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Endometriosis: A Healthcare Professional's Guide

Medically reviewed on Feb 25, 2017 by L. Anderson, PharmD.

Description of Endometriosis

Endometriosis is a gynecological disorder occurring in about 2% to 10% of U.S. women and distinguished by the presence of endometrial tissue lying outside the uterine cavity. Exact prevalence of endometriosis is not known, as some women are asymptomatic or have mild symptoms and may go undiagnosed.

Endometriosis can be painful, inconvenient due to excessive bleeding, and can affect fertility in women in their childbearing years. According to the American Society for Reproductive Medicine, endometriosis can be found in one-quarter to one-half of women who experience infertility.

Estrogen is generally thought to aggravate and be linked with endometriosis, as symptoms drastically improve in the menopausal years and after hysterectomy.

Endometriosis Development

Because endometriosis is hormone-dependent and progressive, it is often diagnosed during the reproductive years in women from 25 to 35 years of age. Pain is thought to be due to misplaced tissue from the endometrium that relocates in the pelvis or elsewhere in the body.

Within the pelvis, common sites for displaced tissue include the ovaries, fallopian tubes, uterine ligaments, areas between vagina and rectum, and the outer surfaces of uterus.

Outside of the pelvic cavity, misplaced endometrial tissue can be found in the bladder, rectum, bowel, vagina, cervix, vulva, and within internal surgical scars. The misplaced tissue responds to monthly hormones and can cause swelling, pain and scar tissue.

Endometriosis Risk Factors

Factors that increase the risk of a woman developing endometriosis include:

  • Nulliparity (no naturally-born children) or having children after age 30
  • Having a first-degree relative with the disease (mother, daughter, sister)
  • Caucasian race
  • Early menarche/late menopause
  • Short or prolonged menstrual cycles
  • Environmental toxins like certain pesticides
The protective factors that may decrease the risk of endometriosis include:
  • Multiple births
  • Extended intervals of lactation
  • Late menarche (after age 14 years)
  • Use of hormonal contraceptives

Endometriosis Pathology and Symptoms

Biologic factors that are hypothesized to lead to endometriosis include:

  • Retrograde menstruation - tissue backs up from fallopian tubes to abdomen
  • Changes in the immune system
  • Genetics and family history
The pain that occurs with endometriosis is hypothesized to be due to an inflammatory reaction from the misplaced tissue and the aggravation of ovarian hormones. Symptoms often associated with endometriosis include: painful menstrual cramps (dysmenorrhea), painful urination or bowel movements during menstruation, pain during intercourse (dyspareunia), heavy menstrual bleeding, and temporary or permanent infertility.

Diagnosis of Endometriosis

After ruling out other causes, treatment can be started for endometriosis with clinical suspicion only. A transvaginal ultrasound (TVUS) may be performed; however, to definitively diagnose endometriosis, a laparoscopy must be performed. A laparoscopy is an outpatient surgery in which a thin laparoscope is inserted through a small incision in the abdominal wall to view the pelvic area. This allows the surgeon to see the misplaced endometrial tissue and allows staging of the disease (location, extent, depth of tissue growths). Abnormal tissue may be removed for biopsy during the procedure. Other procedures may include CT scan or MRI.

Endometriosis is staged levels I-IV, (minimal to severe), but this does not necessarily predict the pain severity. Pain can be minimal or severe in any stage.

Medication Treatments for Endometriosis

The primary goals of treatment for endometriosis include: pain relief, reduction or clearance of endometrial tissue, slowing of disease progression, and return to normal anatomy. Options include drug therapy or surgery, and take into consideration whether or not a woman desires pregnancy. Medication is typically preferred before choosing surgery as an option.

For pain control and to help slow disease progession, a number of treatments are available:

Treatment: NSAIDs

Oral NSAIDs are often used empirically for acute, mild pelvic or abdominal pain in suspected endometriosis. NSAIDs inhibit prostaglandins and lower inflammation and pain theorized to be involved in endometrial growths; however, they have no effect on hormonal levels. In addition, NSAIDs can be easily combined with hormonal contraceptives and other therapies as needed for breakthrough pain.

No individual NSAID has been shown to be superior in endometriosis; selection should be based on preferences for dosing frequency, possible side effects and costs. NSAIDs and/or contraceptives may be all that is needed for mild pain in endometriosis. However, for long-term use be sure to review GI, heart and kidney warnings for use of all NSAIDs with your patients.

Ruling Out Other Complications

Other suspected complications that may be considered in the differential include pelvic inflammatory disease (PID), ovarian cysts, irritable bowel syndrome, fibroids (leiomyomas), adenomyosis, and interstitial cystitis.

Laboratory tests such as a CBC with differential, erythrocyte sedimentation rate, urinalysis, and testing for STDs may be obtained to rule out an infectious or inflammatory process. An ultrasound may be used to visualize the pelvic organs to look for a mass.

