Endometriosis Medication

  • Author: Dharmesh Kapoor, MBBS, MD, MRCOG; Chief Editor: Michel E Rivlin, MD   more...
 
Updated: Feb 21, 2012
 

Medication Summary

Medical therapy for treating endometriosis involves hormonal therapy. Progestins, combination estrogens/progestins, danazol, and gonadotropin-releasing hormone (GnRH) agonists with or without hormone replacement therapy are some of the medications used. Patients should not begin a regimen of danazol or GnRH agonists unless they are monitored by a gynecologist and have a laparoscopically confirmed diagnosis of endometriosis. Evidence for the use of aromatase inhibitors is currently limited.

Suppression of ovulation and menses often occurs with medical management.

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Oral contraceptives

Class Summary

Combination oral contraceptive pills (COCPs) act by ovarian suppression and continuous progestin administration. Initially, a trial of continuous or cyclic COCPs should be given for 3 months. If the patient pain is relieved, this treatment is continued for 6-12 months. Subsequent pregnancy rates are 40-50% upon discontinuation of the contraceptive pill.

Although individual formulations offer few variations, note that the long-term efficacy of multiphasic preparations remains unproven. In addition, continuous noncyclical administration of COCPs, omitting the placebo menstrual tablets, for 3-4 months helps avoid any menstruation and associated pain.

These agents 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-d pack, going directly to the next pack's first active pill).

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Desogestrel and ethinyl estradiol (Desogen, Ortho-Cept, Velivet, Azurette, Cyclessa)

 

The combination of desogestrel and ethinyl estradiol reduces the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary by decreasing the amount of gonadotropin-releasing hormones (GnRHs). This is one example of an oral contraceptive pill (OCP). All the modern formulations are equally efficacious, although some of the newer (so-called third-generation) pills have a larger progestin effect and may offer greater efficacy.

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Norgestimate/ethinyl estradiol (Ortho-Cyclen, Ortho-Prefest, Ortho Tri-Cycle

 

The combination of norgestimate and ethinyl estradiol reduces the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary by decreasing the amount of gonadotropin-releasing hormones (GnRHs).

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Progestational agents

Class Summary

All progestational agents act by decidualization and atrophy of the endometrium. 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 gonadotropin-releasing hormone (GnRH) analogues and seem to have a slightly lower recurrence rate.

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Norethindrone acetate (Aygestin, Camila, Errin)

 

Norethindrone is a common progestin used in many of the oral (PO) contraceptive pills currently available; the dose administered for endometriosis is significantly higher.

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Medroxyprogesterone (Provera, Depo-Provera)

 

Progestins stop endometrial cell proliferation, allowing organized sloughing of cells after withdrawal. These agents typically do not stop acute bleeding episode, but they produce normal bleeding episodes following withdrawal.

Medroxyprogesterone is a common progestin available in both an oral (PO) and an intramuscular (IM) depo form. The efficacy and adverse effects of this drug are similar to those of norethindrone.

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Megestrol (Megace)

 

Megestrol produces results similar to those of medroxyprogesterone.

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Gonadotropin-releasing hormone analogs

Class Summary

Gonadotropin-releasing hormone (GnRH) analogues produce a hypogonadotrophic-hypogonadic state by downregulation of the pituitary gland. Goserelin and leuprolide acetate are commonly used agonists.

Normal menstrual cycles rely on pulsatile delivery of GnRH to the pituitary. The GnRH analogues (agonists) supply constant stimulation of the pituitary receptors, leading to downregulation 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. Owing to 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, thus, a sound recommendation cannot be made currently.

The expense of GnRH analogues 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.

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Goserelin (Zoladex)

 

Goserelin suppresses ovarian and testicular steroidogenesis by decreasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. This agent is administered monthly as a subcutaneous (SC) implant in the upper abdominal wall; it is otherwise similar to the drugs in this class.

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Leuprolide (Lupron, Lupron Depot, Eligard)

 

Leuprolide suppresses ovarian and testicular steroidogenesis by decreasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. This agent is available in a daily subcutaneous (SC) dosing regimen and the much more convenient monthly intramuscular (IM) depo formulation. A 3-month depo dosing formulation is also available, but experience with its use is limited for endometriosis.

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Nafarelin (Synarel)

 

Nafarelin is an analogue of gonadotropin-releasing hormone (GnRH) that is approximately 200 times more potent than natural endogenous GnRH. Upon long-term administration, this agent suppresses gonadotrope responsiveness to endogenous GnRH, thereby reducing secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn reduces ovarian and testicular steroid production.

