The Effects of Reproductive Hormones on Mood and Behavior

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001322
First received: November 3, 1999
Last updated: August 5, 2014
Last verified: November 2013
  Purpose

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.


Condition
Hypogonadism

Study Type: Observational
Official Title: The Central Nervous System Effects of Pharmacologically Induced Hypogonadotropic Hypogonadism With and Without Estrogen and Progesterone Replacement

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 140
Study Start Date: April 1992
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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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;

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001322

Contacts
Contact: Peter J Schmidt, M.D. (301) 496-6120 peterschmidt@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Peter J Schmidt, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00001322     History of Changes
Other Study ID Numbers: 920174, 92-M-0174
Study First Received: November 3, 1999
Last Updated: August 5, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Gonadal Steroids
Mood
Menstrual Cycle
Neuropsychological Testing
Estrogen
Dexamethasone
Progesterone
Central Nervous System Function
Estradiol
GnRH Agonist

Additional relevant MeSH terms:
Hypogonadism
Gonadal Disorders
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 22, 2014