Drug for Heavy Menses More Effective With Increasing Age

SAN DIEGO – Oral tranexamic acid tablets at a dose of up to 3.9 g/day reduced blood loss by a mean of at least 60-65 mL per menstrual period in women aged 30 or older with heavy menstrual bleeding, a pooled analysis of two pivotal trials found.

Dr. Jeffrey B. Baker and his associates analyzed data for 383 women from the two randomized, double-blind, placebo-controlled studies who were randomized to either a 3.9-g/day group or placebo. One study also included a treatment arm using 1.95 g/day of tranexamic acid (Lysteda), but that dosage did not reduce menstrual bleeding by at least 50 mL, the minimum required by the Food and Drug Administration to show a significant difference, he said at the annual meeting of the American College of Obstetricians and Gynecologists.

In November 2010, the FDA approved the 3.9 g/day dosage of Lysteda to treat heavy menstrual bleeding based on results from the pivotal trials (Obstet. Gynecol. 2010;116:865-75; Am. J. Obstet. Gynecol. 2011;205:319.e1-7).

Women who were randomized to the 3.9 g/day groups took the drug for up to 5 days per menstrual cycle for either three or six menstrual cycles, depending on the study. They could decide to take it for no days or for up to 5 days in any one cycle; they averaged 2.5 days of the medication per cycle.

In the current analysis of data pooled from both studies, reductions in menstrual blood loss tended to be greater with increasing patient age. Women younger than 30 years had a mean reduction in menstrual blood loss of approximately 40 mL, below the desired 50-mL threshold. A 60- to 65-mL reduction in bleeding was seen in women in age groups of 30-34 years, 35-39 years, and 40-49 years. The reduction in blood loss in women aged 45 years or older averaged more than 80 mL per period, said Dr. Baker, an ob.gyn. and clinical researcher in private practice in Idaho Falls, Idaho.

For women on placebo in those age groups, the mean change in menstrual blood loss ranged from an approximately 10-mL reduction to slight increases in blood loss.

"What tranexamic acid offers to clinicians and patients is another tool amongst the many tools that are available for heavy menstrual bleeding," he said.

Some of the available hormonal treatments for heavy menstrual bleeding, such as the Mirena IUD, also act as contraceptives. Lysteda is a nonhormonal lysine analog that acts as a competitive plasmin inhibitor; it is not a contraceptive. The studies excluded the use of any hormonal products that might compromise the effectiveness of Lysteda, so women used barrier techniques, tubal ligations, or vasectomies for birth control, he said.

Women with fibroids saw a slightly greater reduction in menstrual blood loss, compared with those without fibroids (approximately 75 mL and 60 mL, respectively). Women with a body mass index less than 25 kg/m² had an approximately 75-mL reduction in blood loss, compared with approximately 65-mL reductions for women in two other BMI categories (25-29, or 30 or greater).

Treatment-emergent serious adverse events in the 3.9-g/day groups included tachycardia in one woman, low blood sugar in one woman, severe ovarian torsion in one woman, and complaints of severe dyspepsia, severe gastritis, and severe chest pain in one woman. The investigators considered these to be unrelated to treatment.

Four women in the 3.9-g/day groups withdrew from the studies. The reasons given were mild myalgias, elevated FSH level, rash, or palpitations, each of which resolved by the time of the follow-up visit.

The most common adverse events in the Lysteda groups were upper respiratory infection (7%), musculoskeletal pain (5%), and myalgia (5%) in one study, and headache (11%), nausea (10%), and menstrual discomfort (8%) in the other study. Most adverse events were mild to moderate in severity. The Lysteda and placebo groups did not differ significantly in treatment-emergent adverse events.

In response to a question from the audience, Dr. Baker said that the studies did not screen patients for underlying thrombophilias.

The studies included adult women with no abnormal findings on pelvic examination as well as normal cervical cytology results and normal findings on transvaginal ultrasound. Women with fibroids or simple ovarian cysts were allowed to participate. The studies excluded women with severe anemia or other identifiable causes of abnormal menstrual bleeding.

Two previous studies found that tranexamic acid reduced menstrual blood loss in women with heavy menstrual bleeding, Dr. Baker noted (Acta Obstet. Gynecol. Scand. 1994;73:274-7; Drugs 2003;63:1417-33).

Ferring Pharmaceuticals, which markets Lysteda, funded the study. Dr. Baker has been a speaker and advisor for Ferring. One of his coinvestigators is an employee of Ferring, and the other has been a speaker and advisor for Ferring and a consultant or researcher for multiple other companies.

