Effects of a Tissue Selective Estrogen Complex (TSEC) on Depression and the Neural Reward System in the Perimenopause"

• Status: Suspended
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

Using neuroimaging, the investigator will study the effects of estrogen on mood and brain function in perimenopausal women with depression.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: Foundation of Hope, North Carolina
• Treatments: Bazedoxifene; Estrogens; Estrogens, Conjugated (USP)

Criteria

Inclusion Criteria:

• The investigators will employ the Stages of Reproductive Aging Workshop (STRAW) criteria to confirm perimenopausal status. The stages are primarily based on the characteristics of the menstrual cycle and secondarily on follicle stimulating hormone (FSH) levels. The anchor for the staging system is the last menstrual period (LMP). The investigators will enroll women who have > 2 skipped cycles with an interval of amenorrhea > 60 days and FSH values > 14, consistent with the late menopause transition (stage-1)*. Women who have taken oral contraceptives continuously for relief of perimenopausal symptoms will be exempt from our LMP criteria, and their perimenopausal status will be determined by FSH alone. Because extremes of body weight (BMI < 18 or > 35 kg/m2) or a history of chronic menstrual cycle irregularity can contribute to inaccurate reproductive staging, these will serve as additional exclusion criteria.

Current diagnosis of MDD with an onset associated with menstrual cycle irregularity. Present or past mania, psychosis, suicide attempts, and alcohol or drug dependence, and current substance abuse, as determined by the Structure Clinical Interview for The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) for Axis I Disorders (SCID) are exclusionary.

• Per the STRAW criteria, FSH values are highly variable in the late menopausal transition (stage -1), and clinicians should "carefully evaluate the appropriate FSH value, depending on the assay they use" (Harlow et al, 2012). For nearly two years following the LMP, FSH values can fluctuate between levels characteristic of the early reproductive years and levels characteristic of menopause (Hale et al, 2014). McLendon Labs at the University of North Carolina at Chapel Hill (UNC) uses an FSH assay that defines levels consistently above ? 21.5 IU/mL as post-menopausal (McLendon Labs, 2016). As FSH values do not stabilize at consistently high levels until post-menopause, the investigators are setting our minimum required FSH value at > 14 IU/mL to carefully select for women in the perimenopause transition.

Exclusion Criteria:

• Patients will not be permitted to enter this protocol if they have any of the following:

1. current medication use (i.e., psychotropics, anti-hypertensives, statins, hormonal preparations, or frequent use of anti-inflammatory agents (> 10 times/month)). Women will be allowed to enroll who take medications without known mood effects (e.g. stable thyroid hormone replacement and occasional (< 5 times/month) use of Ambien);

• all reported prescription medications will be reviewed and cleared by a study physician prior to a participant's enrollment;

2. pregnant, breastfeeding or trying to conceive;

3. LMP more than 12 months prior to enrollment;

• women who have recently taken oral contraceptives continuously for relief of perimenopausal symptoms will be exempt from the final menstrual period (FMP) criteria, and instead, the presence of menstrual irregularity prior to the use of oral contraceptives and elevated FSH will be used to determine their perimenopausal status;

4. history of undiagnosed vaginal bleeding;

5. undiagnosed enlargement of the ovaries;

6. polycystic ovary syndrome;

7. history of breast or ovarian cancer;

8. first degree relative with ovarian cancer;

9. first degree relative with premenopausal onset or bilateral breast cancer;

10. 2+ first degree relatives with breast cancer (regardless of onset);

11. 3+ relatives with postmenopausal breast cancer;

12. abnormal finding in a provider breast exam and/or mammogram;

• participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that were acute in nature and have resolved completely (as indicated by the medical record or follow-up testing) and/or benign will be reviewed by a study physician prior to enrollment. All chronic conditions will be exclusionary.

13. known carrier of BRCA1 or 2 mutation;

14. endometriosis;

15. blood clots in the legs or lungs;

16. porphyria;

17. diabetes mellitus;

18. malignant melanoma;

19. Hodgkin's disease;

20. recurrent migraine headaches that are preceded by aura;

21. gallbladder or pancreatic disease;

• participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that were acute in nature and have resolved completely (as indicated by the medical record or follow-up testing) and/or benign will be reviewed by a study physician prior to enrollment. All chronic conditions will be exclusionary.

22. heart or kidney disease;

• participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that were acute in nature and have resolved completely (as indicated by the medical record or follow-up testing) and/or benign will be reviewed by a study physician prior to enrollment. All chronic conditions will be exclusionary.

23. liver disease;

24. cerebrovascular disease (stroke);

25. current cigarette smoking;

26. current suicidal ideation, mania, psychosis, or alcohol/drug abuse/dependence;

27. past suicide attempts, mania, alcohol/drug dependence, or psychotic episodes;

28. chronic depression (i.e., episode(s) lasting 3+ years);

29. depressive episode(s) within 2 years of enrollment;

30. self-reported claustrophobia;

31. peanut allergy;

32. HIV/AIDS