Hormone Replacement Therapy

As the term implies, hormone replacement therapy (HRT) is the administration of hormones to replace hormones that the ovaries cease to produce following the onset of the menopause, in a bid to restore the hormonal milieu and treat symptoms and prevent disorders (e.g., osteoporosis) associated with the menopause.

Synonymous terms include menopausal hormone therapy (MHT) and oestrogen replacement therapy (ERT).

While oestrogen and progesterone are the best known of the ovarian hormones, it is often not appreciated that the ovaries also produce the hormone testosterone, considered by many to be a “male” hormone, but in fact crucial and critical to normal bodily functions and good health in women too, albeit at a much lower level compared to the levels in men.

Hormone replacement therapy therefore refers to the administration of any of these hormones, often in combination (see below).

Types of HRT

Oestrogen only (no progesterone)

When women have had a hysterectomy, they do not need progesterone to protect the lining of the womb. Oestrogen is then prescribed alone, or in combination with testosterone.

Combined HRT (oestrogen and progesterone)

This is necessary for women who have a womb (uterus). This can be given in two ways:

Continuous combined HRT - oestrogen and progesterone, taken together daily - this means that there will be no withdrawal bleeds/periods.
Sequential HRT - oestrogen only is given for the first 14 days, after which progesterone is added for the remaining 14 days of a 28-day treatment cycle. This results in monthly withdrawal bleeds, mimicking the natural menstrual cycle, but of course the periods are induced by the hormones.

Some clarification:

Women who have had their womb removed (hysterectomy) can safely be given oestrogen alone (with or without testosterone – see below). However, in the presence of the womb, oestrogen given as HRT will stimulate the lining of the womb (the endometrium) to thicken. In the absence of progesterone, this thickening continues, and over the course of time this may lead initially to irregular bleeding due to haphazard shedding of the endometrium, but more importantly cancer may develop in the endometrium (endometrial or womb cancer). In sequential HRT, the addition of progesterone results in the regular shedding of the endometrium, thereby preventing the development of endometrial cancer, and also irregular bleeding as the shedding of the endometrium is regulated. In the continuous combined formulation, the constant presence pf the progesterone prevents the thickening of the endometrium, and therefore again protects against the development of endometrial cancer.

Cyclical HRT is often prescribed to women who are having menopausal symptoms but are still having periods or for those whose periods stopped less than a year ago. Continuous HRT (without bleeds) is more suitable for women who have not had menses for more than one year.

The “hormone coil” or “hormone intrauterine device” (also known as the Mirena or the levonorgestrel intrauterine system) may also be used to protect the endometrium by preventing its thickening – in the menopausal woman there most often no bleeding, and oestrogen can be given without additional progesterone. The coil lasts for 5 years – visit here for further details.

Formulations of HRT – how HRT is given

HRT may be prescribed in the following formulations:

tablets taken by mouth
patches applied to the skin
implants inserted in the fat layer under the skin
gels or sprays applied to the skin
hormone-releasing rings inserted inside the vagina
hormone-releasing coils inserted into the womb
hormone creams or tablets applied into the vagina

The formulation that suits a given woman will usually be advised by the menopause specialist taking on board the woman’s preferences.There are often good reasons why a particular formulation might be advised over another, and sometimes a formulation is prescribed, only to be changed later if it does not suit. At the Menopause Clinic London, transdermal patches/gels or sprays are more frequently prescribed as first line, compared to the oral tablets, because these formulations are associated with fewer risks. This patch/gel/spray is also advantageous for women with diabetes, hypertension, and other cardiovascular risk factors especially with advancing age. Local preparations such vaginal oestrogen creams or pessaries do not carry the same risks associated with oral or transdermal HRT. In addition, as the dose of oestrogen is so low, they do not require the protective effect of progesterone. They are highly effective for symptoms of vaginal dryness, painful sex and urinary frequency.

Their use is safe and not linked to some of the major risks associated with systemic HRT. However, around 10-25% of women still have symptoms with local oestrogen so will require systemic HRT in addition.

