A Treatment Study for Premenstrual Syndrome (PMS)
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|ClinicalTrials.gov Identifier: NCT00001259|
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : June 24, 2020
This study examines the effects of estrogen and progesterone on mood, the stress response, and brain function and behavior in women with premenstrual syndrome.
Previously this study has demonstrated leuprolide acetate (Lupron (Registered Trademark)) to be an effective treatment for PMS. The current 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 women with PMS.
PMS is a condition characterized by changes in mood and behavior that occur during the second phase of the normal menstrual cycle (luteal phase). This study will investigate possible hormonal causes of PMS by temporarily stopping the menstrual cycle with leuprolide acetate and then giving, in sequence, the menstrual cycle hormones progesterone and estrogen. The results of these hormonal studies will be compared between women with PMS and healthy volunteers without PMS (see also protocol 92-M-0174).
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 or disease||Intervention/treatment||Phase|
|Premenstrual Syndrome Menstruation Disturbances||Drug: Leuprolide Drug: Estradiol Patches Drug: Progesterone||Phase 1|
This protocol is designed to accompany Clinical Protocol # 81-M-0126, The Phenomenology and Biophysiology of Menstrually-Related Mood and Behavioral Disorders. Its original purposes were as follows: 1) to evaluate the efficacy of the gonadotropin releasing hormone (GnRH) agonist depot leuprolide acetate (Lupron) in the treatment of menstrually-related mood disorders (MRMD) by determining whether mood and behavioral symptoms are eliminated when the cyclic secretion of both gonadotropic hormones and gonadal steroids is suppressed, and 2) to determine the possible relevance of gonadal steroids to affective state by sequentially replacing estradiol and progesterone during continued GnRH suppression in those patients whose premenstrual symptoms remit following administration of the GnRH agonist. We observed that GnRH agonist induced ovarian suppression was an effective treatment compared to placebo in women with MRMD. Additionally, women with MRMD but not asymptomatic controls (participating in companion protocol 92-M-0174) experienced a recurrence of mood and behavioral symptoms when either estradiol or progesterone (but not placebo) was added back. These data suggest that women with MRMD have a differential sensitivity to the mood destabilizing effects of gonadal steroids.
Having established that women with MRMD show a differential behavioral response to estrogen and progesterone, we now hope to identify the underlying mechanisms and physiologic concomitants of the differential behavioral sensitivity by performing studies (described in companion protocols) under the three hormonal conditions created by this protocol, and comparing results obtained with those seen in normal controls (Protocol #92-M-0174). Planned studies include the following: cognitive testing, brain imaging (3D PET, FMRI, MRS) and genetic studies including induced pluripotent cells.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||64 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||The Treatment of Menstrually-Related Mood Disorders With the Gonadotropin Releasing Hormone (GnRH) Agonist, Depot Leuprolide Acetate (Lupron)|
|Actual Study Start Date :||August 11, 1992|
|Actual Primary Completion Date :||February 6, 2020|
|Actual Study Completion Date :||February 6, 2020|
Experimental: Group 1
Group I will receive 0.1 mg/day of estradiol via skin patch (Estraderm) for a period of five weeks. During the fifth week, progesterone suppositories (200 mgs twice daily) will be added
Drug: Estradiol Patches
0.1 mg/day of estradiol via skin patch (Estraderm) for a period of five weeks.
Experimental: Group II
progesterone suppositories (200 mg BID) will be administered for the first five weeks, followed by a two week washout, and then estradiol 0.1 mg /day for five weeks, with the addition of progesterone during the fifth week of estrogen treatment.
progesterone suppositories (200 mgs twice daily)
3.75 mg of Leuprolide via intramuscular injection on a monthly basis in our clinic for a maximum of twenty-four weeks
- Metabolomic Profile [ Time Frame: Ongoing ]Metabolomic Profile
- Brain Imaging [ Time Frame: ongoing ]Brain Imaging
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001259
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Peter J Schmidt, M.D.||National Institute of Mental Health (NIMH)|