Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Treatment Study for Premenstrual Syndrome (PMS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00001259
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : June 24, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:

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

Detailed Description:

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.

<TAB>

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Progesterone
progesterone suppositories (200 mgs twice daily)

Experimental: Leuprolide
3.75 mg of Leuprolide via intramuscular injection on a monthly basis in our clinic for a maximum of twenty-four weeks
Drug: Leuprolide
3.75mg IMQM




Primary Outcome Measures :
  1. Metabolomic Profile [ Time Frame: Ongoing ]
    Metabolomic Profile

  2. Brain Imaging [ Time Frame: ongoing ]
    Brain Imaging



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

The subjects of this study will be women who meet the criteria for MRMD as described in Protocol No. 81-M-0126, 'The Phenomenology and Biophysiology of Menstrually-related Mood and Behavioral Disorders.' In brief, these criteria include:

  1. history within the last two years of at least six months with menstrually-related mood or behavioral disturbances of at least moderate severity--i.e., disturbances that are distinct in appearance and associated with a notable degree of subjective distress;
  2. symptoms should have a sudden onset and offset;
  3. age 18-50;
  4. not pregnant and in good medical health;
  5. medication free.

    All patients participating in this protocol will have already participated in Protocol No. 81-M-0126 and will have a prospectively confirmed and predictable relationship between their mood disorder and the premenstrual phase of the menstrual cycle, i.e., a 30% change in severity of symptom self rating scales, relative to the range of the scale employed, during the seven days premenstrually compared with the seven days post-menstrually in two out of three months of study.

    The Schedule for Affective Disorders and Schizophrenia will be administered to all patients prior to study entry. Any patient with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.

    Prior to treatment, a complete physical and neurological examination will have been performed and the following routine laboratory data obtained:

    A. Blood

    Complete blood count; thyroid function tests; cortisol; renal function tests, such as BUN and creatinine; electrolytes; glucose; liver function tests.

    B. Urine

    Routine urinalysis; urine pregnancy test.

    GnRH agonist will not be administered to any subject with significant clinical or laboratory abnormalities. The blood tests and urinalysis will be repeated 2 weeks after GnRH agonist administration to rule out any evidence of acute renal, hepatic or hematologic toxicity.

    Results of Pap smear performed within one year of the onset of treatment will be obtained.

    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
    • 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. Specifically, we will exclude any woman with an elevated plasma FSH level (>= 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
    • 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.

Information from the National Library of Medicine

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


Locations
Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
Layout table for investigator information
Principal Investigator: Peter J Schmidt, M.D. National Institute of Mental Health (NIMH)
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00001259    
Other Study ID Numbers: 900088
90-M-0088
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: June 24, 2020
Last Verified: February 10, 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Depression
Menstrual Cycle
Gonadal Steroids
Estradiol
Progesterone
Mood Disorders
Additional relevant MeSH terms:
Layout table for MeSH terms
Syndrome
Premenstrual Syndrome
Menstruation Disturbances
Disease
Pathologic Processes
Leuprolide
Estradiol
Progesterone
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Reproductive Control Agents
Progestins
Fertility Agents, Female
Fertility Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents