Medication for endometriosis and uterine fibroids: Elagolix and other treatments
Elagolix is a new option for treating endometriosis and uterine fibroids
Endometriosis and uterine fibroids are common conditions affecting women most often during their reproductive years. Both conditions can cause severe cramps, abdominal and lower back pain, as well as heavy or abnormal menstrual bleeding. Treatment options include pain relievers, hormones, and surgery. A new oral medicine elagolix (Orilissa) has been approved for use and may offer effective relief. However, it is not without potential side effects and interactions with other medications. A person’s genetics play an essential role in how they respond to elagolix. A precision medicine approach, using pharmacogenetic testing, can help when evaluating different treatment options to find the safest, most effective medication for endometriosis and uterine fibroids.
Underlying hormones of endometriosis and uterine fibroids
Both uterine fibroids and endometriosis are caused by hormonal disbalance. Estrogen and progesterone are two hormones that stimulate the development of the uterine lining during each menstrual cycle and impact the risk of these conditions. Estrogen and testosterone levels are regulated by the gonadotropin-releasing hormone (GnRH). High GnRH levels increase testosterone levels, triggering the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Disbalance in the GnRH function can lead to uterine fibroids or endometriosis. Uterine fibroids are benign growth bodies that can lead to heavy menstrual bleeding and anemia. Excessive estrogen and progesterone levels stimulate the growth of fibroids. Endometriosis is characterized by abnormal tissue growth in fallopian tubes and ovaries and can affect fertility.
Types of medication for endometriosis and uterine fibroids
Endometriosis is treated with drugs that inhibit gonadotropin-releasing hormone function (called GnRH antagonists) such as elagolix. Elagolix works by reducing the production of LH and testosterone.
Contrastingly, uterine fibroid treatment frequently requires drugs that stimulate GnRH production or activate gonadotropin-releasing hormone receptors. These drugs (called GnRH agonists) work by increasing LH and FSH production. GnRH agonists include leuprolide (Lupron, Eligard), goserelin (Zoladex) and triptorelin (Trelstar, Triptodur). These drugs stop menstruation and help to shrink fibroids.
Ironically both GnRH agonists and antagonists can produce similar side effects such as hot flashes, night sweats, and other menopausal symptoms. Other side effects of elagolix are insomnia, anxiety, joint pain, depression, and mood changes.
Genetics plays an important role in selecting treatment
Just as genetics can affect your eye colour, genetics can also affect how you respond to medications. Because of small variations in DNA, two people can take the same dose of the same drug but respond in very different ways. Specific genes in our DNA determine the activity of enzymes that metabolize drugs in the liver. Understanding your genetic profile for these enzymes can hold the key to knowing which medications and dosages will be safest and most effective for you. The following sections outline risk factors for elagolix as well as the genetic drug-metabolizing enzymes involved in medication for endometriosis and uterine fibroids.
Elagolix is prescribed to women of reproductive age, but it is not a contraceptive and should not be used during pregnancy. Other contraindications for this drug include osteoporosis, severe liver impairment, and the use of other medications that can inhibit elagolix metabolism, such as ciclosporin and gemfibrozil. These drugs block liver enzymes CYP3A4 and SLCO1B1, which are involved in the metabolism of elagolix. Elagolix can also reduce the efficacy of statins (medicines used to lower cholesterol levels), which are also metabolized by these enzymes.
Genetic variations in these enzymes can impact the effectiveness of elagolix and affect the risk of side effects. About 15% of people in North America have reduced the CYP3A4 function, while 18% have reduced the SLCO1B1 function. Clinical studies have shown that women with significantly reduced SLCO1B1 function have dramatically increased elagolix blood concentration, making it likely they will experience more severe side effects. If you are starting elagolix medication for endometriosis and uterine fibroids or are experiencing side effects, you and your doctor should consider a pharmacogenetic test such as Pillcheck. Pharmacogenetic testing can help to determine drug tolerability and alternative treatment options. Pillcheck assesses your body’s metabolism for medications and your risk of side effects, especially if you have other prescriptions as well.
Pharmacogenetic-guided medication for endometriosis and uterine fibroids
For women with reduced CYP3A4 or SLCO1B1 function, other treatments are available. For example, abarelix, cetrorelix, degarelix, and ganirelix (peptide-based GnRH antagonists) might be preferable as these drugs do not undergo metabolism by liver enzymes. However, peptide-based medications are injectable drugs, while elagolix is an oral pill.
The Pillcheck service includes a prescription review by an expert clinical pharmacist who will provide insights on how the addition of elagolix can impact other medications you may be taking and assess the risk of interactions. Because CYP3A4 is involved in the metabolism of up to 40% of all drugs and might be induced by other drugs and chemicals, it is important to know how your body processes different medications.
Insight on related medications
Pillcheck will also provide insights on your risk of developing depression or blood clots with oral progestin contraceptives (Beyaz, Yasmin, Yaz). Progestin-releasing intrauterine device (IUD) can relieve heavy bleeding caused by fibroids. A progestin-releasing IUD provides symptom relief only and doesn’t shrink fibroids or make them disappear. It also prevents pregnancy. However, progestin-based contraceptives may significantly increase the risk of deep vein thrombosis and stroke in women that carry mutations in the F5 gene (Factor V Leiden) or F2 gene, which encodes the prothrombin factor.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are also useful in relieving pain related to fibroids, but they don’t reduce bleeding caused by fibroids. Furthermore, NSAIDs are known to reduce blood clotting and may worsen menstrual bleeding and anemia. Women who have reduced NSAID metabolism by CYP2C9 enzyme should avoid long-lasting drugs such as meloxicam and require lower doses of ibuprofen and celecoxib to minimize the risk of GI and menstrual bleeding.
Summary
- Elagolix is a new oral treatment option for women with endometriosis and uterine fibroids
- Elagolix has extensive drug-drug and drug-gene interactions
- Pharmacogenetic testing can provide valuable insights on your risk of developing side effects for elagolix and risk of drug-drug interactions
- Pillcheck can also provide valuable insights on your risk of blood clotting with progestin contraceptives which are also used for uterine fibroids treatment
- Pillcheck includes NSAIDs and other medications important for women’s health
Use Pillcheck to get on the right medications and feel better sooner.
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Selected references
Shebley M., et al. Clinical Pharmacology of Elagolix: An Oral Gonadotropin-Releasing Hormone Receptor Antagonist for Endometriosis. Clin Pharmacokinet (2019).
Yvette N. Lamb Elagolix: First Global Approval Drugs. 2018; 78(14): 1501–1508.
Soluny Jean Isolated pulmonary embolism in a patient with progestin intrauterine device and factor V Leiden J Community Hosp Intern Med Perspect. 2019; 9(3): 264–266.
Adolfo Figueiras et al., CYP2C9 variants as a risk modifier of NSAID-related gastrointestinal bleeding: a case–control study Pharmacogenet Genomics. 2016 Feb; 26(2): 66–73.