Dementia SyndromesNCT00685009
The Women's Health Initiative Memory Study (The WHIMS Study)
An observational study of Dementia Syndromes, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Excessive memory decline or dementia affects an increasing number of women as they become older. The frequency of dementia doubles every 5 years beginning at age 60, making the discovery of ways to prevent or slow the disease imperative. Read more about this study
- Who is it for?
- Ages 65 to 79 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Dementia Syndromes
- What is being tested?
- Estrogen hormone therapy and Estrogen plus progesterone hormone therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7,525 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1996to Mar 2008
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 79 years
- Women only
- Healthy volunteers accepted
- Older adult
Study population: This study will include participants from the hormone therapy trial of the WHI study.
Who may be able to join
- Enrolled in the Women's Health Initiative - Hormone Therapy Trial
- Aged 65 - 79 years of age at time of enrollment
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: Women's Health Initiative Memory Study
Excessive memory decline or dementia affects an increasing number of women as they become older. The frequency of dementia doubles every 5 years beginning at age 60, making the discovery of ways to prevent or slow the disease imperative. Previous studies have indicated that changes in memory may be associated with the female hormonal decline that occurs after menopause, but more research is needed to establish the link between menopause and poorer memory function. It is believed that taking the female hormones estrogen and/or progesterone may help improve women's health by protecting against memory decline. This study will evaluate the effects of female hormone replacement therapy (HRT) on the development and progression of memory loss in older women enrolled in the Women's Health Initiative (WHI) study.
Read the detailed description
Diseases of the memory, including dementia and Alzheimer's disease, are a primary health concern of the aging population. In just the last 30 years, the number of Americans diagnosed with memory diseases has doubled. The beginning signs and symptoms of Alzheimer's and dementia include mild forgetfulness, confusion, and disorientation with time and place. As the diseases advance, people often experience difficulty in carrying out normal activities, recognizing family and friends, and eventually speaking and comprehending. Early identification and treatment for dementia and Alzheimer's may help prevent and slow the progression of symptoms, but the most beneficial means of treatment is still unknown. Previous studies have suggested a link between menopause and reduced memory function in women, possibly attributed to the dramatic decline in the levels of the female hormones estrogen and progesterone. HRT in postmenopausal women may help to curb memory loss and reduce risk of developing memory-related diseases. This study will evaluate the effects of female HRT on the development and progression of memory loss in older women enrolled in the WHI study.
Participants in this study will be drawn from the WHI study and will have previously been assigned to HRT with estrogen, HRT with estrogen plus progesterone, or placebo. During this study, participants will continue to take their assigned treatments from the WHI study.
Participation will last up to 6 years. All participants will undergo baseline memory and thinking tests, including a mood assessment and tasks measuring memory and other brain functions. Study staff will conduct a telephone interview with a close family member or friend. Some participants may additionally undergo a 45-minute interview with a clinician, a blood draw, and a computerized tomography (CT) scan. All participants will repeat the baseline memory and thinking tests once annually for 6 years, and some participants will repeat the interview, blood draw, and CT scan at these annual visits as well.
- Conditions
- Dementia Syndromes
- Being tested
- Estrogen hormone therapy, Estrogen plus progesterone hormone therapy, Placebo
- Keywords
- Cognition, Memory, Hormone Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estrogen hormone therapyDrug
Also called Premarin
Estrogen pill daily
Estrogen plus progesterone hormone therapyDrug
Also called Prempro
Estrogen plus progesterone hormone therapy pill (Prempro) daily
PlaceboDrug
Placebo pill daily
| Study group | Role | What they receive |
|---|---|---|
| 1 | Women from the Women's Health Initiative study taking estrogen hormone therapy Receives: Drug: Estrogen hormone therapy | |
| 2 | Women from the WHI study taking estrogen plus progesterone hormone therapy Receives: Drug: Estrogen plus progesterone hormone therapy | |
| 3 | Women from the WHI study taking placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause dementia
Measured: Measured annually for 6 years
Secondary outcomes (1)
Mild cognitive impairment
Measured: Measured annually for 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2008 (estimated)
- Study startJan 1996
- Primary completionSep 1997
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Dementia SyndromesStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 7,525 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Wake Forest University Health Sciences
- Responsible party
- Sponsor
- Investigators
- Sally A. Shumaker, PhD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00685009
- Sponsor's protocol ID
- 548
- Other IDs
- N01WH44221
- Status last verified
- Oct 2015
- First submitted
- 23 May 2008
- Last updated
- 19 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Shumaker SA, Reboussin BA, Espeland MA, Rapp SR, McBee WL, Dailey M, Bowen D, Terrell T, Jones BN. The Women's Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Control Clin Trials. 1998 Dec;19(6):604-21. doi: 10.1016/s0197-2456(98)00038-5.
