CONTINUOUS LOW-DOSE ESTROGEN AND PROGESTOGEN HORMONE REPLACEMENT THERAPY - A RANDOMIZED TRIAL

Objective: To establish the efficacy and acceptability of combined con tinuous low-dose oestrogen and low-dose progestogen therapy, to determ ine whether any of three commercially available progestogens had any a dvantages or disadvantages in these circumstances and whether use of t he lowest clinically effective oestrogen dose affected other outcomes being measured. Design: A 12-month, prospective, open label, single ce ntre, randomised trial. Patients and methods: Seventy-five postmenopau sal women already receiving hormone replacement therapy in the form of conjugated equine oestrogens (CEE) (0.625 mg daily) and cyclical medr oxyprogesterone acetate (10 mg) and experiencing withdrawal bleeding w ere changed to a continuous daily regimen of 0.3 mg CEE and a random a llocation of one of three low-dose progestogens (medroxyprogesterone a cetate 2.5 mg, levonorgestrel 30 mug or norethisterone 350 mug). Retur n to a dose of 0.625 mg CEE was permitted if required to control menop ausal symptoms with separate analysis of this group when appropriate. Outcomes measured: Menopausal symptom score, clinical bleeding pattern , endometrial biopsy results, forearm bone density and content, serum lipids and side effects. Results: Fifteen women withdrew from the tria l, five because of irregular bleeding. In the remainder, amenorrhoea w as achieved in 53% by three months, in 67% by six months and in 93% by 12 months. Endometrial biopsy showed atrophic endometrium by 12 month s in all but one patient, in whom minimal proliferative activity was s een. Twenty-seven women chose to return to a dose of 0.625 mg CEE. In all groups, final control of symptoms improved. All regimens were bone sparing and the lipid profile was unchanged. Minimal side effects wer e experienced by the patients. There was little difference in outcome between the three progestogens except that norethisterone therapy was associated with a greater prevalence of amenorrhoea at six months than was seen in the levonorgestrel and medroxyprogesterone acetate groups . Conclusions: These low-dose continuous oestrogen and progestogen reg imens appear an appropriate option for the postmenopausal woman wishin g to eliminate withdrawal bleeding and reduce both hormonal side effec ts and menopausal symptoms. The long term benefits of these regimens w ith regard to the prevention of osteoporotic fractures, cardiovascular disease and endometrial cancer need to be further assessed over time.