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Combined Hormone Replacement in Menstrually-Related Mood Disorders
This study is currently recruiting participants.
Verified by National Institutes of Health Clinical Center (CC), February 2008
First Received: March 29, 2000   Last Updated: March 31, 2009   History of Changes
Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00005011
  Purpose

This study investigates the effects on symptoms of combined treatment with estrogen and progesterone in women with severe premenstrual syndrome (PMDD).

Studies indicate that women with PMS experience improvement in symptoms following treatment with leuprolide acetate, when estrogen and progesterone levels are low. Women with PMS, but not women without the disorder, experience a return of symptoms within approximately a week after re-exposure to either estrogen or progesterone. The cause of this hormone-induced depression remains unclear. It is not known whether this depressed mood is due simply to the change in the levels of estrogen and progesterone and whether it would remit following continued exposure to stable levels of estrogen and progesterone. This study will determine whether the maintenance of stable hormone levels will prevent mood disturbances in women with PMS.

Participants in this study will receive leuprolide acetate injections once a month for up to 6 months. After 2 months, women whose symptoms have improved will receive a skin patch containing either estrogen or placebo (an inactive substance) and will be asked to take daily suppositories containing either progesterone or placebo. Women whose symptoms of PMS do not respond to leuprolide treatment after 2 months will end the study and be offered other treatment. Participants will be seen by a nurse in the clinic every two weeks and will fill out ratings and have blood drawn to measure hormone levels.

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Condition Intervention
Premenstrual Syndrome
Depression
Drug: Depot Leuprolide Acetate

MedlinePlus related topics: Depression Premenstrual Syndrome
Drug Information available for: Leuprolide Leuprolide acetate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: The Treatment of Menstrually-Related Mood Disorders With Continuous Gonadal Steroid Replacement

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

Estimated Enrollment: 35
Study Start Date: March 2000
Intervention Details:
    Drug: Depot Leuprolide Acetate
    N/A
Detailed Description:

Results from previous protocols (#90-M-0088 and 92-M-0174) have demonstrated that women with menstrually-related mood disorder (MRMD), but not women lacking this disorder, experience mood deterioration within approximately a week after exposure to either estradiol or progesterone in the context of gonadal suppression (induced by use of the depot gonadotropin releasing hormone agonist, leuprolide acetate). It is unknown whether this hormone-induced depression occurs consequent to changes in gonadal steroid levels or to simple exposure to levels above a critical threshold. Additionally, since the symptoms of depression stimulated by hormone addback appeared to remit by the fourth week of hormone administration, it is unclear whether continued administration of hormone would result in continued or repeated experience of depression or whether no further symptoms would appear subsequent to the initial precipitated episode. To address these points of uncertainty, we first will establish the efficacy of gonadal suppression in our MRMD subjects by administering depot leuprolide acetate for three months and then will administer both estradiol and progesterone in a continuous fashion for three months to determine whether maintenance of stable gonadal steroid levels will prevent the characteristic cyclic mood disorder.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders 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 # 81-M-0126, The Phenomenology and Biophysiology of

Menstrually-related Mood and Behavioral Disorders. In brief, these criteria include the following:

  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 and interference with life activities;
  2. Symptoms with a sudden offset and absence of significant symptomatology during the follicular phase;
  3. Age 18-50;
  4. Regular menstrual cycles (21-35 days in length), not pregnant, and in good medical health;
  5. Not pregnant;
  6. 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. This method formed the basis of the NIMH PMS Workgroup diagnostic guidelines and produces results that are highly convergent with the effect size method for diagnosing PMS.

All subjects will be required to use non-hormonal forms of birth control (e.g. barrier methods with the exception of IUD's) to avoid pregnancy during this study.

EXLUSION CRITERIA:

The following conditions, also, will constitute contraindications to treatment with hormonal therapy and will preclude a patient's participating in this protocol:

  1. Current Axis I psychiatric diagnosis
  2. History of endometriosis;
  3. Diagnosis of ill-defined, obscure pelvic lesions, particularly undiagnosed ovarian enlargement;
  4. Hepatic disease as manifested by abnormal liver function tests;
  5. History of mammary carcinoma;
  6. History of pulmonary embolism or phlebothrombosis;
  7. Undiagnosed vaginal bleeding;
  8. Porphyries;
  9. Diabetes mellitus;
  10. History of malignant melanoma;
  11. Cholecystitis or pancreatitis;
  12. Cardiovascular or renal disease;
  13. Pregnancy;
  14. Significant clinical or laboratory abnormalities
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005011

Contacts
Contact: Linda Simpson-St. Clair, R.N. (301) 496-9576 simpsonl@irp.nimh.nih.gov
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
Sponsors and Collaborators
  More Information

Additional Information:
Publications:
Study ID Numbers: 000103, 00-M-0103
Study First Received: March 29, 2000
Last Updated: March 31, 2009
ClinicalTrials.gov Identifier: NCT00005011     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Depression
Menstrual Cycle
Gonadal Steroids
GnRH Agonist
PMS
Estradiol
Progesterone
Mood
MRMD
PMDD
Menstrually Related Mood Disorders

Study placed in the following topic categories:
Depression
Antineoplastic Agents, Hormonal
Progesterone
Estradiol valerate
Estradiol 17 beta-cypionate
Depressive Disorder
Hormones
Estradiol
Behavioral Symptoms
Deslorelin
Menstruation Disturbances
Mental Disorders
Leuprolide
Estradiol 3-benzoate
Mood Disorders
Polyestradiol phosphate
Premenstrual Syndrome

Additional relevant MeSH terms:
Depression
Disease
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Depressive Disorder
Pharmacologic Actions
Behavioral Symptoms
Pathologic Processes
Menstruation Disturbances
Mental Disorders
Leuprolide
Fertility Agents, Female
Therapeutic Uses
Syndrome
Fertility Agents
Mood Disorders
Premenstrual Syndrome

ClinicalTrials.gov processed this record on May 07, 2009