Trial Outcomes & Findings for Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women (NCT NCT00608062)

NCT ID: NCT00608062

Last Updated: 2020-12-24

Results Overview

Carotid artery compliance measured by carotid artery ultrasound and brachial artery blood pressure

Recruitment status

COMPLETED

Study phase

Target enrollment

155 participants

Primary outcome timeframe

Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment

Results posted on

2020-12-24

Participant Flow

Participants were recruited from the Denver metro area between March 2007 and March 2012. The first participant was enrolled on March 6, 2007 and the last participant was enrolled in March 2012.

A total of 155 women consented to participate. During screening, 33 women did not qualify (12 premenopausal, 14 perimenopausal \[11 early- and 3 late\], and 7 postmenopausal). Twenty-three withdrew from participation before baseline testing and 7 women withdrew from participation after baseline testing but prior to randomization.

Participant milestones

Participant milestones
Measure	Pre1 Premenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre2 Premenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri1 Perimenopausal (early and late combined) - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri2 Perimenopausal (early and late combined) - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post1 Postmenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post2 Postmenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Overall Study STARTED	12	12	19	21	13	15
Overall Study COMPLETED	12	12	19	21	13	15
Overall Study NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pre1 n=12 Participants Premenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre2 n=12 Participants Premenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri1 n=17 Participants Perimenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri2 n=21 Participants Perimenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post1 n=12 Participants Postmenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post2 n=13 Participants Postmenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Total n=87 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	12 Participants n=7 Participants	17 Participants n=5 Participants	21 Participants n=4 Participants	12 Participants n=21 Participants	11 Participants n=10 Participants	85 Participants n=115 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants	2 Participants n=115 Participants
Age, Continuous	32 years STANDARD_DEVIATION 8 • n=5 Participants	33 years STANDARD_DEVIATION 7 • n=7 Participants	49 years STANDARD_DEVIATION 3 • n=5 Participants	50 years STANDARD_DEVIATION 4 • n=4 Participants	56 years STANDARD_DEVIATION 5 • n=21 Participants	60 years STANDARD_DEVIATION 6 • n=10 Participants	47 years STANDARD_DEVIATION 11 • n=115 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	12 Participants n=7 Participants	17 Participants n=5 Participants	21 Participants n=4 Participants	12 Participants n=21 Participants	13 Participants n=10 Participants	87 Participants n=115 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	17 participants n=5 Participants	21 participants n=4 Participants	12 participants n=21 Participants	13 participants n=10 Participants	87 participants n=115 Participants
Body Mass	66.8 kg STANDARD_DEVIATION 15.6 • n=5 Participants	64.2 kg STANDARD_DEVIATION 11.0 • n=7 Participants	65.6 kg STANDARD_DEVIATION 8.1 • n=5 Participants	68.7 kg STANDARD_DEVIATION 11.9 • n=4 Participants	70.5 kg STANDARD_DEVIATION 14.7 • n=21 Participants	69.7 kg STANDARD_DEVIATION 9.3 • n=10 Participants	67.6 kg STANDARD_DEVIATION 11.7 • n=115 Participants
