Change From Baseline in the Monthly Peak Numerical Rating Score (NRS) for Endometriosis Pain
The NRS is an 11-point scale used to measure endometriosis pain and was completed at approximately the same time each day using an electronic diary (e-Diary). Participants were instructed to select a single number between 0 (No pain) and 10 (Worst pain ever) that best described their endometriosis pain at its worst over the past day.
The monthly peak NRS is the maximum of the daily values reported during the 4 weeks prior to each visit.
Change From Baseline in the Monthly Mean Non-menstrual Pelvic Pain Score
Participants assessed their pelvic pain not related to menses and its impact on their daily activities at approximately the same time every day in an e-Diary according to the following response options:
0 = No pelvic pain
1 = Mild pelvic pain; subject could not do some of the things she usually does
2 = Moderate pelvic pain; subject could not do many of the things she usually does
3 = Severe pelvic pain; subject could not do most or all of the things she usually does.
The monthly mean non-menstrual pelvic pain score is the average of the daily values reported during the 4 weeks prior to each visit.
Change From Baseline in the Monthly Mean Dysmenorrhea Score
Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities at approximately the same time each day of their period in an e-Diary according to the following response options:
Subject is not having her period
0 = No pain related to period
1 = Mild pain related to period; subject could not do some of the things she usually does
2 = Moderate pain related to period; subject could not do many of the things she usually does
3 = Severe pain related to period; subject could not do most of or all of the things she usually does.
The monthly mean dysmenorrhea score is the average of the daily values reported during the 4 weeks prior to each visit.
Change From Baseline in the Monthly Mean Sum of Dysmenorrhea and Non-menstrual Pelvic Pain Scores
Participants assessed dysmenorrhea and pelvic pain not related to menses and their impact on daily activities at approximately the same time every day on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe) in an e-Diary. The dysmenorrhea scale included an option for participants who were not having their period.
The sum of the dysmenorrhea and non-menstrual pelvic pain scores on each day were calculated to create a daily total score. On days the participant was not having her period, the dysmenorrhea score was not defined; hence, the total score was equal to the non-menstrual pelvic pain score (range 0 to 3). On days where the participant recorded menstruation the total score ranged from 0 to 6, where higher scores indicate more severe pain. The monthly mean sum of dysmenorrhea and non-menstrual pelvic pain scores is the average of the daily values reported during the 4 weeks prior to each visit.
Change From Baseline in the Percentage of Days of Any Analgesic Use
The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic.
The percentage of days of any analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of an analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").
Change From Baseline in the Percentage of Days of Prescription Analgesic Use
The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic.
The percentage of days of prescription analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of a prescription analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").
Change From Baseline in the Percentage of Days of Narcotic Analgesic Use
The daily use of endometriosis analgesics was reported by participants daily using the e-Diary. Participants reported whether the medication was over-the-counter (OTC) or prescription, and, if prescription, whether the medication was a narcotic.
The percentage of days of narcotic analgesic use is defined as the number of days in the 4 weeks prior to each study visit that the participant reported the use of a narcotic analgesic, divided by the number of study days in the interval that the participant provided an e-Diary report regarding the use of endometriosis analgesics (including a response of "none").
Change From Baseline in Dyspareunia Component of the Composite Pelvic Signs and Symptoms Score (CPSSS)
The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration.
To assess dyspareunia (painful intercourse) participants were asked to select the best description of pain during sexual intercourse over the past 28 days using the following response categories:
0 = Absent; No discomfort during sexual intercourse.
1 = Mild; I can tolerate the discomfort during sexual intercourse.
2 = Moderate; Intercourse is sometime interrupted due to pain.
3 = Severe; I prefer to avoid intercourse because of pain.
Not applicable. I am not sexually active for reasons other than my endometriosis symptoms.
Change From Baseline in Dysmenorrhea Component of the CPSSS
The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration.
To assess dysmenorrhea (pain during menstruation), participants were asked to select the best description of painful menstruation over the past 28 days using the following response categories:
0 = Absent; Amenorrhea (no bleeding) or no discomfort.
