not absolutely necessary but is recommended for histologic confirmation of the diagnosis of endometriosis.

The physical findings associated with early endometriosis may be subtle or nonexistent

To maximize the likelihood of physi- cal findings, the physical examination should be performed dur- ing early menses when implants are likely to be largest and most tender. When more disseminated disease is present, the clinician may find uterosacral nodularity and tenderness on rectovaginal examination or a fixed retroverted uterus. Pain with movement of the uterus can often be seen. When the ovary is involved, a tender, fixed adnexal mass may be palpable on bimanual exami- nation or viewed on pelvic ultrasound (Fig. 15-2).

Symptomatic adenomyosis occurs most often in parous women between age 35 and 50.

When symptoms do occur, the most common are secondary dysmenorrhea (30%) (painful periods/cramps), menorrhagia (50%), (heavy/prolonged abnormal bleeding) or both (20%). Patients typically present with increas- ingly heavy or prolonged menstrual bleeding (menorrhagia). They may also complain of increasingly severe dysmenorrhea that may begin up to 1 week before menses and last until cessa- tion of bleeding. Other patients may only experience pressure on the bladder or rectum due to an enlarged uterus.

The treatment for adenomyosis depends on the severity of the dysmenorrhea and menorrhagia.

Women with minimal symptoms or those near menopause may be expectantly managed or managed with analgesics alone. Nonsteroidal anti-inflammatory drugs ( NSAIDs), cyclic or continuous estrogen-progestin contraceptives (pills, patches, rings) and menstrual suppression with progestins (oral, injectable, or intrauterine) have also been found to be temporarily helpful. Short-term relief has also been achieved using endometrial ablation; however, pain and bleeding recur more frequently when adenomyosis is involved. The levonorgetrel-containing IUD has been found to be the most effective temporary means of managing the symptoms of adenomyosis.

Interestingly, the severity of symptoms does not necessarily correlate with the amount of endometriosis.

Women with widely disseminated endometriosis or a large endometrioma may experience little pain, whereas women with minimal dis- ease in the cul-de-sac may suffer severe chronic pain.

In the case of severe or chronic endometriosis,

a multidisciplinary approach incorporating medical and surgical management as well as pain center involvement and psychiatric support may provide the most comprehensive care.

Another theory

adenomyosis develops de novo from metaplastic transformation of müllerian rests cells located within the myometrium.

Prior to treating adenomyosis,

any patient age 45 or older with change in menstrual quantity or pattern should have a TSH, pelvic ultrasound, and an endometrial biopsy to rule out other causes of abnormal uterine bleeding.

Thirty percent of patients with adenomyosis are asymptomatic or have symptoms minor enough that medical attention is not sought.

asymptomatic or have symptoms minor enough that medical attention is not sought.

Endometrial tissue can be found anywhere in the body,

but the most common sites are the ovary and the pelvic peritoneum including the anterior and posterior cul de sacs.

treatment choice for patients with endometriosis

depends on the extent and location of disease, the severity of symptoms, and the patient's desire for future fertility. mindset that the endometriosis is a chronic disease that may require long-term management and multiple interventions. Expectant management may be used in patients with minimal or nonexistent symptoms.

Other symptoms associated with endometriosis

dysmenorrhea, dyspareunia, abnormal bleeding, bowel and bladder symptoms, and subfertility. Endometriosis is one of the most common diagnoses in the evaluation of infertile couples.

Current medical regimens for the treatment of endometriosis

include NSAIDs, cyclic or continuous estrogen-progestin contraceptives (pills, patches, rings), and menstrual suppression with progestins (oral, injectable, or intrauterine). These treatments induce a state of " pseudopregnancy" by suppressing both ovulation and menstruation and by decidualizing the endometrial implants, thereby alleviating the cyclic pelvic pain and dysmenorrhea. These options are best for patients with mild endometriosis who are NOT currently seeking to conceive.

Side effects associated with OCPs and progestin agents

include irritability, depression, breakthrough bleeding, and bloating.

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, preg- nancy, and adnexal masses.

The differential diagnosis for endometriosis

includes other chronic processes that result in recurring pelvic pain or an ovarian mass such as pelvic inflammatory disease, adenomyosis, irritable bowel syndrome, interstitial cystitis, pelvic adhe- sions, functional ovarian cysts, ectopic pregnancy, and ovarian neoplasms.

Endometriosis

is a chronic disease marked by the presence of endometrial tissue (glands and stroma) outside the endo- metrial cavity.

Adenomyosis

is an extension of endometrial tissue (glands and stroma) into the uterine myometrium

The hallmark of endometriosis

is 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 menses or shortly thereafter. Women with chronic endometriosis and teenagers with endometriosis may not demonstrate this classic pain pattern.

