# Presentation: 944017

## Is the Perimenopause associated with an increased 

**susceptibility to develop Depression?**

**Peter J. Schmidt MD**
**David R. Rubinow MD**
**Behavioral Endocrinology Branch**
**NIMH/NIH/DHHS**

## Estradiol (E2)

**Estradiol (E2)**
**      ****(ng/dL)**

**FSH**
**(IU/L)**

**Progesterone  **
**       ****(ng/mL)**

**LH**
**(IU/L)**

## Does the reversal of hypoestrogenism eliminate

**the symptoms of ****Perimenopausal ****Depression****?**

## Study Entry Criteria

- 	**Serial elevated plasma gonadotropin levels**
**	****Depression:  minor (modified SADS) or major (SCID)**
**	****Absence or presence of ****hot flushes**** confirmed by **
**	****daily ratings over 2 months prior to study entry**

**Notes:**
Study Entry Criteria

## Therapeutic Trial of Estradiol in Perimenopause-Related Mood Disorders

**Therapeutic Trial of Estradiol in ****Perimenopause-Related Mood Disorders**

**0**

**1**

**2**

**3**

**4**

**5**

**6**

**7**

**8**

**Time****(weeks)**

**Double Blind**

**Single****Blind**

**Single****Blind**

**Baseline**

**Patients**

**Group #1**

**Group #2**

**Estradiol 0.05 mg/d**

**Medroxyprogesterone Acetate 10 mg/d**

**Procedures**

**Placebo**

## Effect of E2 on Perimenopausal Symptoms

**0**

**10**

**20**

**30**

**Effect of E****2**** on Perimenopausal Symptoms**

**Depression ± Hot Flushes (n=34)**

**Placebo **

**E****2**

**Baseline**

**Score**

**Baseline**

**Baseline**

**  ****Weeks 2-4**

**Weeks 2-4**

- Center for Epidemiological Studies of Depression

**p <0.01**

## Effect of E2 on Perimenopausal Symptoms

**0**

**10**

**20**

**30**

**Effect of E****2**** on Perimenopausal Symptoms**

**Depression – No Hot Flushes (n=18)**

**Placebo **

**E****2**

**Baseline**

**Score**

**Baseline**

**Baseline**

**  ****Weeks 2-4**

** ****Weeks 2-4**

- Center for Epidemiological Studies of Depression

**p <0.01**

## Effect of E2 on Perimenopausal Symptoms

**0**

**4**

**8**

**12**

**16**

**20**

**Effect of E****2**** on Perimenopausal Symptoms**

**HAM-D****Depressed ± Hot Flushes (n=31)**

**Placebo **

**E****2**

**Baseline**

**SCORE**

**Baseline**

**Baseline**

**Wks 2-4**

**Wks 2-4**

**Wks 5-7**

**Wks 5-7**

## Study Entry Criteria

- 	**Asymptomatic premenopausal**** ****women**
**	****Regular menstrual cycles**

**Measures**

- 	**Structured Diagnostic Interviews**
**	****Cross-sectional and daily mood ratings**
**	****Menstrual cycle diary**
**	****Early follicular phase plasma FSH levels**

**Notes:**
Study Entry Criteria

## Longitudinal Study: Increased Risk of Depression Proximate to the Menopause

- Years Before Last Menstrual Period

- -35

- -30

- -25

- -20

- -15

- -10

- -5

- 0

- Cumulative Years at Risk for Depression

- 0

- 200

- 400

- 600

- 800

- 1000

- 1200

- 1400

- 1600

- Number of Depressive Episodes

- 0

- 1

- 2

- 3

- 4

- 5

- 6

- LMP

**Longitudinal Study: Increased Risk of Depression Proximate to the Menopause**

## Longitudinal Study: Increased Risk of Depression

- 0

- 1

- 2

- 3

- 4

- 5

- 6

- 7

- 36 - 5 years

- 4 - 2 years

- + / - 1 year

- Number of Depressive Episodes per 500 months at Risk

**Longitudinal Study: Increased Risk of Depression**

**Proximate to the Menopause**

- Years Before Final Menstrual Period

## Estradiol Therapy in Perimenopausal Depression:

** ****Demonstrated acute efficacy**
** ****Efficacy in post-menopause unlikely**
** ****Predictors of response unknown**
** ****Duration of efficacy unknown**
** ****Mechanism of efficacy unknown**
** ****Role of estradiol ****withdrawal**** in depression unknown   **