Long-term hormone therapy for perimenopausal and postmenopausal women - PubMed (original) (raw)

Review

Long-term hormone therapy for perimenopausal and postmenopausal women

Jane Marjoribanks et al. Cochrane Database Syst Rev. 2017.

Abstract

BACKGROUND: Hormone therapy (HT) is widely provided for control of menopausal symptoms and has been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of a Cochrane review first published in 2005. OBJECTIVES: To assess effects of long-term HT (at least 1 year's duration) on mortality, cardiovascular outcomes, cancer, gallbladder disease, fracture and cognition in perimenopausal and postmenopausal women during and after cessation of treatment. SEARCH METHODS: We searched the following databases to September 2016: Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO. We searched the registers of ongoing trials and reference lists provided in previous studies and systematic reviews. SELECTION CRITERIA: We included randomised double-blinded studies of HT versus placebo, taken for at least 1 year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via the oral, transdermal, subcutaneous or intranasal route. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias and extracted data. We calculated risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, along with 95% confidence intervals (CIs). We assessed the quality of the evidence by using GRADE methods. MAIN RESULTS: We included 22 studies involving 43,637 women. We derived nearly 70% of the data from two well-conducted studies (HERS 1998; WHI 1998). Most participants were postmenopausal American women with at least some degree of comorbidity, and mean participant age in most studies was over 60 years. None of the studies focused on perimenopausal women.In relatively healthy postmenopausal women (i.e. generally fit, without overt disease), combined continuous HT increased the risk of a coronary event (after 1 year's use: from 2 per 1000 to between 3 and 7 per 1000), venous thromboembolism (after 1 year's use: from 2 per 1000 to between 4 and 11 per 1000), stroke (after 3 years' use: from 6 per 1000 to between 6 and 12 per 1000), breast cancer (after 5.6 years' use: from 19 per 1000 to between 20 and 30 per 1000), gallbladder disease (after 5.6 years' use: from 27 per 1000 to between 38 and 60 per 1000) and death from lung cancer (after 5.6 years' use plus 2.4 years' additional follow-up: from 5 per 1000 to between 6 and 13 per 1000).Oestrogen-only HT increased the risk of venous thromboembolism (after 1 to 2 years' use: from 2 per 1000 to 2 to 10 per 1000; after 7 years' use: from 16 per 1000 to 16 to 28 per 1000), stroke (after 7 years' use: from 24 per 1000 to between 25 and 40 per 1000) and gallbladder disease (after 7 years' use: from 27 per 1000 to between 38 and 60 per 1000) but reduced the risk of breast cancer (after 7 years' use: from 25 per 1000 to between 15 and 25 per 1000) and clinical fracture (after 7 years' use: from 141 per 1000 to between 92 and 113 per 1000) and did not increase the risk of coronary events at any follow-up time.Women over 65 years of age who were relatively healthy and taking continuous combined HT showed an increase in the incidence of dementia (after 4 years' use: from 9 per 1000 to 11 to 30 per 1000). Among women with cardiovascular disease, use of combined continuous HT significantly increased the risk of venous thromboembolism (at 1 year's use: from 3 per 1000 to between 3 and 29 per 1000). Women taking HT had a significantly decreased incidence of fracture with long-term use.Risk of fracture was the only outcome for which strong evidence showed clinical benefit derived from HT (after 5.6 years' use of combined HT: from 111 per 1000 to between 79 and 96 per 1000; after 7.1 years' use of oestrogen-only HT: from 141 per 1000 to between 92 and 113 per 1000). Researchers found no strong evidence that HT has a clinically meaningful impact on the incidence of colorectal cancer.One trial analysed subgroups of 2839 relatively healthy women 50 to 59 years of age who were taking combined continuous HT and 1637 who were taking oestrogen-only HT versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT: Their absolute risk remained low, at less than 1/500. However, other differences in risk cannot be excluded, as this study was not designed to have the power to detect differences between groups of women within 10 years of menopause.For most studies, risk of bias was low in most domains. The overall quality of evidence for the main comparisons was moderate. The main limitation in the quality of evidence was that only about 30% of women were 50 to 59 years old at baseline, which is the age at which women are most likely to consider HT for vasomotor symptoms. AUTHORS' CONCLUSIONS: Women with intolerable menopausal symptoms may wish to weigh the benefits of symptom relief against the small absolute risk of harm arising from short-term use of low-dose HT, provided they do not have specific contraindications. HT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer (such as breast cancer, in women with a uterus). The risk of endometrial cancer among women with a uterus taking oestrogen-only HT is well documented.HT is not indicated for primary or secondary prevention of cardiovascular disease or dementia, nor for prevention of deterioration of cognitive function in postmenopausal women. Although HT is considered effective for the prevention of postmenopausal osteoporosis, it is generally recommended as an option only for women at significant risk for whom non-oestrogen therapies are unsuitable. Data are insufficient for assessment of the risk of long-term HT use in perimenopausal women and in postmenopausal women younger than 50 years of age.