1 = Mild; Some loss of work efficiency; occasional use of analgesics.
2 = Moderate; In bed part of one day, occasional loss of work; regular use of analgesics.
3 = Severe; In bed ≥ 1 day, incapacitation; requirement for strong analgesics.
Change From Baseline in Non-menstrual Pelvic Pain CPSSS Component
The CPSSS consists of 5 components that address dysmenorrhea, dyspareunia, non-menstrual pelvic pain, pelvic tenderness, and pelvic induration.
To assess non-menstrual pelvic pain, participants were asked to select the best description of pelvic pain over the past 28 days using the following response categories:
0 = Absent; No discomfort.
1 = Mild; Occasional pelvic discomfort that can be treated with NSAIDs.
2 = Moderate; Noticeable discomfort or pain for most of cycle requiring regular use of NSAID or weak opiate.
3 = Severe; Pain persisting during the cycle or pain requiring strong analgesics.
Patient Global Impression of Change at Weeks 4, 8 and 12
The Patient Global Impression of Change (PGIC) is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories:
Very Much Improved
Much Improved
Minimally Improved
Not Changed
Minimally Worse
Much Worse
Very Much Worse
Percentage of Participants With a PGIC Response of Minimally Improved, Much Improved, or Very Much Improved
The PGIC is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories:
Very Much Improved
Much Improved
Minimally Improved
Not Changed
Minimally Worse
Much Worse
Very Much Worse
Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved
The PGIC is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories:
Very Much Improved
Much Improved
Minimally Improved
Not Changed
Minimally Worse
Much Worse
Very Much Worse
Change From Baseline in Endometriosis Health Profile-5 (EHP-5) at Week 12
The EHP-5 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-5 consists of two parts:
A core questionnaire consisting of five questions that measure the areas of pain, control and powerlessness, emotional well-being, social support, and self-image with five response categories for each item (Never, Rarely, Sometimes, Often, Always)
A supplemental questionnaire consisting of six additional questions which assess the areas of work, relationship with children, sexual intercourse, feelings about the medical profession, treatment, and infertility with the same five response categories plus an additional response category of Not Relevant which was not scored.
The scores associated with each possible outcome category are as follows: never (0), rarely (25), sometimes (50), often (75), and always (100). A negative change from baseline score indicates improvement in quality of life.
Concentration of Serum Estradiol
The concentration of serum estradiol (E2) was quantified using liquid chromatography with tandem mass spectrophotometry (LC/MS/MS). Serum estradiol concentrations below the limit of quantification (BLQ) were set equal to the lower limit of quantification (2.5 pg/mL).
Percent Change From Baseline in Bone Mineral Density of the Femur at Week 12
Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA).
Percent Change From Baseline in Bone Mineral Density of the Spine at Week 12
Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA).
Percent Change From Baseline in Bone Mineral Density of the Femur at Week 24
Bone mineral density (BMD) of the femur (total hip) was measured by dual-energy X-ray absorptiometry (DXA).
Percent Change From Baseline in Bone Mineral Density of the Spine at Week 24
Bone mineral density (BMD) of the spine was measured by dual-energy X-ray absorptiometry (DXA).
Change From Baseline in Serum N-telopeptide Concentration at Week 12
Blood samples to determine N-telopeptide concentrations were analyzed by a central laboratory using an enzyme-linked immunosorbent assay (ELISA).
Average Number of Hot Flashes Per Day
Hot flashes, if any, were reported daily by participants during the study using the e-Diary.
The average number of hot flashes per day was calculated for each participant as the total number of hot flashes divided by total days in the phase.
Percentage of Days With Uterine Bleeding
Uterine bleeding was reported daily by participants during the study using the e-Diary.
The percentage of days a participant reported any bleeding was calculated as the total number of days the participant reported any bleeding ( light, moderate, or heavy) divided by the total number of days the participant had a non-missing eDiary report of vaginal bleeding in the phase.
Number of Days to First Posttreatment Menses
Defined as the number of days from the last dose of study drug until the start date of the first post-treatment menses.