See estrone.
One of the major problems of the menopause which does not give rise to symptoms until many years later is osteoporosis (see BONE, DISORDERS OF). After the menopause, 1 per cent of the bone is lost per annum to the end of life. This is a factor in the frequency of fractures of the femur in elderly women as a result of osetoporosis, but it can be prevented by hormone replacement therapy (see below).
Hormone replacement therapy (HRT) This term has become synonymous with the scienti?cally correct term ‘OESTROGENS replacement therapy’ to signify the treatment of menopausal symptoms and signs with oestrogens, now usually combined with PROGESTOGEN. Oestrogen and combined treatment relieve the short-term symptoms such as hot ?ushes, sweats and vaginal dryness. Atrophic vaginitis and vulvitis (shrinking of the tissues of VULVA and VAGINA due to fall in natural oestrogen levels) also usually respond to treatment with oestrogens.
Cyclical therapy is necessary to avoid abnormal bleeding in women who have reached the menopause. If oestrogens are given alone, there is an increased risk of endometrial hyperplasia (overgrowth of the ENDOMETRIUM) which may lead to endometrial cancer, so these are restricted to women who have had a hysterectomy and are no longer at risk. Other women can be given oestrogen-progestogen combinations.
There is good evidence that oestrogen alone or in combination can prevent the bone-loss associated with the menopause by reducing the demineralisation of bone which normally occurs after the menopause; and, if it is started early and continued for years, it may prevent the development of osteoporosis. Oestrogen is far more e?ective than calcium supplements and has been shown greatly to reduce fractures affecting the spine, wrists and legs after the age of 50.
However, HRT is no longer licensed for ?rst-line treatment to prevent osteoporosis, as increased risk of stroke, breast cancer and coronary heart disease cannot justify treatment for long periods – unless the woman has severe menopausal symptoms. HRT is recommended for short-term use only in menopausal women whose lives are inconvenienced by vasomotor instability (severe ?ushes, etc.) or vaginal atrophy, although the latter may respond to local oestrogen treatment – creams or pessaries. In terms of oestrogenic activity, natural oestrogen such as oestradiol, oestrone and oestriol are more appropriate for HRT than synthetic oestrogens like ethinyloestradiol, mestranol and diethylstilboestrol.
Many experts believe that controversy surrounding the risks and bene?ts of HRT have been settled by a large randomised trial (the Women’s Health Initiative), published in 2003, which showed that combined treatment increases the risk of breast tumours, stroke and coronary heart disease (in the ?rst year). Oestrogen alone (given to women who have had a hysterectomy) also increases the risk of stroke. Five years of combined treatment may double the risk of breast cancer, and the heart-disease risk is nearly doubled during the ?rst year of use. This is in spite of the bene?cial effects of HRT on blood lipids. However, there are others who consider that di?erent dose combinations of di?erent hormones may one day prove bene?cial, so research continues.
HRT can also provoke minor adverse effects such as breast tenderness, ?uid retention, leg cramps and nausea. The risk of abnormal blood clotting means that HRT is not normally recommended for women who smoke heavily or have had THROMBOSIS, severe HYPERTENSION, stroke or liver disease. HRT has, however, brought symptomatic bene?ts to many menopausal women, who can then justify taking the other increased risks – only fully understood since the large trial results were published.
As the evidence stands at present, careful consideration of each woman’s medical history and the severity of her menopausal symptoms is necessary in deciding what combination of drugs should be given and for how long. In general, the indications should be severe menopausal symptoms that can be controlled by the lowest dose for the shortest time. Using HRT to alleviate mild symptoms, or to prevent future bone loss, is probably of insu?cient bene?t to counter the other risks described above.... menopause
The oestrogenic hormones of the ovary are OESTRADIOL and oestrone. The rapid degradation of natural oestrogens limits their use as therapeutic agents. Chemical substitution of the steroid molecule, as in ethinyl oestradiol, or the use of a non-steroidal synthetic oestrogen such as STILBOESTROL, greatly reduces the rate of degradation and enhances the therapeutic action. A further development has been the use of compounds which are not actually oestrogenic themselves, but which are slowly metabolised to oestrogenic substances, or substances such as chlorotrianisene, which are taken up in the body fat and then slowly released into the circulation. There is in fact little to choose between the various synthetic oestrogens. Ethinyl oestradiol is the most potent oral oestrogen, being 20 times more active than stilboestrol.
Other commonly used oestrogen drugs are dienoestrol and oestrol. The use of oestrogens in hormone replacement therapy (HRT) is dealt with in the entry on the MENOPAUSE.... oestrogens
Naturally occurring and synthetic oestrogens are used to treat *amenorrhoea and menopausal symptoms (see hormone replacement therapy), as well as androgen-dependent cancers (e.g. cancer of the prostate). Synthetic oestrogens are a major constituent of *oral contraceptives. Side-effects of oestrogen therapy may include nausea and vomiting, headache and dizziness, irregular vaginal bleeding, fluid and salt retention, and feminization in men. Oestrogens should not be used in patients with a history of cancer of the breast, uterus, or genital tract. —oestrogenic adj.... oestrogen
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