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Conflict of interest statement

Cindy Farquhar is a director/shareholder of a gynaecology clinic and undertakes private practice within those premises. She has received travel/accommodation/meeting expenses from ESHRE or ASRM for attendance at scientific meetings.

JL, AL, JM and HR have no interests to declare.

Figures

1

1

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

2

2

Study flow diagram.

3

3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

1.1

1.1. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 1 Death from any cause: oestrogen‐only HT.

1.2

1.2. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 2 Death from any cause: combined HT.

1.3

1.3. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 3 Death from any cause: oestrogen with or without sequential progesterone vaginal gel.

1.4

1.4. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 4 Death from coronary heart disease: oestrogen‐only HT.

1.5

1.5. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 5 Death from coronary heart disease: combined continuous HT.

1.6

1.6. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 6 Death from coronary heart disease: combined sequential HT.

1.7

1.7. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 7 Death from stroke: oestrogen‐only HT.

1.8

1.8. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 8 Death from stroke: combined sequential HT.

1.9

1.9. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 9 Death from stroke: combined continuous HT.

1.10

1.10. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 10 Death from colorectal cancer: oestrogen‐only HT.

1.11

1.11. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 11 Death from breast cancer: combined continuous HT.

1.12

1.12. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 12 Death from breast cancer: oestrogen‐only HT.

1.13

1.13. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 13 Death from colorectal cancer: combined continuous HT.

1.14

1.14. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 14 Death from lung cancer: oestrogen‐only HT (moderate dose).

1.15

1.15. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 15 Death from lung cancer: combined continuous HT (moderate dose).

1.16

1.16. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 16 Death from lung cancer: combined sequential HT (low dose oestrogen).

1.17

1.17. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 17 Death from any cancer: combined continuous HT.

1.18

1.18. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 18 Coronary events (MI or cardiac death): oestrogen‐only HT.

1.19

1.19. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 19 Coronary events (MI or cardiac death): combined continuous HT.

1.20

1.20. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 20 Coronary events (MI or cardiac death): combined sequential HT.

1.21

1.21. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 21 Coronary events (MI or cardiac death): oestrogen with or without sequential progesterone vaginal gel.

1.22

1.22. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 22 Stroke: unopposed oestrogen.

1.23

1.23. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 23 Stroke: combined continuous HT.

1.24

1.24. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 24 Stroke: combined sequential HT.

1.25

1.25. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 25 Stroke: combined sequential HT.

1.26

1.26. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 26 Transient ischaemic attack: oestrogen‐only HT.

1.27

1.27. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 27 Transient ischaemic attack: combined sequential HT.

1.28

1.28. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 28 Transient ischaemic attack: oestrogen with or without sequential progesterone vaginal gel.

1.29

1.29. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 29 Stroke or transient ischaemic attack.

1.30

1.30. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 30 Venous thromboembolism (DVT or PE): oestrogen‐only HT.

1.31

1.31. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 31 Venous thromboembolism (DVT or PE): combined sequential HT.

1.32

1.32. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 32 Venous thromboembolism (DVT or PE): combined continuous HT.

1.33

1.33. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 33 Venous thromboembolism (DVT or PE): oestrogen with or without sequential progesterone vaginal gel.

1.34

1.34. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 34 Global cognitive function.

1.35

1.35. Analysis

Comparison 1 Women without major health problems (selected outcomes: death, CVD, cognition, QOL), Outcome 35 Probable dementia.

2.1

2.1. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 1 Death from any cause: oestrogen‐only HT.

2.2

2.2. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 2 Death from any cause: oestrogen‐only or combined sequential HT.

2.3

2.3. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 3 Death from any cause: combined continuous HT.

2.4

2.4. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 4 Death from coronary heart disease: oestrogen‐only HT.

2.5

2.5. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 5 Death from CHD: oestrogen‐only or combined sequential HT.

2.6

2.6. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 6 Death from CHD: combined continuous HT.

2.7

2.7. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 7 Coronary event (MI or cardiac death): oestrogen‐only HT.

2.8

2.8. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 8 Death from stroke: oestrogen‐only or combined sequential HT.

2.9

2.9. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 9 Death from cancer: combined continuous HT.

2.10

2.10. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 10 Coronary event (MI or cardiac death): oestrogen‐only HT.

2.11

2.11. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 11 Coronary event: oestrogen‐only or combined sequential HT.

2.12

2.12. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 12 Coronary event (MI or cardiac death): combined continuous HT.

2.13

2.13. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 13 Stroke (first or recurrent): oestrogen‐only HT or combined sequential.

2.14

2.14. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 14 Stroke (first or recurrent): oestrogen‐only HT (mod dose).

2.15

2.15. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 15 Stroke (first or recurrent): combined continuous HT (mod dose oestrogen).

2.16

2.16. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 16 Transient ischaemic attack: oestrogen‐only HT (mod dose).

2.17

2.17. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 17 Transient ischaemic attack: oestrogen‐only or combined sequential HT.

