Trial Outcomes & Findings for Vascular Mechanisms for the Effects of Loss of Ovarian Hormone Function on Cognition in Women (NCT NCT02122198)

Results Overview

Changes in patterns of brain activation in the prefrontal cortex using functional magnetic resonance imaging (fMRI) during a task of working memory will be measured at baseline, 6 months, and 9 months (GnRH agonist arm only). Beta weight is the percent signal change on the FMRI from one condition to another. The FMRI is measuring blood oxygen levels and blood flow in different regions of the brain and using that to determine activity changes in the brain. A positive number/increase indicates more blood flow and brain activity in that area.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

17 participants

Primary outcome timeframe

Baseline, 6 months

Results posted on

2022-01-10

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Overall Study STARTED	5	12
Overall Study COMPLETED	3	10
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vascular Mechanisms for the Effects of Loss of Ovarian Hormone Function on Cognition in Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=5 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=12 Participants Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.	Total n=17 Participants Total of all reporting groups
Age, Continuous	45.6 years STANDARD_DEVIATION 2.5 • n=93 Participants	47.7 years STANDARD_DEVIATION 4.0 • n=4 Participants	47.1 years STANDARD_DEVIATION 3.7 • n=27 Participants
Sex: Female, Male Female	5 Participants n=93 Participants	12 Participants n=4 Participants	17 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=93 Participants	12 Participants n=4 Participants	15 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants	11 Participants n=4 Participants	14 Participants n=27 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, 6 months

Changes in patterns of brain activation in the prefrontal cortex using functional magnetic resonance imaging (fMRI) during a task of working memory will be measured at baseline, 6 months, and 9 months (GnRH agonist arm only). Beta weight is the percent signal change on the FMRI from one condition to another. The FMRI is measuring blood oxygen levels and blood flow in different regions of the brain and using that to determine activity changes in the brain. A positive number/increase indicates more blood flow and brain activity in that area.

Outcome measures

Outcome measures
Measure	Placebo n=2 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=7 Participants Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Prefrontal Cortex Brain Activation at 6 Months Frontal Pole (L)	90.64 beta-weight Standard Deviation 3.88	-62.20 beta-weight Standard Deviation 57.61
Changes in Prefrontal Cortex Brain Activation at 6 Months Frontal Orbital Cortex (L)	28.07 beta-weight Standard Deviation 37.48	-79.04 beta-weight Standard Deviation 71.85
Changes in Prefrontal Cortex Brain Activation at 6 Months Superior Frontal Gyrus (R)	92.45 beta-weight Standard Deviation 33.66	-53.05 beta-weight Standard Deviation 41.13

PRIMARY outcome

Timeframe: Baseline, 9 months

Population: This outcome measure was only collected for a subset of the GnRH Agonist group.

Changes in patterns of brain activation in the prefrontal cortex using functional magnetic resonance imaging (fMRI) during a task of working memory will be measured at baseline, 6 months, and 9 months (GnRH agonist arm only). Beta weight is the percent signal change on the FMRI from one condition to another. The FMRI is measuring blood oxygen levels and blood flow in different regions of the brain and using that to determine activity changes in the brain. A positive number/increase indicates more blood flow and brain activity in that area.

Outcome measures

Outcome measures
Measure	Placebo n=2 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Prefrontal Cortex Brain Activation at 9 Months Frontal Pole (L)	-27.15 beta-weight Standard Deviation 67.37	—
Changes in Prefrontal Cortex Brain Activation at 9 Months Frontal Orbital Cortex (L)	-88.87 beta-weight Standard Deviation 0.34	—
Changes in Prefrontal Cortex Brain Activation at 9 Months Superior Frontal Gyrus (R)	-77.23 beta-weight Standard Deviation 68.22	—

SECONDARY outcome

Timeframe: Baseline, 6 months

Population: This outcome cannot be reported due to corruption of the collected image data.

Changes in endothelial function will be measured using brachial artery flow-mediated dilation at baseline, 6 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Outcome measure was collected for a subset of the GnRH agonist arm only. This outcome cannot be reported due to corruption of the collected image data.

Changes in endothelial function will be measured using brachial artery flow-mediated dilation at baseline, 9 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 6 months

Changes in carotid artery compliance will be measured using ultrasound in at baseline, 6 months.

Outcome measures

Outcome measures
Measure	Placebo n=4 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=3 Participants Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Artery Compliance at 6 Months	-0.048 mm^2/mmhgx10^-1 Standard Deviation 0.057	-0.095 mm^2/mmhgx10^-1 Standard Deviation 0.011

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Outcome measure was only collected for a subset of the GnRH agonist arm.

Changes in carotid artery compliance will be measured using ultrasound in at baseline, 9 months.

Outcome measures

Outcome measures
Measure	Placebo n=2 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Artery Compliance at 9 Months	-0.002 mm^2/mmhgx10^-1 Standard Deviation 0.006	—

SECONDARY outcome

Timeframe: Baseline, 6 months

Change in time (seconds) to complete Trails A test between baseline and 6 months. Negative value indicates faster time (better performance) at 6 months compared to baseline.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=8 Participants Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Trails A, 6 Months	2.79 seconds Standard Deviation 8.54	-5.82 seconds Standard Deviation 3.11

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Outcome measure was only collected for a subset of the GnRH agonist arm.

Change in time (seconds) to complete Trails A test between baseline and 9 months. Negative value indicates faster time (better performance) at 9 months compared to baseline.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Trails A, 9 Months	-5.46 time (seconds) Standard Deviation 7.12	—

SECONDARY outcome

Timeframe: Baseline, 6 months

Change in Rey Auditory Verbal Learning Test from baseline to 6 months. Score is the change in the number of items correct on delayed recall trial. Scores on the RAVLT range from 0-15 with higher scores indicating better performance. A positive change indicates improvement in recall.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=8 Participants Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: RAVLT, 6 Months	-1.00 number of items recalled Standard Deviation 2.65	-1.38 number of items recalled Standard Deviation 1.85

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Outcome measure was only collected for a subset of the GnRH agonist arm.