PubMed 9875839Shadyab AH, Zhang B, LaCroix AZ, McEvoy LK. Randomization to hormone therapy and changes in plasma biomarkers of Alzheimer's pathology: The women's health initiative memory study. Maturitas. 2026 Apr;207:108873. doi: 10.1016/j.maturitas.2026.108873. Epub 2026 Feb 11.
PubMed 41678876Harris WS, Tintle NL, Manson JE, Metherel AH, Robinson JG. Effects of menopausal hormone therapy on erythrocyte n-3 and n-6 PUFA concentrations in the Women's Health Initiative randomized trial. Am J Clin Nutr. 2021 Jun 1;113(6):1700-1706. doi: 10.1093/ajcn/nqaa443.
PubMed 33710263Lo K, Liu Q, Madsen T, Rapp S, Chen JC, Neuhouser M, Shadyab A, Pal L, Lin X, Shumaker S, Manson J, Feng YQ, Liu S. Relations of magnesium intake to cognitive impairment and dementia among participants in the Women's Health Initiative Memory Study: a prospective cohort study. BMJ Open. 2019 Nov 3;9(11):e030052. doi: 10.1136/bmjopen-2019-030052.
PubMed 31685499Haring B, Wu C, Coker LH, Seth A, Snetselaar L, Manson JE, Rossouw JE, Wassertheil-Smoller S. Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women's Health Initiative Memory Study. Am J Hypertens. 2016 Feb;29(2):202-16. doi: 10.1093/ajh/hpv081. Epub 2015 Jul 1.
PubMed 26137952Espeland MA, Pettinger M, Falkner KL, Shumaker SA, Limacher M, Thomas F, Weaver KE, Stefanick ML, McQuellon C, Hunt JR, Johnson KC. Demographic and health factors associated with enrollment in posttrial studies: the Women's Health Initiative Hormone Therapy Trials. Clin Trials. 2013;10(3):463-72. doi: 10.1177/1740774513477931. Epub 2013 Mar 12.
PubMed 23480899
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Women's Health Initiative Memory Study
- ClinicalTrials.gov ID
- NCT00685009
- Acronym / sponsor ID
- 548
- Conditions
- Dementia Syndromes
- Keywords
- Cognition, Memory, Hormone Therapy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 7,525 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Collaborators
- Wake Forest University Health Sciences
- Study start
- Jan 1996
- Primary completion
- Sep 1997 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 28 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Excessive memory decline or dementia affects an increasing number of women as they become older. The frequency of dementia doubles every 5 years beginning at age 60, making the discovery of ways to prevent or slow the disease imperative. Previous studies have indicated that changes in memory may be associated with the female hormonal decline that occurs after menopause, but more research is needed to establish the link between menopause and poorer memory function. It is believed that taking the female hormones estrogen and/or progesterone may help improve women's health by protecting against memory decline. This study will evaluate the effects of female hormone replacement therapy (HRT) on the development and progression of memory loss in older women enrolled in the Women's Health Initiative (WHI) study.
Detailed description
Diseases of the memory, including dementia and Alzheimer's disease, are a primary health concern of the aging population. In just the last 30 years, the number of Americans diagnosed with memory diseases has doubled. The beginning signs and symptoms of Alzheimer's and dementia include mild forgetfulness, confusion, and disorientation with time and place. As the diseases advance, people often experience difficulty in carrying out normal activities, recognizing family and friends, and eventually speaking and comprehending. Early identification and treatment for dementia and Alzheimer's may help prevent and slow the progression of symptoms, but the most beneficial means of treatment is still unknown. Previous studies have suggested a link between menopause and reduced memory function in women, possibly attributed to the dramatic decline in the levels of the female hormones estrogen and progesterone. HRT in postmenopausal women may help to curb memory loss and reduce risk of developing memory-related diseases. This study will evaluate the effects of female HRT on the development and progression of memory loss in older women enrolled in the WHI study.
