eMedicine Specialties > Pediatrics: Surgery > Gynecology
Endometriosis: Treatment & Medication
Updated: May 15, 2006
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
- The dependence of endometriosis on the woman's cyclic production of menstrual cycle hormones provides the basis for medical therapy.
- Medications currently recommended include gonadotropin-releasing hormone (GnRH) agonists, progestins, oral contraceptive pills, and androgens. Each of these interrupts the normal cyclic production of reproductive hormones. There is some data supporting the use of aromatase inhibitors for refractory or recurrent endometriosis.
Surgical Care
Surgical efforts are aimed at removal of the endometrial implants and correction of anatomic distortions.
- Implants can be ablated using either laser energy or electrosurgical techniques.
- Resection of the implants and adjacent peritoneum is considered the treatment of choice by some authors.
- A radical surgical approach involves total hysterectomy and bilateral salpingo-oophorectomy. This is generally reserved for women who have completed their reproductive career or for women with severely disabling pain that is unresponsive to more conservative approaches.
Consultations
- Consultation with an obstetrician/gynecologist is generally recommended when this diagnosis is suggested.
- If extensive disease is present, specialists in reproductive endocrinology, urology, colorectal surgery, and even gynecologic oncology may be required.
Medication
Medications for the treatment of endometriosis fall into 1 of 5 categories: GnRH agonists (GnRH analogs), progestins, oral contraceptive pills, androgens, and aromatase inhibitors. Evidence for the use of aromatase inhibitors is currently very limited.
Gonadotropin-releasing hormone analogs
Normal menstrual cycles rely on pulsatile delivery of GnRH to the pituitary. The GnRH analogs (agonists) supply constant stimulation of the pituitary receptors, leading to down-regulation and eventual suspension of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. This suspension results in a profound hypoestrogenic state, similar to menopause. Because endometrial implants are dependent on estrogen stimulation, they subsequently regress. Because of hypoestrogenic adverse effects, the use of these drugs is limited to 6-months duration. The use of so-called add-back therapy, addition of low-dose estrogen with or without a progestin, for prolonged therapy has been investigated. The results are mixed, and, currently, a sound recommendation cannot be made. The expense of GnRH analogs is a significant limitation to their long-term use. GnRH agonists should be used with caution in adolescents younger than 16 years because of adverse effects on bone density.
Leuprolide acetate (Lupron, Lupron Depot)
Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels. Available in a daily SQ dosing regimen and the much more convenient monthly IM depo formulation. A 3-month depo dosing formulation is also available, but experience is limited for endometriosis.
Adult
3.75 mg IM qmo
11.25 mg IM q3mo
Not recommended for more than a total 6-mo treatment period without add-back therapy
Pediatric
Adolescents: Administer as in adults
None reported
Documented hypersensitivity; pernicious anemia; prepubertal patients
Pregnancy
X - Contraindicated in pregnancy
Precautions
Resulting hypoestrogenic state can lead to serious medical consequences if of a prolonged duration; significant bone mineral loss commonly occurs with even a 6-mo course but quickly recovers after discontinuation of the drug; bone density surveillance is usually not indicated for therapy of normal duration
Nafarelin (Synarel)
Analog of GnRH that is approximately 200 times more potent than natural endogenous GnRH. Upon long-term administration, suppresses gonadotrope responsiveness to endogenous GnRH, thereby reducing secretion of LH and FSH, which in turn reduces ovarian and testicular steroid production.
Available as nasal solution (2 mg/mL). Administration is delivered via a nasal spray, which requires bid dosing; otherwise similar to the other drugs in this category.
Adult
200 mcg (1 spray) in 1 nostril in the am and 1 spray in the alternate nostril in the pm
Pediatric
Adolescents: Administer as in adults
None reported
Documented hypersensitivity; pernicious anemia; prepubertal patients
Pregnancy
X - Contraindicated in pregnancy
Precautions
Resulting hypoestrogenic state can lead to serious medical consequences if of a prolonged duration; significant bone mineral loss commonly occurs with even a 6-mo course but quickly recovers after discontinuation of the drug; bone density surveillance is usually not indicated for therapy of normal duration
Goserelin (Zoladex)
Administered monthly as an SC implant in the upper abdominal wall; otherwise similar to the drugs in this class.
