Busting HRT confusion

What is the difference between oral and trans-dermal oestrogen in terms of safety protocol and why are micronised progesterone or the Mirena coil the preferred options if women need progesterone? Dr Vikram Talaulikar and Professor Isaac Manyonda clarify things

Trans-dermal oestrogen is safer than oral oestrogen in relation to the risk of blood clotting.

Hormone replacement therapy (HRT) is available for prescription in several different forms. It can be administered as a skin patch or gel, oral tablet, implant under the skin, vaginal ring and progestogen (derivative with progesterone-like activity) releasing uterine coil, as well as vaginal cream or pessaries. Some types work best for certain symptoms.

As trans-dermal oestrogen (patches / gel) is associated with fewer risks than oral HRT, it may be preferable for many women. This route is particularly advantageous for women with diabetes, hypertension and other cardiovascular risk factors which tend to increase with advancing age.

The principle risks of HRT are thromboembolic disease (blood clots in veins and lungs), stroke, cardiovascular event, gallbladder disease, breast cancer and endometrial (womb) cancer. Large studies such as the Women's Health Initiative (WHI) and the Million Women Study (MWS) caused concerns and controversy over the use of HRT when their findings were published. However, re-analysis of some of the data and findings from recent studies over the past decade has shown that, in women with symptoms or other indications, initiating HRT near the menopause will provide a favourable benefit-to-risk ratio.

Oral HRT

Oral HRT (combined oestrogen and progestogen or oestrogen only) after a natural menopause increases the risk of venous thromboembolism (VTE - venous blood clots), pulmonary embolism (blood clot in lungs) and stroke. The risk of VTE is increased two to three times with oral HRT. In one large study over 5 years, less than one in 100 women taking HRT got a blood clot in their lungs. However, this was approximately twice the number of women who were not taking HRT. Overall, the risk is significantly less than the risk associated with pregnancy.

The risk increases with age and with other risk factors such as obesity, previous thromboembolic disease, smoking and immobility. In healthy women below 60 years, the absolute risk of VTE is low and mortality risks from VTE are low. The type, dose and delivery system of both oestrogen and progestogen influence the risk of thromboembolic disease. The VTE risk appears to be higher among users of oestrogen plus progestogen than among users of oestrogen alone. The risk is increased, especially during the first year of treatment. Previous users of HRT have a similar risk to never users.

The risk of stroke appears to be increased in women taking oestrogen-only and combined HRT. The risk is estimated to be one additional case per 1000 women using combined or oestrogen-only HRT between 50 and 59 years and three additional cases per 1000 women between 60 and 69 years compared to non-HRT users (for a 5-year use period).

Trans-dermal HRT

Trans-dermal delivery of oestrogen and progestogen is superior to oral HRT as its use is not associated with an increased risk of blood clotting in women who take HRT as compared to general population. These hormone preparations may also be useful for women who have had blood clots in the past, but such treatment should be planned in liaison with a menopause specialist and a haematologist. While natural body-identical oestrogen 17-beta-oestradiol (which is part of the commonly used patches / gels) is the best form of oestrogen in HRT, natural micronised progesterone such as Utrogestan or Mirena intrauterine coil are the safest progestogens to minimise the risk of blood clots in comparison to oral synthetic progestogens.

For most healthy women suffering from menopausal symptoms, the risks from HRT are very small, but women need to talk to their healthcare professionals to weigh up their individual risks and benefits. Doctors often advise that women should take the lowest dose of HRT that controls their symptoms for the shortest duration of time possible. However, there is no arbitrary upper age limit for the use of HRT. For the women who continue to have symptoms, the benefits from HRT usually outweigh any risks.

Progesterone

The type and dose mainly affect the risk of blood clotting and breast cancer.

Combined (oestrogen and a progestogen) hormone replacement therapy (cHRT) is associated with an increased risk of breast cancer, while oestrogen replacement therapy appears not to be. Whatever the underlying mechanism, it is the progestogen in cHRT that seems to increase the risk. Fear of breast cancer is a major limiting factor in the use of hormone replacement therapy and when women discontinue cHRT because of side effects, the latter are often attributable to the progestogen component. cHRT is given to women with an intact uterus to protect against the effects of un-opposed oestrogen such as an increased risk of endometrial (womb) cancer. Oestrogen replacement therapy suffices for women with a prior hysterectomy.

The absolute risk of developing breast cancer on HRT remains low and this is a key message that needs to be communicated clearly to women and health professionals. For 50-year-old women in the UK who have started experiencing symptoms of the menopausal transition and who are considering taking combined oestrogen and progestogen HRT for five years, the current best evidence suggests that, if 1000 such women take HRT for five years, 66 would be expected to get breast cancer by the age of 70. If these women did not take HRT, then 58 would be expected to get breast cancer. A difference of 8 in 1000. Most of that increase happens in the first five years when the women are taking HRT.

There is a clear distinction in risk and side-effect profile between cHRT and oestrogen replacement therapy. Apart from being the most effective treatment for menopausal symptoms, oestrogen prevents osteoporosis, and may also have a potential role in prevention of Alzheimer's Dementia, now the biggest killer of women in the United Kingdom. The aim of modern HRT is, therefore, to use the minimum required dose of progesterone for womb safety and the safest type of progesterone available so as to minimise risks of blood clotting and breast cancer. At the present time, the levonorgestrel intrauterine system (Mirena coil) and the oral body-identical micronised progesterone (Utrogestan), closely followed by dydrogesterone, appear to be the safest progesterone options (with better breast safety profile and lower risk with long-term use) as compared to synthetic progestogens such as norethisterone or medroxyprogesterone which form a part of other HRT preparations. These are therefore the progesterone preparations of choice over traditional progestogens.

echo For more information, you can contact Professor Manyonda and Mr Talaulikar at the Menopause Clinic, London