Clinical Pearls & Morning Reports
Published July 5, 2017
Endometriosis symptoms include dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia, as well as the less common symptoms of pain at ovulation, constipation, and painful urination. Taylor et al. performed two similar multicenter, double-blind, randomized, placebo-controlled, phase 3 trials of 6-month treatment with elagolix at two doses in women with moderate or severe endometriosis-associated pain. Read the Original Article here.
Q. What are some of the current first- and second-line therapies for endometriosis-associated pain?
A. First-line therapies for endometriosis-related pain include nonsteroidal antiinflammatory drugs and progestin-containing oral contraceptives. Second-line therapies involve injectable depot formulations of gonadotropin-releasing hormone agonists, such as leuprolide acetate.
Q. What are some of the limitations of currently available therapies for endometriosis-associated pain?
A. Although the injectable agents are effective and reduce estrogen levels to postmenopausal levels, they are associated with side effects (e.g., progressive bone loss and severe vasomotor symptoms), which limit their use to 6 months without hormone-replacement therapy. Medical options remain limited. Progestins are associated with bleeding, weight gain, and mood changes, and endometriosis is often associated with progesterone resistance. Androgenic agents such as danazol are associated with acne, hirsutism, and changes in lipid profiles. Surgical ablation or excision of lesions can be effective; however, symptoms often recur within 12 months, and more radical surgery (hysterectomy or oophorectomy) is a last resort. Pain management usually requires repeated courses of medical therapies or multiple surgical treatments until menopause.
A: In the trials by Taylor et al., eligible women were randomly assigned to receive 150 mg of elagolix once daily (lower-dose group), 200 mg of elagolix twice daily (higher-dose group), or placebo. The authors found that women with moderate or severe endometriosis-associated pain who received two different doses of elagolix had significantly lower scores for dysmenorrhea and nonmenstrual pelvic pain than did those who received placebo after 3 months and 6 months of treatment. At 3 months and 6 months, women who received the higher dose of elagolix were taking a significantly lower amount of any rescue analgesic agent (as determined by the mean pill counts of nonsteroidal antiinflammatory drugs, opioids, or both) than were those who received placebo; women in the lower-dose group did not have a significant reduction in the use of such agents. Significantly more women taking either dose of elagolix reported “much” or “very much” improvement on the Patient Global Impression of Change scale at 6 months than did those taking placebo.
A: In the trials by Taylor et al., the three most frequently reported adverse events in each trial were hot flushes, headache, and nausea; the incidence of hot flushes was significantly higher with each dose of elagolix than with placebo. At 6 months in the two trials, mean decreases from baseline in bone mineral density at the lumbar spine, femoral neck, and total hip were significantly greater in the elagolix groups than in the placebo group. The only exception was the between-group difference in bone mineral density at the femoral neck in one of the two trials, which was not significant in the lower-dose group. Elagolix treatment was associated with increases from baseline to 6 months in lipid measurements, including total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. There were no adverse effects on the endometrium after 6 months of elagolix treatment.