Hormone replacement therapy (HRT) refers to the administration of artificial hormones to patients who are in a state of oestrogen deficiency. This most commonly occurs at the time of menopause on average at 52 years of age or earlier following surgical removal of the ovaries. Menopause is a normal ageing process and is marked by the cessation of menstrual periods, however, if there is any doubt, particularly in patients who have previously undergone a hysterectomy, the diagnosis can be confirmed by the findings of an elevated serum FSH and LH together with a low serum oestradiol level. Oestrogen is the hormone produced by the ovaries which has an effect on almost every organ in the body. The absence of oestrogen can have wide ranging manifestations on the brain, urogenital, cardiovascular and skeletal symptoms. In the short term, oestrogen deficiency causes vasomotor disturbances, including hot flushes and sweating, which can prove to be quite distressing to some women prompting them to seek medical attention. In others, mood changes, irritability, insomnia, poor memory and loss of self-esteem may be the more subtle end-result of oestrogen deficiency. The genitourinary tract may be affected after some time to cause urinary incontinence although this is often associated with genital prolapse. Vaginal dryness, low libido and painful intercourse may cause sexual dysfunction for the patient who is often in her early 50’s or younger.
The long term effects of oestrogen deficiency relate to the effect on the skeletal system causing osteoporosis. This may result in fractures of the neck of femur, forearm or vertebral bodies resulting in pain, disability and increased dependence on family and community resources.
The administration of HRT involves the taking of oestrogen which exerts its effects by binding to oestrogen receptors (ER) distributed throughout the various organs of the body. Oestrogens can be given orally in the form of tablets, through the skin by way of a gel or patches and by implants inserted below the skin. If the uterus is still present the patient will also need to take a progestagen in order to prevent stimulation of the endometrial lining. The progestagen can be given in a cyclical fashion to produce regular withdrawl periods each month or continuously if the patient prefers not to have a monthly menstrual cycle.
Contraindications to the use of HRT include the presence of pre-existing hormone sensitive tumours such as breast or endometrial cancers. In these patients symptomatic hot flushes can be treated by the use of other medications including progesterone. A past history of deep vein thrombosis, hypertension (high blood pressure) or stable liver disease do not necessarily contraindicate the use of HRT in selected patients.
The fear of many patients and also some doctors with regard to taking HRT relate to the perceived risk of developing breast cancer. Breast cancer can occur at any age but the incidence increases progressively from 50 years onwards this coinciding with the use of HRT. It should be emphasized that HRT is not known to be oncogenic (causing breast cancer) and that the risk of developing breast cancer is age related with increasing incidence with advancing age. The optimal time for taking HRT is up to 55 years of age when the risk is arguably the lowest, with mammography performed at 50 years of age and continued every 2 years thereafter for the early detection of any breast tumours.
For those patients with symptoms and who do not wish to take HRT or in whom HRT is contraindicated, alternative options include the use of phytoestrogens as found in plants (soybeans), which can often relieve symptoms of hot flushes. Biphosphonates can also be given to postmenopausal women to prevent bone loss especially when HRT is not able to be used. Other agents such as Raloxifene (Evista) can prevent bone loss by its action on ER in bone, although it has no effect and may in fact aggravate hot flushes. Raloxifene reduces the incidence of breast cancer through its ER antagonist effect on the breast but does not have any beneficial effect on hot flushes. Another medication such as Tibolone (Livial) is metabolized in the liver with the end products having tissue specific effects on oestrogen receptors (ER), progesterone receptors (PR) and also androgen receptors (AR). It is therefore effective in treating hot flushes and low libido while at the same time not having any significant effect on the endometrium. Its effect is mediated by binding to the ER, PR and AR receptors in the various tissues of the body to provide the desired effect. The other major benefit of Tibolone is its ease of administration as a single agent without the need to take progestogen when the uterus is in situ.
It must be remembered that the average life expectancy of the modern woman is 80 years or more and, as a result, the last 30 years may be spent in a state of oestrogen deficiency. The current evidence would favour the use of HRT at the time of menopause, particularly to relieve symptoms of hot flushes and to continue this treatment for a period of five years. The patient should be made aware of the risks and benefits of this treatment so that she can make an informed decision on whether to participate in this important aspect of preventive medicine.