Menopause and Hormone Replacement Therapy

Hormone replacement therapy (HRT) does exactly what its name suggests – it replaces the hormones that a woman’s body ceases to produce after the menopause.

Eternal youth

HRT has been touted as an ‘elixir of life’, a magic potion that can reverse the effects of ageing, keeping a woman young forever. HRT is not the answer to eternal youth, but it can make many women feel younger. Successful treatment of exhausting hot flushes and sleepless nights restores energy. In turn, feeling better means it is easier to take regular exercise and follow a healthy diet, both of which have their own benefits.

Critics are sceptical that the menopause requires any medical intervention and see it as a natural event that should run its own course. This is fuelled by the fact that not every woman becomes severely oestrogen-deficient after ‘the change’. Although the ovaries are the main source of oestrogen, the adrenal glands produce small amounts and oestrogen is also formed in fat. These extra-ovarian sources are insufficient to restore fertility but may be adequate to prevent the development of severe menopausal symptoms.

Fear of cancer, particularly breast cancer, is another cause for concern but studies suggest that the risks are minimal if HRT is taken for less than 10 years. Even then, the evidence for increased risk is controversial.

Many women accept these risks once they realise the benefits of HRT, although some find it hard to cope with a return of monthly ‘periods’ and the regular pill taking that many regimens require.

Progesterone protection

Although oestrogen replacement effectively relieves the symptoms of the menopause, it is not without its problems. Doctors noticed a sudden increase in cancer of the lining of the womb, the endometrium, that was clearly linked to treatment. The oestrogen was stimulating growth of the endometrium resulting in the formation of potentially cancerous cells. In a percentage of women, true cancer developed but in a form that, in most cases, responded to treatment. Fortunately, a simple means of prevention was found -a 12-day course of synthetic progesterone (called progestogens) taken each month ‘opposes’ the oestrogens creating an artificial bleed similar to a ‘period’, which expels any cancerous cells. Women who have had a hysterectomy are not at risk of endometrial cancer and can safely take ‘unopposed’ oestrogens.

Refuting myths

Many of the fears associated with HRT are due to its effects being confused with those of the oral contraceptive pill. In fact, they are entirely different.

The oral contraceptive pill contains high doses of synthetic oestrogens which are up to eight times more potent than the natural oestrogens used for HRT. These high doses are necessary to prevent the ovaries releasing an egg each   month, producing a contraceptive effect. A disadvantage of synthetic oestrogens is that they make blood more sticky, increasing the risk of clots and thromboses in veins and arteries, which can lead to heart attacks and strokes. In contrast, natural oestrogens have minimal effects on blood clotting, and the dose used for HRT is equivalent to the amount produced in the body during the normal menstrual cycle. Natural oestrogens reduce the risk of clots in arteries, so heart attacks and strokes are less likely to occur. The risk of a clot in the veins (venous thrombosis) in a woman taking HRT is the same risk as she would have during her re­productive years, although this is greater than for a postmenopausal woman who is not using HRT.

Because of these important differ­ences, women who were unable to take the ‘pill’ can safely take HRT.

Unfortunately many myths surround the use of HRT and misinformation abounds, even within the medical profession. Research shows that women obtain most of their information from non-experts, especially the media, so it is not surprising that there is so much confusion about HRT.

How to Take HRT

The choice of different regimens for HRT depends on whether or not you have had a hysterectomy.

Women with a womb

Continuous oestrogen plus cyclical progestogen

This is the most common regimen. Oestrogens are taken continuously, without a break, either daily in tablet form, once or twice weekly in patch form, a gel or, occasionally, as an implant. Progestogens are added every month, either as a 10 to 14 day course of tablets, or as a double patch combined with oestrogen, replaced twice weekly for two weeks. Calendar packs are available to help you remember when to take the progestogens.

The choice of different regimens for HRT depends on whether or not you have had a hysterectomy.

Women with a womb

Continuous oestrogen plus cyclical progestogen

This is the most common regimen. Oestrogens are taken continuously, without a break, either daily in tablet form, once or twice weekly in patch form, a gel or, occasionally, as an implant. Progestogens are added every month, either as a 10 to 14 day course of tablets, or as a double patch combined with oestrogen, replaced twice weekly for two weeks. Calendar packs are available to help you remember when to take the progestogens. If oestrogens and progestogens are prescribed separ­ately, most doctors recommend that you begin the progestogen course on the first day of every calendar month. All these regimens should result in a withdrawal bleed near, or shortly after, the progestogen course. You should report any bleeding occurring at other times to your doctor.