2.18

2.18. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 18 Transient ischaemic attack: combined continuous HT.

2.19

2.19. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 19 Stroke or transient ischaemic attack: oestrogen‐only HT.

2.20

2.20. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 20 Stroke or transient ischaemic attack: combined continuous HT.

2.21

2.21. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 21 VTE (first or recurrent PE or DVT): oestrogen‐only HT.

2.22

2.22. Analysis

Comparison 2 Women with cardiovascular disease (selected outcomes: death, CVD, cognition, QOL), Outcome 22 VTE (first or recurrent PE or DVT): combined continuous HT.

3.1

3.1. Analysis

Comparison 3 Women with dementia, Outcome 1 Worsening of dementia on treatment (by ADCS‐CGIC score): oestrogen‐only HT.

4.1

4.1. Analysis

Comparison 4 Women post surgery for early‐stage endometrial cancer (selected outcomes: death, recurrence), Outcome 1 Death from any cause: oestrogen‐only HT.

4.2

4.2. Analysis

Comparison 4 Women post surgery for early‐stage endometrial cancer (selected outcomes: death, recurrence), Outcome 2 Death from endometrial cancer: oestrogen‐only HT.

4.3

4.3. Analysis

Comparison 4 Women post surgery for early‐stage endometrial cancer (selected outcomes: death, recurrence), Outcome 3 Death from CHD: oestrogen‐only HT.

5.1

5.1. Analysis

Comparison 5 Women hospitalised with chronic illness (selected outcomes: death, CVD, VTE), Outcome 1 All‐cause death: combined sequential HT.

5.2

5.2. Analysis

Comparison 5 Women hospitalised with chronic illness (selected outcomes: death, CVD, VTE), Outcome 2 Myocardial infarction: combined sequential HT.

5.3

5.3. Analysis

Comparison 5 Women hospitalised with chronic illness (selected outcomes: death, CVD, VTE), Outcome 3 Venous thromboembolism (DVT or PE): combined sequential HT.

6.1

6.1. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 1 Breast cancer: oestrogen‐only HT.

6.2

6.2. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 2 Breast cancer: oestrogen‐only or combined HT.

6.3

6.3. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 3 Breast cancer: combined continuous HT.

6.4

6.4. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 4 Breast cancer: combined sequential HT.

6.5

6.5. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 5 Breast cancer: oestrogen with or without sequential progesterone vaginal gel.

6.6

6.6. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 6 Colorectal cancer: oestrogen‐only HT.

6.7

6.7. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 7 Colorectal cancer: oestrogen‐only or combined HT.

6.8

6.8. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 8 Colorectal cancer: combined continuous HT.

6.9

6.9. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 9 Colorectal cancer: combined sequential HT.

6.10

6.10. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 10 Colorectal cancer: oestrogen with or without sequential progesterone vaginal gel.

6.11

6.11. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 11 Lung cancer: oestrogen‐only HT (moderate dose).

6.12

6.12. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 12 Lung cancer: combined continuous HT (mod dose oestrogen).

6.13

6.13. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 13 Lung cancer: combined sequential HT.

6.14

6.14. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 14 Endometrial cancer: oestrogen‐only HT.

6.15

6.15. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 15 Endometrial cancer: combined continuous HT (mode dose oestrogen).

6.16

6.16. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 16 Endometrial cancer: combined sequential HT.

6.17

6.17. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 17 Recurrent endometrial cancer: oestrogen‐only HT.

6.18

6.18. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 18 Ovarian cancer: combined continuous HT.

6.19

6.19. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 19 Ovarian cancer: oestrogen with or without sequential progesterone vaginal gel.

6.20

6.20. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 20 Gallbladder disease requiring surgery: oestrogen‐only HT.

6.21

6.21. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 21 Gallbladder disease requiring surgery: combined continuous HT.

6.22

6.22. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 22 Gallbladder disease requiring surgery: combined sequential HT.

6.23

6.23. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 23 Hip fractures: oestrogen‐only HT.

6.24

6.24. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 24 Hip fractures: oestrogen‐only or combined sequential HT.

6.25

6.25. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 25 Hip fractures: combined continuous HT.

6.26

6.26. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 26 Hip fractures: combined sequential HT.

6.27

6.27. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 27 Vertebral fractures: oestrogen‐only HT.

6.28

6.28. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 28 Vertebral fractures: combined continuous HT.

6.29

6.29. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 29 All clinical fractures: oestrogen‐only or combined sequential HT.

6.30

6.30. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 30 All clinical fractures: oestrogen‐only HT (moderate dose).

6.31

6.31. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 31 All clinical fractures: oestrogen‐only or combined HT.

6.32

6.32. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 32 All clinical fractures: combined continuous HT.

6.33

6.33. Analysis

Comparison 6 All women (selected outcomes: cancer, cholecystic disease, fractures), Outcome 33 All clinical fractures: combined sequential HT.

