Volunteers participating in this study will be women meeting the following criteria:
Between the ages of 18 and 50 years,
In good medical health,
No history of menstrual-related mood or behavioral disturbances.
Additionally, we will recruit a subsample of 20 asymptomatic women who will meet all inclusion and exclusion criteria in this protocol except they will have a history of a past major depressive episode.
Finally, a third sample of 10 women who meet all the inclusion and exclusion criteria listed above for this protocol will be recruited to establish the dose range of transvaginal estradiol for this and related protocols (i.e., 90-M-0088 and 05-M-0059).
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 (with the exception of this women with a past major depression who will be studied on this protocol);
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;
History of malignant melanoma;
Cholecystitis or pancreatitis;
Cardiovascular or renal disease;
Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for the perimenopause (129). Specifically, we will exclude any woman with an elevated plasma FSH level (greater than or equal to 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, as will 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.
Participants who have an active condition that places them at an increased risk for osteoporosis will be excluded from this protocol.