The different types of hormone therapy

Hormone replacement therapy (HRT) is a treatment used to relieve symptoms of the menopause.

Hormone replacement therapy (HRT) is the replacement of the female hormones, oestrogen and progesterone, which the ovaries do not produce any more at the menopause.

Oestrogen is usually taken in HRT unless there are contraindications. Most products contain oestradiol or conjugated oestrogen. Oestradiol is sourced from soy and yam, and conjugated oestrogen from pregnant horse urine. Both are considered natural compounds.

Prolonged exposure of the uterus to only oestrogen increases the risk of cancer of the lining of the uterine cavity (endometrium).

The addition of progesterone or its synthetic version – progestogen – for at least 12-14 days per month reduces the risk of endometrial cancer to nearly the same level as that of women not using oestrogen.

As such, oestrogen-only (ET) products are prescribed in women whose uterus has been removed surgically (hysterectomy). All other women on HRT will be prescribed an oestrogen-progestogen combination (EPT).

There are different types of progestogens. They have similar effects on the endometrium and bone. However, they have different metabolic and vascular effects. Thus, the type of progestogen used may be important for appropriate management of HRT.

The side effects of the different progestogens are different; thus, tailoring of the appropriate progestogen is essential for continuance of HRT.

The treatment regimens may be cyclical or continuous. Women who have had a hysterectomy are usually prescribed continuous oestrogen. Women who have a uterus may take HRT either cyclically or continuously.

Cyclical HRT may be monthly or three-monthly. Monthly HRT is usually prescribed for women with regular periods and three-monthly for women with irregular periods.

In perimenopausal women with a uterus, cyclical EPT (monthly or three-monthly) with daily oestrogen plus progestogen in the latter part of the cycle is preferred. There is a predictable withdrawal bleed unlike continuous HT, which often cause irregular bleeding.

It is more convenient for combined EPT to be taken. If taken separately, it is easy for the progestogen, which causes more side effects, to be omitted.

As such, it is important to remember the endometrial-protective effect of progestogen, if oestrogen and progestogen are taken separately.

In post-menopausal women with a uterus, cyclical EPT (monthly or three-monthly) will produce a predictable withdrawal bleed. Continuous EPT is also suitable as it causes endometrial atrophy and does not produce a withdrawal bleed. However, irregular bleeding or spotting may occur in the initial four to six months of treatment.

Tibolone is a selective oestrogen receptor modulator (SERM) with mixed oestrogenic, progestogenic and androgenic actions. It is prescribed for post-menopausal women and has to be taken continuously. It is used to treat vasomotor, psychological and libido problems, and is an alternative no-bleed regimen for post-menopausal women.

HRT can be taken in various ways. It is advisable to have a discussion with the doctor who can advise on the appropriate route.

The choice of delivery route depends partly on patients’ preference, but there are also certain advantages for different routes.

Non-oral preparations have less effect on clotting factors, reduce triglycerides, and are more suitable for women who experience nausea with oral preparations.

They are also better for those with liver disease, gallstones, migraine or diabetes; those who are at risk of thrombosis; or those who are taking enzyme-inducing medicines.

Oral preparations are in the form of tablets of ET alone, EPT or progestogen alone.

Oral oestrogens are more likely to cause nausea. The oral route is usually avoided in women taking hepatic enzyme-inducing medicines. The progestogens in EPT are 17-hydroxyprogesterone derivatives or 19-nortesterone derivatives. Progestogen-only tablets are taken when the oestrogen component is taken through another route, eg transdermal or nasal.

Transdermal patches and gels contain ET or EPT. These reservoir or matrix patches are usually placed on the buttocks. They may cause a skin reaction sometimes, more so in reservoir patches.

Some patches contain different strengths of oestrogen, thereby permitting dose titration.

The levonorgestrel-releasing intra-unterine device plus oestrogen component may be used if there are side-effects with other progestogen preparations and delivery routes, contraception is still needed, or there is persistent heavy bleeding on cyclical EPT and normal investigations.

Nasal oestrogen spray is available and has been reported to be as effective as oestrogen delivered by other routes. Progestogen needs to be added if the uterus is intact.

The common side effects are nasal symptoms like running nose, sneezing, nosebleeds and breast tenderness (mastalgia).

Oestrogen-only implants can be inserted below the skin under local, general or regional anaesthesia. As oestradiol is released over several months, there is no need to remember to take medicine. However, implants may cause scars, and sometimes, may not be easily removed.

Vaginal oestrogen preparations are in the form of creams, tablets or pessaries. They are useful for vaginal and urinary symptoms, but do not provide total HRT. There is very low systemic absorption. If vaginal oestrogens are used for the short term, progestogen need not be added.

If vaginal oestrogens are used for the long term, an oral progestogen is usually prescribed for 12-14 days each month for endometrial protection because systemic absorption is higher.


Dr Milton Lum is a member of the board of Medical Defence Malaysia. The views expressed do not represent that of organisations that the writer is associated with.

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