Treatment: Hormonal Contraceptives

Oral hormonal contraceptives are considered first-line therapy for endometriosis and pain control.

Oral contraceptives inhibit production of estrogen via negative feedback and lessen endometrial tissue build-up. Low-dose, continuous or cyclic oral contraceptives can steadily inhibit ovarian hormones and suppress endometrium growth, although breakthrough bleeding may occur in the first few months.

Limitations to hormonal contraceptive use may be side effects related to thromboembolic disease in women, especially in smokers over age 35 years, and the possible return of endometriosis upon discontinuation.

Treatment: Gn-RH Agonists

If pain is moderate-to-severe and is not controlled with NSAIDs and/or hormonal contraceptives, a gonadotropin-releasing hormone (Gn-RH) agonist may be used. In addition, Gn-RH agonists have been shown to lessen the size of ectopic implants, although they will not effect fertility. Gn-RH agonists can be used empirically or after laparoscopy. Gn-RH agonists stop ovarian hormonal production, creating a drug-induced 'menopause'.

Common Gn-RH agonists include:

Select each drug above for detailed prescribing information.

Side Effects: Gn-RH

Gn-RH agonist treatment is limited to six months due to side effects such as vasomotor symptoms (flushing, vaginal dryness), headache and early bone loss. However, treatment can be lengthened when a Gn-RH agonist is used with a daily oral 'add-back' therapy (such as norethindrone 5 mg; or conjugated estrogen 0.625 mg plus medroxyprogesterone 5 mg). Lupaneta Pack is a combination package of leuprolide depot and norethindrone tablets, but it is very costly; it is more affordable to combine these generically. Use of Lupaneta Pack for longer than a total of 12 months is not recommended.

Gn-RH treatment can be expensive and may be a limiting factor for some women. Also, when early bone loss is a concern, progestins may be a preferred option.

Treatment: Progestins

Progestins are effective as monotherapy in the treatment of pain due to endometriosis; however some women may not tolerate treatment due to side effects such as weight gain, bleeding, spotting, breast tenderness, or mood changes/depression. Progestin options include:

Progestins are effective in roughly 75 percent of women with endometriosis. The levonorgestrel IUD may be especially effective in women with more severe disease and does not have to be replaced for 5 years.

Side Effects: Progestins

A lowering of bone density is a serious concern with long-term use of high-dose oral medroxyprogesterone or the depot form, although bone density may improve if treatment is stopped.

Higher dose norethindrone can negatively affect lipids by increasing LDL/HDL ratio and triglycerides. Laboratory monitoring for lipids and bone mineral density may be needed for long-term treatment.

Other common side effects include weight gain, spotting, and mood changes. The levonorgestrel IUD may be preferable if bone density or lipids are a concern.

Treatment: Danazol

Due to a bothersome side effect profile, androgen therapy like danazol is usually reserved for 4th-line therapy of endometriosis, after hormonal contraceptives, Gn-RH agonists, and progestin therapy. The danazol mechanism is via suppression of the hypothalamic-pituitary-ovarian axis which leads to amenorrhea and subsequent clinical effect.

Androgen side effects such as hirsutism (facial hair growth), acne, decreased breast size, weight gain, mood changes, and male-pattern hair loss may occur with danazol use. In addition, clinical reports have linked danazol with the occurrence of ovarian cancer.

Treatment: How to Choose

There are no definitive clinical trials that prove that one medical therapy is superior to another for pain control or maintenance of fertility in endometriosis. Therefore, treatment should be a shared decision between doctor and patient, taking into account the age of the patient, severity of pain, extent of disease, whether a woman desires contraception or pregnancy, drug preferences, side effect profiles, and cost concerns.

In women who have severe acute, disease or anatomical abnormalities, surgery may be the preferred treatment.

Recent studies have suggested that women with a diagnosis of endometriosis may be at a higher risk for heart disease, as well, so assessment of this condition may be needed.

Endometriosis: Costs of Treatment

Healthcare providers should discuss insurance coverage and cost concerns with patients prior to prescribing medications for endometriosis.

Birth control, NSAIDs, and generic progestins can be more affordable for many patients. However, brand name products and newer treatments without generics can be very expensive if paying cash, often in the thousands of dollars. In addition, some products are only available via a specialty pharmacy. A levonorgestrel IUD, while expensive initially, may be fully covered by insurance and only needs replacement every 5 years. Some pharmaceutical companies may offer a patient assistance program to those who qualify.

Join Other Women in the Fight

While treatments are available for endometriosis, for many women it is a chronic condition that requires ongoing control. Seeking out others with similar challenges can add strength to your patient's ongoing medical care.

Women worldwide can join the Endometriosis Support Group to share concerns, ask questions, and stay on top of breaking news.

Finished: Endometriosis: A Healthcare Professional's Guide

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