Phase 2 N=25 Other

Postmenopausal Women Estrogen and Progesterone Infusion

Postmenopause · Aging

Bottom Line

View on ClinicalTrials.gov: NCT00455741 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

May 2018

Primary outcome: Primary: Effect of Aging on Estrogen Negative Feedback on LH — -52.8; -53.2 % change from baseline — p=0.90

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Estradiol infusion (Drug); Progesterone infusion (Drug)
Age: Adult, Older Adult · 45+ yrs
Sex: Female
Sponsor: Massachusetts General Hospital
Primary completion: Feb 2007

Outcome Measures

Outcome	Result	p-value
PRIMARY Effect of Aging on Estrogen Negative Feedback on LH	-52.8; -53.2	0.90
PRIMARY Effect of Aging on Estrogen Positive Feedback on LH	4544.6; 2885.5	=0.03 sig
SECONDARY 18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Negative Feedback	45.8; 48.4	0.49
SECONDARY 18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Negative Feedback	69.0; 63.1	<0.02 sig
SECONDARY 18 FDG Uptake at the Pituitary During Estrogen Infusion: LH Positive Feedback	48.0; 54.3	<0.03 sig
SECONDARY 18 FDG Uptake at the Hypothalamus During Estrogen Infusion: LH Positive Feedback	63.1; 66.2	0.07

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).

Eligibility Criteria

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

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Data sourced from ClinicalTrials.gov (NCT00455741). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.