Adult
Implant: 3.6 mg SC q28d
Pediatric
Adolescents: Administer as in adults
None reported
Documented hypersensitivity; pernicious anemia; prepubertal patients
Pregnancy
X - Contraindicated in pregnancy
Precautions
Resulting hypoestrogenic state can lead to serious medical consequences if of a prolonged duration; significant bone mineral loss commonly occurs with even a 6 mo course, but quickly recovers after discontinuation of the drug; bone density surveillance is usually is not indicated for therapy of normal duration
Progestins
Use of this category of drugs relies on high-dose hormones to suppress the hypothalamus through negative feedback. This results in a hypoestrogenic state. Evidence for direct inhibition of endometrial implants by progestins also exists. These medications provide pain relief equivalent to the GnRH analogs and seem to have a slightly lower recurrence rate.
Norethindrone acetate (Aygestin, Norlutate)
A common progestin used in many of the PO contraceptive pills currently available; dose for endometriosis is significantly higher.
Adult
5 mg PO qd for 2 wk, then 10 mg PO qd for 2 wk; followed by 15 mg PO qd to complete a total of 6 mo of therapy
Pediatric
Adolescents: Administer as in adults
Phenobarbital, phenytoin, aminoglutethimide, paramethadione, carbamazepine, troglitazone, rifampicin, rifampin, and griseofulvin induce enzymes that may decrease levels of contraceptive steroids; PO anticoagulants may increase thromboembolic potential
Documented hypersensitivity; cerebral apoplexy; undiagnosed vaginal bleeding; thrombophlebitis; liver dysfunction
Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in impaired liver function, CHF, and HTN; patients may notice weight gain (usually lean body mass), worsening of acne, and depressed mood; while these drugs are frequently listed as those increasing the risk of thromboembolic disease, this was because of their associated use in PO contraceptive pills; no currently available evidence suggests that progestins when used alone increase the occurrence of these events
Medroxyprogesterone acetate (Amen, Cycrin, Provera, Depo-Provera)
Common progestin available in both a PO and a depo form; efficacy and adverse effects are similar to norethindrone.
Adult
10-30 mg PO qd for a 6-mo treatment period
150-400 mg IM q1-3mo for a 6-mo treatment period
Note: 150 mg/mo IM (contraceptive dose) can sometimes be used for prolonged periods as maintenance after the 6-mo therapeutic dose
Pediatric
Adolescents: Administer as in adults
Aminoglutethimide and rifampin may increase hepatic clearance, thus decreasing efficacy
Documented hypersensitivity; known progestin-dependent tumors; undiagnosed vaginal bleeding; thrombophlebitis; liver dysfunction
Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in impaired liver function, CHF, and HTN; patients may notice weight gain (usually lean body mass), worsening of acne, and depressed mood; while these drugs are frequently listed as increasing the risk of thromboembolic disease because of their associated use in PO contraceptive pills, currently no available evidence suggests that progestins not in combination with estrogens increase the occurrence of these events
Oral contraceptive pills
OCPs are generally progestin dominant and work to suppress the hypothalamic-ovarian axis and, thus, endometriosis implants. Clinically, they probably work better for suppression of the disease rather than actual therapy. Some patients gain significant pain relief with this class of medication, especially when the pills are taken continuously (ie, the patient skips the placebo week of each 28-day pack, going directly to the next pack's first active pill).
Desogestrel and ethinyl estradiol (Desogen)
Reduces the secretion of LH and FSH from the pituitary by decreasing amount of gonadotropin-releasing hormones. This is one example of an OCP. All the modern formulations are equally efficacious, although some of the newer (so-called third-generation) pills have a larger progestin effect and might offer greater efficacy.