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References

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    1. Asthana S, Gleason CE, Wharton W, Dowling MN, Carlsson CM, et al. The Kronos Early Estrogen Prevention Study: results of the cognitive and affective substudy (KEEPS‐Cog). Menopause: 23rd Annual meeting of North American Menopause Society, October 3‐October 6 2012, Orlando 2012;19(12):1365‐404.
    1. FIles JA, Miller VM, Cha S, Pruthi S. Effects of different hormone therapies on breast pain in recently postmenopausal women: findings from the Mayo Clinic KEEPS Breast Pain Ancillary Study. Journal of Womens Health 2014;23(10):801‐5. - PMC - PubMed
    1. Gleason C, Wharton W, Dowling M, Brinton E, Santoro N, et al. The Kronos Early Estrogen Prevention Study ‐ Cognitive and Affective Sub‐study (KEEPS‐CA): menopausal hormone therapy effects on mood, quality of life and memory complaints. Menopause: 23rd Annual meeting of North American Menopause Society, October 3‐October 6 2012, Orlando 2012;19(12):1402 (P‐89).
    1. Gleason CE, Dowling NM, Wharton W, Manson JE, Miller VM, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized controlled KEEPS‐Cognitive and Affective Study. PLoS Medicine 2015;12(6):e1001833. - PMC - PubMed
    1. Harman SM. Effects of oral conjugated estrogen or transdermal estradiol plus oral progesterone treatment on common carotid artery intima media thickness (CIMT) & coronary artery calcium (CAC) in menopausal women: initial results from the Kronos Early Estrogen Prevention Study (KEEPS). Menopause: 23rd Annual meeting of North American Menopause Society, October 3‐October 6 2012, Orlando 19;12:1365‐1404. 2012;19(12):1365‐404.
Mulnard 2000 {published data only}
    1. Mulnard R, Cotman C, Kawas C, Dyck C, Sano M, Doody R, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. JAMA 2000;283(8):1007‐15. - PubMed
Nachtigall 1979 {published data only}
    1. Nachtigall LE, Nachtigall RH, Nachtigall RD, Beckman EM. Estrogen replacement therapy II: a prospective study in the relationship to carcinoma and cardiovascular and metabolic problems. Obstetrics and Gynecology 1979;54(1):74‐9. - PubMed
Notelovitz 2002 {published data only}
    1. Notelovitz M, John VA, Good WR. Effectiveness of Alora estradiol matrix transdermal delivery system in improving lumbar bone mineral density in health, postmenopausal women. Menopause 2002;9(5):343‐53. - PubMed
Obel 1993 {published and unpublished data}
    1. Bech P. Personal communication with J. Marjoribanks. December 2003.
    1. Bech P, Munk‐Jensen N, Obel EB, Ulrich LG, Eiken P, Pors Nielsen SP. Combined versus sequential hormonal replacement therapy: a double blind placebo‐controlled study on quality of life‐related measures. Psychotherapy and Psychosomatics 1998;67:259‐65. - PubMed
    1. Obel EB, Munk‐Jensen N, Svenstrup B, Bennett P, Micic S, Henrik‐Nielsen R, et al. A two‐year double‐blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment. Maturitas 1993;16:13‐21. - PubMed
PEPI 1995 {published data only}
    1. Barrett‐Connor E, Slone S, Greendale G, Kritz‐Silverstein D, Espeland M, Johnson SR, et al. The postmenopausal estrogen/progestin interventions study: primary outcomes in adherent women. Maturitas 1997;27:261‐74. - PubMed
    1. Cushman M, Legault C, Barrett‐Connor E, Stefanick ML, Kessler C, Judd HL, et al. Effect of postmenopausal hormones on inflammation‐sensitive proteins. Circulation 1999;100:717‐22. - PubMed
    1. Espeland MA, Bush TL, Mebane‐Sims I, Stefanick ML, Johnson S, Sherwin R, et al. Rationale, design and conduct of the PEPI trial. Controlled Clinical Trials 1995;16:3S‐19S. - PubMed
    1. Greendale GA, Reboussin BA, Slone S, Wasilauskas C, Pike MC, Ursin G. Postmenopausal hormone therapy and change in mammographic density. Journal of the National Cancer Institute 2003;951(1):30‐7. - PubMed
