Table 1 Aims for the Seattle Midlife Women’s Health Study by Phase

Phase 1: 1990–1996

The aim of Phase I was to test a model relating menopausal status, stress exposure, socialization for midlife, personal and social factors modulating midlife experiences, reproductive health history, and health behaviors to health status and health-seeking behavior in midlife women between the ages of 35 and 55.

Phase 2: 1996–2001

Aim 1. Describe the progression through stages of the perimenopuse (pre transition, early transition, middle transition, late transition, and postmenopause as determined from annual health updates and daily menstrual calendars) for women over a nine year period with respect to:

 a) Symptoms, including vasomotor, dysphoric mood, insomnia, somatic, and discomfort symptoms, recorded in a daily health diary for three days monthly (coinciding with hormone assays);

 b) Altered ovarian function (estrone, testosterone (T), and FSH), measured in first morning urine samples at monthly intervals;

 c) perceived stress (stressful life events, income inadequacy) measured annually and perceived stress measured 3 days each month in the health diary;

 d) stress arousal (urinary levels of cortisol and catecholamines) measured in the first morning urine samples at monthly intervals; and

 e) symptom management, including use of health services and hormone replacement therapy assessed annually in a health update questionnaire and interview.

Aim 2. Test the following hypotheses regarding symptoms during the three stages of the transition to menopause (early to middle to late):

 a) women who experience more severe vasomotor symptoms during the transition to menopause will have: higher levels of perceived stress, lower levels of estrone, and higher levels of catecholamines and cortisol;

 b) women who experience more severe dysphoric mood symptoms during the transition to menopause will have: higher levels of perceived stress, higher levels of cortisol, and norepinepherine, and a lower estrogen:androgen ratio;

 c) women who experience more sever insomnia symptoms during the transition to menopause will have: higher levels of perceived stress, lower levels of estrone, and higher levels of catecholamines.

Aim 3. Test the relationship within individual women among HPO axis hormones (estrone, FSH, testosterone), indicators of physiologic stress arousal (cortisol and catecholamines), daily stress ratings, and symptoms (especially vasomotor, dysphoric mood, and insomnia), measured monthly over a nine year period, using auto-correlation and cross-correlation techniques.

Aim 4. To estimate the stability of symptom patterns women have recorded in daily health diaries each year with symptom patterns women experience during the menopausal transition (over the period of 1991 to 1995, 1996–2000 and 2001–2005).

Phase 3: 2002–2006

Aim 1. Describe and compare women in the menopausal transition (early, middle and late transition), in the early postmenopause, and those who use HRT, on indicators of pituitary-ovarian hormone changes, perceived stress, physiologic stress arousal, vasomotor, dysphoric mood, somatic, discomfort and insomnia symptoms.

Aim 1 Hypotheses:

Hypothesis 1: Women in late transition will have higher levels of urinary FSH, cortisol and norepinepherine, higher perceived stress and higher vasomotor symptom severity than women in early or middle transition.

Hypothesis 2: Women in the postmenopause will have lower levels of urinary estrone and testosterone, lower perceived stress and higher levels of FSH and vasomotor symptoms than women in the three menopausal transition stages.

Hypothesis 3: There will be no group differences among women in the three menopausal transition stages for urinary estrone, testosterone and epinephrine, depressed mood or the 5 symptom clusters except for vasomotor symptoms.

Hypothesis 4: Women on HRT will have higher estrone levels and lower perceived stress, urinary cortisol, and vasomotor symptoms than women who are not on HRT, those in the menopausal transition or those who are postmenopausal.

Aim 2. Compare women in the menopausal transition and early postmenopause with different estrogen metabolism and catabolism gene polymorphisms with respect to estradiol and estrone levels, age of onset of middle and late menopausal transition stage and menopause, and heaviness of menstrual blood flow.

Aim 3. Compare women in the menopausal transition and early postmenopause with different estrogen receptor gene polymorphisms with respect to estradiol and estrone levels, age of onset of middle and late menopausal transition stage and menopause, and heaviness of menstrual blood flow.

Phase 4: 2007–2013

Continuation of aims from Phases 1 –3.

Additional aims for the Symptom Cluster Study that was part of Phase 4.

1. Identify symptom clusters (SC) SMWHS participants experienced during the late reproductive, early menopausal transition stages and early postmenopause using latent class analysis to complement the preliminary analyses of the late stage SCs;

2. Determine the consistency of SCs with the clusters identified for the late menopausal transition stage across the late reproductive stage, early menopausal transition stage and early postmenopause;

3. Test models hypothesizing the relationship between SC groups and profiles of:

 a) gene polymorphisms in the estrogen synthesis pathways (CYP 19 and 17 HSD) and genes polymorphisms in neuroendocrine pathways modulated by estrogen (5HTTLPR, NPY, BDNF);

 b) hypothalamic-pituitary-ovarian (HPO) biomarkers (E, T, FSH), and hypothalamic-pituitary-adrenal (HPA – cortisol) and autonomic nervous system (ANS- epinephrine, norepinephrine) biomarkers;

 c) reproductive aging stages (late reproductive, early and late menopausal transition, and early postmenopause);

 d) socio-behavioral risk factors (e.g. high stress, role burden, low income adequacy, employment, education, social support);

 e) symptom vulnerability factors (e.g. history of sexual abuse, low mastery, self-consciousness, low self esteem); and outcomes of well-being and interference with work and relationships;

 4. Based on a systematic review of controlled clinical trials for managing hot flashes, identify treatment effects on co-occuring symptoms and reported adverse treatment effects, including sleep disturbances, mood, pain and cognitive symptoms;

 5. Synthesize results of the empirical analyses (aims 1–3) and systematic review (aim 4) to develop novel symptom cluster management protocols to be tested in a future feasibility study.

Additional aims for Urinary Incontinence Study that was part of Phase 4.

 1. Determine the influence of age and menopausal transition factors on the experience of urinary incontinence (stress, urge and any incontinence) among midlife women;

 2. Assess the influence of lifespan health factors and life context (personal and social resources and stress) on urinary incontinence; and

 3. Determine the relationship between urinary incontinence and well-being, symptoms (fatigue, disrupted sleep, anxiety and depressed mood) and interference with daily living (work and relationships).