Treatment of Menstrually Related Disorders With Continuous v. Interrupted Oral Contraceptives
Condition: Premenstrual Syndrome; PMS; Premenstrual Dysphoric Disorder; PMDD; Depression
MeSH terms: Premenstrual Syndrome; Premenstrual Dysphoric Disorder; Depression
Intervention: Ethinyl Estradiol/Drospirenone; Placebo; CDB 2914
Intervention description: Drug administered dependent upon arm.
Intervention MeSH terms: Drospirenone; Ethinyl Estradiol; Drospirenone and ethinyl estradiol combination; Estradiol; Progesterone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 5.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Depression; Menstrual Cycle; Gonadal Steroids; Ethinyl Estradiol; Drospirenone; Menstrually Related Mood Disorder; MRMD

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).

      ...
    

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.