Postmenopausal Women Estrogen and Progesterone Infusion

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00455741
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 177.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to study the effects of aging, estrogen and progesterone on the brain. Specifically, we want to look at how the hypothalamus and pituitary (two small glands in the brain) respond to estrogen. The pituitary gland is controlled by the hypothalamus. The hypothalamus secretes GnRH (Gonadotropin-Releasing Hormone) that signals the pituitary to secrete the reproductive hormones, LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone). These hormones act on the ovaries and signal the ovaries to produce estrogen and progesterone. Estrogen in the bloodstream then acts on the brain to modulate this system with changes in LH and FSH. Early changes associated with low levels of estrogen are inhibitory (estrogen negative feedback) while higher levels of estrogen (such as those present when a follicle in the ovary is ready to ovulate) stimulate LH to cause ovulation (positive feedback). This study will determine: 1) hypothalamic and pituitary levels of glucose uptake (as a measure of brain metabolic activity) at baseline and in association with estrogen negative feedback on LH (24 hr) and estrogen positive feedback on LH (72 hr); and 2) the effect of aging on estrogen feedback on LH, assessing negative feedback (nadir ~ 24 hr) and positive feedback (peak between 72 and 96 hr).

Condition or Disease	Intervention/Treatment	Phase
Postmenopause; Aging	Drug: Estradiol infusion; Drug: Progesterone infusion	Phase 1/Phase 2

Detailed Description

The transition to menopause is characterized by a decline in the numbers of functional ovarian follicles followed by a decrease in levels of inhibin A and B and complex changes in estradiol, which include an initial increase followed by an inevitable decrease. Therefore, there are dynamic changes in the hypothalamic-pituitary feedback from the aging ovary, prior to the ultimate loss of feedback that occurs with the complete cessation of ovarian function. While there is ample evidence that the loss of ovarian function is a major contributor to the menopause, there is evidence from animal models that primary age-related neuroendocrine changes may also contribute to reproductive aging. Specifically, there is evidence for changes in the hypothalamic and pituitary responses to estrogen negative and positive feedback. An understanding of the age-related changes in the physiology of the hypothalamic and pituitary responsiveness to gonadal steroid feedback is critical in determining whether hypothalamic and pituitary changes per se contribute to the menopause and the impact of the loss of reproductive function on the brain.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Estradiol and progesterone infusion to assess negative and positive feedback on the hypothalamus and pituitary in young and older postmenopausal women.Estradiol and progesterone infusion to assess negative and positive feedback on the hypothalamus and pituitary in young and older postmenopausal women.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Effect of Age on Gonadotropin Responses to Short-Term Negative and Positive Feedback Effects of Gonadal Steroids Using PET Scanning
• Study Start Date: Nov 1, 2000
• Actual Primary Completion Date: Feb 1, 2007
• Actual Study Completion Date: Aug 22, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Young postmenopausal women Graded estradiol infusion to young postmenopausal women. Graded progesterone infusion to young postmenopausal women.	Drug: Estradiol infusion; Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr and 0.2 mcg/kg/hr for 60 hr.; Drug: Progesterone infusion; Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
Active Comparator: Older postmenopausal women Graded estradiol infusion to young postmenopausal women. Graded progesterone infusion to young postmenopausal women..	Drug: Estradiol infusion; Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr and 0.2 mcg/kg/hr for 60 hr.; Drug: Progesterone infusion; Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.

Outcome Measures

Primary Outcome Measures

1. Effect of Aging on Estrogen Negative Feedback on LH [Baseline at 0 time before infusion, nadir occurred between 8 and 60 hr (mean 24 hr)]

   Difference between baseline LH (average of 3 samples drawn 15 min apart) and nadir LH based on a 3-point moving average of blood samples drawn every 4 hours over 120 hr, expressed as a percent of baseline (% baseline).

2. Effect of Aging on Estrogen Positive Feedback on LH [Onset of surge (average of 61 hr from beginnning of infusion until the end of the study (120 hr)]

   LH area under the curve in response to estrogen positive feedback. Area under the curve was calculated from blood samples drawn every 4 hours from the onset of positive feedback until the end of the study (120 min). The onset of positive feedback is defined as the time when LH first exceeds mean + 2SD of the previous three time points and shows a sustained rise.

Secondary Outcome Measures

1. 18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Negative Feedback [Baseline vs 24 hr after the onset of steroid infusion]

   Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.

2. 18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Negative Feedback [0 vs 24 hr]

   Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.

