A 10-year follow-up of the effect of continuous-combined hormone replacement therapy and its discontinuation on bone in postmenopausal women

Abstract

Objective

To establish the effect on bone mineral density (BMD) of long-term (nine years) continuous-combined hormone replacement therapy (ccHRT) with estradiol valerate/medroxyprogesterone acetate (E₂V/MPA) and follow-up one year after discontinuation of ccHRT.

Study design

A total of 279 women were treated with daily dosages of E₂V + MPA: 1 mg + 2.5 mg (n = 69), 1 mg + 5 mg (n = 70) or 2 mg + 5 mg (n = 140) (Indivina®, Orion Pharma, Espoo, Finland) for 8.5 years; all subjects received the lowest dosage for the next six months. BMD was measured at baseline, between 6 and 12 months, annually until the end of study and at one-year postdiscontinuation of ccHRT.

Main outcome measure

Change in BMD during nine years of treatment with ccHRT and at one-year post-discontinuation of ccHRT.

Results

Progressive increase of vertebral BMD was observed with all dosage regimens throughout nine years, with corresponding reduction in the proportion of women fulfilling criteria for osteoporosis or osteopaenia. Femoral neck BMD reached a peak at about five to six years, whereas in the lumbar spine the BMD increase was sustained until the end of the study treatment. Mean BMD declined after cessation of ccHRT use but remained substantially above baseline levels. In a subset of women (n = 58) there was a rapid (≤4%) loss of vertebral BMD in the year after termination of ccHRT use. These women had lower than average BMD at baseline but no other factor was identified that distinguished them from the overall study population.

Conclusions

Low-dose ccHRT in postmenopausal women is associated with increases in lumbar spine BMD for at least nine years. These gains are not sustained after cessation of therapy but the rate of BMD loss varies between individuals.