Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Combined Hormone Replacement in Menstrually-Related Mood Disorders

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:
NCT00005011
First received: March 29, 2000
Last updated: November 11, 2014
Last verified: July 2014

March 29, 2000
November 11, 2014
March 2000
Not Provided
Not Provided
Not Provided
Complete list of historical versions of study NCT00005011 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Combined Hormone Replacement in Menstrually-Related Mood Disorders
The Treatment of Menstrually-Related Mood Disorders With Continuous Gonadal Steroid Replacement

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.

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.

Observational
Not Provided
Not Provided
Not Provided
Not Provided
Not Provided
  • Premenstrual Syndrome
  • Depression
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
Not Provided
Not Provided
  • 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
Female
18 Years to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00005011
000103, 00-M-0103
Not Provided
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
National Institute of Mental Health (NIMH)
Not Provided
Principal Investigator: Peter J Schmidt, M.D. National Institute of Mental Health (NIMH)
National Institutes of Health Clinical Center (CC)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP