Clinical trial NCT00089414: Treatment of Menstrually Related Disorders With Continuous v. Interrupted Oral Contraceptives
Official title: The Treatment of Menstrually-Related Mood Disorders With Extended Versus Interrupted Oral Contraceptives
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Premenstrual Syndrome
PMS
Premenstrual Dysphoric Disorder
PMDD
Depression
Keywords: Depression
Menstrual Cycle
Gonadal Steroids
Ethinyl Estradiol
Drospirenone
Menstrually Related Mood Disorder
MRMD
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2004-08-05
Enrollment: 5
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will determine whether uninterrupted treatment with birth control pills over several menstrual cycles prevents severe premenstrual syndrome (PMDD).

Previous studies have shown that the hormones estrogen and progesterone regulate mood in women with MRMD. This study will use various treatment regimens with birth control pills and placebo (sugar pill) to clarify the relationships among estrogen and progesterone, the menstrual cycle, and mood.

Healthy women between 18 and 45 years of age who menstruate may be eligible for this 15-week study. Candidates are screened with a physical examination, blood and urine tests, an electrocardiogram, and 3 months of symptoms ratings to confirm MRMD.

Participants are randomly assigned to one of three treatment groups. Group 1 takes a birth control pill every day and on three occasions takes a placebo capsule. Group 2 takes a birth control pill most but not all days and on three occasions takes a placebo capsule. Group 3 takes a birth control pill every day and on three occasions takes another medication called CDB-2914 that causes menstrual bleeding to occur.

Participants come to the NIH clinic every other week for blood tests and measurement of vital signs (blood pressure, pulse, and temperature) and to complete symptoms ratings scales. Subjects who develop breakthrough bleeding (menstruation earlier than expected) will have a transvaginal ultrasound. For this procedure, a probe is inserted into the vagina for about 10 minutes. The probe gives off and receives sound waves that can be used to form a picture of the endometrium (lining of the uterus).

...

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 one to two weeks 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). Preliminary results of protocol 00-M-0103 suggest that this hormone-induced depression occurs consequent to changes in gonadal steroid levels and not to simple exposure to basal levels above a critical threshold. Additionally, continued administration of hormone for three months resulted in no further symptoms subsequent to the initial precipitated episode. These data suggest the potential therapeutic benefit of extended oral contraceptive (OC) regimens with reduced pill-free intervals in MRMD to minimize the mood destabilizing effects of changing hormone levels. In this protocol we examine whether the effects of 15 weeks of continuous oral contraceptive administration causes a remission of symptoms in women with MRMD.

Eligibility criteria: * INCLUSION CRITERIA (are from protocol 81-M-0126 and are as follows):
* Subjects who meet criteria for MRMD are healthy (by physical exam, normal pelvic exam and pap smear, and normal lab values) and medication free will be included in this study.
* Oral contraceptives (and CDB-2914 in arm #3) will not be administered to any subject with significant clinical or laboratory abnormalities.

EXCLUSION CRITERIA:

Any patient with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.

Subjects taking psychotropic agents (e.g. antidepressants, anxiolytics or mood stabilizers) will likewise be excluded from the study.

Women who have received glucocorticoid or megestrol therapy within the last year (and thus may experience residual suppression of the compensatory HPA axis response to CDB-2914-induced glucocorticoid receptor antagonism) will be also excluded, albeit almost entirely on theoretical grounds.

Women who have any chronic medical conditions or are taking medications will be excluded.

Women who have a medical condition or are taking any chronic medications that may increase serum potassium levels will also be excluded.

Those patients who would be uncomfortable with extending the length of their menstrual cycles will not be enrolled in this study and will either be offered participation in another study or an outside referral for treatment in the community.

The following conditions will constitute contraindications to treatment with continuous oral contraception or the use of the progesterone antagonist, CDB-2914, and will preclude a patient's participating in this protocol:

* history of endometriosis, or recent, rapid growth of uterine fibroid tumors (defined as doubling in size in six month period);
* diagnosis of ill-defined, obscure pelvic lesions, particularly undiagnosed ovarian enlargement;
* hepatic disease as manifested by abnormal liver function tests;
* history of breast carcinoma;
* history of pulmonary embolism or phlebothrombosis;
* undiagnosed vaginal bleeding;
* porphyria;
* history of malignant melanoma;
* history of cholecystitis or pancreatitis;
* history of hypercholesterolemia, hypertension, diabetes, or renal disease;
* recurrent migraine headaches (greater than or equal to 3 per year) in women 35 or older;
* pregnancy or lactation;
* cigarette smoking in women 35 or older, or more than 10 cigarettes per day in women under 35; or
* use of oral, injectable, or inhaled glucocorticoids or megestrol within the last year.

Primary outcomes:
measure: Change in Premenstrual Tension Syndrome Scale (PMTS) Factors Associated With Premenstrual Symptoms.
timeFrame: Every 2 weeks for 3 months
Secondary outcomes:
measure: Change in Clinical Global Impression Scale (CGI) Factors Associated With Premenstrual Symptoms.
timeFrame: Every 2 wks for 3 months
measure: Change in Beck Depression Inventory (BDI) Factors Associated With Premenstrual Symptoms
timeFrame: Every 2 weeks for 3 months
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Institute of Mental Health (NIMH)
name: Pedro E Martinez, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Backstrom T, Sanders D, Leask R, Davidson D, Warner P, Bancroft J. Mood, sexuality, hormones, and the menstrual cycle. II. Hormone levels and their relationship to the premenstrual syndrome. Psychosom Med. 1983 Dec;45(6):503-7. doi: 10.1097/00006842-198312000-00004.
citation: Schmidt PJ, Nieman LK, Grover GN, Muller KL, Merriam GR, Rubinow DR. Lack of effect of induced menses on symptoms in women with premenstrual syndrome. N Engl J Med. 1991 Apr 25;324(17):1174-9. doi: 10.1056/NEJM199104253241705.
citation: Muse KN, Cetel NS, Futterman LA, Yen SC. The premenstrual syndrome. Effects of "medical ovariectomy". N Engl J Med. 1984 Nov 22;311(21):1345-9. doi: 10.1056/NEJM198411223112104.