    1. Miller VT, Byington RL, Espeland MA, Langer R, Marcus R, Shumaker S, et al. Baseline characteristics of the PEPI particpants. Controlled Clinical Trials 1995;16:54S‐65S. - PubMed
Tierney 2009 {published data only}
    1. Tierney MC, Oh P, Moineddin R, Greenblatt EM, Snow WG, Fisher RH, et al. A randomized double‐blind trial of the effects of hormone therapy on delayed verbal recall in older women. Psychoneuroendocrinology 2009;34(7):1065‐74. - PubMed
WAVE 2002 {published data only}
    1. Bittner V, Tripputi M, Hsia J, Gupta H, Steffes M. Remnant‐like lipoproteins, hormone therapy and angiographic and clinical outcomes: the Women's Angiographic Vitamin and Estrogen trial. American Heart Journal 2004;147:293‐9. - PubMed
    1. Hsia J, Alderman EL, Verter JI, Rogers WJ, Thompson P, Howard BV, et al. Women's angiographic vitamin and estrogen trial: design and methods. Controlled Clinical Trials 2002;23:708‐27. - PubMed
    1. Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women. JAMA 2002;288(19):2432‐40. - PubMed
WEST 2001 {published data only}
    1. Kernan WN, Brass LM, Viscoli CM, Sarrel PM, Makuch R, Horowitz RI. Estrogen after ischemic stroke: dlinical basis and design of the Women's Estrogen for Stroke trial. Journal of Stroke and Cardiovascular Diseases 1998;7(1):85‐95. - PubMed
    1. Stefanick ML, Anderson GL, Margolis KL, Hendix SL, Rodabough RJ, Paskett ED, et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006;295:1647‐57. - PubMed
    1. Viscoli C, M, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horowitz RI. Estrogen therapy and risk of cognitive decline: results from the Women's Estrogen for Stroke Trial (WEST). American Journal of Obstetrics and Gynecology 2004;192:387‐93. - PubMed
    1. Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horowitz RI. A clinical trial of estrogen‐replacement therapy after ischemic stroke. New England Journal of Medicine 2001;345(17):1243‐9. - PubMed
WHI 1998 {published data only}
    1. Anderson GL, Chlebowski RT, Aragaki AK, Kuller LH, Manson JE, Gass M, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow‐up of the Women's Health Initiative randomised placebo‐controlled trial. The Lancet 2012;13:476‐86. - PMC - PubMed
    1. Anderson GL, Chlebowski RT, Rossouw JE, Rodabough RJ, McTiernan A, Margolis KL, et al. Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. Maturitas 2006;55:103‐15. - PubMed
    1. Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SAA, Pettinger M, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures. Journal of the American Medical Association 2003;290(13):1739‐48. - PubMed
    1. Barnabei VM, Cochrane BB, Aragaki AK, Nygaard I, Willliams RS, McGovernn PG, et al. Menopausal symptoms and treatment‐related effects of estrogen and progestin in the Women's Health Initiative. Obsterics and Gynecology 2005;105(5 Part 1):1063‐73. - PubMed
    1. Brunner RL, Gass M, Aragaki A, Hays J, Granek I, Woods N, et al. Effects of conjugated equine estrogen on health‐related quality of life in postmenopausal women with hysterectomy. Archives of Internal Medicine 2005;165:1976‐86. - PubMed
WISDOM 2007 {published data only}
    1. Vickers MR, MacLennan AH, Lawton B, Ford D, Martin J, Meredith SK, et al. Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. BMJ Online First 2007;335:239. - PMC - PubMed
    1. Vickers MR, Martin J, Meade TW, the WISDOM Study Team. The women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial. BMC Women's Health 2007;7(2):1‐17. - PMC - PubMed
    1. Welton AJ, Vickers MR, Kim J, Ford D, Lawton BA, MacLennan AH, et al. the Wisdom Team. Health related quality of life after combined hormone replacement therapy: randomised controlled trial. BMJ 2008;337(212):a1190. - PMC - PubMed
Yaffe 2006 {published data only}
    1. Yaffe K, Vittinghoff E, Ensrud KE, Johnson KC, Diem S, Hanes V, et al. Effects of ultra‐low‐dose transdermal estradiol on cognition and health‐related quality of life. Archives of Neurology 2006;63:945‐50. - PubMed