3. 18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Positive Feedback [24 hr vs 72 hr]

   Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.

4. 18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Positive Feedback [24 vs 72 hr]

   Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 80 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

postmenopausal women young (age 45-55) or old (age 70-80) History of natural menopause defined by the absence of menses for at least 12 months (or history of surgical menopause defined as bilateral oophorectomy) Normal TSH, PRL and CBC, and Factor V activity Normal BUN and Creatinine (< 2 times the upper limit of normal) BMI between 18 to 30 kg/m2 An increased FSH measured at the screening visit will be consistent with menopause. If the initial determination is low, a repeat sample may be drawn.

Exclusion criteria:

Hormonal medication or herbal supplements and/or over the counter menopause therapy in the 2 months prior to study Any absolute contraindications to the use of physiologic replacement doses of estrogen and/or progesterone History of coronary artery disease Medications thought to act centrally on the GnRH pulse generator History of breast cancer or blood clots Smoking more than 10 cigarettes/day Prior history of allergic reaction to any dyes used with x-rays or scans and/ or any other contraindications to PET scans No metal implants, pacemakers, aneurysm clips, implanted hearing aids and/or any other contraindications to MRI scan

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Janet E Hall, M.D., Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janet E. Hall, MD, Associate Physician, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00455741
• Other Study ID Numbers: 2000P-002496; R01AG013241
• First Posted: Apr 4, 2007
• Last Update Posted: May 18, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Janet E. Hall, MD, Associate Physician, Massachusetts General Hospital: menopause; estrogen; progesterone; hormone replacement; aging; PET
• Additional relevant MeSH terms: Estradiol; Progesterone

Study Results

Participant Flow

Recruitment Details	36 subjects consented; 6 failed screening, 2 decided not to participate.
Pre-assignment Detail	1 subject terminated during study (hemoglobin drop) for a total of 24 completed.

Arm/Group Title	Younger PMW	Older PMW
Arm/Group Description	Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.	Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
Period Title: Overall Study
STARTED	13	12
COMPLETED	13	11
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Younger PMW	Older PMW	Total
Arm/Group Description	Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.	Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.	Total of all reporting groups
Overall Participants	13	12	25
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.9 (3.8)	75.2 (3.6)	61.3 (13.4)
Sex: Female, Male (Count of Participants)
Female	13 100%	12 100%	25 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 38.5%	0 0%	5 20%
White	8 61.5%	12 100%	20 80%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%	12 100%	20 80%

Outcome Measures

1. Primary Outcome

Title	Effect of Aging on Estrogen Negative Feedback on LH
Description	Difference between baseline LH (average of 3 samples drawn 15 min apart) and nadir LH based on a 3-point moving average of blood samples drawn every 4 hours over 120 hr, expressed as a percent of baseline (% baseline).
Time Frame	Baseline at 0 time before infusion, nadir occurred between 8 and 60 hr (mean 24 hr)

Outcome Measure Data

Analysis Population Description

NOTE: 2 older and 2 younger postmenopausal women excluded from this analysis as estradiol levels exceeded physiological exposure levels

Arm/Group Title	Younger PMW	Older PMW
Arm/Group Description	Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.	Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
Measure Participants	11	9
Mean (Standard Error) [% change from baseline]	-52.8 (3.0)	-53.2 (2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Younger PMW, Older PMW
	Comments	effect of age on estrogen negative feedback ( nadir LH as % of baseline LH)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Younger PMW, Older PMW
	Comments	positive feedback
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.03
	Comments	a priori threshold for significance is p<0.05
	Method	ANOVA
	Comments

2. Primary Outcome

Title	Effect of Aging on Estrogen Positive Feedback on LH
Description	LH area under the curve in response to estrogen positive feedback. Area under the curve was calculated from blood samples drawn every 4 hours from the onset of positive feedback until the end of the study (120 min). The onset of positive feedback is defined as the time when LH first exceeds mean + 2SD of the previous three time points and shows a sustained rise.
Time Frame	Onset of surge (average of 61 hr from beginnning of infusion until the end of the study (120 hr)

Outcome Measure Data

Analysis Population Description

NOTE: 2 older and 2 younger postmenopausal women excluded from this analysis as estradiol levels exceeded physiological exposure levels