Nafarelin is available as a nasal solution (2 mg/mL). Administration of this agent is delivered via a nasal spray, which requires twice daily (bid) dosing; it is otherwise similar to the other drugs in this category.

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Antigonadotropic agents

Class Summary

Antigonadotropic agents work to suppress both the hypothalamic-ovarian axis and endometriosis at a local level and act by inhibiting the midcycle follicle-stimulating hormone (FSH) and luteinizing hormone (LH) surge and preventing steroidogenesis in the corpus luteum. These are the most extensively studied agents for endometriosis. Danazol has been shown to be as effective as any of the newer agents, but it has a higher incidence of adverse effects.

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Danazol

 

Danazol is a synthetic steroid analogue with strong antigonadotropic activity (inhibits luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and weak androgenic action.

However, although efficacious, androgens 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 months to determine its effectiveness.

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Aromatase Inhibitors

Class Summary

Aromatase inhibitors 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.

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Letrozole (Femara)

 

Letrozole is a competitive inhibitor of the aromatase enzyme system that leads to a reduction in plasma estrogen levels in postmenopausal women. Although this agent has been used extensively in breast cancer treatment, experience to date in endometriosis management is limited. Letrozole 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.

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Contributor Information and Disclosures
Author

Dharmesh Kapoor, MBBS, MD, MRCOG  Consultant Gynecologist, Royal Bournemouth Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Elizabeth Alderman, MD  Director of Fellowship Training Program, Director of Adolescent Ambulatory Service, Professor of Clinical Pediatrics, Department of Pediatrics, Division of Adolescent Medicine, Albert Einstein College of Medicine and Children's Hospital at Montefiore

Elizabeth Alderman, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, North American Society for Pediatric and Adolescent Gynecology, and Society for Adolescent Medicine

Disclosure: Merck Honoraria Speaking and teaching

Mark K Y Hiraoka, MD  Assistant Professor of Obstetrics and Gynecology, University of Hawaii, John A Burns School of Medicine; Consulting Staff, Department of Obstetrics and Gynecology, Queen's Medical Center

Mark K Y Hiraoka, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, and Association of Professors of Gynecology and Obstetrics

Disclosure: Nothing to disclose.

G Willy Davila, MD  Chairman, Department of Gynecology, Section of Urogynecology and Reconstructive Pelvic Surgery, Cleveland Clinic Florida

G Willy Davila, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Colorado Medical Society, and Florida Medical Association

Disclosure: American Medical Systems Consulting fee Consulting; Astellas Consulting fee Consulting; Watson Pharma Consulting fee Consulting; CL Medical Consulting fee Consulting; Warner Chilcott Honoraria Speaking and teaching

Specialty Editor Board

Thomas Michael Price, MD  Associate Professor, Division of Reproductive Endocrinology, Director of Reproductive Fellowship Training Program, Duke University Medical Center

Thomas Michael Price, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American Medical Association, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Endocrine Society, Phi Beta Kappa, Society for Gynecologic Investigation, Society for Reproductive Endocrinology and Infertility, and South Carolina Medical Association

Disclosure: Clinical Advisors Group Consulting fee Consulting; MEDA Corp Consulting Consulting fee Consulting; Gerson Lehrman Group Advisor Consulting fee Consulting; Adiana Grant/research funds PI

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Frederick B Gaupp, MD  Consulting Staff, Department of Family Practice, Hancock Medical Center

Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians

Disclosure: Nothing to disclose.

Chief Editor

Michel E Rivlin, MD  Professor, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine

Michel E Rivlin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Mississippi State Medical Association, and Royal College of Surgeons of Edinburgh

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Tod C Aeby, MD,to the development and writing of a source article.

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Powder-burn lesions of endometriosis.
Endometriosis. Chocolate cyst of the ovary.
Endometriosis. Red lesions on the sigmoid colon and cul-de-sac.
Adhesions due to endometriosis.
Endometriosis. Red lesions on various organs.
Active endometriosis with red and powder-burn lesions and adhesions from old scarring.
Scarring due to old disease and active endometriosis.
Endometriosis. Moderate-to-severe disease.
Typical appearance of minimal endometriosis on the uterosacral ligaments. Note that some are pigmented (contain hemosiderin), whereas others are not.
Peritoneal erosions and adhesions in the posterior cul-de-sac. These are typical of more severe endometriosis.
 
 
 
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