Bio-identical HRT

Many private clinics offering HRT often seek to boost their appeal by boasting that they provide “bio-identical HRT” or “bio-identical hormones” or “natural hormones”. These terms are synonymous, and refer to the use of hormones that are identical at a molecular level with the hormones found in the body (also called endogenous hormones). The idea of taking the “natural” hormone has an obvious appeal, both from a potential effectiveness, as well as potential safety point of view (“natural” means safe…, “natural” means effective!”). In reality, the “bio-identical” concept is largely hype and misleading.

When HRT is indicated, women are advised to take only those hormone therapies that are regulated and approved by the MHRA, which include hormones which are natural and identical to those produced in the body. There is lack of sufficient data regarding safety and efficacy of unregulated custom compounded hormones. Most commercially available and approved HRT preparations contain 17-beta oestradiol form of natural oestrogen along with progestogens - compounds which have progesterone like actions. Micronised progesterones are natural progesterones devoid of any androgenic as well as glucocorticoid activities. These appear to be the optimal progesterone in terms of cardiovascular effects, blood pressure, VTE, probably stroke and even breast cancer. Utrogestan is the only one currently available to prescribe in the UK.

What is ‘bio-identical’ or ‘body-identical’ HRT

What are the common side effects of HRT?

What are the risks associated with use of HRT?

Alternatives to HRT - conventional therapies

Alternatives to HRT - complementary therapies

When HRT should not be taken

Tests that are needed before or after starting HRT

When you start HRT, the doctor will discuss your age, symptoms and medical conditions before looking at the risks and benefits of HRT which are specific to you. These can change and will usually be discussed at yearly reviews. A baseline pelvic ultrasound scan may be offered at the initial consultation to assess lining of the womb and rule out pathologies such as uterine fibroids or ovarian cysts. Further pelvic scans are usually not necessary unless there is abnormal bleeding or pelvic pain. In such situations, you will be asked to have additional pelvic ultrasound scans to assess lining of the womb and a biopsy of the womb lining may be performed. If there is a personal or family history of VTE/blood clotting - a thrombophilia screen (blood test to look for tendency to develop blood clots easily) may be helpful. If there is a high risk of breast cancer, you will be asked to consider a mammography or MRI scan and referred to familial breast cancer services depending on the level of your risk. A blood test for lipid and glucose profile will be requested if you have risk factors associated with cardiovascular disease.

Please NOTE - HRT is not a contraceptive

HRT is not a contraceptive. Women may be potentially fertile for up to two years after their last menstrual period if they are under 50 years of age and for one year if they are over 50 years. They should therefore use appropriate contraception during this time to avoid pregnancy.

NB: Unlike the contraceptive pill, oestrogen in the HRT aims to mimic the actions of the natural molecule. The contraceptive pill contains a much stronger form and dose of synthetic oestrogen which takes a long time to be cleared from the body unlike natural oestrogen.

Women on HRT need follow-up

You will generally be offered a follow-up consultation after starting HRT in about three months’ time. Most menopausal symptoms are likely to have responded to oestrogen in this time period and any residual problems may require alternative management. If the chosen HRT suits you and appears effective, you may wish to see your doctor once or twice every year to review the on-going need for and safety of continuing the HRT. Both mammography and cervical screening as per national guidelines are recommended in postmenopausal women on HRT.

When to stop HRT

There are no arbitrary limits to taking HRT and treatment can continue as long as benefits outweigh risks for the individual. Many women can stop taking HRT after their menopausal symptoms diminish, which is usually three to five years after they first appear.

Gradually decreasing HRT dose is usually recommended, rather than stopping suddenly. Some women may have a relapse of menopausal symptoms after stopping HRT, but these should pass within a few months. If symptoms persist for several months after stopping HRT, or if there are particularly severe symptoms, treatment may need to be restarted, usually at a lower dose. After stopping systemic HRT, some women need additional treatment to prevent vaginal dryness and osteoporosis.

Additional resources for information:

British Menopause Society
International Menopause Society
European Menopause and Andropause Society
NHS Choices
Menopause Exchange