More recently, long cycle HRT has been introduced. This involves taking oestrogens every day as usual, but only taking the progestogen course every three months, i.e. four with­drawal bleeds every year. Unfort­unately a week of placebo (dummy) tablets is included in the packet and some women notice a return of their symptoms during this time. As a result of this, some doctors recommend skipping the placebo week. The other disadvantage is that a relatively high dose of progestogen is necessary which can lead to side effects as well as heavy and/or prolonged bleeding. Despite this, long cycle HRT can still be useful for women who are not yet able, or are unable, to take the no-bleed HRT and who wish to reduce the number of withdrawal bleeds.

Continuous oestrogen plus continuous progestogen

One approach to overcome the regular withdrawal bleeds is to take a combination of oestrogen and pro­gestogen continuously – taking both hormones together prevents any thickening of the lining of the womb so a withdrawal bleed is unnecessary. Unpredictable bleeding is not un­common during the first few months, sometimes heavy and prolonged.

However, in most women who continue on this treatment, the bleeding usually settles within 12 months. Bleeding is less likely the longer a woman has been post­menopausal before she starts this regimen. For this reason, continuous combined regimens are only recommended for women who have been postmenopausal for at least one year. In these cases continuous combined HRT can be highly satisfactory, although missed pills are frequently associated with some spotting.

Postmenopausal women who have been taking cyclical HRT and who wish to change to a ‘no-bleed’ regimen should start the new tablets at the end of a withdrawal bleed, i.e. several tablets into a fresh pack of their old cyclical HRT. This reduces the likelihood of any further bleeding because the lining of the womb will be thin. A recent advance has been to give continuous oestrogens to women using the levonorgestrel-releasing intrauterine system (IUS), used for contraception. This has the particular advantage for women who are still menstruating and at risk of pregnancy. Further, the progestogen is released locally so side effects are few. Similar to other no-bleed regimens, irregular bleeding in the early months can be a problem but most women have no bleeding within one year. Although the IUS is used for contraception, at the time of writing it is not licensed for use as HRT combined with oestrogens.

As a result of the limited use of no-bleed HRT, the long-term effects of this treatment on cancer of the womb, or indeed on osteoporosis, heart disease and breast cancer, have yet to be fully evaluated.

Cyclical oestrogens

An early regimen advocated oes­trogen treatment for three out of every four weeks, omitting pro­gestogen therapy. This method is associated with increased risk of cancer of the womb and a return of menopausal symptoms during the oestrogen-free week. For these reasons it is neither safe nor effective. If you are using this regimen, see your doctor and change to a recommended one.

Women who have had a hysterectomy

Continuous oestrogen

Hysterectomised women have the advantage of not requiring proges­togens, which reduces side effects and maximises benefits. The choice of treatment is daily oestrogen tablets, once or twice weekly patches, oestrogen gel or six-monthly implants.

Doses of oestrogen

The correct dose of oestrogen depends on the reason for taking it. Relief of severe symptoms obviously requires a higher dose than relief of mild   symptoms.   Many   women wonder why levels of hormones are not tested; the simple answer is that, because normal levels of oestrogen vary so much, it is more appropriate to monitor symptom control. If symp­toms are not adequately controlled, the dose of oestrogen needs in­creasing; if side effects are a problem, the dose is too high. There is a minimum daily dose of oestrogen necessary to protect bone loss. The doses in the various preparations are as follows:

– 0.625 milligram conjugated oestrogens (daily tablets)

– 2 milligrams oestradiol (daily tablets)

– 40-50 micrograms oestradiol (once/twice weekly patches)

– 1.5 milligrams oestradiol – two metered doses (daily gel)

– 50 milligrams  oestradiol   (six-monthly implant).

Doses of progestogen

The correct dose of progestogen is critical because it can almost completely eliminate the risk of cancer of the womb. A minimum duration of 12 days of treatment is recommended but the dose depends on the type of progestogen:

– 0.7-2.5 milligrams norethisterone

– 150 micrograms L-norgestrel

– 10-20 milligrams dydrogesterone

– 5-10 milligrams medroxyproges­terone acetate

– 200-400 milligrams micronised progesterone.

When to start HRT

It is never too late to start HRT; older women with fractures or heart disease will still benefit. But the most rapid loss of bone occurs soon after the menopause and the risk of heart disease starts to increase, so the earlier you start HRT, the better. If you start HRT while you are still menstruating, some adjustment of the timing of the progestogen phase may be necessary to prevent irregular bleeding.

When to stop HRT

If you use HRT just to control menopausal symptoms you will probably need to take it for two to three years, although occasionally it may be necessary to continue for as long as five years. For long-term protection against osteoporosis and heart disease, at least five years, and possibly up to 10 years, of treatment are recommended. If you are happy taking HRT there is no reason why you should not continue treatment indefinitely, so long as you are aware of the possible increased risks associated with long-term use.