User login
Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.
After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.
About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.
“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.
Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”
The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.
Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.
Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).
The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.
Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.
Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.
“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.
Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.
SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
The recent trial by Zigler et al. showed that ulipristal acetate may reduce bleeding days in contraceptive implant users, but larger studies are needed, and concerns about logistics, dose, and toxicity must be addressed before clinical roll out, according to Eve Espey, MD.
The FDA halted the present trial after another ulipristal study overseas detected liver toxicity. The overseas study (for uterine leiomyoma) involved daily administration of ulipristal (5 mg) for 3 months, which is significantly longer than the present study for breakthrough bleeding. The European Medicines Agency has since determined that women with liver issues should not receive ulipristal and that others should have close liver monitoring before, during, and after ulipristal therapy.
Despite the above concerns, ulipristal still holds promise for a common clinical problem.
“This study contributes to the literature on management of bothersome bleeding with the contraceptive implant,” Dr. Espey said. “It is an important area because bothersome bleeding leads both to dissatisfaction and method discontinuation. As a recent Cochrane review pointed out, although several different medications have been used, studies are small and not yet conclusive. Despite these caveats, the findings were promising, similar to findings of prior work with a similar compound, mifepristone. Future directions would include clinical trials utilizing ulipristal acetate in a larger population powered for discontinuation.”
Dr. Espey is a professor in and chair of the department of obstetrics and gynecology and the family planning fellowship director at the University of New Mexico, Albuquerque. These comments are adapted from an interview. Dr. Espey said she had no relevant financial disclosures.
Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.
After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.
About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.
“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.
Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”
The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.
Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.
Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).
The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.
Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.
Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.
“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.
Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.
SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.
After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.
About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.
“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.
Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”
The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.
Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.
Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).
The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.
Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.
Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.
“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.
Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.
SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.
FROM OBSTETRICS & GYNECOLOGY
Key clinical point:
Major finding: Treatment with ulipristal was associated with 5 fewer bleeding days per month, compared with placebo (P = .002).
Study details: The double-blind, placebo-controlled trial involved 65 women with etonogestrel implants who reported more than one bleeding episode in a 24-day time frame.
Disclosures: The study was funded by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences (NCATS). The authors reported financial disclosures related to Bayer and Merck.
Source: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.