Endometriosis: Not for adults only

June 9, 2020
Marc Laufer, MD

,
Jessica Y. Shim, MD

Volume 65, Issue 06

Endometriosis is classically diagnosed by presence of endometrial glands and stroma outside the uterine lining. While it may be a more common entity diagnosed among adults, endometriosis is the leading cause of secondary dysmenorrhea and chronic pelvic pain in adolescents.1

The symptoms can be debilitating, limiting adolescents in their participation in school or extracurricular activities.2 The presentation of endometriosis in this population also can be misleading, as its signs and symptoms differ from those in adult women.

Awareness of and early intervention in adolescent endometriosis is critical to avoid diagnostic delay and progression of disease.

Evaluation of endometriosis

Evaluation of endometriosis begins in the office with a thorough medical history. Unlike adults, adolescents rarely present with endometriomas or infertility.

Endometriosis most commonly is identified in adolescents who present with pelvic pain. In a survey of adult women affected by endometriosis, two-thirds of respondents reported their first pelvic symptoms before age 20, and one in three women had pain before age 15.3

While endometriosis is typically considered to be a disease that manifests after years of menstruation, symptomatic cases have been reported prior to menarche without an associated obstructive anomaly, and also as soon as one month after menarche.4,5 These instances suggest alternative hypotheses to Samson’s theory on retrograde menstruation as the cause of endometriosis.

Endometriosis in adults presents with dysmenorrhea but adolescents may exhibit other symptoms. A study from our institution in the 1990s identified that the classic adult symptom of cyclic pain was present by itself in only 9.4% of adolescents, whereas 28.1% of patients had acyclic pain alone, and 62.5% had both cyclic and acyclic pain.6

Therefore, the majority of adolescents with endometriosis (90.6%) had acyclic pain.6 Endometriosis is also associated with gastrointestinal (GI) symptoms such as diarrhea or constipation, and urinary symptoms such as urgency and dysuria.

In a case series of adolescents with laparoscopically diagnosed endometriosis, over half the patients reported at least one GI symptom (56%) or one genitourinary symptom (52%).7

Adolescents affected by endometriosis also have a higher prevalence of migraines compared to their peers without endometriosis.8

Several red flags in a patient’s history should raise suspicion for endometriosis. Endometriosis appears to have a hereditary component; a young woman with a first-degree relative affected by endometriosis has a four to seven times higher risk of developing endometriosis than that in the general population.9

A history of childhood sexual and physical abuse has also been found to have an association with increased risk of endometriosis.10

Endometriosis is associated with obstructive Mullerian anomalies, such as imperforate hymen, transverse vaginal septum, and agenesis of the lower vagina. Even if a patient were to have surgical correction of an obstructive anomaly, that might not resolve their risk of endometriosis.11

A recent systematic review of observational, population-based studies suggests an increased comorbidity risk of autoimmune diseases including systemic lupus erythematosus, Sjögren’s syndrome, rheumatoid arthritis, autoimmune thyroid disorder, celiac disease, multiple sclerosis, inflammatory bowel disease, and Addison’s disease.12

After obtaining a thorough history, a physical exam should be performed to assess for any other etiologies of the pain; these may include gastrointestinal, urinary, or musculoskeletal etiologies, or a pelvic mass or reproductive tract anomaly. In an adolescent, particularly one who has no genital complaints, a pelvic exam is not always necessary.

Uterosacral nodularity or distorted anatomy are findings of more advanced stage or deep infiltrating disease, which is less common in adolescents. If there is concern for an obstructive anomaly or a mass, a rectal-abdominal exam may be performed, or a Q-tip can be inserted into the vagina to assess for vaginal patency.

A physical exam may not exclude endometriosis, but it is an opportunity to exclude alternative explanations for a patient’s complaints.

Imaging does not need to be routinely obtained in adolescents with dysmenorrhea, but ultrasound imaging may be helpful when other gynecologic pathologies such as an adnexal cyst, torsion, or a reproductive tract anomaly need to be excluded.

Transvaginal imaging is unnecessary and invasive, and it can be traumatic for a younger and/or non-sexually active teen; a transabdominal ultrasound (U/S) of the pelvis is acceptable. Magnetic resonance imaging may be indicated if the exam or U/S findings are concerning for a complex congenital anomaly of the reproductive tract.

More than likely, endometriosis will not be appreciated on imaging as it is typically superficial peritoneal disease (stage I or II disease) and only deeply infiltrative disease, adhesions or endometriomas will be appreciated on U/S. In addition, endometriomas are less common in adolescents than in adults.13

Currently, there are no specific blood tests or serum markers to identify endometriosis. Other laboratory tests that may be helpful to obtain include a pregnancy test, sexually transmitted infection testing, and a urinalysis.

