Hormone Therapy for Postpartum Depression

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Peter J Schmidt, M.D.

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: National Institute of Mental Health (NIMH)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Determine whether postpartum depression is triggered by the abrupt withdrawal of estrogen and progesterone. The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a "scaled-down" hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major effective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estrogen and progesterone for an additional month. Outcome measures will include mood, behavioral and hormonal parameters (a separate protocol done in collaboration with NICHD).

Do I have to stop taking my current medications to join the trial?

Yes, participants must be medication-free, including birth control pills, to join the trial.

What data supports the idea that Hormone Therapy for Postpartum Depression is an effective treatment?

The available research shows mixed results for hormone therapy as a treatment for postpartum depression. Some studies suggest that estrogen therapy might help with severe cases, but these studies have limitations and potential side effects. Progesterone has been reported to help prevent postpartum depression in some uncontrolled studies, but synthetic progesterone might actually cause depression. Compared to standard antidepressants, which are commonly used but have slow effects, hormone therapy could be a natural alternative, especially for breastfeeding mothers. However, more research is needed to confirm its effectiveness and safety. Meanwhile, a new drug called brexanolone has been approved and shows promise in treating postpartum depression more quickly. ^{1 2 3 4 5}

What safety data exists for hormone therapy in treating postpartum depression?

The safety data for hormone therapy, specifically estradiol, in treating postpartum depression is still being evaluated. Preliminary evidence suggests that transdermal estradiol may be effective, but more research is needed to confirm its efficacy and safety, especially regarding maternal tolerability, long-term safety, and its passage into breast milk. Current studies highlight the need for randomized clinical trials to establish safety and efficacy before routine clinical use. Additionally, the safety of infant exposure during lactation is a concern that requires further investigation. ^{3 4 6 7 8}

Is the drug Estradiol, Progesterone a promising treatment for postpartum depression?

Estradiol, a form of estrogen, shows promise as a treatment for postpartum depression because it addresses hormone changes after childbirth. However, more research is needed to confirm its effectiveness and safety. ^{2 4 9 10 11}

Research Team

Peter J Schmidt, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Eligibility Criteria

This trial is for women aged 18-50 who have experienced major depression or mood disorders within three months after childbirth, are in good health, and have had a stable menstrual cycle for at least three months. They should not be pregnant or breastfeeding and must have been well for at least one year without any history of severe postpartum mental health issues.

Inclusion Criteria

I am a woman aged 18-50, had postpartum depression but have been well for over a year, not on medication, and have regular menstrual cycles.

I am a woman aged 18-50, with past depression but well for a year, not on medication, and have regular periods.

Group 3: Normal Controls: Controls will meet all criteria specified except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders.

Exclusion Criteria

Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any history of the following: endometriosis; undiagnosed enlargement of the ovaries; liver disease; breast cancer; a history of blood clots in the legs or lungs; undiagnosed vaginal bleeding; porphyria; diabetes mellitus; malignant melanoma; gallbladder or pancreatic disease; heart or kidney disease; cerebrovascular disease (stroke); cigarette smoking; a history of suicide attempts or psychotic episodes requiring hospitalization; recurrent migraine headaches; pregnancy (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods; pregnancy-related medical conditions such as hyperemesis gravidarum, pretoxemia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis; Any woman with a first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol; Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for the perimenopause will be excluded from participation. 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 who are unable to provide informed consent; NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy.

Treatment Details

Interventions

• Estradiol (Hormone Therapy)
• Placebo (Other)
• Progesterone (Hormone Therapy)

Trial Overview The study tests if hormone changes trigger postpartum depression by simulating pregnancy hormones with Estradiol and Progesterone, then suddenly stopping them. Some participants will continue the hormones longer to compare effects on mood and behavior.

Participant Groups

Group I: Group 2, Continued Replacement Group Active Control 2 Interventions

12 weeks of hormone addback

Group II: Group 1, Hormone and Placebo Group Placebo Group 3 Interventions

8 weeks of hormonal addback plus 4 weeks of placebo

Estradiol is already approved in European Union, United States, Canada for the following indications:

🇪🇺 Approved in European Union as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

🇺🇸 Approved in United States as Estradiol for:

• Moderate to severe vasomotor symptoms due to menopause
• Vulvar and vaginal atrophy due to menopause
• Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
• Prevention of postmenopausal osteoporosis
• Palliative treatment of breast cancer
• Palliative treatment of prostate cancer

🇨🇦 Approved in Canada as Estradiol for:

• Menopausal symptoms
• Hypoestrogenism
• Osteoporosis prevention
• Breast cancer palliation
• Prostate cancer palliation

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, MD

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3007

Patients Recruited

2,852,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefit of oestrogens and progestogens in postnatal depression. Karuppaswamy, J., Vlies, R.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oestrogen therapy for postpartum depression: efficacy and adverse effects. A double-blind, randomized, placebo-controlled pilot study. Kettunen, P., Koistinen, E., Hintikka, J., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in pharmacotherapy for postpartum depression: a structured review of standard-of-care antidepressants and novel neuroactive steroid antidepressants. Kaufman, Y., Carlini, SV., Deligiannidis, KM.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal estradiol for postpartum depression: a promising treatment option. Moses-Kolko, EL., Berga, SL., Kalro, B., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used? Faden, J., Citrome, L.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical profiles of progestins used in formulations of oral contraceptives and hormone replacement therapy. Hammond, GL., Rabe, T., Wagner, JD.[2019]

In a 12-week study involving 50 perimenopausal women with clinically significant depressive disorders, 68% of those treated with transdermal 17beta-estradiol experienced remission of depression, compared to only 20% in the placebo group, indicating its strong efficacy.

The treatment was well tolerated with rare adverse events, and the antidepressant benefits were sustained even after a 4-week washout period, although some somatic complaints increased.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Soares, CN., Almeida, OP., Joffe, H., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New products and regimens (since 2003). Panay, N.[2015]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development. Frieder, A., Fersh, M., Hainline, R., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current pharmacotherapy approaches and novel GABAergic antidepressant development in postpartum depression. Carlini, SV., Osborne, LM., Deligiannidis, KM.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroendocrine insights into neurosteroid therapy for postpartum depression. Reddy, DS.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

The benefit of oestrogens and progestogens in postnatal depression. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Oestrogen therapy for postpartum depression: efficacy and adverse effects. A double-blind, randomized, placebo-controlled pilot study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Advances in pharmacotherapy for postpartum depression: a structured review of standard-of-care antidepressants and novel neuroactive steroid antidepressants. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Transdermal estradiol for postpartum depression: a promising treatment option. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used? [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Preclinical profiles of progestins used in formulations of oral contraceptives and hormone replacement therapy. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

New products and regimens (since 2003). [2015]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Current pharmacotherapy approaches and novel GABAergic antidepressant development in postpartum depression. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Neuroendocrine insights into neurosteroid therapy for postpartum depression. [2023]