References to studies excluded from this review

AHT 2015 {published and unpublished data}
    1. Eeles RA, Morden JP, Gore M, Mansi J, Glees J, Wenzel M, et al. Adjuvant hormone therapy may improve survival in epithelial ovarian cancer: results of the AHT randomized trial. Journal of Clinical Oncology 2015;33(35):4138‐44. - PubMed
Aitken 1971 {published data only}
    1. Aitken JM, Lorimer AR, McKay Hart D, Lawrie TDV, Smith DA. The effects of oophorectomy and long‐term mestranol therapy therapy on the serum lipids of middle‐aged women. Clinical Science 1971;41:597‐603. - PubMed
    1. Aitken JM, McKay Hart D. Oestrogen in oophorectomized women. British Medical Journal 1971;2(5758):400‐1. - PMC - PubMed
Aitken 1973 {published data only}
    1. Aitken JM, Hart DM, Lindsay R, Anderson JB, Smith DA, Wilson GM. Prevention of bone loss following oophorectomy in premenopausal women: a retrospective assessment of the effects of oophorectomy and a prospective controlled trial of the effects of mestranol therapy. Israel Journal of Medical Sciences 1976;12(7):607‐14. - PubMed
    1. Aitken JM, Lindsay R, Hart DM. Long‐term oestrogens for the prevention of post‐menopausal osteoporosis. Postgraduate Medical Journal 1976;52 Suppl 6:18‐25. - PubMed
    1. Aitken M, Hart DM, Lindsay R. Oestrogen replacement therapy for prevention of osteoporosis after oophorectomy. British Medical Journal 1973;3:515‐8. - PMC - PubMed
    1. Lindsay R, Aitken JM, Anderson JB, Hart DM, MacDonald EB, Clarke AC. Long‐term prevention of postmenopausal osteoporosis by oestrogen. The Lancet 1976;1(7968):1038‐40. - PubMed
Angerer 2000 {published data only}
    1. Angerer P, Stork S, Kothny W, Schmitt P, Schacky C. Effect of oral postmenopausal hormone replacement on progression of atherosclerosis: a randomised controlled trial. Arteriosclerosis, Thrombosis and Vascular Biology 2001;21(2):262‐8. - PubMed
Bloch Thomsen 2002 {published data only}
    1. Bloch Thomsen A, Silvestri S, Haarbo J, Christiansen C, Bjarnason N. Association between target organ responses during hormone replacement therapy. Abstracts of posters:10th World Congresss on Menopause, Climacteric 2002;5 Suppl 1:57.
Chen 2001 {published data only}
    1. Chen FP, Lee N, Soong YK, Huang KE. Comparison of transdermal and oral estrogen‐progestin replacement therapy: effects on cardiovascular risk factors. Menopause: The Journal of the North American Menopause Society 2001;8(5):347‐52. - PubMed
Christiansen 1981 {published data only}
    1. Christiansen C, Christensen MS, Jensen J, Hagen C, Stocklund K, Transbol I. Effects of natural oestogen/gestagen and thiazide on coronary risk factors in normal postmenopausal women: a 2 year double‐blind placebo study [Naturlig ostrogen/gestagen og tiazids virkning pa kardiovaskulaere risikofaktorer hos postmenopausale kvinder]. Ugeskrift for Laeger 1981;143:2230‐4. - PubMed
Corrado 2002 {published data only}
    1. Corrado F, Altavilla D, D'Anna R, Cancellieri F, Cannata ML. Effects of the phytoestrogen genistein and hormone replacement therapy on bone mineral density and metabolism in early post‐menopausal women: a randomised double blind placebo‐controlled study. Abstracts of Posters: 10th World Congress on Menopause: Climacteric 2002;5 (Supplement 1):173.
Corson 1999 {published data only}
    1. Corson SL, Richart RM, Caubel P, Lim P. Effect of a unique constant‐estrogen, pulsed‐progestin hormone replacement therapy containing 17‐Beta estradiol and norgestimate on endometrial histology. International Journal of Fertility 1999;44(6):279‐85. - PubMed
de Roo 1999 {published data only}
    1. Vogelvang TE, Mijatovic V, Kamp O, Netelenbos JC, Neele SJM, Pines A, et al. Neither long‐term treatment with raloxifene nor hormone replacement therapy modulate cardiac function in health postmenopausal women: two randomized, placebo‐controlled, 2‐year studies. American Journal of Obstetrics and Gynaecology 2002;186:729‐36. - PubMed
    1. Valk‐de Roo GW, Stehouwer CDA, Meijer P, Mijatovic V, Kluft C, Kenemans P, et al. Both raloxifene and estrogen reduce major cardiovascular risk factors in healthy postmenopausal women: a 2‐year placebo‐controlled study. Arteriosclerosis, Thrombosis and Vascular Biology 1999;19:2993‐3000. - PubMed
Eiken 1996 {published data only}
    1. Eiken P, Kolthoff N, Pors Nielsen SP. Effect of 10 years' hormone replacement therapy on bone mineral content in postmenopausal women. Bone 1996;5 Suppl:191S‐193S. - PubMed
Estratab 1977 {published data only}
    1. Genant HK, Lucas J, Weiss S, Akin M, Emkey R, McNaney‐Flint H, et al. Low‐dose esterified estrogen therapy. Archives of Internal Medicine 1997;157:2609‐15. - PubMed
    1. Trabal JF, Lenihan JP, Melchione TE, Stoltz RR, Khairi S, Yang HNM, et al. Low‐dose unopposed estrogens: preliminary findings on the frequency and duration of vaginal bleeding in postmenopausal women receiving esterified estrogens over a two‐year period. Menopause: The Journal of the North Amercian Menopause Society 4;3:130‐8.