Diagnosing endometriosis

A clinical diagnosis of endometriosis should be considered if the evaluation of the patient’s symptoms, history, physical examination, and/or imaging raise suspicion.

A recent call to action proposes moving from a histological diagnosis of endometriosis to a clinical diagnosis. This shift in focus may help lessen diagnostic delay, and it emphasizes the chronic, inflammatory, and progressive nature of endometriosis.14

When there is a concern for endometriosis, a trial of nonsteroidal anti-inflammatory drugs, progestin-only or estrogen/progestin therapy should be offered.

We do not routinely initiate a first-line trial of empiric gonadotropin-releasing hormone (GnRH) agonist or antagonist therapy in adolescents due to the potential detrimental effects on bone marrow density with long-term use. A trial of combination estrogen/progestin or progestin therapy is typically at least 3 months in duration.

If a patient’s pain persists despite medical therapy, laparoscopy should be considered for definitive diagnosis and surgical management. Adolescents may experience debilitating symptoms that limit their school and social activities; in these scenarios, laparoscopy may be indicated prior to 3 months of medical therapy.

If pain persists on one combination pill, changing to another pill is not usually useful and will only delay diagnosis and surgical treatment. Laparoscopy is supported by the American College of Obstetricians and Gynecologists.15

The provider should feel comfortable operating on adolescents and knowledgeable about the visual appearance of superficial peritoneal lesions typically found in adolescents (Figures 1 to 3). The variable appearance of endometriosis has been described in the revised American Society for Reproductive Medicine Classification of Endometriosis.15 Red and clear vesicular lesions are frequently appreciated in adolescent endometriosis and are often the most painful lesions.16

“Powder-burn” lesions represent older, more advanced implants and are less commonly identified in adolescents. We have found that adjusting the magnification and moving the laparoscope closer to the peritoneum may identify subtle lesions.17

Another technique for visualization of lesions is by filling the pelvis with irrigation fluid (e.g. normal saline or lactated Ringer’s) and submerging the laparoscope underneath the fluid; subtle, clear lesions may be seen floating under the fluid.18 If no suspicious lesions are identified, random cul-de-sac biopsies may be beneficial as endometriosis may be microscopic in appearance.19

Management of endometriosis

There is no medical or surgical cure for endometriosis. Surgery can provide significant pain relief, but because there is no cure from surgery, medical therapy is needed after surgery.

During surgery, after identification of endometriotic lesions in the pelvis, the surgeon should feel comfortable with destroying/removing as much of the disease as possible and attempting to restore normal anatomy. Lysis of adhesions should also be performed if needed.

Implants can be treated via electrocautery, endocoagulation, laser ablation, or excision. At our institution, we destroy superficial peritoneal disease with a monopolar L-hook electrode instrument, and excise deeper infiltrating lesions. “Radical excisional surgery” or “peritoneal stripping” should not be used in adolescents as it may increase extensive adhesive formation and has not been shown to have clinical benefit.20

Patients should be managed after surgery with medical therapy to prevent recurrence or progression of disease. Combined surgical-medical management has been demonstrated to retard disease progression in adolescents who elected a subsequent laparoscopic procedure.21

We recommend that patients to stay on hormonal therapy long -term until they want to become pregnant. Hormonal therapy includes combination estrogen/progestin therapy, progestin-only therapy, exogenous androgens, and GnRH agonists or antagonist.

When prescribing continuous combination oral contraceptives (COC), we prefer to use monophasic regimens because multiphasic regimens will be less successful in suppressing menstruation. There are no data suggesting one combination estrogen/progestin pill formulation treats endometriosis-associated symptoms better than another.

Alternatives to COCs, including the vaginal ring and transdermal patch, are also acceptable and may be more tolerable for patients who are not compliant with daily pill use. All these methods can be administered in extended fashion or continuously to suppress menses and endometriosis-associated pain.

Progestin-only methods include the “mini-pill,” (norethindrone), norethindrone acetate, medroxyprogesterone acetate, the etonogestrel implant, and the levonorgestrel intrauterine system (LNG-IUS). Norethindrone acetate (5-15 mg daily) is an effective treatment that can be titrated to achieve amenorrhea and pain relief.22

Norethindrone acetate is different from norethindrone in that it is not a US Food and Drug Administration-approved contraceptive, and there is small peripheral conversion of norethindrone acetate to ethinyl estradiol.23 Medroxyprogesterone acetate can be used, with administration every 3 months, in intramuscular or subcutaneous formulation.

