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
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.
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
|First Submitted Date||November 03, 1999|
|Last Update Posted Date||February 22, 2018|
|Start Date||April 25, 1992|
|Primary Completion Date||N/A|
|Results First Submitted Date||N/A|
|Received Results Disposit Date||N/A|
Current Primary Outcome Measures
Original Primary Outcome Measures
Current Secondary Outcome Measures
Original Secondary Outcome Measures
|Brief Title||The Effects of Reproductive Hormones on Mood and Behavior|
|Official Title||The Central Nervous System Effects of Pharmacologically Induced Hypogonadotropic Hypogonadism With and Without Estrogen and Progesterone Replacement|
|Target Follow-Up Duration|| N/A|
- INCLUSION CRITERIA:|
Volunteers participating in this study will be women meeting the following criteria:
Between the ages of 18 and 50 years,
In good medical health,
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).
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
Hepatic disease as manifested by abnormal liver function tests;
History of mammary carcinoma;
History of pulmonary embolism or phlebothrombosis;
Undiagnosed vaginal bleeding;
History of malignant melanoma;
Cholecystitis or pancreatitis;
Cardiovascular or renal disease;
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
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.
|Age||18 Years to 50 Years|
|Accepts Healthy Volunteers||Accepts Healthy Volunteers|
|Listed Location Countries
|Other Study ID Numbers
|Has Data Monitoring Committee||No|
|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
Peter J Schmidt, M.D.
National Institute of Mental Health (NIMH)