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Menopause & HRT

The menopause is defined as the last spontaneous menstrual period a woman has, and marks a degree of the decline in function of the ovaries where there is not enough oestrogen being produced to make the lining of the womb grow. The menopause most commonly occurs around age 51 years, but may rarely be as late as 56 or as early as 15. The main hormone produced by the ovary is oestrogen, and it is lack of oestrogen that causes the symptoms of the menopause.

Symptoms

Vasomotor: The commonest symptoms of the menopause are hot flushes, which can occur up to twenty times a day in extreme cases. The flush occurs from the upper chest into the face, lasts a few minutes, and may be accompanied by sweating. Night sweats can be troublesome, waking the woman and sometimes necessitating changes of night attire during the night. This sleep disturbance can contribute to mood changes, which are also seen with the menopause. 

Psychological: Anxiety, depression, irritability and mood swings are quite common, and some women may experience palpitations and panic attacks. Women may also find difficulty with short-term memory and concentration.

Genito-urinary: Dryness of the vagina may occur, causing intercourse to become painful. This in turn may contribute to loss of sexual interest. Feelings of bladder irritability (cystitis), sometimes with burning of the urine (but not due to infection) may arise, as may frequency and urgency to pass urine and sometimes even incontinence (leakage). 

Testosterone deficiency: Some women become deficient in testosterone following menopause. This is more commonly seen in women who have had the surgical removal of both ovaries. Symptoms include a loss of sexual desire and often a generalised tiredness or exhaustion. The response to oestrogen may be lessened in women who are also lacking testosterone.

Long term effects

Osteoporosis: Loss of oestrogen leads to loss of bone, causing thinning which may result in brittle bones (osteoporosis). Osteoporosis can lead to fractures with only minor trauma, particularly of the spine, the wrist and the hip. Such fractures are painful and may sometimes be life-threatening. Thinning of the skin and poor wound healing may also occur.

Cardiovascular: Furring up of the arteries accelerates after the menopause and may result in coronary heart disease (angina and heart attacks). Microvascular angina (angina but without blockage of the main coronary arteries) is also more common around the menopause. 


Cognitive: Changes in brain function also occur as a result of loss of oestrogen, with certain functions, including memory, being affected.

Treatment

Hormone replacement therapy (HRT) is the main treatment for preventing or reversing the effects of the menopause.

HRT: The main hormone given is oestrogen, which reduces or abolishes hot flushes, psychological problems and vaginal dryness. It also prevents osteoporosis and fractures, and may help prevent the development of coronary heart disease and possibly dementia later in life. Oestrogen can be given as tablets, skin patches, skin gels and implants (oestrogen pellets inserted under the skin). Oestrogen stimulates the lining of the womb, making it grow, and if this is allowed to progress unchecked it can lead to cancerous change. A second hormone, progestogen, is therefore added to oestrogen in HRT. This is similar to the second hormone, progesterone, produced by the ovary in premenopausal women, which is responsible for menstrual periods. Progestogens can be given as tablets or skin patches, combined with oestrogen. Recently, an oral HRT preparation has been developed whereby the progestogen is substituted by a selective estradiol receptor modulator (SERM – similar to the anti-breast cancer drug Tamoxifen) which also protects the womb lining. 

With cyclical HRT, usually given to women around the time of the menopause (peri-menopause) or soon after the menopause, the oestrogen is given continuously but the progestogen is added for 12 – 14 each month, resulting in a menstrual-type bleed. This sheds the lining of the womb and thus prevents it from becoming cancerous. Women who have had a hysterectomy do not need a progestogen.

Women beyond the menopause may be given continuous combined HRT, where the oestrogen and progestogen are given together continuously. The progestogen prevents the oestrogen from causing the lining of the womb to grow, and thus prevents any bleeding occurring. Some spotting or bleeding may be seen in the first few months of such treatment, but this usually ceases.

HRT is usually started with the lowest available dose being given. If symptoms have not been satisfactorily relieved after about 3 months, the dose can be increased. There is no limit to the duration of use of HRT.

For women with only genito-urinary symptoms, oestrogen can be given locally into the vagina using tablets, creams and rings.

Side-effects of HRT include breast tenderness, nausea and with HRT tablets a transient increase in risk of blood clots (including deep vein thrombosis – DVT – and pulmonary embolism) and stroke particularly if the dose is too high. Some formulations of oestrogen combined with progestogen may possibly lead to a small increase in risk of breast cancer, similar to that arising from drinking a glass of alcohol daily, but much less than the increase in risk arising from being obese. It is not known if all oestrogen-progestogen combinations increase this risk, and oestrogen given alone does not appear to increase the risk of breast cancer.

Tibolone is a drug which acts like both an oestrogen and a progestogen. It is given as a tablet, and is effective in reducing or abolishing menopausal symptoms such as hot flushes. It also prevents menopausal bone loss. It does not produce vaginal bleeding, but may have the same effect as HRT on the breast. Effects on the heart are unknown, but it has unfavourable effects on glucose and insulin metabolism.

Raloxifene is a SERM (selective oestrogen receptor modulator), which acts like an oestrogen on the bones but as an anti-oestrogen on the breast and the womb. It helps prevent bone loss and osteoporotic fractures, but not hip fractures. It is associated with a reduction in breast cancer, but may produce or aggravate hot flushes. It increases the risk of blood clots similar to oestrogen. It may reduce coronary disease if started soon after menopause but not if started later in life. It does not cause bleeding, but does not relieve genito-urinary symptoms. Effects on the brain are unknown. Bazedoxifene is another SERM used for prevention of osteoporosis.

Testosterone can be given as a gel applied to the skin. There is currently no specific formulation for women, but the use of male testosterone gel preparations at 1/5th to 1/7th of the daily dose provides suitable female replacement.

Anti-depressants: SSRIs (selective serotonin re-uptake inhibitors) and SNRIs (selective norepinephrine re-uptake inhibitors) can help to reduce hot flushes, but they do not help other symptoms and have side-effects of their own.

Alternative therapies: plant extracts, such as phytoestrogens, red clover, black cohosh, have not been shown to be as effective as HRT and often their safety is unknown. They may prove of benefit for relieving symptoms in some women. Some “natural” products, such as progesterone creams, are without any obvious effect. So-called “bio-identical hormones” are wrongly claimed to be safer than licensed HRT products. They are simply the same oestradiol and progesterone as can be found in licensed products made by pharmaceutical companies but put together by unregulated compounding pharmacies. They should be avoided.

Address

Dr John C Stevenson
Royal Brompton Hospital
Sydney Street
London SW3 6NP

Contacts

Email: j.stevenson@imperial.ac.uk
Secretary (Angela):
020 7351 8112