Hormone Replacement Therapy Versus the Combined Oral Contraceptive Pill in Premature Ovarian Failure: A Randomized Controlled Trial of the Effects on Bone Mineral Density

Context: Women with premature ovarian failure (POF) face many years of estrogen deficiency. One of the major consequences is bone loss. The optimal form of estrogen replacement is unknown and management is not evidence based. The 2 broad options are combined hormone replacement therapy (HRT) or the combined oral contraceptive pill (COCP). Objectives: To compare the effects of HRT and COCP on bone density and turnover in women with spontaneous POF and to observe the effects of no treatment. Design: Two-year open randomized trial comparing HRT and COCP and nonrandomized observation of women declining treatment using the same protocol. Setting: London teaching hospital. Participants: A total of 59 women with spontaneous POF aged 18-44, 30 women elected to take treatment and were randomized, and 29 declined treatment. Intervention: Randomization was to HRT (Nuvelle) or COCP (Microgynon 30). Main Outcome Measures: The primary outcome was change in lumbar spine bone mineral density. Changes in total hip and femoral neck bone density and bone turnover markers were also assessed. Results: A total of 36 women (61%) completed the trial (no treatment 52%; HRT 60%; COCP 80%). In comparison with COCP, treatment with HRT increased bone density at the lumbar spine at 2 years (+0.050 g/cm(2); 95% confidence interval 0.007-0.092; P = .025). Bone turnover markers showed similar reductions in the 2 treatment groups. In the no treatment group, bone density dropped at all sites and bone turnover markers remained relatively unchanged. Conclusions: The results suggest that HRT is superior to COCP in increasing bone density at the lumbar spine in women with spontaneous POF. The limitations of a small sample size and high drop-out rate mean that further research is required to confirm the findings. However, either treatment is clearly superior to no treatment.