Adult
1 tab PO qd to complete the pack; some authors suggest using active pills daily, without the usual hormone-free 7-d period; risks and benefits of this regimen have not been well studied
Pediatric
Adolescents: Administer as in adults
May reduce hypoprothrombinemic effects of anticoagulants; estrogen levels may be reduced with coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes; an increase in corticosteroid levels may occur when administered concurrently with ethinyl estradiol; use of ethinyl estradiol with hydantoins may cause spotting, breakthrough bleeding, and pregnancy; increase in fluid retention caused by estrogen intake may reduce seizure control; antibiotics may alter GI flora and cause a reduction in absorption of PO contraceptives, which may reduce efficacy
Documented hypersensitivity; prepubertal girls; undiagnosed vaginal bleeding; known hormonally sensitive cancers; active liver disease; history of thromboembolic disorders; family history of thromboembolic disorders, use caution
Pregnancy
X - Contraindicated in pregnancy
Precautions
Monitor patients for evidence of increased blood pressure and thromboembolic disease; appropriately evaluate any reports suggestive of thromboembolic disease
Androgens
These medications work to suppress both the hypothalamic-ovarian axis and endometriosis at a local level.
Danazol (Danocrine)
Synthetic steroid analog with strong antigonadotropic activity (inhibits LH and FSH) and weak androgenic action. Androgens, although efficacious, have fallen out of favor because of their unpleasant adverse effects and because newer medications work as well or better. These drugs may represent a less expensive alternative, or better choice, for certain patients and remain part of the armamentarium. Danazol requires at least 3-6 mo to determine effectiveness.
Adult
100-400 mg PO bid for 3-6 mo, then adjust dose
Pediatric
Adolescents: Administer as in adults
Decreases insulin requirements and increases effects of anticoagulants; may increase carbamazepine levels
Documented hypersensitivity; seizure disorders; hepatic or renal insufficiency; lactation; conditions influenced by edema; undiagnosed genital bleeding; porphyria
Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in migraine headaches, impaired liver function, CHF, and seizure disorders; cause weight gain, hirsutism, virilization, and acne; thromboembolic disease may be increased
Aromatase Inhibitors
These medications work by blocking the aromatase activity in extraovarian sites that suppress the conversion of androstenedione and testosterone to estrogen. This action may result in suppression of endometriosis at a local level.
Letrozole (Femara)
Competitive inhibitor of the aromatase enzyme system. This leads to a reduction in plasma estrogen levels in postmenopausal women. Although used extensively in breast cancer treatment, experience to date in endometriosis management is limited. May decrease pain in patients whose conditions have previously failed other treatments. Although initial results appear promising, further studies are required to establish the role of aromatase inhibitors in the management of endometriosis.
Adult
2.5 mg PO qd for 6 mo; administer with norethindrone acetate 2.5 mg PO qd
Adjust dose for patients with severe hepatic impairment
Pediatric
Adolescents: Not studied
Strong inhibitor of CYP450 2A6, moderate inhibitor of CYP450 2C19; increases the effects of CYP2A6 substrates (eg, dexmedetomidine, ifosfamide); coadministration with tamoxifen reduces letrozole plasma levels by 38%
Documented hypersensitivity
Pregnancy
D - Unsafe in pregnancy
Precautions
Caution in impaired liver function, impaired renal function, seizure disorder, and cardiac or pulmonary disease; may cause vasomotor symptoms, dizziness, fatigue, or loss of bone density; patients should be cautioned before operating machinery or driving
More on Endometriosis |
| Overview: Endometriosis |
| Differential Diagnoses & Workup: Endometriosis |
 Treatment & Medication: Endometriosis |
| Follow-up: Endometriosis |
| Multimedia: Endometriosis |
| References |
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References
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Kontoravdis A, Hassan E, Hassiakos D, et al. Laparoscopic evaluation and management of chronic pelvic pain during adolescence. Clin Exp Obstet Gynecol. 1999;26(2):76-7. [Medline].
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Further Reading
Keywords
endometriosis, secondary dysmenorrhea, endometriosis externa, endometrioma