Change in Rey Auditory Verbal Learning Test from baseline to 9 months. Score is the change in the number of items correct on delayed recall trial. Scores on the RAVLT range from 0-15 with higher scores indicating better performance. A positive change indicates improvement in recall.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: RAVLT, 9 Months	0 number of items recalled Standard Deviation 2.00	—

SECONDARY outcome

Timeframe: Baseline, 6 months

Change in time (seconds) to complete Trails B test between baseline and 6 months. Negative value indicates faster time (better performance) at 6 months compared to baseline.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=8 Participants Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Trails B, 6 Months	14.23 time (seconds) Standard Deviation 4.77	-4.32 time (seconds) Standard Deviation 16.27

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Outcome measure was only collected for a subset of the GnRH agonist arm.

Change in time (seconds) to complete Trails B test between baseline and 9 months. Negative value indicates faster time (better performance) at 9 months compared to baseline.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Trails B, 9 Months	14.14 time (seconds) Standard Deviation 12.09	—

SECONDARY outcome

Timeframe: Baseline, 6 months

Change in number of correct responses in one minute on Stroop Color Word Interference test between baseline and 6 months. A positive number indicates more items correct indicating better performance. There is no maximum score because the test measures how many correct responses a participant can return within one minute (minimum = 0), however 40 or fewer is considered low. The change in the number of correct responses is reported, and so a positive number indicates more correct responses and better/improved cognitive function.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=8 Participants Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Stroop, 6 Months	-0.67 number correct in one minute Standard Deviation 10.97	0.25 number correct in one minute Standard Deviation 13.76

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Outcome measure was only collected for a subset of the GnRH agonist arm.

Change in number of correct responses in one minute on Stroop Color Word Interference test between baseline and 9 months. Positive number indicates more items correct indicating better performance. There is no maximum score because the test measures how many correct responses a participant can return within one minute (minimum = 0), however 40 or fewer is considered low. The change in the number of correct responses is reported, and so a positive number indicates more correct responses and better/improved cognitive function.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Stroop, 9 Months	7.33 number correct in one minute Standard Deviation 3.06	—

SECONDARY outcome

Timeframe: Baseline, 6 months

Change in score on the Digit Span Test between baseline and 6 month. Raw scores on the Digit Span test range from 0-16 (Digits Forward) and 0-10 (Digits Backward) with higher scores indicating better performance. A positive change score indicates improved performance.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=8 Participants Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Digits Span Forward and Backward, 6 Months Digits Forward (trials correct)	1.00 number of correct trials Standard Deviation 1.00	-0.88 number of correct trials Standard Deviation 1.89
Changes in Executive Cognitive Function: Digits Span Forward and Backward, 6 Months Digits Backward (trials correct)	-0.67 number of correct trials Standard Deviation 3.06	0.00 number of correct trials Standard Deviation 1.51

SECONDARY outcome

Timeframe: Baseline, 9 months

Population: Outcome measure was only collected for a subset of the GnRH agonist arm.

Change in score on the Digit Span Test between baseline and 9 months. Raw scores on the Digit Span test range from 0-16 (Digits Forward) and 0-10 (Digits Backward) with higher scores indicating better performance. A positive change score indicates improved performance.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Digits, 9 Months Digits Forward (trials correct)	1.00 number of trials correct Standard Deviation 3.61	—
Changes in Executive Cognitive Function: Digits, 9 Months Digits Backward (trials correct)	1.0 number of trials correct Standard Deviation 1.0	—

SECONDARY outcome

Timeframe: Baseline, 6 months

Change in sum of scores on 3 COWAT trials (letters, F, A, and S) between baseline and 6 months. Participants are given one minute to think up as many words as they can associated with each letter (F, A, or S). Raw scores are the total number of words generated across all trials. Higher scores indicate more words generated and better performance. Positive change score indicates an increase in words generated, or improved performance.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=8 Participants Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Controlled Oral Word Association Test, 6 Months	-5.33 words generated Standard Deviation 7.77	0.25 words generated Standard Deviation 9.50

SECONDARY outcome

Timeframe: Baseline, 9 months

Change in sum of scores on 3 COWAT trials (letters, F, A, and S) between baseline and 9 months. Participants are given one minute to think up as many words as they can associated with each letter (F, A, or S). Raw scores are the total number of words generated across all trials. Higher scores indicate more words generated and better performance. Positive change score indicates an increase in words generated, or improved performance.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Changes in Executive Cognitive Function: Controlled Oral Word Association Test, 9 Months	7.33 words generated Standard Deviation 5.51	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

GnRH Agonist

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=5 participants at risk Monthly placebo injections for 6 months under parent study (FAME) protocol (NCT01712230) Placebo: placebo	GnRH Agonist n=12 participants at risk Monthly injections of leuprolide acetate 3.75mg for 9 months; first 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study protocol. Weekly application of estradiol patch 0.075mg/d months 6-9. Daily medroxyprogesterone acetate 5mg by mouth for 12 days at week 30. Leuprolide acetate: Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study. Estradiol: Climara transdermal patch 0.075mg/day applied weekly months 6-9 Medroxyprogesterone: Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
Nervous system disorders calcification of the falx cerebri right of midline	0.00% 0/5 • 9 months	8.3% 1/12 • Number of events 1 • 9 months

Additional Information

Kerry Hildreth, MD

University of Colorado Denver

Phone: 3037241111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place