Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R01AG027678 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to find out why women's arteries stiffen as they go through menopause, and how this is affected by estrogen loss. We believe that arteries stiffen with the loss of estrogen because of "oxidative stress," the production of molecules that can damage cells and tissues in the body, and because the arteries lose their ability to expand, or dilate.
As women get older and go through menopause, estradiol levels decrease. Also with aging, the arteries that are located around the heart get stiffer. Over time this increase in arterial stiffness can lead to a number of health problems such as high blood pressure and heart disease. In this study we want to find out if a short-term drop in estrogen levels in premenopausal and perimenopausal women can cause arteries to become stiffer, and why this happens. Additionally, in postmenopausal women, we want to find out if a short-term increase in estrogen levels causes their arteries to become more flexible (less stiff).
Arterial health (i.e., stiffness) will be examined in premenopausal, perimenopausal and postmenopausal women before and after they are given a drug called Ganirelix™ (for 7 days), which will markedly lower their reproductive hormones. After the first 4 days of taking Ganirelix™, the women will be randomly placed into 1 of 2 treatment groups to take either estrogen (0.075 mg/d skin patch) replacement or placebo for the rest of the Ganirelix treatment. This is to increase estrogen levels back to the normal level. After having the patch on for 4 days, arterial health will be examined again.
Pre-specified Outcome Measures were divided into unit-of-measurement specific Outcome Measure tables for the purposes of results reporting to ClinicalTrials.gov
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pre1 | Experimental | Premenopausal - GnRHant plus estradiol |
|
| Pre2 | Placebo Comparator | Premenopausal - GnRHant plus placebo |
|
| Peri1 | Experimental | Perimenopausal (early) - GnRHant plus estradiol |
|
| Peri2 | Placebo Comparator | Perimenopausal (early) - GnRHant plus placebo |
|
| Peri3 | Experimental | Perimenopausal (late) - GnRHant plus estradiol |
|
| Peri4 | Placebo Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GnRHant - Ganirelix acetate | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Arterial Stiffness (Carotid Artery Compliance) During Saline | Carotid artery compliance measured by carotid artery ultrasound and brachial artery blood pressure | Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment |
| Endothelial Function | 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. | Baseline, day 4 of GnRHant and Day 7 of GnRHant and estradiol or placebo treatment |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Supine Brachial Blood Pressures | Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment | |
| Estradiol | 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. |
Inclusion Criteria:
Healthy women of all races and ethnic backgrounds in one of the following groups:
All postmenopausal women will have undergone natural menopause
No oral contraceptive or Hormone Replacement Therapy (HRT) use for at least 6 months
Resting blood pressure less than 140/90 mmHg
Plasma glucose concentrations less than 110 mg/dl under fasting conditions
Sedentary or recreationally active (less than 3 days of vigorous aerobic exercise)
No use of medications that might influence cardiovascular function
Nonsmokers
No use of vitamin supplements or willing to stop use for duration of the study
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kerrie L Moreau, PhD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Anschutz Medical Center, Clinical Translational Research Center and Exercise Research Laboratory | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12618248 | Background | Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res. 2003 Mar;57(3):861-8. doi: 10.1016/s0008-6363(02)00777-0. | |
| 15867135 | Background | Moreau KL, Gavin KM, Plum AE, Seals DR. Ascorbic acid selectively improves large elastic artery compliance in postmenopausal women. Hypertension. 2005 Jun;45(6):1107-12. doi: 10.1161/01.HYP.0000165678.63373.8c. Epub 2005 May 2. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | 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) |
| FG002 | 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) |
| FG003 | 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) |
| FG004 | 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) |
| FG005 | 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) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
For primary outcome brachial artery FMD, 91 completed the study. Four participants did not have usable FMD data due to poor ultrasound image quality or technical issues with image acquisition; baseline analysis and results for the remaining 87 women are presented.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Arterial Stiffness (Carotid Artery Compliance) During Saline | Carotid artery compliance measured by carotid artery ultrasound and brachial artery blood pressure | Early and late perimenopausal were collapsed into 1 perimenopausal group | Posted | Mean | Standard Deviation | mm2/mm Hg×10-1 | Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment |
|
Not provided
Participants were asked at each vascular visit to complete a symptom questionnaire. These data were reviewed immediately by the PI and the study physician. Further, these data were summarized for the Safety Officer annually.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiovascular/neurology | Injury, poisoning and procedural complications | Systematic Assessment | Vasal vagal to nitrogylcerine |
Budget cuts lead to: 1) endothelial cell protein expression outcome not analyzed and deleted; 2) small numbers of early and late perimenopausal groups, thus, it was collapsed into 1 peri group. Ultrasound image quality also lead to small numbers.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kerrie Moreau. PI | University of Colorado Anschutz Medical Campus | 303-724-1914 | kerrie.moreau@cuanschutz.edu |
Not provided
| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C061018 | ganirelix |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Perimenopausal (late) - GnRHant plus placebo |
|
| Post1 | Experimental | Postmenopausal - GnRHant plus estradiol |
|
| Post2 | Placebo Comparator | Postmenopausal - GnRHant plus placebo |
|
|
| Transdermal estradiol patch | Drug | 0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7) |
|
| Transdermal placebo patch | Drug | Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7) |
|
| Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment |
| Progesterone | 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. | Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back |