Body Mass Index (BMI)	23.8 kg/m2 STANDARD_DEVIATION 5.6 • n=5 Participants	24.4 kg/m2 STANDARD_DEVIATION 5.3 • n=7 Participants	24.1 kg/m2 STANDARD_DEVIATION 3.2 • n=5 Participants	25.2 kg/m2 STANDARD_DEVIATION 3.9 • n=4 Participants	26.7 kg/m2 STANDARD_DEVIATION 5.9 • n=21 Participants	26.5 kg/m2 STANDARD_DEVIATION 2.7 • n=10 Participants	25.1 kg/m2 STANDARD_DEVIATION 4.4 • n=115 Participants
Systolic Blood Pressure	109 mmHg STANDARD_DEVIATION 8 • n=5 Participants	110 mmHg STANDARD_DEVIATION 7 • n=7 Participants	113 mmHg STANDARD_DEVIATION 14 • n=5 Participants	115 mmHg STANDARD_DEVIATION 11 • n=4 Participants	117 mmHg STANDARD_DEVIATION 14 • n=21 Participants	120 mmHg STANDARD_DEVIATION 14 • n=10 Participants	114 mmHg STANDARD_DEVIATION 12 • n=115 Participants
Diastolic Blood Pressure	70 mmHg STANDARD_DEVIATION 7 • n=5 Participants	72 mmHg STANDARD_DEVIATION 5 • n=7 Participants	71 mmHg STANDARD_DEVIATION 9 • n=5 Participants	73 mmHg STANDARD_DEVIATION 6 • n=4 Participants	73 mmHg STANDARD_DEVIATION 8 • n=21 Participants	74 mmHg STANDARD_DEVIATION 10 • n=10 Participants	72 mmHg STANDARD_DEVIATION 8 • n=115 Participants
VO2peak	35.3 ml/kg/min STANDARD_DEVIATION 6.0 • n=5 Participants	31.0 ml/kg/min STANDARD_DEVIATION 5.5 • n=7 Participants	27.7 ml/kg/min STANDARD_DEVIATION 4.0 • n=5 Participants	27.5 ml/kg/min STANDARD_DEVIATION 5.8 • n=4 Participants	24.8 ml/kg/min STANDARD_DEVIATION 3.9 • n=21 Participants	24.1 ml/kg/min STANDARD_DEVIATION 2.9 • n=10 Participants	28.2 ml/kg/min STANDARD_DEVIATION 5.9 • n=115 Participants
Glucose	4.7 mmol/L STANDARD_DEVIATION 0.3 • n=5 Participants	4.6 mmol/L STANDARD_DEVIATION 0.6 • n=7 Participants	4.5 mmol/L STANDARD_DEVIATION 0.3 • n=5 Participants	4.7 mmol/L STANDARD_DEVIATION 0.5 • n=4 Participants	5.0 mmol/L STANDARD_DEVIATION 0.7 • n=21 Participants	4.6 mmol/L STANDARD_DEVIATION 0.6 • n=10 Participants	4.7 mmol/L STANDARD_DEVIATION 0.5 • n=115 Participants
Insulin	38 pmol/L n=5 Participants	42 pmol/L n=7 Participants	28 pmol/L n=5 Participants	28 pmol/L n=4 Participants	28 pmol/L n=21 Participants	31 pmol/L n=10 Participants	35 pmol/L n=115 Participants
Total Cholesterol	3.7 mmol/L STANDARD_DEVIATION 0.7 • n=5 Participants	4.0 mmol/L STANDARD_DEVIATION 0.9 • n=7 Participants	4.5 mmol/L STANDARD_DEVIATION 0.9 • n=5 Participants	4.2 mmol/L STANDARD_DEVIATION 0.6 • n=4 Participants	4.7 mmol/L STANDARD_DEVIATION 0.9 • n=21 Participants	4.7 mmol/L STANDARD_DEVIATION 0.9 • n=10 Participants	4.3 mmol/L STANDARD_DEVIATION 0.9 • n=115 Participants
Low-density Lipoprotein	2.3 mmol/L STANDARD_DEVIATION 0.5 • n=5 Participants	2.2 mmol/L STANDARD_DEVIATION 0.7 • n=7 Participants	2.7 mmol/L STANDARD_DEVIATION 1.0 • n=5 Participants	2.4 mmol/L STANDARD_DEVIATION 0.5 • n=4 Participants	2.9 mmol/L STANDARD_DEVIATION 0.8 • n=21 Participants	2.8 mmol/L STANDARD_DEVIATION 0.9 • n=10 Participants	2.6 mmol/L STANDARD_DEVIATION 0.8 • n=115 Participants
High-density Lipoprotein	1.1 mmol/L STANDARD_DEVIATION 0.1 • n=5 Participants	1.3 mmol/L STANDARD_DEVIATION 0.2 • n=7 Participants	1.3 mmol/L STANDARD_DEVIATION 0.2 • n=5 Participants	1.3 mmol/L STANDARD_DEVIATION 0.3 • n=4 Participants	1.3 mmol/L STANDARD_DEVIATION 0.3 • n=21 Participants	1.3 mmol/L STANDARD_DEVIATION 0.3 • n=10 Participants	1.3 mmol/L STANDARD_DEVIATION 0.3 • n=115 Participants

PRIMARY outcome

Timeframe: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment

Population: Early and late perimenopausal were collapsed into 1 perimenopausal group