Participants in this study will be drawn from the WHI study and will have previously been assigned to HRT with estrogen, HRT with estrogen plus progesterone, or placebo. During this study, participants will continue to take their assigned treatments from the WHI study.
Participation will last up to 6 years. All participants will undergo baseline memory and thinking tests, including a mood assessment and tasks measuring memory and other brain functions. Study staff will conduct a telephone interview with a close family member or friend. Some participants may additionally undergo a 45-minute interview with a clinician, a blood draw, and a computerized tomography (CT) scan. All participants will repeat the baseline memory and thinking tests once annually for 6 years, and some participants will repeat the interview, blood draw, and CT scan at these annual visits as well.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Drug: Estrogen hormone therapyWomen from the Women's Health Initiative study taking estrogen hormone therapy |
| 2 | – | Drug: Estrogen plus progesterone hormone therapyWomen from the WHI study taking estrogen plus progesterone hormone therapy |
| 3 | – | Drug: PlaceboWomen from the WHI study taking placebo |
Who may qualify
- Ages
- 65 to 79 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Older adult
- Study population
- This study will include participants from the hormone therapy trial of the WHI study.
Key inclusion criteria (2 listed)
- Enrolled in the Women's Health Initiative - Hormone Therapy Trial
- Aged 65 - 79 years of age at time of enrollment
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Estrogen hormone therapyAlso: PremarinEstrogen pill daily | Drug | 1 |
| Estrogen plus progesterone hormone therapyAlso: PremproEstrogen plus progesterone hormone therapy pill (Prempro) daily | Drug | 2 |
| PlaceboPlacebo pill daily | Drug | 3 |
Primary outcome
All-cause dementia
Time frame: Measured annually for 6 years
1 secondary outcome
Mild cognitive impairment
Time frame: Measured annually for 6 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2015.
- Background: PubMed 9875839Shumaker SA, Reboussin BA, Espeland MA, Rapp SR, McBee WL, Dailey M, Bowen D, Terrell T, Jones BN. The Women's Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Control Clin Trials. 1998 Dec;19(6):604-21. doi: 10.1016/s0197-2456(98)00038-5.
- Derived from this study: PubMed 41678876Shadyab AH, Zhang B, LaCroix AZ, McEvoy LK. Randomization to hormone therapy and changes in plasma biomarkers of Alzheimer's pathology: The women's health initiative memory study. Maturitas. 2026 Apr;207:108873. doi: 10.1016/j.maturitas.2026.108873. Epub 2026 Feb 11.
- Derived from this study: PubMed 33710263Harris WS, Tintle NL, Manson JE, Metherel AH, Robinson JG. Effects of menopausal hormone therapy on erythrocyte n-3 and n-6 PUFA concentrations in the Women's Health Initiative randomized trial. Am J Clin Nutr. 2021 Jun 1;113(6):1700-1706. doi: 10.1093/ajcn/nqaa443.
- Derived from this study: PubMed 31685499Lo K, Liu Q, Madsen T, Rapp S, Chen JC, Neuhouser M, Shadyab A, Pal L, Lin X, Shumaker S, Manson J, Feng YQ, Liu S. Relations of magnesium intake to cognitive impairment and dementia among participants in the Women's Health Initiative Memory Study: a prospective cohort study. BMJ Open. 2019 Nov 3;9(11):e030052. doi: 10.1136/bmjopen-2019-030052.
- Derived from this study: PubMed 26137952Haring B, Wu C, Coker LH, Seth A, Snetselaar L, Manson JE, Rossouw JE, Wassertheil-Smoller S. Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women's Health Initiative Memory Study. Am J Hypertens. 2016 Feb;29(2):202-16. doi: 10.1093/ajh/hpv081. Epub 2015 Jul 1.
- Derived from this study: PubMed 23480899Espeland MA, Pettinger M, Falkner KL, Shumaker SA, Limacher M, Thomas F, Weaver KE, Stefanick ML, McQuellon C, Hunt JR, Johnson KC. Demographic and health factors associated with enrollment in posttrial studies: the Women's Health Initiative Hormone Therapy Trials. Clin Trials. 2013;10(3):463-72. doi: 10.1177/1740774513477931. Epub 2013 Mar 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sally A. Shumaker, PhD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dementia Syndromes, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause dementia (time frame: Measured annually for 6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00685009, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2015.