SAN DIEGO – Oral tranexamic acid tablets at a dose of up to 3.9 g/day reduced blood loss by a mean of at least 60-65 mL per menstrual period in women aged 30 or older with heavy menstrual bleeding, a pooled analysis of two pivotal trials found.

Dr. Jeffrey B. Baker and his associates analyzed data for 383 women from the two randomized, double-blind, placebo-controlled studies who were randomized to either a 3.9-g/day group or placebo. One study also included a treatment arm using 1.95 g/day of tranexamic acid (Lysteda), but that dosage did not reduce menstrual bleeding by at least 50 mL, the minimum required by the Food and Drug Administration to show a significant difference, he said at the annual meeting of the American College of Obstetricians and Gynecologists.

In November 2010, the FDA approved the 3.9 g/day dosage of Lysteda to treat heavy menstrual bleeding based on results from the pivotal trials (Obstet. Gynecol. 2010;116:865-75; Am. J. Obstet. Gynecol. 2011;205:319.e1-7).

Women who were randomized to the 3.9 g/day groups took the drug for up to 5 days per menstrual cycle for either three or six menstrual cycles, depending on the study. They could decide to take it for no days or for up to 5 days in any one cycle; they averaged 2.5 days of the medication per cycle.

In the current analysis of data pooled from both studies, reductions in menstrual blood loss tended to be greater with increasing patient age. Women younger than 30 years had a mean reduction in menstrual blood loss of approximately 40 mL, below the desired 50-mL threshold. A 60- to 65-mL reduction in bleeding was seen in women in age groups of 30-34 years, 35-39 years, and 40-49 years. The reduction in blood loss in women aged 45 years or older averaged more than 80 mL per period, said Dr. Baker, an ob.gyn. and clinical researcher in private practice in Idaho Falls, Idaho.

For women on placebo in those age groups, the mean change in menstrual blood loss ranged from an approximately 10-mL reduction to slight increases in blood loss.

"What tranexamic acid offers to clinicians and patients is another tool amongst the many tools that are available for heavy menstrual bleeding," he said.

Some of the available hormonal treatments for heavy menstrual bleeding, such as the Mirena IUD, also act as contraceptives. Lysteda is a nonhormonal lysine analog that acts as a competitive plasmin inhibitor; it is not a contraceptive. The studies excluded the use of any hormonal products that might compromise the effectiveness of Lysteda, so women used barrier techniques, tubal ligations, or vasectomies for birth control, he said.

Women with fibroids saw a slightly greater reduction in menstrual blood loss, compared with those without fibroids (approximately 75 mL and 60 mL, respectively). Women with a body mass index less than 25 kg/m² had an approximately 75-mL reduction in blood loss, compared with approximately 65-mL reductions for women in two other BMI categories (25-29, or 30 or greater).

Treatment-emergent serious adverse events in the 3.9-g/day groups included tachycardia in one woman, low blood sugar in one woman, severe ovarian torsion in one woman, and complaints of severe dyspepsia, severe gastritis, and severe chest pain in one woman. The investigators considered these to be unrelated to treatment.

Four women in the 3.9-g/day groups withdrew from the studies. The reasons given were mild myalgias, elevated FSH level, rash, or palpitations, each of which resolved by the time of the follow-up visit.

The most common adverse events in the Lysteda groups were upper respiratory infection (7%), musculoskeletal pain (5%), and myalgia (5%) in one study, and headache (11%), nausea (10%), and menstrual discomfort (8%) in the other study. Most adverse events were mild to moderate in severity. The Lysteda and placebo groups did not differ significantly in treatment-emergent adverse events.

In response to a question from the audience, Dr. Baker said that the studies did not screen patients for underlying thrombophilias.

The studies included adult women with no abnormal findings on pelvic examination as well as normal cervical cytology results and normal findings on transvaginal ultrasound. Women with fibroids or simple ovarian cysts were allowed to participate. The studies excluded women with severe anemia or other identifiable causes of abnormal menstrual bleeding.

Two previous studies found that tranexamic acid reduced menstrual blood loss in women with heavy menstrual bleeding, Dr. Baker noted (Acta Obstet. Gynecol. Scand. 1994;73:274-7; Drugs 2003;63:1417-33).

Ferring Pharmaceuticals, which markets Lysteda, funded the study. Dr. Baker has been a speaker and advisor for Ferring. One of his coinvestigators is an employee of Ferring, and the other has been a speaker and advisor for Ferring and a consultant or researcher for multiple other companies.