Carotid artery compliance measured by carotid artery ultrasound and brachial artery blood pressure

Outcome measures

Outcome measures
Measure	Peri1 n=19 Participants Perimenopausal (early and late combined) - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri2 n=21 Participants Perimenopausal (early and late combined) - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post1 n=13 Participants Postmenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post2 n=15 Participants Postmenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre1 n=12 Participants Premenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre2 n=12 Participants Premenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Arterial Stiffness (Carotid Artery Compliance) During Saline Baseline	0.90 mm2/mm Hg×10-1 Standard Deviation 0.27	1.02 mm2/mm Hg×10-1 Standard Deviation 0.33	0.89 mm2/mm Hg×10-1 Standard Deviation 0.25	0.74 mm2/mm Hg×10-1 Standard Deviation 0.23	1.31 mm2/mm Hg×10-1 Standard Deviation 0.27	1.34 mm2/mm Hg×10-1 Standard Deviation 0.18
Arterial Stiffness (Carotid Artery Compliance) During Saline GnRHant alone	0.89 mm2/mm Hg×10-1 Standard Deviation 0.27	0.94 mm2/mm Hg×10-1 Standard Deviation 0.29	0.85 mm2/mm Hg×10-1 Standard Deviation 0.24	0.79 mm2/mm Hg×10-1 Standard Deviation 0.22	1.27 mm2/mm Hg×10-1 Standard Deviation 0.27	1.19 mm2/mm Hg×10-1 Standard Deviation 0.34
Arterial Stiffness (Carotid Artery Compliance) During Saline GnRHant + Add-Back	0.98 mm2/mm Hg×10-1 Standard Deviation 0.27	0.94 mm2/mm Hg×10-1 Standard Deviation 0.27	0.92 mm2/mm Hg×10-1 Standard Deviation 0.27	0.80 mm2/mm Hg×10-1 Standard Deviation 0.19	1.29 mm2/mm Hg×10-1 Standard Deviation 0.26	1.14 mm2/mm Hg×10-1 Standard Deviation 0.38

PRIMARY outcome

Timeframe: Baseline, day 4 of GnRHant and Day 7 of GnRHant and estradiol or placebo treatment

Population: Numbers for some groups are reduced because of poor ultrasound image quality.

Brachial artery flow-mediated dilation (FMD) assessed by ultrasound. This other outcome measure was originally specified as "Secondary" in error and has been updated to "Primary" to be consistent with the protocol.

Outcome measures

Outcome measures
Measure	Peri1 n=17 Participants Perimenopausal (early and late combined) - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri2 n=21 Participants Perimenopausal (early and late combined) - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post1 n=12 Participants Postmenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post2 n=13 Participants Postmenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre1 n=12 Participants Premenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre2 n=12 Participants Premenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Endothelial Function Baseline	7.7 % Diameter Change Standard Deviation 2.6	6.1 % Diameter Change Standard Deviation 2.7	5.4 % Diameter Change Standard Deviation 1.7	5.3 % Diameter Change Standard Deviation 2.2	9.8 % Diameter Change Standard Deviation 2.5	11.3 % Diameter Change Standard Deviation 2.5
Endothelial Function Day 4 of GnRHant alone	5.8 % Diameter Change Standard Deviation 2	6.6 % Diameter Change Standard Deviation 2	4.9 % Diameter Change Standard Deviation 1.5	4.9 % Diameter Change Standard Deviation 1.4	7.1 % Diameter Change Standard Deviation 2.3	8.9 % Diameter Change Standard Deviation 2.7
Endothelial Function Day 7 of GnRHant plus treatment	9.6 % Diameter Change Standard Deviation 3.3	6.1 % Diameter Change Standard Deviation 2.7	8.4 % Diameter Change Standard Deviation 2.4	4.2 % Diameter Change Standard Deviation 1.7	10.6 % Diameter Change Standard Deviation 3.3	7.8 % Diameter Change Standard Deviation 3.0
Endothelial Function Acute Vitamin C Infusion Day 7	9.3 % Diameter Change Standard Deviation 3.4	11.2 % Diameter Change Standard Deviation 3.6	7.8 % Diameter Change Standard Deviation 3.4	6.7 % Diameter Change Standard Deviation 2.8	8.4 % Diameter Change Standard Deviation 3.1	11.2 % Diameter Change Standard Deviation 4.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment

