The Effects of Reproductive Hormones on Mood and Behavior

ID: NCT00001322
Status: Recruiting
Phase: N/A
Start Date: April 25, 1992
First Submitted: November 03, 1999
Last Updated: February 22, 2018
Results: N/A
Sponsors & Collaborators: National Institute of Mental Health (NIMH)
Location: United States
Conditions: Hypogonadism
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Study Description

Brief Summary

This study evaluates the effects of estrogen and progesterone on mood, the stress response, and brain function in healthy women.

The purpose of this study is to evaluate how low levels of estrogen and progesterone (that occur during treatment with leuprolide acetate) compare to menstrual cycle levels of estrogen and progesterone (given during individual months of hormone add-back) on a variety of physiologic measures (brain imaging, stress testing, etc.) in healthy volunteer women without PMS.

This study will investigate effects of reproductive hormones by temporarily stopping the menstrual cycle with leuprolide acetate and then giving, in sequence, the menstrual cycle hormones progesterone and estrogen. Tests (such as brain imaging or stress testing, etc.) will be performed during the different hormonal conditions (low estrogen and progesterone, progesterone add-back, estrogen add-back). The results of these studies will be compared between women without PMS and women with PMS (see also protocol 90-M-0088).

At study entry, participants will undergo a physical examination. Blood, urine, and pregnancy tests will be performed. Cognitive functioning and stress response will be evaluated during the study along with brain imaging and genetic studies.

Detailed Description

Evidence suggests that the gonadal steroids may exert clinically significant effects on central nervous system function. For example, the menstrual cycle may influence the occurrence of seizures in some female epileptics and the performance on certain cognitive tests. Central nervous system effects of gonadal steroids have been inferred largely from changes in behavior occurring in association with presumed changes in gonadal steroids during the normal menstrual cycle, during the administration of ovarian hormones, or in a gender-specific context. These inferences are, by definition, indirect and associational in nature and further are incapable of disentangling the effects of hormones which are simultaneously present in women of reproductive age. This study is designed to address those problems by comparing measures during Lupron-induced hypogonadism with those during replacement with estrogen or progesterone. On the basis of prior findings from our group and from others, we will be asking the following questions: 1) Is the decreased r-CBF that we observed in the prefrontal cortex during the hypogonadal state confirmed in individual women using new imaging techniques; 2) Will variation in genotype (e.g., COMT val/met, BDNF val/met) confer differential sensitivity to ovarian steroids in brain circuitry and 3) Are the menstrual cycle phase-related changes in reward systems that we previously observed related to estradiol or progesterone actions within the brain (1). Additionally, this protocol will serve as a control study for protocol # 90-M-0088.
Condition or disease Intervention/treatment Phase

Hypogonadism

N/A

Tracking Information

First Submitted DateNovember 03, 1999
Last Update Posted DateFebruary 22, 2018
Start DateApril 25, 1992
Completion DateN/A
Primary Completion DateN/A
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

Not Available

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

Not Available

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleThe Effects of Reproductive Hormones on Mood and Behavior
Official TitleThe Central Nervous System Effects of Pharmacologically Induced Hypogonadotropic Hypogonadism With and Without Estrogen and Progesterone Replacement
Brief Summary

This study evaluates the effects of estrogen and progesterone on mood, the stress response, and brain function in healthy women.

The purpose of this study is to evaluate how low levels of estrogen and progesterone (that occur during treatment with leuprolide acetate) compare to menstrual cycle levels of estrogen and progesterone (given during individual months of hormone add-back) on a variety of physiologic measures (brain imaging, stress testing, etc.) in healthy volunteer women without PMS.

This study will investigate effects of reproductive hormones by temporarily stopping the menstrual cycle with leuprolide acetate and then giving, in sequence, the menstrual cycle hormones progesterone and estrogen. Tests (such as brain imaging or stress testing, etc.) will be performed during the different hormonal conditions (low estrogen and progesterone, progesterone add-back, estrogen add-back). The results of these studies will be compared between women without PMS and women with PMS (see also protocol 90-M-0088).

At study entry, participants will undergo a physical examination. Blood, urine, and pregnancy tests will be performed. Cognitive functioning and stress response will be evaluated during the study along with brain imaging and genetic studies.