SAN DIEGO – Oral tranexamic acid tablets at a dose of up to 3.9 g/day reduced blood loss by a mean of at least 60-65 mL per menstrual period in women aged 30 or older with heavy menstrual bleeding, a pooled analysis of two pivotal trials found.

Dr. Jeffrey B. Baker and his associates analyzed data for 383 women from the two randomized, double-blind, placebo-controlled studies who were randomized to either a 3.9-g/day group or placebo. One study also included a treatment arm using 1.95 g/day of tranexamic acid (Lysteda), but that dosage did not reduce menstrual bleeding by at least 50 mL, the minimum required by the Food and Drug Administration to show a significant difference, he said at the annual meeting of the American College of Obstetricians and Gynecologists.

In November 2010, the FDA approved the 3.9 g/day dosage of Lysteda to treat heavy menstrual bleeding based on results from the pivotal trials (Obstet. Gynecol. 2010;116:865-75; Am. J. Obstet. Gynecol. 2011;205:319.e1-7).

Women who were randomized to the 3.9 g/day groups took the drug for up to 5 days per menstrual cycle for either three or six menstrual cycles, depending on the study. They could decide to take it for no days or for up to 5 days in any one cycle; they averaged 2.5 days of the medication per cycle.

In the current analysis of data pooled from both studies, reductions in menstrual blood loss tended to be greater with increasing patient age. Women younger than 30 years had a mean reduction in menstrual blood loss of approximately 40 mL, below the desired 50-mL threshold. A 60- to 65-mL reduction in bleeding was seen in women in age groups of 30-34 years, 35-39 years, and 40-49 years. The reduction in blood loss in women aged 45 years or older averaged more than 80 mL per period, said Dr. Baker, an ob.gyn. and clinical researcher in private practice in Idaho Falls, Idaho.

For women on placebo in those age groups, the mean change in menstrual blood loss ranged from an approximately 10-mL reduction to slight increases in blood loss.

"What tranexamic acid offers to clinicians and patients is another tool amongst the many tools that are available for heavy menstrual bleeding," he said.

Some of the available hormonal treatments for heavy menstrual bleeding, such as the Mirena IUD, also act as contraceptives. Lysteda is a nonhormonal lysine analog that acts as a competitive plasmin inhibitor; it is not a contraceptive. The studies excluded the use of any hormonal products that might compromise the effectiveness of Lysteda, so women used barrier techniques, tubal ligations, or vasectomies for birth control, he said.

Women with fibroids saw a slightly greater reduction in menstrual blood loss, compared with those without fibroids (approximately 75 mL and 60 mL, respectively). Women with a body mass index less than 25 kg/m² had an approximately 75-mL reduction in blood loss, compared with approximately 65-mL reductions for women in two other BMI categories (25-29, or 30 or greater).

Treatment-emergent serious adverse events in the 3.9-g/day groups included tachycardia in one woman, low blood sugar in one woman, severe ovarian torsion in one woman, and complaints of severe dyspepsia, severe gastritis, and severe chest pain in one woman. The investigators considered these to be unrelated to treatment.

Four women in the 3.9-g/day groups withdrew from the studies. The reasons given were mild myalgias, elevated FSH level, rash, or palpitations, each of which resolved by the time of the follow-up visit.

The most common adverse events in the Lysteda groups were upper respiratory infection (7%), musculoskeletal pain (5%), and myalgia (5%) in one study, and headache (11%), nausea (10%), and menstrual discomfort (8%) in the other study. Most adverse events were mild to moderate in severity. The Lysteda and placebo groups did not differ significantly in treatment-emergent adverse events.

In response to a question from the audience, Dr. Baker said that the studies did not screen patients for underlying thrombophilias.

The studies included adult women with no abnormal findings on pelvic examination as well as normal cervical cytology results and normal findings on transvaginal ultrasound. Women with fibroids or simple ovarian cysts were allowed to participate. The studies excluded women with severe anemia or other identifiable causes of abnormal menstrual bleeding.

Two previous studies found that tranexamic acid reduced menstrual blood loss in women with heavy menstrual bleeding, Dr. Baker noted (Acta Obstet. Gynecol. Scand. 1994;73:274-7; Drugs 2003;63:1417-33).

Ferring Pharmaceuticals, which markets Lysteda, funded the study. Dr. Baker has been a speaker and advisor for Ferring. One of his coinvestigators is an employee of Ferring, and the other has been a speaker and advisor for Ferring and a consultant or researcher for multiple other companies.