Table 1.
Representative MHT clinical trials and their CVD outcome
| Clinical Trial |
Type | Subjects Number, Condition |
Mean follow-up Period |
MHT Type | MHT Route |
Outcome | Ref |
|---|---|---|---|---|---|---|---|
| PEPI | Multi-center, RDBPC | 875 45–64 yr Healthy | 3 yr (1991–1994) | CEE 0.625 mg CEE+progestin or placebo | Oral | CEE or CEE+progestin improves lipoproteins and lowers fibrinogen levels. | [112] |
| HERS | RDBPC | 2763 44–79 yr Average 67 yr with CVD | 4.1 yr (1993–1997) | CEE 0.625 mg +MPA 2.5 mg or placebo | Oral | No overall reduction in CVD events in women with established coronary disease. High risk of CVD in first year | [12] |
| HERS II | RDBPC Follow-up | 2321 Average 67 yr | 6.8 (2.7 yr added to HERS) (1993–1999) | CEE+MPA | Oral | MHT did not reduce risk of cardiovascular events in women with CHD | [6] |
| HERS - UA (Uric Acid) | RDBPC | 2763 44–79 yr | 4.1 yr (1993–1997) | CEE+MPA | Oral | CEE+MPA lowered serum UA levels slightly, but neither baseline UA nor change in UA affected CHD risk. | [113] |
| WHI | RDBPC | 16608 50–79 yr mean 63 Healthy with uterus 10739 Healthy without uterus |
5.2 yr (1993–1998) | CEE+MPA or placebo CEE or placebo | Oral | Overall health risks exceeded benefits. Overall doubling of VTE events in CEE+MPA arm. 30% to 40% increased risk of stroke. | [7] |
| WEST | RDBPC | 664 Mean 71 yr | Mean 2.8 yr (Dec. 1993 - May 1998) | E2 or placebo | Oral | No significant difference in incidence of stroke or death. | [17] |
| PHOREA | RDBPC | 321 >55 yr | 48 wk (1995–1996) | E2+ gestodene | Oral | Studied if MHT slows atherosclerosis measured by intima-media thickness in carotid. No benefit of MHT. | [114] |
| ERA | Three-arm, RDBPC | 309 Mean 65.8 yr with coronary disease | 3.2 yr (1996–1999) | CEE CEE+MPA or placebo | Oral | Angiography detected no difference in progression of coronary atherosclerosis despite increased HDL and decreased LDL | [54] |
| WISDOM | Multicenter, RDBPC | 5692 50–69 yr Mean 62.8 | Median 1 yr (1999- 2002) | CEE CEE+MPA or placebo | Oral | MHT increases CVD and VTE risk when started many years after menopause. | [115] |
| WAVE | RDBPC | 423 >55 yr With 15–75% coronary stenosis | 2.8 yr (July 1999 -January 2002) | CEE+MPA Vitamin E, C or placebo | Oral | No cardiovascular benefit of MHT or Vitamin C, E | [116] |
| ESTHER | Multicenter, case-control study | 881 271-case 610-control 45–70 yr | 6 yr (1999–2006) | Current MHT users classified by route of estrogen and type of progestogen | Oral vs Trans-dermal | Oral but not transdermal estrogen increases VTE risk. Norpregnanes may be thrombogenic. Micronized P4 and pregnanes are safe with respect to thrombotic risk. | [117] |
| RUTH | Multi-center, RDBPC | 10,101 Mean 67.5 yr | 5.6 yr (2000–2005) | Raloxifene daily or placebo | Oral | Raloxifene did not affect risk of CVD. Benefits of raloxifene in reducing risk of invasive breast cancer and vertebral fracture should be weighed against risk of VTE and stroke. | [31] |
| EPAT | RDBPC | 222 Mean 57 yr | 2 yr (2001–2003) | E2 | Oral | Average rate of progression of subclinical atherosclerosis slower in healthy Post-MW taking E2 | [118] |
| KEEPS | DBRCT of secondary prevention | 720 42–58 yr 6–36 month postmeno pause | 5yr (2005–2010) | CEE 0.45mg/d +E2 50µg/d/wk +Micronized P4 200mg/d, 12d/m | Oral Trans-dermal Oral | The study will examine whether MHT prevents progression of carotid intima thickness and accrual of coronary calcium. | [111] |
| ELITE | DBRCT | 643 <6 yr or >10 yr Postmeno pausal | 2005–2012 | E2 1mg/day ±P4 gel 4% or placebo | Oral Vaginal | The study will examine progression of carotid intima thickness, accrual of coronary calcium and lesions, and neurocognitive function and | [19] |
PEPI, Postmenopausal Estrogen/Progestin Interventions; HERS, Heart and Estrogen/progestin Replacement Study; WHI, Women’s Health Initiative; WEST, Women’s Estrogen for Stroke Trial; PHOREA, Postmenopausal Hormone REplacement against Atherosclerosis; ERA, Estrogen Replacement and Atherosclerosis; WISDOM, Women's International Study of long Duration Oestrogen after Menopause; WAVE, Women's Angiographic Vitamin and Estrogen trial; ESTHER, EStrogen and THromboEmbolism Risk study; RUTH, Raloxifene Use for The Heart; EPAT, Estrogen in the Prevention of Atherosclerosis Trial; KEEPS, Kronos Early Estrogen Prevention Study; ELITE, Early versus Late Intervention Trial with Estradiol; CEE, conjugated equine estrogen; CVD, cardiovascular disease; CHD, coronary heart disease; MPA, medroxyprogesterone acetate; RCT, randomized clinical trial; RDBPC, randomized double-blinded placebo-controlled; UA, uric acid; VTE, venous thrombo-embolism