Detailed Description

Evidence suggests that the gonadal steroids may exert clinically significant effects on central nervous system function. For example, the menstrual cycle may influence the occurrence of seizures in some female epileptics and the performance on certain cognitive tests. Central nervous system effects of gonadal steroids have been inferred largely from changes in behavior occurring in association with presumed changes in gonadal steroids during the normal menstrual cycle, during the administration of ovarian hormones, or in a gender-specific context. These inferences are, by definition, indirect and associational in nature and further are incapable of disentangling the effects of hormones which are simultaneously present in women of reproductive age. This study is designed to address those problems by comparing measures during Lupron-induced hypogonadism with those during replacement with estrogen or progesterone. On the basis of prior findings from our group and from others, we will be asking the following questions: 1) Is the decreased r-CBF that we observed in the prefrontal cortex during the hypogonadal state confirmed in individual women using new imaging techniques; 2) Will variation in genotype (e.g., COMT val/met, BDNF val/met) confer differential sensitivity to ovarian steroids in brain circuitry and 3) Are the menstrual cycle phase-related changes in reward systems that we previously observed related to estradiol or progesterone actions within the brain (1). Additionally, this protocol will serve as a control study for protocol # 90-M-0088.

Study TypeObservational
Study PhaseN/A
Estimated Enrollment
150
Allocation
Not Available
Interventional Model
Not Available
Masking
Not Available
Primary Purpose
Not Available
Conditions
Hypogonadism
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Not Available
Study Groups/Cohorts
Not Available
Study Arms
Not Available
Arm Intervention/Treatment

Recruitment Information

Recruitment Status:Recruiting
Enrollment150
Completion DateN/A
Eligibility Criteria: - INCLUSION CRITERIA:
Volunteers participating in this study will be women meeting the following criteria:
Between the ages of 18 and 50 years,
Not pregnant,
In good medical health,
Medication free,
No history of menstrual-related mood or behavioral disturbances.
Additionally, we will recruit a subsample of 20 asymptomatic women who will meet all inclusion and exclusion criteria in this protocol except they will have a history of a past major depressive episode.
Finally, a third sample of 10 women who meet all the inclusion and exclusion criteria listed above for this protocol will be recruited to establish the dose range of transdermal estrogen gel for this and related protocols (i.e., 90-M-0088 and 05-M-0059).
EXCLUSION CRITERIA:
The following conditions will constitute contraindications to treatment with hormonal therapy and will preclude a subject's participation in this protocol:
Current Axis I psychiatric diagnosis (with the exception of this women with a past major depression who will be studied on this protocol);
History consistent with endometriosis;
Diagnosis of ill-defined, obscure pelvic lesions, particularly undiagnosed ovarian enlargement;
Hepatic disease as manifested by abnormal liver function tests;
History of mammary carcinoma;
History of pulmonary embolism or phlebothrombosis;
Undiagnosed vaginal bleeding;
Porphyria;
Diabetes mellitus;
History of malignant melanoma;
Cholecystitis or pancreatitis;
Cardiovascular or renal disease;
Pregnancy;
Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for the perimenopause (129). Specifically, we will exclude any woman with an elevated plasma FSH level (greater than or equal to 14 IU/L) and with menstrual cycle variability of > 7 days different from their normal cycle length.
NIMH employees/staff and their immediate family members will be excluded from the study per NIMH policy.
Subjects taking birth control pills will be excluded from the study.
Subjects taking diuretics, prostaglandin inhibitors, or pyridoxine (putative treatments for MRMD) will similarly be excluded from the study, as will patients taking psychotropic agents (e.g., lithium carbonate, tricyclic antidepressants).
All subjects will be required to use non-hormonal forms of birth control (e.g., barrier methods) to avoid pregnancy during this study.
Participants who have an active condition that places them at an increased risk for osteoporosis will be excluded from this protocol.
GenderFemale
Age18 Years to 50 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT00001322
Other Study ID Numbers
920174
92-M-0174
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible PartyN/A
Study Sponsor
National Institute of Mental Health (NIMH)
Collaborators
Not Available
Investigators
Principal Investigator
Peter J Schmidt, M.D.
National Institute of Mental Health (NIMH)