| Total Antioxidant Status (TAS) | 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. | Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back |
| Endothelin-1 (ET-1) | 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. | Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back |
| Plasma Norepinephrine | 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. | Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back |
| 10811592 | Background | Virdis A, Ghiadoni L, Pinto S, Lombardo M, Petraglia F, Gennazzani A, Buralli S, Taddei S, Salvetti A. Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women. Circulation. 2000 May 16;101(19):2258-63. doi: 10.1161/01.cir.101.19.2258. |
| 12411396 | Background | Ihionkhan CE, Chambliss KL, Gibson LL, Hahner LD, Mendelsohn ME, Shaul PW. Estrogen causes dynamic alterations in endothelial estrogen receptor expression. Circ Res. 2002 Nov 1;91(9):814-20. doi: 10.1161/01.res.0000038304.62046.4c. |
| 14754992 | Background | Eskurza I, Monahan KD, Robinson JA, Seals DR. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol. 2004 Apr 1;556(Pt 1):315-24. doi: 10.1113/jphysiol.2003.057042. Epub 2004 Jan 30. |
| 22692329 | Background | Gavin KM, Jankowski C, Kohrt WM, Stauffer BL, Seals DR, Moreau KL. Hysterectomy is associated with large artery stiffening in estrogen-deficient postmenopausal women. Menopause. 2012 Sep;19(9):1000-7. doi: 10.1097/gme.0b013e31825040f9. |
| 22245769 | Background | Moreau KL, Meditz A, Deane KD, Kohrt WM. Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women. Am J Physiol Heart Circ Physiol. 2012 Mar 1;302(5):H1211-8. doi: 10.1152/ajpheart.01065.2011. Epub 2012 Jan 13. |
| 22969140 | Result | Moreau KL, Hildreth KL, Meditz AL, Deane KD, Kohrt WM. Endothelial function is impaired across the stages of the menopause transition in healthy women. J Clin Endocrinol Metab. 2012 Dec;97(12):4692-700. doi: 10.1210/jc.2012-2244. Epub 2012 Sep 11. |
| BG001 | 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) |
| BG002 | Peri1 | 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) |
| BG003 | Peri2 | 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) |
| BG004 | 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) |
| BG005 | 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) |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass | Mean | Standard Deviation | kg |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m2 |
|
| Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Diastolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| VO2peak | Mean | Standard Deviation | ml/kg/min |
|
| Glucose | Mean | Standard Deviation | mmol/L |
|
| Insulin | Median | Inter-Quartile Range | pmol/L |
|
| Total Cholesterol | Mean | Standard Deviation | mmol/L |
|
| Low-density Lipoprotein | Mean | Standard Deviation | mmol/L |
|
| High-density Lipoprotein | Mean | Standard Deviation | mmol/L |
|
| 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) |
| OG002 | 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) |
| OG003 | 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) |
| OG004 | 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) |
| OG005 | 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) |
|
|
| Primary | Endothelial Function | 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. | Numbers for some groups are reduced because of poor ultrasound image quality. | Posted | Mean | Standard Deviation | % Diameter Change | Baseline, day 4 of GnRHant and Day 7 of GnRHant and estradiol or placebo treatment |
|
|
|
|
| Other Pre-specified | Supine Brachial Blood Pressures | Posted | Mean | Standard Deviation | mmHg | Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment |
|
|
|
| Other Pre-specified | Estradiol | 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. | Data are for subsample of women who completed FMD with useuable data | Posted | Median | Inter-Quartile Range | pmol/L | Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment |
|
|
|
|
| Other Pre-specified | Progesterone | 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. | Data presented are from those women who had FMD with usable images | Posted | Median | Inter-Quartile Range | nmol/L | Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back |
|
|
|
|
| Other Pre-specified | Total Antioxidant Status (TAS) | 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. | Data are presented from participants that completed the endothelial function testing and who had usable images. | Posted | Mean | Standard Deviation | nmol/L | Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back |
|
|
|
| Other Pre-specified | Endothelin-1 (ET-1) | 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. | Data are presented from women who completed endothelial function testing and whom had usable images | Posted | Mean | Standard Deviation | pg/mL | Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back |
|
|
|
| Other Pre-specified | Plasma Norepinephrine | 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. | Data are presented from women who completed endothelial function testing and whom had useable images. | Posted | Median | Inter-Quartile Range | pg/mL | Baseline, Day 4 GnRHant, Day 7 GnRHant+Add-back |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 8 |
| 12 |
| EG001 | 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) | 0 | 12 | 0 | 12 | 4 | 12 |
| EG002 | 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) | 0 | 19 | 0 | 19 | 9 | 19 |
| EG003 | 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) | 0 | 21 | 0 | 21 | 8 | 21 |
| EG004 | 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) | 0 | 13 | 0 | 13 | 5 | 13 |
| EG005 | 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) | 0 | 15 | 0 | 15 | 4 | 15 |
|
| Bloating | Gastrointestinal disorders | Systematic Assessment |
|
| Breast tenderness | Reproductive system and breast disorders | Systematic Assessment |
|
| Injection site reaction | Skin and subcutaneous tissue disorders | Systematic Assessment | Dermatology |
|
| Joint Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Patch irritation | Skin and subcutaneous tissue disorders | Systematic Assessment | Transdermal patch irritation, redness |
|
| Vaginal bleeding | Reproductive system and breast disorders | Systematic Assessment |
|
| Other urogenital | Reproductive system and breast disorders | Systematic Assessment | Vaginal discharge, dryness |
|
Not provided
Not provided
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
|
|
|
| Day 4 of GnRHant alone |
|
|
| Day 7 of GnRHant plus treatment |
|
|
| Acute Vitamin C Infusion Day 7 |
|
|
| Day 4 of GnRHant alone |
|
| Day 7 of GnRHant plus treatment |
|
| GnRHant alone |
|
| GnRhant+Add-back |
|
| GnRHant alone |
|
| GnRhant+Add-back |
|
| GnRHant alone |
|
| GnRhant+Add-back |
|
| GnRHant alone |
|
| GnRhant+Add-back |
|
| GnRHant alone |
|
| GnRhant+Add-back |
|