Risks and benefits of HRT for specific outcomes
Osteoporosis | Coronary Heart Disease | Stroke | Dementia | Ovarian
cancer | Venous thromboembolism | Breast cancer
Osteoporosis: There is strong evidence that HRT is beneficial
in reducing the risk of postmenopausal osteoporotic fracture and increasing bone density.2 Although some evidence
suggests that a few years treatment around the time of menopause can be beneficial in fracture reduction,7 it
is generally agreed that life long use of HRT is required to prevent bone fractures. HRT is however not first line treatment
for women with low bone mineral density due to the increased risk of other negative outcomes.
Hazard ratio for increased risk of fracture (95% CI): Combined treatment 0.76 (0.69 - 0.85). Oestrogen only treatment
0.70 (0.63 - 0.79).
Coronary Heart Disease: There is conflicting evidence of the effect
of HRT on cardiovascular risk. The timing hypothesis may explain this conflict. It theorises that oestrogen in recently
menopausal women could prevent the development of coronary artery plaque but would have no effect, or even cause harm
if given to older women with compromised plaque.8
The Women's Health Initiative trial (WHI) found an overall increase in coronary heart disease in the first year of use
of combined HRT.9 However, overall a non-significant reduction in the risk of coronary heart disease was observed
in women aged 50-59 years (oestrogen only trial) and in women for whom menopause had occurred within the previous ten
years (combined trial).10
An increased risk of cardiac events was observed in the Women's International Study of Long Duration Oestrogen (WISDOM),
in women using combined treatment. However, most of these women were over 64 years at trial entry and had one or more
cardiovascular risk factors.11
Hazard ratio for increased risk of coronary heart disease (95% CI): Combined treatment overall 1.24 (1.00 - 1.54),
first year of use 1.81(1.09-3.01). Oestrogen only treatment 0.95 (0.70 - 1.16).
Stroke: An increased rate of stroke was observed in the WHI study,
with both combined treatment and oestrogen only treatment. The absolute risk of stroke was lower for women under 60 or
in whom menopause had occurred within the previous five years.2
Hazard ratio for increased risk of ischaemic stroke (95% CI): Combined treatment 1.41 (1.07 - 1.85). Oestrogen only
treatment 1.39 (1.10 - 1.77).
Dementia: HRT does not prevent cognitive decline in older postmenopausal
women.12 There is some evidence that HRT may increase the risk of dementia when given to women over 65 years
of age.2 A beneficial effect on cognition has been observed when HRT is used in younger women, however evidence
is inconsistent. In the WHI study, a two-fold increase in dementia was found in women over 75 years taking HRT.7
Hazard ratio for increased risk of dementia (>65 years) (95% CI): Combined treatment 2.05 (1.21 -3.48). Oestrogen
only treatment 1.49 (0.83 - 2.66).
Ovarian cancer: Although evidence is conflicting, it has been concluded
that HRT, especially oestrogen only therapy is associated with an increased risk of ovarian cancer.13, 14 A
meta analysis found that the risk was increased by 1.28 with oestrogen therapy and 1.11 with combined therapy.14
Venous thromboembolism (VTE): a significant increase in the risk of VTE
has been observed in post menopausal women using HRT. The risk appears to be greatest during the first one to two years
of treatment and decreases over time.2, 7 Although HRT increases the risk of VTE up to twofold, the absolute
risk is small, with a baseline risk of 1.7 events per 1000 women over 50 not taking HRT.7
Younger age, lower HRT doses, transdermal HRT and oestrogen treatment alone may also be associated with less risk.2,
5, 7 Women who have previously suffered a VTE event have an increased risk of recurrence in the first year of HRT
use.7 Older age, obesity and underlying thrombotic disorders also significantly increase risk.2
Hazard ratio for increased risk of DVT (95% CI): Combined treatment 1.95 (1.43 - 2.67). Oestrogen only treatment
1.47 (1.06 - 2.06).
Breast cancer: Combined treatment with oestrogen and progestogen increases
the risk of breast cancer diagnosis or recurrence. Oestrogen treatment alone does not appear to increase this risk. The
greatest risk is with use of combined treatment for more than five years, when treatment is started over 50 years of age,
increasing with duration of use. It is not known if the risk is different for continuous or sequential use of progestogen.2,
In the WHI study, an increase in invasive cancers was observed in women using combined treatment for five or more years
and a non-statistically significant decrease in those using oestrogen alone, after an average of 7.1 years. There is limited
observational data that oestrogen use for more than 15 years may be associated with increased risk of breast cancer.2
Combined HRT treatment and to a lesser extent, oestrogen only treatment, increases breast cell proliferation, breast
pain and mammographic density and may impede the diagnostic interpretation of mammograms.2
Hazard ratio for increased risk of breast cancer (95% CI): Combined treatment 1.24 (1.01 - 1.54). Oestrogen only
treatment 0.77 (0.59 - 1.01).