An answer to the ‘one dose fits all’ WHI study.
Published Nov 2007.
The WHI study worked on the assumption that one dose would fit all asymptomatic post menopausal women. The investigators therefore often used the wrong dose, of the wrong hormones on the wrong patients and therefore came to many wrong conclusions. Different combinations of different hormones are necessary for different symptoms and different age groups. HRT may be commenced in the peri-menopausal phase, the early post menopause, the late post menopause or after hysterectomy and bilateral salpingo-oophorectomy or a premature menopause. These all require different treatments. Similarly various indications such as vasomotor symptoms, sexual problems, depression or the treatment/prevention of osteoporosis all need different combinations of oestradiol and possibly progestogen and testosterone according to the specific requirements of the patient.
Two major well publicised studies, the Women’s Health Initiative (WHI) (1) and the Million Women Study (MWS) (2) has shaken the faith in the safety of HRT for doctors and post menopausal women alike in spite of the criticism of the design and conclusions of the WHI study (3-5) and the many anxieties about the MWS data collection. (6-8) It is now difficult to respond to the WHI study in an optimistic way and for this to be considered and published. Following the NAMS/NIH statement of October 2002 (9) many proscriptive guidelines from advisory bodies in Europe and North America have appeared, which advise prescribing hormone therapy at the lowest dose principally for menopausal vasomotor symptoms, and for the shortest time. (10) It was also recommended that it was not to be used as a primary treatment for low bone density and that it has no place in the prevention of coronary heart disease. In view of later consideration of the data both items of advice are questionable. There is no protest about the uncontroversial recommendation that the lowest dose should be used and the appropriateness of continuing HRT should be reviewed each year with full discussion of benefits and risks. However the ‘lowest dose’ varies from patient to patient and should be one that is effective for a particular indication.
What is missing from statements from regulatory authorities is the understanding that treatment should be individualised for a particular patient, her expectations and her pathology. Such variation of therapy is sound clinical practice but it is notable that the great fault of the WHI study is that there was no individualisation with the assumption that one dose of Prempro fitted all patients regardless of age and general health even though they were, by their inclusion criteria, asymptomatic and did not require therapy.
The epidemiologists and investigators who designed the WHI were not aware, or chose to ignore the basic tenant of good practice relating to HRT. This is the knowledge that different women, require a different dose, by a different route, of different combinations, of different hormones, for different symptoms. This would also vary depending upon the surgical status, the age of the patient and there will also be a difference depending on the clinical needs of the woman. This paper is an attempt to correct that omission by stating the variations necessary for effective treatment with estrogens with the possible addition of progestogens and androgens..