Arm/Group Title	Young Postmenopausal Women	Older Postmenopausal Women
Arm/Group Description	Graded estradiol infusion to young postmenopausal women. Graded progesterone infusion to young postmenopausal women. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.	Graded estradiol infusion to young postmenopausal women. Graded progesterone infusion to young postmenopausal women.. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
Measure Participants	11	9
Mean (Standard Error) [IU*hr/L]	4544.6 (636.3)	2885.5 (316.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Younger PMW, Older PMW
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.03
	Comments	a priori significance level p<0.05
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Negative Feedback
Description	Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.
Time Frame	Baseline vs 24 hr after the onset of steroid infusion

Outcome Measure Data

Analysis Population Description

postmenopausal women

Arm/Group Title	Baseline Pituitary	Negative Feedback Pituitary
Arm/Group Description	18 FDG uptake at the pituitary at baseline	18 FDG uptake at the pituitary at 24 hr associated with estrogen induced negative feedback on LH
Measure Participants	11	11
Mean (Standard Error) [units]	45.8 (4.5)	48.4 (4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Younger PMW, Older PMW
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments	threshold for significance p<0.05
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Negative Feedback
Description	Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.
Time Frame	0 vs 24 hr

Outcome Measure Data

Analysis Population Description

postmenopausal women

Arm/Group Title	Baseline Hypothalamus	Negative Feedback Hypothalamus
Arm/Group Description	18 FDG uptake at the hypothalamus at baseline	18 FDG uptake at the at the hypothalamus at 24 hr associated with estrogen induced negative feedback on LH
Measure Participants	11	11
Mean (Standard Error) [units]	69.0 (3.3)	63.1 (2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Younger PMW, Older PMW
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.02
	Comments	a priori threshold for significance p<0.05
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Positive Feedback
Description	Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.
Time Frame	24 hr vs 72 hr

Outcome Measure Data

Analysis Population Description

postmenopausal women

Arm/Group Title	Pituitary at 24 hr	Pituitary at 72 hr
Arm/Group Description	18 FDG uptake at the pituitary at 24 hr	18 FDG uptake at the pituitary at 72 hr associated with estrogen induced positive feedback on LH
Measure Participants	11	11
Mean (Standard Error) [units]	48.0 (4.0)	54.3 (4.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Younger PMW, Older PMW
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.03
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Positive Feedback
Description	Regional cerebral glucose metabolism (rCMRglu) is used as a measure of neuronal metabolic activity and calculated as average uptake (voxels) of 18 flurodeoxyglucose within the region of interest (ROI) and expressed simply as units. Normalized uptake refers to co-registration of the PET with the MRI to provide more accurate anatomic correlates.
Time Frame	24 vs 72 hr

Outcome Measure Data

Analysis Population Description

postmenopausal women

Arm/Group Title	Hypothalamus at 24 hr	Hypothalamus 72 hr
Arm/Group Description	18 FDG uptake at the hypothalamus at 24 hr	18 FDG uptake at the pituitary at 72 hr associated with estrogen induced positive feedback on LH
Measure Participants	11	11
Mean (Standard Error) [unit]	63.1 (2.8)	66.2 (3.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Younger PMW, Older PMW
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments	a priori significance set at p<0.05
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	60 days for each subject; 4 years in total
Adverse Event Reporting Description	As in clinicaltrials.gov
Arm/Group Title	Younger PMW		Older PMW
Arm/Group Description	Postmenopausal women (PMW) ages 45-55 receiving the following hormone infusions. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.		Postmenopausal women (PMW) ages 70-80 receiving the following hormone infusions. Estradiol infusion: Graded estradiol infusion of 0.1 mcg/kg/hr for 12 hr, 0.135 mcg/kg/hr for 12 hr, 0.165 mcg/kg/hr for 12 hr, and 0.2 mcg/kg/hr for 60 hr. Progesterone infusion: Progesterone infusion of 4.77 nmol/kg/hr (1.5 mcg/kg/hr) for 24 hr and 6.36 nmol/kg/hr (2 mcg/kg/hr) for the final 24 hr of the 5-day study.
All Cause Mortality
	Younger PMW		Older PMW
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Serious Adverse Events
	Younger PMW		Older PMW
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Younger PMW		Older PMW
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/13 (15.4%)		1/12 (8.3%)
Blood and lymphatic system disorders
anemia	0/13 (0%)	0	1/12 (8.3%)	1
Vascular disorders
vasomotor symptoms	2/13 (15.4%)	2	0/12 (0%)	0

Limitations/Caveats

PET scan data addresses hypothalamic vs pituitary sites of negative and positive estrogen feedback on LH, but there was insufficient power to address the effect of aging on these secondary measures..

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.