Oestrogen is the treatment of choice for women who seek relief from vasomotor symptoms. At least 40 randomized controlled clinical trials have shown that hormone replacement therapy reduces the severity of vasomotor symptoms, often with improvement beginning within the first week. Transdermal oestradiol, intranasal 17ОІ-oestradiol spray, and oral oestrogen are equally effective.
Women prescribed oestrogen who have an intact uterus must take a progestogen for a minimum of 12 days per month or daily in order to prevent endometrial hyperplasia and cancer. Doses shown in Table 3.1 protect the endometrium. Approximately 70% of women given oestrogen with cyclical progestogens will have predictable cyclical bleeding as long as this treatment is continued. Continuous combined oestrogen plus progestogen causes unpredictable light spotting or bleeding, which ceases in the first year of treatment in 90%. Young women may prefer cyclical regimens to avoid unpredictable bleeding, whereas older women usually prefer continuous regimens without cyclical bleeding. Women with a longer duration since menopause have less bleeding when beginning hormone replacement therapy. Regimens combined in one tablet or patch offer convenience and the added safety of ensuring that the progestogen is taken. A well-referenced review of hormone replacement therapy prescription options has been published.
|Table Range of hormone replacement therapy for menopause symptom management|
A commonly used hormone replacement therapy in the UK and USA is conjugated equine oestrogen (0.625 mg) given alone to women who have had a hysterectomy or in combination with progesterone for at least 12 days per cycle to women with a uterus. This combined daily regimen was used in the Heart and Estrogen/Progestin Replacement Study (HERS), the largest published controlled clinical trial of hormone replacement therapy and symptoms, which included 2763 women aged 44 – 79 years. Among HERS women who reported severe hot flushes at baseline, 85% had improved after one year of hormone therapy (Prempro) compared to 48% of women on placebo. Nevertheless, nearly all women said their hot flushes had not completely resolved. Among women who reported trouble sleeping before treatment, a similar low proportion on hormone replacement therapy (37%) and placebo (33%) reported improvement after one year.
The lowest effective dose of oestrogen is presumably the safest dose (although there is no convincing evidence of a dose – response effect for cancer risk). For years the standard dose of oestrogen was 0.625 mg/day of Premarin or its equivalent, based on bone maintenance. It is now clear that many women have satisfactory symptom relief, bone preservation, and less bleeding with half this dose. For example, in one trial conducted in women who reported 8 – 10 hot flushes per day, daily Premarin doses of 0.625, 0.45, or 0.3 mg in combination with medroxyprogesterone acetate (at doses of 2.5 or 1.5 mg/day) were equally effective in reducing the severity and number of hot flushes in the first year of treatment; when oestrogen was given without a progestogen, however, the 0.625 dose was more effective than the lower doses. But in another trial of norethindrone plus ethinyl oestradiol (femhrtВ®) in women who reported at least 10 hot flushes a week, there was a dose-related decrease in hot flush frequency and severity with the best response at the highest dose.
Women with premature ovarian failure or induced menopause may need higher doses for symptom relief. Some, but not all, studies suggest that adding testosterone to oestrogen reduces the oestrogen dose necessary to relieve hot flushes after induced menopause. After women reach the age of natural menopause, some can be encouraged to reduce the dose gradually to the lowest level compatible with their symptoms.
Some women respond well to one dose, drug, or route of administration when another regimen is unacceptable. It is unknown whether differing responses reflect differences in therapy or differences in women. Not all women prescribed hormone replacement therapy feel wonderful, and a majority quit therapy within 2 years. Bleeding, breast pain, and fear of cancer are frequent reasons for non-adherence. On the other hand, women who abruptly stop hormones after years of use (for example, in response to news headlines about oestrogen’s risks) often restart – in order to “feel like their old selves” again.
|Table hormone replacement therapy side effects and contraindications|