The drawback to danazol

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

Dyspareunia

is usually associated with deep penetration that can aggravate endometrial lesions in the cul-de-sac or on the uterosacral ligaments.

Endometriosis is also a cause of infertility.

lthough the exact mechanism is unclear, moderate to severe endometriosis can cause dense adhesions, which can distort the pelvic archi- tecture, interfere with tubal mobility, impair oocyte release, and cause tubal obstruction.

Definitive surgical therapy

ncludes total hysterectomy and bilateral salpingo-oophorectomy (by abdominal or lapa- roscopic approach), lysis of adhesions, and removal of any visible 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 medi- cal or surgical treatment.

If postsurgical hormone replacement therapy is started after hysterectomy and oophorectomy,

some providers will still employ combination hormone therapy due to the theoretical possibility of stimulating transformation of residual implants into an endometrial cancer by the use of estrogen-only replacement therapy.

Patients with moderate to severe endometriosis can also be placed in a reversible state of pseudomenopause with

the use of 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, resulting in decreased stimulation of endometrial implants. Subsequently, existing endometrial implants atrophy, and new implants are prevented.

Dysmenorrhea

usually begins in the third decade, worsens with age, and should raise concern for endometriosis in women who develop dysmenorrhea after years of pain-free cycles.

Hysterectomy is the only definitive treatment for adeno- myosis

Endometrial biopsy should be performed to rule out concomitant endometrial hyperplasia and cancer in women >45 before a hysterectomy is performed for adenomyosis.

The incidence of adenomyosis is generally estimated to be about 20%.

However, 40 - 65% of hysterectomy specimens contain some evidence of adenomyosis. -parous women in their late 30s or early 40s. -occurs very infrequently in nulliparous women.

MRI is the most accurate imaging tool for identifying adenomyosis.

However, because the cost of MRI can be prohibitive, pelvic ultrasound is the most common imaging modality. MRI is then used if adenomyosis is suggested by pelvic ultrasound by an indistinct endometrial-myometrial junction or glandular tissue within the myometrium. This is usually reserved for situations where myomectomy is being planned and it is important to distin- guish adenomyosis from uterine fibroids. Ultimately, hysterec- tomy is the only definitive means of diagnosing adenomyosis.

When the clinical impression and initial evaluation is consistent with endometriosis, empiric medical therapy is often favored over surgical intervention as a safe approach to management.

However, the only way to definitively diagnose endometriosis is through direct visualization with laparoscopy or laparotomy.

Prior to the surgery, it also is particularly important to distinguish adenomyosis from uterine fibroids

If adenomyosis is mistaken for uterine fibroids, a surgeon attempting a myomectomy may find only diffuse adenomyosis and be forced to perform a hys- terectomy instead.

Once the diagnosis of endometriosis is confirmed, the anatomic location and extent of the disease can be used to properly classify the operative findings.

In general, endome- triosis is categorized as minimal, mild, moderate, or severe. The American Fertility Society's revised classification schema is reproduced in Table 15-1. Although not commonly used, this classification method uses a point system to stage endo- metriosis based on the location, depth, and diameter of lesions and density of adhesions.

Leiomyoma

Local proliferations of smooth muscle cells within the myometrium, 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.

There is no role for medical management in patients attempt- ing to conceive.

Medical management does not improve con- ception rates and serves only to delay attempts at conception and/or employment of surgical treatments that have been shown to improve conception rates.

severe endometriosis treatment

More recently, aromatase inhibitors such as anastrozole (Arimidex) and letrozole (Femara) have been used off-label. These medications lower circulating estrogen levels by blocking conversion of androgens to estrogens in the ovary, brain, and periphery. These have not been approved for use in endometriosis, can cause bone loss, hot flashes, and nau- sea and vomiting, and must be used with combination OCPs or GnRH agonists to prevent development of follicular cysts.

The estimated prevalence of endometriosis is between 10% and 15%.

Because surgical confirmation is necessary for the diagnosis of endometriosis, the true prevalence of the disease is unknown. It is found almost exclusively in women of repro- ductive age, and is the single most common reason for hospi- talization of women in this age group. Approximately 20% of women with chronic pelvic pain and 30% to 40% of women with infertility have endometriosis.

Women with advanced endometriosis, endometriomas, and infertility may be best served by surgical management. Surgical treatment for endometriosis can be classified as either conser- vative or definitive.

Conservative surgical therapy typically involves laparoscopy and fulguration or excision of any visible endometrial implants. Endometriomas are best treated using lap- aroscopic cystectomy with removal of as much of the cyst wall as possible (Fig. 15-4). With conservative therapy, the uterus and ovaries are left in situ. For these women, the pregnancy rate after conservative surgical treatment depends on the extent of the disease at the time of surgery (Table 15-2). 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.