Professor of Gynaecology, The London PMS Menopause Centre, London.
Until recently it was believed that HRT was an extremely safe treatment for vasomotor symptoms, osteoporosis, depression and a major preventative measure for heart disease, colon cancer, Alzheimer's disease and probably strokes. This has all been turned upside down by two greatly flawed studies, The Women's Health Initiative, (WHI) and the Million Women Study (MWS). These will be discussed.
There is no evidence that oestradiol given in the appropriate dose in women below the age of 60 is associated with serious side effects although the addition of continuous progestogen may be the harmful factor in the causation of cardiovascular disease.
The WHI study studied a single preparation, Prempro (not available in this country), in the belief that one dose fits all patients. This is untrue because different women require different dose via a different route with different combinations of different hormones for different symptoms for different symptoms with different surgical status and for different ages. There was an added fault in that patients were recruited who were without symptoms - hence none of them needed this inappropriate therapy anyway.
This paper describes the different therapies required in women after hysterectomy and bilateral salpingo-oophorectomy, for premature menopause, for the perimenopausal patients with depression or libido problems, for women in the early post menopausal state and for older women in the late menopausal state.
Women with vasomotor symptoms or pelvic atrophy are easily treated with low dose oestradiol either by the oral route or by transdermal gel or patch. The treatment can last for the duration of the symptoms and there is no reason to limit therapy to 5 or 10 years. In patients with a uterus they will require endometrial protection with a progestogen which can be for the orthodox 14 days or continuously or, with patients with progestogen intolerance for 7 days each month.
Young women with premature ovarian failure need oestrogen therapy to protect their bones and their cardiovascular system as well as prevent symptoms until at least the age of 50 - the time of the normal menopause. If there is a suggested limit for the duration of HRT then the counting starts from the age of 50, the age of the normal menopause. It is important to check the bone density of these patients before treatment and every 3 years.
After hysterectomy and bilateral salpingo-oophorectomy, women need oestrogens, sometimes in the higher dose than for more mild symptoms. If they have lost their ovarian androgens, they benefit from the addition of testosterone. These women often suffer symptoms of the female androgen deficiency syndrome, (FADS) which is loss of energy, loss of libido and loss of self confidence, depression and headache. The ideal way to treat these patients is by implantation of oestradiol 25 mgs and testosterone 75 mgs every 6 months.
Patients with perimenopausal depression which is often linked with cyclical premenstrual depression are better treated with transdermal oestrogens in the form of oestradiol patches 100 mcgs or even 200 mcgs. This not only wipes out the cycles producing the cyclical symptoms of PMS but has a mental tonic effect for the perimenopausal women. These women of course require cyclical progestogen tablets but as these women with hormone responsive depression, (perhaps better called reproductive depression) are progestogen intolerant, a Mirena IUS should be considered.
Osteoporosis can usually be prevented by oestradiol therapy and the bone density can be increased in established osteoporosis by the use of oestrogens which produce plasma oestradiol levels of at least 300 pmol/L. This is a most effective therapy, more effective than bisphosphonates or SERMS but of course will not correct any deformity that may have occurred in established osteoporosis.
Many patients have loss of energy and loss of libido and these respond well to a higher dose of oestradiol with or without testosterone. Patients should have a clear explanation of the advantages and the putative dangers of HRT and their need for HRT assessed every year. The lowest effective dose should be used for the appropriate symptom or indication remembering that a higher dose is required for depression or correction of osteoporosis than for vasomotor symptoms.
Older post menopausal women who need oestrogens for pelvic atrophy or established osteopenia or osteoporosis should initially have a very low dose possibly with unopposed oestrogens because the major side effects of the WHI study occur in older women receiving combined oestrogen and progestogen therapy.
The strange syndrome of chronic fatigue syndrome/PMS is associated with low plasma oestradiol levels, low bone density and an excellent response to transdermal oestrogens with or without testosterone. This infrequently recognised condition needs further study.
There may be an increased risk of breast cancer after 5 or 10 years but these data are disputed and on a practical level it is very difficult to persuade women who feel well on HRT to discontinue. Until this issue is clarified, I believe patients should be advised to have a mammogram every 18 months.