Patients may experience unwanted side effects from progestins, such as irregular bleeding, weight gain, and mood changes; we therefore recommend a trial of oral progestins prior to injectables or long-acting reversible contraception as these can be quickly discontinued if poorly tolerated.

Limited studies have evaluated use of the implant or the LNG-IUS in adolescents with endometriosis, but both treatments appear to be effective in reducing endometriosis-associated pain.24

We have noticed the systemic level of hormone from the LNG-IUS may not be high enough to treat endometriosis-associated pain and potential disease progression, therefore we often use the device in conjunction with continuous low-dose estrogen/progestin or progestin-only therapy.25

In our experience, adolescents have tolerated the LNG-IUS well and we offer placement in the outpatient setting or at time of laparoscopy, to eliminate the possible insertional pain. We do not routinely use the subdermal implant given the risk of unwanted menstrual changes.26

Exogenous androgens used in treatment of endometriosis include danazol and methyltestosterone. Both of these methods have effects that are dose-dependent, such as acne, hirsutism, and weight gain, and some that may be irreversible, such as deepening of the voice.27

We do not routinely prescribe these medications due to their side effect profiles, however, transgender male patients may find these side effects desirable and preferable compared to the side effects from estrogen/progestin or progestin-only therapies.28

Second-line options for treatment of adolescent endometriosis-associated symptoms include GnRH agonists or antagonists. GnRH agonist therapy is generally reserved for adolescents above age 16 because of the potential detrimental effects on bone mineral density (BMD).

GnRH agonists are available in many formulations, but we prefer the nasal spray or the 3-month injectables to improve patient compliance. When starting GnRH agonist therapy, patients should be warned about the “flare effect;” pain and withdrawal bleeding may occur 21 to 28 days post-initiation due to an initial production of follicle stimulating hormone and luteinizing hormone prior to down-regulation.29

If pain and bleeding persist beyond the first month, obtaining estradiol levels may be helpful in determining if up-titrating the GnRH agonist is necessary.

Add-back therapy should be initiated with the start of GnRH agonist therapy to decrease hypoestrogenic side effects. We found the combination of norethindrone acetate (5 mg/day) plus conjugated equine estrogen (0.625 mg/day) add-back to be more effective for increasing total body BMD compared to norethindrone acetate monotherapy.30

COCs are not an appropriate add-back therapy as they negate the effects of the GnRH agonist. Bone density surveillance should be performed with dual energy X-ray absorptiometry, beginning at 8 months and repeating at least every 2 years on therapy. Discontinuation of GnRH agonist therapy is advised if a patient experiences unwanted symptoms or a decrease in BMD.

GnRH antagonists are a newer alternative to agonist therapies. The oral antagonist Elagolix is approved for moderate to severe endometriosis-related pain, however, its clinical trials did not include adolescents younger than age 18.31

Antagonist therapies are effective immediately and do not cause a “flare effect.” Elagolix does not always suppress ovulation and is not approved as a contraceptive. In addition, women may still experience menstrual bleeding as the incidence of amenorrhea varied from 13.9 to 65.6% in their clinical trials.32

Other treatments include use of aromatase inhibitors. The use of letrozole has been endorsed by ACOG as an option for treatment of endometriosis-associated pain.33

Complementary treatments can be helpful in addition to medical management of endometriosis. Japanese-style acupuncture is an effective and safe adjunct therapy for adolescent endometriosis.34

A multidisciplinary approach to endometriosis is also helpful and includes referral to pain medicine and physical therapy specialists to address pelvic pain sensitization and pelvic floor trigger point pain.

While alternative therapies warrant further research, it should be emphasized that medical therapy is the mainstay to prevent progression of disease.

Conclusion

Endometriosis is a chronic and currently incurable disease with frequent onset in adolescence. Early diagnosis and intervention can help prevent progression of the disease and significantly improve quality of life.

A variety of surgical, medical, and complementary treatment modalities exist to help manage endometriosis. Treatment should be tailored to the individual adolescent, to improve patient compliance and decrease any unwanted side effects.

In our experience, in most clients diagnosed early, disease progression can be retarded, one surgical procedure is performed during their lifetime, and they have no difficulty conceiving a pregnancy.

Adolescents can obtain patient educational information on endometriosis at youngwomenshealth.org and bostoncenterendometriosis.org with specific information relating to the diagnosis, treatments emotional support, and college planning.

We also offer monitored, monthly chat rooms for safe, educational, and age-based discussions at youngwomenshealth.org.

References

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