Treatment of Menstrually Related Disorders With Continuous v. Interrupted Oral Contraceptives
Premenstrual Syndrome, PMS, Premenstrual Dysphoric Disorder
About this trial
This is an interventional treatment trial for Premenstrual Syndrome focused on measuring Depression, Menstrual Cycle, Gonadal Steroids, Ethinyl Estradiol, Drospirenone, Menstrually Related Mood Disorder, 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.
Sites / Locations
- National Institutes of Health Clinical Center, 9000 Rockville Pike
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Active Comparator
Active Comparator
1
2
3
Treatment arm # 1 consists of the continuous administration of Yasmin oral contraceptive (a combination of 30 µg of ethinyl estradiol and 3 mg of drospirenone) for 15 weeks starting on day 2 to 5 of the first menstrual cycle.
Treatment arm # 2 (interrupted Yasmin administration) will be identical to arm # 1 with the exception that the continuous administration of Yasmin will be interrupted by the substitution of placebo for Yasmin for one week during weeks 3, 8, and 14 of the study. The women participating in this treatment arm will experience episodes of menstruation after Yasmin withdrawal (when they are on placebo).
Yasmin oral contraceptive; CDB 2914 progesterone antagonist. Treatment arm # 3 is identical to treatment arm # 1 with the exception that the continuous administration of Yasmin will also include the administration of progesterone antagonist CDB-2914 during weeks 3, 8, and 14. Menses is anticipated to occur within 2-3 days of CDB-2914 administration. Women in treatment arms # 3 and # 1 will be exposed to continuous levels of Yasmin, but due to the local effects of the progesterone antagonist on the endometrium, women in arm # 3 will experience menses.