    1. Watts NB, Nolan JC, Brennan JJ, Yang HM, ESTRATAB/Osteoporosis Study Group. Esterified estrogen therapy in postmenopausal women. Relationships of bone marker changes and plasma estradiol to BMD changes: a two year study. Menopause 2000;7(6):375‐82. - PubMed
EWA 2000 {published data only}
    1. Os I, Hofstad AE, Brekke M, Abdelnoor M, Nesheim BI, Jacobsen AF, et al. The EWA (Estrogen in Women with Atheroscelerosis) Study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins. Journal of Internal Medicine 2000;247:433‐41. - PubMed
Genant 1990 {published data only}
    1. Genant HK, Baylink DJ, Gallagher JC, Harris ST, Steiger P, Herber M. Effect of estrone sulfate on postmenopausal bone loss. Obstetrics and Gynaecology 76;4:579‐84. - PubMed
Graser 2001 {published data only}
    1. Graser T, Muller A, Druckman R, Oettel M. Effects of a combination of 2 mg estradiol valerate and 3 mg dienogest on coagulation, lipid profile and glucose metabolism in postmenopausal women. Drugs of Today 2001;37 Suppl:87‐99.
HABITS 2004 {published data only}
    1. Holmberg L, Anderson H, for the HABITS Steering and Data Monitoring Committees. HABITS (hormonal replacement therapy after breast cancer ‐ is it safe?), a randomised comparison: trial stopped. The Lancet 2004;363:453‐5. - PubMed
Haines 2003 {published data only}
    1. Haines CJ, Fan Yim S, Chung TKH, Lan CWK, Lau EWC, Ng MHL, et al. A prospective, randomized, placebo‐controlled study of the dose effect of oral oestradiol on menopausal symptoms, psychological well being and quality of life in postmenopausal Chinsese women. Maturitas 2003;44:207‐14. - PubMed
Hall 1998 {published data only}
    1. Hall G, Pripp U, Schenck‐Gustafsson K, Landgren B‐M. Longterm effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease. Maturitas 1998;28:235‐42. - PubMed
Jensen 1985 {published data only}
    1. Jensen J, Christiansen C, Rodbro P. Cigarette smoking, serum estrogens and bone loss during hormone‐replacement therapy early after menopause. New England Journal of Medicine 1985;313:973‐5. - PubMed
Kuopio 1998 {published data only}
    1. Komulainen MH, Kroger H, Tuppurainen MY, Heikkinen A‐M, Alhava E, Honkanen R, et al. HRT and vit D in prevention of non‐vertebral fractures in postmenopausal women: a 5 year randomized trial. Maturitas 1998;31:45‐54. - PubMed
Lufkin 1992 {published data only}
    1. Lufkin EG, Wahner HW, O'Fallon WM, Hodgson SF, Kotowicz MA, Lane AW, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Annals of Internal Medicine 1992;117(1):1‐9. - PubMed
Maki 2004 {published data only}
    1. Maki PM, Resnick SM, Brandt J, Dobs AR, Durso SC, McCrae RR. Changes in self‐reported personality coincident with declines in cognition: results from parallel hormone therapy trials in elderly men and women. Neurobiology of Aging 2004;25 Suppl 2:106.
Mizunuma 2010 {published data only}
    1. Mizunuma H, Taketani Y, Ohta H, Honjo H, Gorai I, Itabashi A, et al. Dose effects of oral estradiol on bone mineral density in Japanese women with osteoporosis. Climacteric 2010;13:72‐83. - PubMed
Newhouse 2000 {unpublished data only}
    1. Newhouse 2000. Effects of Estrogen on Memory in Post‐Menopausal Women and Patients With Alzheimer Disease. Clinical trials.gov.2003.
Ng 1992 {published data only}
    1. Ng HT, Chang SP, Yanfg TZ, Cho MP, Wei TC. Estradiol administered in a percutaneous gel for the prevention of postmenopausal bone loss. Asia‐Oceania Journal of Obstetrics and Gynaecology 1993;19(2):115‐9. - PubMed
Nielsen 2006 {published data only}
    1. Nielsen T, Ravn P, Pitkin J, Christiansen C. Pulsed estrogen therapy improves postmenopausal quality of life: a 2‐year placebo‐controlled study. Maturitas 2006;53(2):184‐90. - PubMed
    1. Nielsen TF, Ravn P, Bagger YZ, Warming L, Christiansen C. Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2‐year randomized, double blind, placebo‐controlled study. Osteoporosis International 2004;15(2):168‐74. - PubMed
Ory 1998 {published data only}
    1. Ory SJ, Field CS, Herrmann RR, Zinsmeister AR, Riggs BL. Effects of long‐term transdermal administration of estradiol on serum lipids. Mayo Clinic Proceedings 1998;73:735‐8. - PubMed
Os 2002 {published data only}
    1. Os I, Os A, Sandset PM, Bolling S, Seljeflot I, Djurovic S, et al. Hormone replacement therapy does not affect plasma homocysteine in postmenopausal women with coronary artery disease. Cardiology 2002;98:6‐12. - PubMed
Paoletti 2015 {published data only}
    1. Paoletti AM, Cagnacci A, Carlo C, Orru MM, Neri M, D'Alterio MN, et al. Clinical effect of hormonal replacement therapy with estradiol associated with noretisterone or drosperinone. A prospective randomized placebo controlled study. Gynecological Endocrinology 2015;31(5):384‐9. - PubMed
