NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

The Treatment of Menstrually-Related Mood Disorders with the Gonadotropin Releasing Hormone (GnRH) Agonist, Depot Leuprolide Acetate (Lupron)

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

90-M-0088

Sponsoring Institute

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Female
Min Age: 18
Max Age: 45

Referral Letter Required

No

Population Exclusion(s)

Male;
Children

Keywords

Depression;
Menstrual Cycle;
Gonadal Steroids;
Estradiol;
Progesterone

Recruitment Keyword(s)

Mood Disorders

Condition(s)

Premenstrual Syndrome;
Menstruation Disturbances

Investigational Drug(s)

Lupron/estradiol/progesterone

Investigational Device(s)

None

Intervention(s)

Drug: Leuprolide
Drug: Estradiol Patches
Drug: Progesterone
Drug: Placebo injection
Drug: Placebo patch
Drug: Placebo suppository

Supporting Site

National Institute of Mental Health

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.

--Back to Top--

Eligibility

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 blood urea nitrogen (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 follicle stimulating hormone (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.


--Back to Top--

Citations:

Changes in plasma hormones across the menstrual cycle in patients with menstrually related mood disorder and in control subjects

Lack of effect of induced menses on symptoms in women with premenstrual syndrome

Differential behavioral effects of gs in women with PMS

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Peter J. Schmidt, M.D.
National Institute of Mental Health (NIMH)
NIHBC 10 - CLINICAL CENTER BG RM 4C404
10 CENTER DR
BETHESDA MD 20892
(301) 496-6120
peterschmidt@mail.nih.gov

Peter J. Schmidt, M.D.
National Institute of Mental Health (NIMH)
NIHBC 10 - CLINICAL CENTER BG RM 4C404
10 CENTER DR
BETHESDA MD 20892
(301) 496-6120
peterschmidt@mail.nih.gov

Peter J. Schmidt, M.D.
NIHBC 10 - CLINICAL CENTER BG RM 4C404
10 CENTER DR
BETHESDA MD 20892
(301) 496-6120
peterschmidt@mail.nih.gov

Clinical Trials Number:

NCT00001259

--Back to Top--