Outcome measures

Outcome measures
Measure	Peri1 n=17 Participants Perimenopausal (early and late combined) - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri2 n=21 Participants Perimenopausal (early and late combined) - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post1 n=12 Participants Postmenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post2 n=13 Participants Postmenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre1 n=12 Participants Premenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre2 n=12 Participants Premenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Supine Brachial Blood Pressures Baseline	111 mmHg Standard Deviation 13	109 mmHg Standard Deviation 15	117 mmHg Standard Deviation 10	123 mmHg Standard Deviation 13	102 mmHg Standard Deviation 10	108 mmHg Standard Deviation 9
Supine Brachial Blood Pressures Day 4 of GnRHant alone	112 mmHg Standard Deviation 12	108 mmHg Standard Deviation 13	116 mmHg Standard Deviation 9	115 mmHg Standard Deviation 8	107 mmHg Standard Deviation 7	111 mmHg Standard Deviation 13
Supine Brachial Blood Pressures Day 7 of GnRHant plus treatment	108 mmHg Standard Deviation 13	109 mmHg Standard Deviation 16	112 mmHg Standard Deviation 10	111 mmHg Standard Deviation 8	103 mmHg Standard Deviation 10	110 mmHg Standard Deviation 14

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment

Population: Data are for subsample of women who completed FMD with useuable data

This other outcome measure was originally specified as "Secondary" in error and has been updated to "Other, Pre-specified" to be consistent with the protocol. Serum estradiol for clinical characteristics and to detect changes in estradiol levels with the interventions.

Outcome measures

Outcome measures
Measure	Peri1 n=17 Participants Perimenopausal (early and late combined) - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri2 n=21 Participants Perimenopausal (early and late combined) - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post1 n=12 Participants Postmenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post2 n=13 Participants Postmenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre1 n=12 Participants Premenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre2 n=12 Participants Premenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Estradiol Baseline	360 pmol/L Interval 46.0 to 508.0	147 pmol/L Interval 62.0 to 316.0	39 pmol/L Interval 37.0 to 49.0	37 pmol/L Interval 37.0 to 42.0	229 pmol/L Interval 117.0 to 332.0	270 pmol/L Interval 128.0 to 484.0
Estradiol GnRHant alone	92 pmol/L Interval 37.0 to 468.0	99 pmol/L Interval 37.0 to 321.0	37 pmol/L Interval 37.0 to 42.0	37 pmol/L Interval 37.0 to 42.0	147 pmol/L Interval 87.0 to 183.0	127 pmol/L Interval 96.0 to 243.0
Estradiol GnRhant+Add-back	187 pmol/L Interval 81.0 to 569.0	106 pmol/L Interval 37.0 to 321.0	165 pmol/L Interval 128.0 to 223.0	37 pmol/L Interval 37.0 to 39.0	202 pmol/L Interval 140.0 to 481.0	134 pmol/L Interval 117.0 to 183.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back

Population: Data presented are from those women who had FMD with usable images

This other outcome measure was originally specified as "Secondary" in error and has been updated to "Other, Pre-specified" to be consistent with the protocol. Serum progesterone was measured for clinical characteristics and to determine changes in sex hormones.

Outcome measures

Outcome measures
Measure	Peri1 n=17 Participants Perimenopausal (early and late combined) - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri2 n=21 Participants Perimenopausal (early and late combined) - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post1 n=12 Participants Postmenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post2 n=13 Participants Postmenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre1 n=12 Participants Premenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre2 n=12 Participants Premenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Progesterone Baseline	1.1 nmol/L Interval 0.6 to 1.9	1.3 nmol/L Interval 1.0 to 1.9	1.1 nmol/L Interval 0.6 to 1.3	0.9 nmol/L Interval 0.6 to 1.3	1.8 nmol/L Interval 0.7 to 2.5	2.1 nmol/L Interval 1.0 to 3.1
Progesterone GnRHant alone	1.0 nmol/L Interval 0.6 to 1.9	1.0 nmol/L Interval 0.6 to 2.5	1.0 nmol/L Interval 0.3 to 1.3	0.6 nmol/L Interval 0.3 to 1.1	1.3 nmol/L Interval 0.4 to 2.9	1.7 nmol/L Interval 0.7 to 3.7
Progesterone GnRhant+Add-back	0.8 nmol/L Interval 0.6 to 3.6	1.6 nmol/L Interval 0.7 to 4.9	1.0 nmol/L Interval 0.6 to 1.0	0.6 nmol/L Interval 0.6 to 1.1	1.0 nmol/L Interval 0.5 to 2.7	1.0 nmol/L Interval 0.6 to 2.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back

Population: Data are presented from participants that completed the endothelial function testing and who had usable images.

This other outcome measure was originally specified as "Secondary" in error and has been updated to "Other, Pre-specified" to be consistent with the protocol. TAS is an antioxidant and is a biomarker of oxidative stress.

Outcome measures

Outcome measures
Measure	Peri1 n=17 Participants Perimenopausal (early and late combined) - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri2 n=21 Participants Perimenopausal (early and late combined) - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post1 n=12 Participants Postmenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post2 n=13 Participants Postmenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre1 n=12 Participants Premenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre2 n=12 Participants Premenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Total Antioxidant Status (TAS) Baseline	1.3 nmol/L Standard Deviation 0.2	1.3 nmol/L Standard Deviation 0.1	1.3 nmol/L Standard Deviation 0.2	1.3 nmol/L Standard Deviation 0.2	1.4 nmol/L Standard Deviation 0.2	1.4 nmol/L Standard Deviation 0.2
Total Antioxidant Status (TAS) GnRHant alone	1.3 nmol/L Standard Deviation 0.2	1.3 nmol/L Standard Deviation 0.2	1.3 nmol/L Standard Deviation 0.1	1.4 nmol/L Standard Deviation 0.3	1.4 nmol/L Standard Deviation 0.2	1.5 nmol/L Standard Deviation 0.1
Total Antioxidant Status (TAS) GnRhant+Add-back	1.3 nmol/L Standard Deviation 0.1	1.3 nmol/L Standard Deviation 0.1	1.3 nmol/L Standard Deviation 0.2	1.3 nmol/L Standard Deviation 0.2	1.4 nmol/L Standard Deviation 0.1	1.4 nmol/L Standard Deviation 0.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back

Population: Data are presented from women who completed endothelial function testing and whom had usable images

This other outcome measure was originally specified as "Secondary" in error and has been updated to "Other, Pre-specified" to be consistent with the protocol.

Outcome measures

Outcome measures
Measure	Peri1 n=17 Participants Perimenopausal (early and late combined) - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Peri2 n=21 Participants Perimenopausal (early and late combined) - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post1 n=12 Participants Postmenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Post2 n=13 Participants Postmenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre1 n=12 Participants Premenopausal - GnRHant plus estradiol GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal estradiol patch: 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)	Pre2 n=12 Participants Premenopausal - GnRHant plus placebo GnRHant - Ganirelix acetate: 1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7 Transdermal placebo patch: Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)
Endothelin-1 (ET-1) Baseline	5.9 pg/mL Standard Deviation 1.3	6.2 pg/mL Standard Deviation 1.6	6.2 pg/mL Standard Deviation 1.4	6.4 pg/mL Standard Deviation 1.1	5.2 pg/mL Standard Deviation 1.5	5.2 pg/mL Standard Deviation 0.9
Endothelin-1 (ET-1) GnRHant alone	6.0 pg/mL Standard Deviation 1.8	5.9 pg/mL Standard Deviation 0.9	6.5 pg/mL Standard Deviation 2.1	6.5 pg/mL Standard Deviation 0.9	5.5 pg/mL Standard Deviation 1.7	5.5 pg/mL Standard Deviation 0.9
Endothelin-1 (ET-1) GnRhant+Add-back	5.9 pg/mL Standard Deviation 1.6	5.7 pg/mL Standard Deviation 1.9	6.0 pg/mL Standard Deviation 1.8	6.4 pg/mL Standard Deviation 0.9	6.0 pg/mL Standard Deviation 1.1	5.0 pg/mL Standard Deviation 0.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back

Population: Data are presented from women who completed endothelial function testing and whom had useable images.

This other outcome measure was originally specified as "Secondary" in error and has been updated to "Other, Pre-specified" to be consistent with the protocol.