Papworth 2002 {published data only}
    1. Clarke SC, Kelleher J, Lloyd‐Jones H, Slack M, Schofield PM. A study of hormone‐replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. British Journal of Obstetrics and Gynaecology 2002;109:1056‐62. - PubMed
Pefanco 2007 {published data only}
    1. Pefanco MA, Kenny AM, Kaplan RF, Kuchel G, Walsh S, Kleppinger A, et al. The effect of 3‐year treatment with 0.25 mg/day of micronized 17beta‐estradiol on cognitive function in older postmenopausal women. Journal of the American Geriatrics Society 2007;55(3):426‐31. - PubMed
Post 2001 {published data only}
    1. Post MS, Mooren MJ, Baal WM, Neel SJM, Netelenbos JC, Kenemans P. Raloxifene reduces impedance to flow within the uterine artery in early postmenopausal women: a 2‐year randomized placebo‐controlled comparative study. American Journal of Obstetrics and Gynaecology 2001;185:557‐62. - PubMed
    1. Vogelvang TE, Mijatovic V, Kamp O, Netelenbos JC, Neele SJM, Pines A, et al. Neither long‐term treatment with raloxifene nor hormone replacement therapy modulate cardiac function in health postmenopausal women: two randomized, placebo‐controlled, 2‐year studies. American Journal of Obstetrics and Gynaecology 2002;186:729‐36. - PubMed
Rasgon 2014 {published data only}
    1. Rasgon NL, Geist CL, Kenna HA, Wroolie TE, Williams KE, Silverman DH. Prospective randomized trial to assess effects of continuing hormone therapy on cerebral function in postmenopausal women at risk for dementia. PLoS One 2014;9(3):e89095. - PMC - PubMed
Saitta A 2001 {published data only}
    1. Saitta A, Altavilla D, Cucinotta D, Morabito N, Frisina N, Corrado F, et al. Randomized, double‐blind, placebo‐controlled study on effects of raloxifene and hormone replacement therapy on plasma NO concentrations, endothelin‐1 levels, and endothelium‐dependent vaso‐dilation in postmenopausal women. Arteriosclerosis, Thrombosis and Vascular Biology 2001;21(9):1512‐9. - PubMed
Sanchez‐Guerrero 2007 {published data only}
    1. Sanchez‐Guerrero J, Gonzalez‐Perez M, Durand‐Carbajal M, Lara‐Reyes P, Jimenez‐Santana L, Romero‐Diaz J, et al. Menopause hormonal therapy in women with systemic lupus erythematosus. Arthritis and Rheumatism 2007;56(9):3070‐9. - PubMed
Schierbeck 2012 {published data only}
    1. Scheirbeck LL, Rejnmakr L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012;345(e6409):1‐11. - PubMed
SMART 2016 {published and unpublished data}
    1. Mirkin S, Pinkerton JV, Kagan R, Thompson JR, Pan K, Pickar JH, et al. Gynaecologic safety of conjugated estrogens plus bazedoxifene: pooled analysis of five phase 3 trials. Journal of Womens Health 2016;25(5):431‐9. - PubMed
Steiner 2007 {published data only}
    1. Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, et al. Unopposed estradiol therapy in postmenopausal women. Obstetrics and Gynecology 2007;109:581‐7. - PubMed
Teede 2002 {published data only}
    1. Teede HJ, Liang YL, Kotsopoulos D, Zoungas S, Craven R, McGrath BP. Placebo‐controlled trial of transdermal estrogen therapy alone in postmenopausal women: effects on arterial compliance and endothelial function. Climacteric 2002;5:160‐69. - PubMed
ULTRA 2005 {published data only}
    1. Diem S, Grady D, Quan J, Vittinghoff E, Wallace R, Hanes V, et al. Effects of ultralow‐dose transdermal estradiol on postmenopausal symptoms in women aged 60 to 80 years. Menopause 2006;1:130‐8. - PubMed
    1. Waetjen LE, Brown JS, Vittinghoff E, Ensrud KE, Pinkerton J, Wallace R, et al. The effect of ultralow‐dose transdermal estradiol on urinary incontinence in postmenopausal women. Obstetrics and Gynecology 2005;1:946‐52. - PMC - PubMed
Virtanen 1999 {published data only}
    1. Virtanen I, Polo‐Kantola P, Erkkola R, Polo O, Ekholm E. Climacteric vasomotor symptoms do not imply autonomic dysfunction. British Journal of Obstetrics and Gynaecology 1999;106:155‐64. - PubMed
Wharton 2011 {published data only}
    1. Wharton W, Baker LD, Gleason CE, Dowling M, Barnet JH, Johnson S, et al. Short‐term hormone therapy with transdermal estradiol improves cognition for postmenopausal women with Alzheimer's disease: results of a randomized controlled trial. Journal of Alzheimer's Disease 2011;26:495‐505. - PMC - PubMed

Additional references

Abelin 2012
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Anderson 2003
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Anderson 2006
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Anderson 2012
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Canonico 2007
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Cauley 2003
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Chlebowski 2003
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Chlebowski 2004
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Chlebowski 2008
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