Hormone Replacement Therapy (HRT)

​​Hormone replacement therapy (HRT) with small doses of oestrogen (together with a progestogen in women with a uterus) is appropriate for alleviating menopausal symptoms such as vaginal atrophy or vasomotor instability. Oestrogen given systemically in the perimenopausal and postmenopausal given in the postmenopausal period also diminishes postmenopausal osteoporosis. Menopausal atrophic vaginitis may respond to a short course of a topical vaginal oestrogen preparation used for a few weeks and repeated if necessary.

HRT may be used in women with early natural or surgical menopause (before age 45 years) since they are at high risk of osteoporosis. For early menopause, HRT can be given until the approximate age of natural menopause (i.e. until age 50 years). Alternatives to HRT should be considered if osteoporosis is the main concern.

HRT increases the risk of venous thromboembolism, stroke, endometrial cancer (reduced by a progestogen), breast cancer, and ovarian cancer; there is an increased risk of coronary heart disease in women who start combined HRT more than 10 years after menopause. For details of these risks see HRT Risk table below.

The minimum effective dose of HRT should be used for the shortest duration. Treatment should be reviewed at least annually. HRT does not prevent coronary heart disease or protect against a decline in cognitive function and it should not be prescribed for these purposes. The experience of treating women over 65 years with HRT is limited.

For the treatment of menopausal symptoms, the benefits of short-term HRT outweigh the risks in the majority of women, especially in those aged under 60 years.

Risk of breast cancer

In a recent study from the Collaborative Group on Hormonal Factors in Breast Cancer published in The Lancet in September 2019, new data have confirmed that the risk of breast cancer is increased during use of all types of HRT, except vaginal oestrogens, and have also shown that an excess risk of breast cancer persists for longer after stopping HRT than previously thought. 

Key findings:

  • All forms of systemic HRT are associated with a significant excess incidence of breast cancer, irrespective of the type of estrogen or progestogen or route of delivery (oral or transdermal)

  • There is little or no increase in risk with current or previous use of HRT for less than 1 year; however, there is an increased risk with HRT use for longer than 1 year

  • Risk of breast cancer increases further with longer duration of HRT use

  • Risk of breast cancer is lower after stopping HRT than it is during current use, but remains increased in ex-HRT users for more than 10 years compared with women who have never used HRT

  • Risk of breast cancer is higher for combined estrogen-progestogen HRT than estrogen-only HRT

  • For women who use HRT for similar durations, the total number of HRT-related breast cancers by age 69 years is similar whether HRT is started in her 40s or in her 50s

  • The study found no evidence of an effect on breast cancer risk with the use of low doses of estrogen applied directly via the vagina to treat local symptoms

Estimates of number of extra cases of breast cancer for 5 years HRT use starting around the time of menopause

  • In the UK about 1 in 16 never-users of HRT (about 63 per 1000) will be diagnosed with breast cancer between the ages of 50 years and 69 years.

  • Among women of average weight who start using systemic HRT from menopause in their 40s or 50s, and continue for 5 years, the extra number of cases of breast cancer by age 69 years is estimated from the study1 to be:around 1 extra case per 200 women (corresponding to about 5 extra cases per 1000 women) who use estrogen-only HRT

  • Around 1 extra case per 70 women (corresponding to about 14 extra cases per 1000 women) who use estrogen combined with a progestogen for part of each month (sequential or cyclical HRT)

  • Around 1 extra case per 50 women (corresponding to about 20 extra cases per 1000 women) who use estrogen combined with daily progestogen HRT (continuous HRT)

  • The number of extra cases up to age 69 years is approximately double these values for women who use systemic HRT for 10 years compared with those who use HRT for 5 years.

Radiological detection of breast cancer can be made more difficult as mammographic density can increase with HRT use.

Risk of endometrial cancer

The increased risk of endometrial cancer depends on the dose and duration of oestrogen-only HRT.
In women with a uterus, the addition of a progestogen cyclically (for at least 10 days per 28-day cycle) reduces the additional risk of endometrial cancer; this additional risk is eliminated if a progestogen is given continuously. However, this should be weighed against the increased risk of breast cancer.

Risk of ovarian cancer

Long-term use of combined HRT or oestrogen-only HRT is associated with a small increased risk of ovarian cancer, this excess risk disappears within a few years of stopping.

Risk of venous thromboembolism

Women using combined or oestrogen-only HRT are at an increased risk of deep vein thrombosis and of pulmonary embolism especially in the first year of use.

In women who have predisposing factors (such as a personal or family history of deep vein thrombosis or pulmonary embolism, severe varicose veins, obesity, trauma, or prolonged bed-rest) it is prudent to review the need for HRT, as in some cases the risks of HRT may exceed the benefits.
Travel involving prolonged immobility further increases the risk of deep vein thrombosis.

Risk of stroke

Risk of stroke increases with age, therefore older women have a greater absolute risk of stroke. Combined HRT or oestrogen-only HRT slightly increases the risk of stroke.

Risk of coronary heart disease

HRT does not prevent coronary heart disease and should not be prescribed for this purpose. There is an increased risk of coronary heart disease in women who start combined HRT more than 10 years after menopause. Although very little information is available on the risk of coronary heart disease in younger women who start HRT close to menopause, studies suggest a lower relative risk compared with older women.

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Mo Salhab MD, MS, PG Dip, FRCS 

Oncoplastic & Aesthetic Breast Surgeon